Specification
THERAPEUTIC APPLICATIONS IN THE CARDIOVASCULAR FIELD OF
QUINAZOLINEDIONE DERIVATIVES
A subject-matter of the invention is the use of quinazolinedione derivatives as
medicaments or for manufacturing a medicament intended for the treatment and/or
prevention of at least one cardiovascular disease.
The invention relates more particularly to the use of quinazolinedione derivatives
capable of acting as inhibitors of phosphodiesterase 7 (PDE7), indeed even, for some of
these derivatives, capable of also acting as inhibitors of phosphodiesterase 8 (PDE8), it
being known that it is not ruled out for these same quinazolinedione derivatives also to be
capable of acting via other biological/biochemical routes on the cardiovascular system,
with the aim of treating one or more cardiovascular condition(s) and/or preventing the
appearance of such condition(s).
Phosphodiesterases (PDEs) are intracellular enzymes responsible for the
hydrolysis of cAMP (cyclic adenosine 3',5'-monophosphate) and cGMP (cyclic guanosine
3',5'-monophosphate) secondary messengers to give inactive 5'-monophosphate
nucleotides. cAMP and cGMP play an essential role in cell signalling pathways and are
involved in numerous physiological processes.
The inhibition of phosphodiesterases is reflected by an increase in intracellular
concentrations of cAMP and cGMP, resulting in the specific activation of phosphorylation
pathways involved in varied functional responses. The increase in the intracellular
concentrations of cAMP or of cGMP using selective inhibitors of phosphodiesterases
appears to be a promising approach in the treatment of various diseases (Bender and
Beavo, Pharmacol. Rev., (2006) 58, 488-520). The inhibitors of phosphodiesterases are
thus of interest as therapeutic agents and as pharmacological tools.
To date, eleven families of phosphodiesterases have been identified. They are
distinguished by their primary structure, their substrate specificity and their sensitivity with
regard to various effectors and inhibitors specific for PDEs. Each family is composed of
one or more genes which are expressed in various tissues in the form of splicing variants
(Bender and Beavo, Pharmacol. Rev, (2006) 58, 488-520; Lugnier, Pharmacol.
Therapeut., (2006) 109, 366-398).
PDE4, PDE7 and PDE8 specifically hydrolyse cAMP and PDE5, PDE6 and PDE9
specifically hydrolyse cGMP.
The family PDE7 is represented by the isoforms PDE7A and PDE7B originating
from two distinct genes.
Human PDE7A (Michaeli et al., J. Biol. Chem, (1993) 268, 12925-12932; Han et
al, J. Biol. Chem., (1997) 272, 16152-16157; Wang et al., Biochem. Biophys. Res.
Commun, (2000) 276, 1271-1277) and human PDE7B (Sasaki et al, Biochem. Biophys.
Res. Commun, (2000), 271, 575-583; Gardner et al, Biochem. Biophys. Res. Commun,
(2000) 272, 186-192) selectively hydrolyse cAMP with Michaelis constants (Km) of 0.1 to
0.2 pM and 0.13 to 0.2 uM respectively. The catalytic part of PDE7B exhibits
approximately 67% homology with that of PDE7A.
Three splicing variants are known for PDE7A. PDE7A1 and PDE7A3 are
expressed mainly in the cells of the immune system and of the lungs, while PDE7A2 is
above all expressed in the muscles of the skeleton, the heart and the kidneys. For
PDE7B, three variants have also recently been identified (Giembycz and Smith, Drugs
Future, (2006)31,207-229).
The tissue distribution profiles for PDE7A and PDE7B are very different,
suggesting that these two isoforms have distinct functions from the physiological
viewpoint. PDE7A is copiously expressed in haematopoietic cells, the lungs, the
placenta, the spleen, the muscles of the skeleton, the heart, Leydig cells, the collecting
tubes of the kidneys, and the adrenal glands. Strong expression of PDE7B is detected in
the pancreas, the heart, the thyroid and the muscles of the skeleton (Giembycz and
Smith, Drugs Future, (2006) 31, 207-229; Wang etal., Biochem. Biophys. Res. Commun.
(2000), 276, 1271-1277). Coexpression of the messenger RNAs (mRNAs) of PDE7A and
PDE7B is observed in some tissues. This is the case in the osteoblasts (Ahlstrom et al.,
Cell Mol. Biol. Lett., (2005) 10, 305-319) and in some regions of the brain: several areas
of the cortex, the dentate gyrus, the majority of the components of the olfactory system,
the striatum, numerous nuclei of the thalamus and the pyrimidal cells of the hippocampus
(Miro et al., Synapse, (2001) 40, 201-214; Reyes-lrisarri et al., Neuroscience, (2005) 132,
1173-1185). In contrast, in some areas of the brain, only one of the two isoforms is
expressed. Thus, only the mRNAs of PDE7A are present in many nuclei of the brain
stem. Likewise, the mRNAs of PDE7B are present at high concentrations in the nucleus
accombens and the dorsal motor nucleus of the vagus nerve, while the mRNAs of
PDE7A are not detected there (Miro et al„ Synapse, (2001) 40, 201-214; Reyes-lrisarri et
al., Neuroscience, (2005) 132, 1173-1185).
A subject-matter of the present invention is in particular therapeutic applications of
quinazolinedione derivatives, which can prove to be powerful inhibitors of PDE7, or of
PDE7 and of PDE8, according to the derivatives, or which can act by other biological
routes.
The invention relates to the use of a compound corresponding to the following
general formula (I):
in which
— A represents an aryl group or a heteroaryl group;
— R1represents:
■ a hydrogen atom,
■ -C(O)R in which R is a hydrogen atom, a (C1-C6) alkoxy group, an aryl group, a
(C3-C6) cycloalkyl group or a (C1-C6) alkyl group, the said alkyl optionally being
substituted by:
. one or more hydroxyl group(s),
. a benzyloxy group,
. a (C1-C6) alkoxy group, optionally substituted by an aryl, or
. a (C3-C6) cycloalkyl group,
■ an optionally substituted (C1-C6) alkyl group;
— R2 represents:
■ a hydrogen atom,
■ a halogen atom,
■ a cyano group,
■ a nitro group,
■ a (C1-C6) alkyl group optionally substituted by an -NH2 or else by an
-NHC(O)Rb group, with Rb as defined below,
■ an -ORa group in which Ra represents:
. a hydrogen atom,
. a (C1-C6) alkyl group optionally substituted by one or more halogen
atom(s), by one or more hydroxyl group(s), by an aryl group and/or by one or
more cyano group(s),
. a (C2-C6) alkynyl group,
. an aryl group;
— R3 represents:
■ a hydrogen atom,
■ a halogen atom,
■ a hydroxyl group,
■ a cyano group,
■ an -SCF3 group,
■ a nitro group,
■ an -S(O)0-2-alkyl group, an -S(O)0-2-heterocycloalkyl group, an -O-SO2-aryl
group optionally substituted by one or more halogen atom(s);
■ an -alkylaminoalkyl or -cycloalkylaminoalkyl group, each optionally substituted
on the end alkyl,
■ an optionally substituted sulphonamide group,
■ an aryl group or a heteroaryl group, the said group being monocyclic or
polycyclic and in addition optionally being substituted by a (C1-C6) alkyi group, by
one or more halogen atom(s) or by a (C1-C6) alkoxy group,
■ a heterocycloalkyl group optionally substituted by a (C1-C6) alkyl group,
■ a (C1-C6) alkyl group optionally substituted by:
- one or more halogen atom(s),
- an aryl group which can be substituted by one or more halogen atom(s)
or by one or more hydroxyl group(s),
- a heteroaryl group,
- one or more hydroxyl group(s) which can be substituted by an aryl group
itself optionally substituted by one or more halogen atom(s), or
- a heterocycloalkyl group optionally substituted by a CO(O)Ra group or by
a (C1-C6) alkyl group, Ra being as defined above,
■ a -C(O)NRbRc group, with Rb and Rc being as defined below,
■ a -C(O)ORc group or an -O-C(O)ORc group, with Rc being as defined below,
■ a (C1-C6) alkoxy group, optionally substituted by
- an aminoalkyl group,
- an aminocycloalkyl group,
- a cycloalkyl group,
- a heterocycloalkyl group,
- a monocyclic or polycyclic heteroaryl group,
- one or more hydroxyl group(s),
- one or more halogen atom(s),
- a (C1-C6) alkoxy group,
- a -C(O)ORc group, with Rc being as defined below,
- a -C(O)NRbRc group, with Rb and Rc being as defined below, and/or
-an aryl group, itself optionally substituted by one or more halogen
atom(s), a cyano group, a (C1-C6) alkoxy group, an -O-haloalkyl group and/or a
haloalkyl group,
■ an -O-cycloalkyl group, an -O-aryl group or an -O-heterocycloalkyl group, each
optionally substituted by
-an aryl group, itself optionally substituted by one or more halogen
atom(s) or by a (C1-C6) alkyl group,
- one or more halogen atom(s), and/or
- a (C1-C6) alkyl group, which can itself be substituted by an aryl group,
■ an -NH-CO-NH-aryl group, an -NH-CO-NH-heteroaryl group or an -NH-CO-
NH-(C1-C6) alkyl group, each optionally being substituted by one or more halogen
atom(s), by a cyano group, by a nitro group, by one or more hydroxyl group(s) or by a
(C1-C6) alkoxy group,
■ an -N-(C1-C6) alkyl group, it being possible for the (C1-C6) alkyl group to be
substituted by
one or more aryl group(s) optionally substituted by one or more halogen atom(s)
and/or by an SO2 group,
■ an -NH-CO-aryl group or an -NH-CO-heteroaryl group, each optionally being
substituted by one or more halogen atom(s);
or else R3 forms, with A, a polycyclic heteroaryl group optionally substituted by a (C1-C6)
alkoxy group or a (C1-C6) alkyl group optionally substituted by an aryl group which can
itself be substituted by one or more halogen atom(s);
— R4 represents a hydrogen atom or a (C1-C6)alkyl group;
— Rb represents:
. a hydrogen atom,
. a (C1-C6) alkyl group optionally substituted by one or more halogen atom(s), by
one or more hydroxyl, cyano, amino, heterocycloalkyl or (C1-C6) alkoxy group(s) or by an
aryl group optionally substituted by one or more halogen atom(s),
. a (C3-C6) cycloalkyl group,
. a (C2-C6) alkynyl group,
. a (C1-C6) alkoxy group,
. an aryl group optionally substituted by one or more halogen atom(s);
— Rc represents a hydrogen atom or a (C1-C6) alkyl group optionally substituted
by one or more halogen atom(s);
or then Rb and Rc form, together with the nitrogen atom to which they are attached, a
polycyclic heteroaryl group or a heterocycloalkyl group;
— m and n represent, independently of one another, the value 0, 1 or 2, it being
understood that m+n<3;
— p and p' represent, independently of one another, the value 1, 2 or 3, it being
understood that, when p is greater than or equal to 2, then the R2 groups are on separate
carbon atoms and can be different from one another and, when p' is greater than or
equal to 2, then the R3 groups are on separate carbon atoms and can be different from
one another;
— q represents the value 0 or 2, it being understood that, when q = 0, then the
nitrogenous heterocyclic group attached to the nitrogen situated in the 1 position of the
2,4-dioxo-1,2,3,4-tetrahydroquinazoline ring system is no longer bridged and is of the
type:
with R-1, R4, m and n as defined above,
— r represents the value 0 or 1,
as medicament or for the preparation of a medicament which are intended to treat at
least one cardiovascular disease and/or to prevent the appearance of at least one
cardiovascular disease.
The compounds of general formula (I) can comprise one or more asymmetric
carbons. They can thus exist in the form of enantiomers or of diastereoisomers. These
enantiomers or diastereoisomers, and their mixtures, including racemic mixtures, come
within the invention.
Due to their structure, the compounds of general formula (I) can also exist in the
form of isomers of rotamer or atropisomer type.
The compounds of formula (I) can also exist in the form of bases or addition salts
with acids. Such addition salts come within the invention.
These salts are advantageously prepared with pharmaceutical^ acceptable acids
but the salts of other acids, for example of use in the purification or separation of the
compounds of general formula (I) also come within the invention.
The compounds of general formula (I) can also occur in the crystalline,
amorphous or oily form, these forms coming within the invention.
The compounds of general formula (I) can in addition occur in the form of
hydrates or of solvates, namely in the form of combinations or of associations with one or
more molecules of water or with a solvent. Such hydrates and solvates also come within
the invention.
According to the present invention, the N-oxides of the compounds comprising an
amine also come within the invention.
The compounds of formula (I) in accordance with the invention also comprise
those in which one or more hydrogen, carbon or halogen, in particular chlorine or
fluorine, atoms have been replaced by their radioactive isotopes, for example tritium, in
order to replace hydrogen, or carbon-14, in order to replace carbon-12. Such labelled
compounds are of use in research, metabolism or pharmacokinetic studies or in
biological and pharmacological assays as tools.
In the context of the invention, the following definitions apply:
- in (C1.C6)' the numerical indices determine the possible number of carbon atoms
present in a chain or a ring. Thus, by way of example, C1-C6 represents a carbon chain
which can have from 1 to 6 carbon atoms. Likewise, by way of example, (C1-C5)
represents a carbon chain which can have from 1 to 5 carbon atoms or also (C3-C6) can
represent a saturated carbon ring which can have from 3 to 6 carbon atoms;
-alkoxy: an -O-alkyl group comprising a saturated, linear or branched, aliphatic
chain;
- alkynyl: a mono- or polyunsaturated, linear or branched, aliphatic group comprising,
for example, one or two acetylenic unsaturations. For example, a (C2-C6) alkynyl group
can represent an ethynyl, propynyl, and the like;
- alkyl: a saturated, linear or branched, aliphatic group; for example, a (C1-C6) alkyl
group represents a linear or branched carbon chain of 1 to 6 carbon atoms, in particular
a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl or pentyl;
- aminoalkyl: an -NH(C1-C6) alkyl or also -N((C1-C6) alkyl)2 group;
- aryl: an optionally substituted monocyclic aromatic system comprising from 5 to
14 members per ring, preferably from 5 to 10 members per ring. Mention may be made,
as examples of monocyclic aryl groups, of phenyl or naphthyl; the aryl group can be
substituted by a group which can be one or more halogen atom(s), a hydroxyl group, a
cyano group, a trifluoromethylthio group, a nitro group, an alkyl group, an alkoxy group,
an alkylthio group, a methylsulphonyl group, an alkylaminoalkyl group or
alkylaminocycloalkyl group which is optionally substituted, an alkylaminoalkoxy or
cycloalkylaminoalkoxy group or a sulphonamide group, for example:
- polycyclic aryl: an optionally substituted polycyclic aromatic system comprising from
5 to 14 members per ring, preferably from 5 to 10 members per ring, and comprising
from 2 to 10 rings, at least one of the rings of which is aromatic. Mention may be made,
as examples of polycyclic aryl groups, of aceanthrylene, anthracene, azulene, coronene,
rubicene or naphthalene; the polycyclic aryl group can be substituted by a group which
can be one or more halogen atom(s), a hydroxyl group, a cyano group, a
trifluoromethylthio group, a nitro group, an alkyl group, an alkoxy group, an alkylthio
group, a methylsulphonyl group, an alkylaminoalkyl or alkylaminocycloalkyl group which
is optionally substituted, an alkylaminoalkoxy or cycloalkylaminoalkoxy group or a
sulphonamide group, for example;
- a bridged ring: a bicyclic structure comprising, according to the invention, a
nitrogen atom, in which at least two carbon atoms are connected via a single bond or a
carbon chain which can comprise 2 carbon atoms. By way of example, the
abovementioned ring is of the type:
with q = 1 or 2 and with the other groups and indices as defined above;
- cycloalkyl: a saturated cyclic aliphatic group comprising from 3 to 8 carbon atoms.
Mention may be made, by way of example, of a cyclopropyl, methylcyclopropyl,
cyclobutyl, cyclopentyl or cyclohexyl group;
- halogen: a fluorine, a chlorine, a bromine or an iodine;
- haloalkyl: (C1-C6) alkyl substituted by one to three halogen atom(s);
- heteroaryl: a monocyclic aromatic system comprising from 5 to 14 ring members,
preferably from 5 to 10 ring members, and comprising one to several heteroatoms, such
as nitrogen, oxygen or sulphur atoms. The nitrogen atoms can be in the form of
N-oxides. For example, a monocyclic heterocycle can be a pyran, a pyrazine, a pyrazole,
a pyridazine, a pyridine, a pyrimidine, a pyrrole, an isothiazole, an isoxazole, a furan, an
imidazole, a morpholine, a thiophene, a piperazine, a diazetidine, a dihydropyrrolidine, a
piperidine, an azepine, and the like; a bicyclic heterocycle can be an isoquinoline, a
pteridine, a chroman, and the like; a tricyclic heterocycle can be a phenanthroline, a
xanthene, and the like;
- polycyclic heteroaryl: an optionally substituted polycyclic aromatic system
comprising from 5 to 14 members per ring, preferably from 5 to 10 members per ring,
and comprising from 2 to 10 rings, additionally comprising one to several heteroatoms,
such as nitrogen, oxygen or sulphur atoms, in at least one of the rings, and at least one
of the rings of which is aromatic. Mention may be made, as examples of polycyclic
heteroaryl groups, of indole, benzofuran, benzimidazole, benzothiophene, benzotriazole,
benzothiazole, benzoxazole, quinoline, isoquinoline, indazole, quinazoline, phthalazine,
quinoxaline, naphthyridine, 2,3-dihydro-1H-indole, 2,3-dihydrobenzofuran, 2,3-dihydro-
indene, tetrahydroquinoline, tetrahydroisoquinoline or tetrahydroisoquinazoline;
- a heterocycloalkyl: an optionally substituted saturated ring comprising from 3 to
8 atoms and comprising one to several heteroatoms, such as nitrogen, oxygen or sulphur
atoms, in at least one of the rings, or several heteroatoms which are identical to or
different from one another. For example, a heterocycloalkyl can be a pyrrolidine, a
morpholine, a piperazine, a diazetidine, a dihydropyrrolidine, a piperidine, a piperadine,
an azepan, an imidazolidine, a thiomorpholine, a tetrahydropyran, a tetrahydrothiopyran,
a piperazine, a diazepan, and the like;
- hydroxyl: an -OH group;
- nitro: an -N02 group;
- oxo: a -C(O)- group;
- sulphonamide: group corresponding to the formula SO2-N-alkyl or SO2-N-cyclo-
alkyl, alkyl and cycloalkyl being as defined above;
- trifluoromethylthio is defined by the formula -S-CF3.
Furthermore, it is understood that, in the present description, when an atom or a
group is substituted or optionally substituted by one or more defined group(s) or atom(s),
the substituents can be identical to or different from one another and may be carried, if
appropriate, by the same atom or different atoms.
Mention may be made, among the compounds which are a subject-matter of the
invention, of a group of compounds of formula (I) in which A represents an aryl group, in
particular a phenyl or heteroaryl group, in particular a pyridyl group, and all the other
substituents and indices are as defined in the general formula (I) defined above.
Mention may be made, among the compounds in accordance with the invention, of a
group of compounds of formula (I) in which q = 0, m and n each represents 1, and all the
other substituents and indices are as defined in the general formula (I) defined above.
Mention may be made, among the compounds in accordance with the invention, of a
group of compounds of formula (I) in which R2 represents a (C1-C6) alkyl group, in
particular a methyl, substituted by an -NHC(O)Rb group in which Rb and the other
substituents and indices are as defined for the compound of general formula (I) defined
above.
Mention may be made, among the compounds in accordance with the invention, of a
group of compounds of general formula (I) in which R2 represents an -ORa group, the Ra
group and all the other substituents and indices being as defined in the general formula
(I) defined above.
Mention may be made, among the compounds in accordance with the invention, of a
group of compounds of general formula (I) in which R2 is a halogen atom or a cyano or a
hydrogen or a hydroxyl or a (C1-C6) alkyl optionally substituted by an -NH2, or else by an
-NHC(O)Rb group, Rb and the other substituents and indices being as defined in the
general formula (I) defined above.
Mention may be made, among the compounds in accordance with the invention, of a
group of compounds of general formula (I) in which A is a phenyl, R, is a -C(O)R group in
which R represents a hydrogen atom, q is equal to 0, n and m each have the value 1,
and R2 represents -ORa, Ra and the other substituents and indices being as defined in
the general formula (I) defined above.
Mention may be made, among the compounds in accordance with the invention, of a
group of compounds of general formula (I) in which A is a phenyl, R, is a -C(O)R group in
which R represents a hydrogen atom, q is equal to 0, n and m each have the value 1, p is
equal to 2, one of the R2 groups is -ORa and the other of the R2 groups is a halogen
atom, Ra and the other substituents and indices being as defined in the general formula
(I) defined above.
Mention may be made, among the compounds in accordance with the invention, of a
group of compounds of general formula (I) in which A is a phenyl, R1 is a -C(O)R group in
which R represents a hydrogen atom, q is equal to 0, n and m each have the value 1,
p = 1 and R2 is a methyl substituted by an -NH-CO-Rb group, Rb and the other
substituents and indices being as defined in the general formula (I) defined above.
Advantageously, in the compounds of formula (I), the R2 group is in the 6 position of
the 2,4-dioxo-1,2,3,4-tetrahydroquinazoline ring system. The compounds of formula (I)
can also have an R2 group in the 7 position of the 2,4-dioxo-1,2,3,4-tetrahydroquinazoline
ring system. The R2 groups in the 6 and 7 positions can be identical or different.
Advantageously, in the compounds of formula (I), p is equal to 1 or 2.
The compounds of general formula (I) can be in the base, hydrate or solvate form, in
the form of isomers or in the form of their mixtures.
In a specific form, when p' = 2, then the two R3 groups are in the 3 and 4 positions of
the ring system A and can be different from one another.
The combinations of the groups of compounds in accordance with the invention
mentioned above also come within the invention.
Mention may be made, as examples of preferred compounds in accordance with the
invention, of the following compounds:
No. 1: 2-{[3-(3,4-dimethoxybenzyl)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]oxy}propanenitrile
No. 2: 1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-6-hydroxyquinazoline-
2,4(1 H,3H)-dione
No. 3: {[1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]oxy}acetonitrile
No. 4: 2-{[1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]oxy}propanenitrile
No. 5: {[3-(3,4-dimethoxybenzyl)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]oxy}acetonitrile
No. 11: 4-[3-(3,4-dimethoxybenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-
3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 12:1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-6-[2-fluoro-1-
(fluoromethyl)ethoxy]quinazoline-2,4(1H,3H)-dione
No. 13:4-[3-(3,4-dimethoxybenzyl)-2,4-dioxo-6-(2,2,2-trifluoroethoxy)-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 14: 1-(1-acetylpiperidin-4-yl)-6-(2,2-difluoroethoxy)-3-(3,4-
dimethoxybenzyl)quinazoline-2,4(1H,3H)-dione
No. 16: 4-[6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 20: N-{[3-(3,4-dimethoxybenzyl)-1-(1-formylpiperidir-4--yl)-2,4dioxo-1 ,2,3,4-
tetrahydroquinazolin-6-yl]methyl}acetamide
No. 22: 1-(1-acetylpiperidin-4-yl)-6-(aminomethyl)-3-(3,4-
dimethoxybenzyl)quinazoline-2,4(1 H,3H)-dione hydrochloride
No. 23: N-{[3-(3,4-dimethoxybenzyl)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]methyl}formamide
No. 24: N-{[1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]methyl}formamide
No. 25: N-{[1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]methyl}acetamide
No. 32:4-[6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-
yl]piperidine-1 -carbaldehyde
No. 33:4-[3-(3,4-dichlorobenzyl)-6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 34:4-[3-(4-chlorobenzyl)-6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 35: methyl 4-{[6-(2,2-difluoroethoxy)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,4-
dihydroquinazolin-3(2H)-yl]methyl}benzoate
No. 36: 4-{[6-(2,2-difluoroethoxy)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,4-
dihydroquinazolin-3(2H)-yl]methyl}benzoicacid
No. 37: 4-{[6-(2,2-difluoroethoxy)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,4-
dihydroquinazolin-3(2H)-yl]methyl}-N-(2-methoxyethyl)benzamide
No. 38: 4-t3-(3,4-dimethoxybenzyl)-6-methyl-2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-
yl]piperidine-1 -carbaldehyde
No. 39:4-[6-(2,2-difluoroethoxy)-3-(3-hydroxy-4-methoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 40:4-[6-(2,2-difluoroethoxy)-3-[3-(2-hydroxyethoxy)-4-methoxybenzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 41:4-[6-(2,2-difluoroethoxy)-3-(3-ethoxy-4-methoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 42:4-[6-(2,2-difluoroethoxy)-3-[4-methoxy-3-(2-methoxyethoxy)benzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 43:4-[6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]azepane-1-carbaldehyde
No. 47:4-[6-(2,2-difluoroethoxy)-3-[3-(3-hydroxypropoxy)-4-methoxybenzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 48: 4-[5-chloro-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-
yl]piperidine-1 -carbaldehyde
No. 49:4-{3-[3-(cyclopentyloxy)-4-methoxybenzyl]-6-(2,2-difluoroethoxy)-2,4-dioxo-
3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 50: 2-(5-{[6-(2,2-difluoroethoxy)-1 -(1-formylpiperidin-4-yl)-2,4-dioxo-1,4-
dihydroquinazolin-3(2H)-yl]methyl}-2-methoxyphenoxy)acetamide
No. 51: 4-[6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]-3-methylpiperidine-1-carbaldehyde
No. 52:3-[6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]-8-azabicyclo[3.2.1]octane-8-carbaldehyde
No. 56: 4-{3-[4-(cyclopentyloxy)-3-methoxybenzyl]-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 57: 4-[3-(3-chlorobenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 58:4-[3-(4-chlorobenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 59: 4-{3-[3-(cyclopentyloxy)-4-methoxybenzyl]-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 72: 4-[3-(3,4-dimethoxybenzyl)-6-(2-hydroxyethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 74: 4-[3-(3,4-dichlorobenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 76: 4-{3-[(6-chloropyridin-3-yl)methyl]-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 78: 4-[3-(3-chloro-4-methoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 79: 4-[3-(3,4-dimethoxybenzyl)-6-(2-fluoroethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 89:2-[5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-2,4-
dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxyphenoxy]acetamide
No. 90: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-(3-hydroxy-4-methoxybenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 91: 4-[3-(3,4-dimethoxybenzyl)-6-ethoxy-2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-
yl]piperidine-1 -carbaldehyde
No. 97: 4-[5,7-dichloro-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-
1 (2H}-yl]piperidine-1 -carbaldehyde
No. 102: 4-[7-chloro-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-
1 (2H)-yl]piperidine-1 -carbaldehyde
No. 108: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-fluoro-4-methoxybenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 111: 4-[6-(difluoromethoxy)-3-(3,4-dimethoxybenzyl)-2l4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 112: 4-[3-(3 AdimethoxybenzyO-e-O-methylethoxy^^-dioxo-S^-
dihydroquinazolin-I^HJ-yOpiperidine-l^arbaldehyde
No. 114: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-methoxy-3-(1-
methylethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 116:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-(3-methoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 117: 4-{3-[3,5-bis(trifluoromethyl)benzyl]-6-[2-fluoro-1-(fluoromethyl)ethoxy]-
2,4-dioxo-3>4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 118: 4-[3-(3-ethoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 124:4-{3-[3-chloro-4-(2-methoxyethoxy)benzyl]-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 130:4-[3-(3,4-diethoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-
3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 131:4-[3-(4-ethoxy-3-methoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 133: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(4-methoxy-3-methylbenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 134: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-
(trifluoromethyl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 135: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-
(trifluoromethyl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 143: 4-{3-[4-(benzyloxy)-3-methoxybenzyl]-6-[2-fluoro-1-(fluoromethyl)ethoxy]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 145:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-(3-methoxy-4-nitrobenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 155: 4-[3-(4-ethoxybenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 158: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-t4-(morpholin-4-ylmethyl)benzylj-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 160: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(4-(morpholin-4-yl)benzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 165: 4-[3-(biphenyl-4-ylmethyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-
3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 166:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(methylsulphanyl)benzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 167: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyridin-3-yl)benzyl)-
3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 170: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-methylbenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 175: 2-[2-(cyclopentyloxy)-5-({6-t2-fluoro-1-(fluoromethyl)ethoxy]-1-(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]acetamide
No. 178: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-(3-methoxy-4-propoxybenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 183:2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
methylacetamide
No. 184:2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N,N-
dimethylacetamide
No. 185:2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
methoxy-N-methylacetamide
No. 186: 4-{3-[4-(cyclopentyloxy)-3-ethoxybenzyl]-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 188: 4-{3-[4-(cyclopentyloxy)-3-(1 -methylethoxy)benzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 189: 4-{3-[4-(cyclopentyloxy)-3-propoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 190: 4-{3-[4-(cyclopentyloxy)-3-hydroxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 193: 4-{3-[4-(difluoromethoxy)-3-methoxybenzyl]-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 194: 4-{3-[4-(difluoromethoxy)-3-ethoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 200: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(thiophen-3-yl)-
benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 201: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyridin-4-yl)benzyl)-
3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 203:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(1-methyl-1H-indol-6-yl)methyl]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 206: 4-{3-[4-(cyclopropylmethoxy)-3-methoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidin6-1-carbaldehyde
No. 207: 2-[4-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-2,4-
dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxyphenoxy]-N-methylacetamide
No. 212: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-(1 H-pyrazol-1 -
yl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 213: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyridin-2-yl)benzyl)-
3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 215: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(thiophen-2-yl)-
benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 216: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(quinolin-7-ylmethyl)-
3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 218: 4-{6-t2-fluoro-1-(fluoromethyl)ethoxy]-3-[(6-methoxynaphthalen-2-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 223: 4-{3-[4-(1 H-benzimidazol-1 -yl)benzyl]-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 224: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(2-
methylpropoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 226: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(tetrahydrofuran-3-
yloxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 228: 4-[3-{4-[(1 -benzylpyrrolidin-3-yl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 230: 4-[3-(1-benzothiophen-5-ylmethyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 232: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[3-methoxy-4-(1-
methylethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 233: 4-[3-(3,4-dimethoxybenzyl)-7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 234: 4-[3-{4-[(1 -acetylpyrrolidin-3-yl)oxy]-3-methoxybenzyl}-6-t2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 239: 4-[3-{4-[(4-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 240: 4-[3-{4-[(4-chlorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 242: 4-[3-{4-[(3-chlorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 243:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(3-(thiophen-3-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 245: 4-[3-(4-ethoxy-3-methoxybenzyl)-6-(2-hydroxyethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 246: 4-[3-{4-[2-(2,3-dihydro-1 H-indol-1-yl)-2-oxoethoxy]-3-methoxybenzyl}-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 250: 4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3>4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 251:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[3-methoxy-4-(2-oxo-2-(piperidin-
1-yl)ethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 254: 4-{3-[3-ethoxy-4-(thiophen-2-ylmethoxy)benzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 258:4-[3-(3,4-dimethoxybenzyl)-6-[2-fluoro-1-(hydroxymethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 263: (2R)-2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]propanoic
acid
No. 264:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(1-methyl-3-(thiophen-2-yl)-1H-
pyrazol-5-yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 270: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(5-methyl-1,2,4-oxadiazol-3-
yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 275: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyrimidin-5-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 276: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(1-methyl-3-phenyl-1H-pyrazol-5-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 278: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-{[6-(1H-pyrazol-1-
yl)pyridin-3-yl]methyl}-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 279: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-[(2-(thiophen-2-
yl)pyrimidin-5-yl)methyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 280: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(1-methyl-1H-pyrazol-3-
yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 282: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(3-methyl-1,2,4-oxadiazol-5-
yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 283: [2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1I4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]aceticacid
No. 285: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(thieno[2,3-b]pyridin-2-
ylmethyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 286: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-t(6-phenylpyridin-3-
yl)methyl]-3,4-dihydroquinazoiin-1(2H)-yl}piperidine-1-carbaldehyde
No. 287: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(6-(morpholin-4-yl)pyridin-3-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 289: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[(6-(thiophen-2-
yl)pyridin-3-yl)methyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 292: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(1-methyl-5-phenyl-1 H-pyrazol-3-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 294: 4-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-2,4-dioxo-
1,4-dihydroquinazolin-3(2H)-yl}methyl)biphenyl-2-carbonitrile
No. 295: (2R)-2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
methylpropanamide
No. 297: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(thiophen-2-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 298: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(morpholin-4-
ylmethyl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 299: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[3-methoxy-4-(piperidin-1-
ylmethyl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 300: 4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydraquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 301: 2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
ethylacetamide
No. 302: (2S)-2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]propanoic
acid
No. 305: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-{[(3R)-2-oxo-1-
phenylpyrrolidin-3-yl]oxy}benzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 306: 4-{3-[4-(cyclobutylmethoxy)-3-methoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 307: 4-{3-[4-(benzyloxy)-3-methoxybenzyl]-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 308: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(4-hydroxy-3-
methoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 309: 4-{3-[4-(cyclopropylmethoxy)-3-methoxybenzyl]-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 310: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-
(2-methylpropoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 311: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[3-methoxy-4-
(1-methylethoxy)benzyl]-2,4-dioxo-3,4-dihyclroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 312: 4-[3-(4-ethoxy-3-methoxybenzyl)-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 315: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-{[6-(3-
methoxyphenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 316: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-{[6-(2-
fluorophenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 317: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-{[6-(4-
fluorophenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 318: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{[6-(4-
methoxyphenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 319: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-[(6-(thiophen-2-
yl)pyridin-3-yl)methyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 320: 4-{3-t3-ethoxy-4-(thiophen-2-ylmethoxy)benzyl]-7-fluoro-6-t2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 321: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(1 -methyl-1 H-pyrazol-
3-yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 322:4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyrimidin-5-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 323: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[(1 -methyl-3-(thiophen-2-
yl)-1 H-pyrazol-5-yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-yl}piperidine-1 -
carbaldehyde
No. 324: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(2-oxo-2-
(piperidin-1-yl)ethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 325: 4-[3-{4-[2-(2,3-dihydro-1 H-indol-1-yl)-2-oxoethoxy]-3-methoxybenzyl}-7-
fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]piperidine-1 -carbaldehyde
No. 326: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(5-methyl-1,2,4-
oxadiazol-3-yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 327: 4-[3-{4-[(3-chlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-t2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 328:4-[3-{[6-(3,5-dichlorophenyl)pyridin-3-yl]methyl}-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 329:4-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)biphenyl-2-carbonitrile
No. 330: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-(1 H-pyrazol-
1-yl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 331: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{[6-(3-
fluorophenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 332: 3-[5-({7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -formylpiperidin-4-
yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)pyridin-2-yl]benzonitrile
No. 333:4-[3-(3,4-diethoxybenzyl)-7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 334: 4-[3-{4-[(4-chlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 335: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[4-(morpholin-4-
ylmethyl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 336: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-{[6-(1 H-pyrazol-
1 -yl)pyridin-3-yl]methyl}-3,4-dihydroquinazolin-1 (2H)-yl}piperidine-1 -carbaldehyde
No. 337: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-(4-(morpholin-4-yl)-
benzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 338:4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-(3-methoxy-4-
propoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 339: 4-{3-[4-(1 H-benzimidazol-1 -yl)benzyl]-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 340: 5-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxybenzonitrile
No. 341: 3-(3,4-dimethoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-7-carbonitrile
No. 342: 4-[3-(4-bromobenzyl)-7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 343: 4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-(2-methoxyethoxy)benzyl}-7-fluoro-6-
[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 344: 4-{3-[4-(benzyloxy)benzyl]-7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 345: 4-f3-{4-[(3,4-dichlorobenzyl)oxy]-3-ethoxybenzyl}-7-fluoro-5-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 349:4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-(2-fluoroethoxy)benzyl}-7-fluoro-6-[2-
fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-yl]piperidine-1 -
carbaldehyde
No. 350: 4-[3-{4-[(2-chloro-4-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 351: 4-[3-{4-[(2,4-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 352: 4-[3-{4-[(2-chloro-6-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 353: 4-[3-{4-[(2,6-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 354: 4-[3-{4-[(2-chlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 355: 4-[7-fluoro-3-{4-[(2-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 357: 2-[(3,4-dichlorobenzyl)oxy]-5-({7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-
1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)benzonitrile
No. 358: 4-[3-{4-t(3,4-dichlorophenoxy)methyl]-3-methoxybenzyl}-7-fluoro-6-t2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 360:4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-(2-
phenylethyl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 362:4-[3-{4-[(4,5-dichloro-2-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 369: 4-[3-{4-[(4-chlorophenoxy)methyl]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 371:4-[3-{3-chloro-4-[(4-chlorobenzyl)oxy]-5-ethoxybenzyl}-7-fluoro-6-[2-fluoro-
1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 373: 4-[3-{3-chloro-4-[(2,4-dichlorobenzyl)oxy]-5-ethoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 375: 4-[7-fluoro-3-{4-[(4-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 376: 4-[3-{4-[(3,5-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 377: 4-[3-(4-{[4-chloro-3-(trifluoromethyl)benzyl]oxy}-3-methoxybenzyl)-7-
fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquina2olin-1(2H)-
yl]piperidine-1 -carbaldehyde
No. 379: 4-[3-{4-[(3-chlorophenoxy)methyl]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 380: 4-[3-{4-[(3,5-difluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2)4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 381:4-{3-[4-(benzyloxy)-3-methoxybenzyl]-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 382:4-[3-{4-[(3-chloro-5-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 383: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-{[4-
(trifluoromethyl)benzyl]oxy}benzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 384: 4-[3-{4-[(2,5-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 385: 4-{[4-({7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -formylpiperidin-4-
yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-
methoxyphenoxy]methyl}benzonitrile
No. 386: 3-{[4-({7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -formylpiperidin-4-
yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-
methoxyphenoxy]methyl}benzonitrile
No. 387: 4-[3-{4-[(4-chloro-2-fluorobenzyl)oxy]-3-methoxybenzylf7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 388:4-[3-{4-[1-(3,4-dichlorophenyl)ethoxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 389: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{4-[(3-hydroxybenzyl)oxy]-
3-methoxybenzyl}-2>4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 390: 4-[7-fluoro-3-{4-[(3-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 391: 4-[3-{4-[(3,4-difluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 392: 4-{3-[4-(5,6-dichloro-1H-benzimidazol-1-yl)-3-methoxybenzyl]-7-fluoro-6-
[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 393: 4-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenyl3,4-dichlorobenzenesulphonate
No. 394: 4-({7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxyphenyl3,4-dichloro benzene-
sulphonate
No. 403: 3,4-dichloro-N-[4-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-
methoxyphenyl]benzamide
The compounds in accordance with the invention can be prepared by the methods
illustrated in the following Schemes 1 to 4.
In that which follows, the term "leaving group" is understood to mean a group
which can be easily substituted, with departure of an electron pair, by cleavage of a
heterolytic bond. This group can thus be easily replaced by another group, for example
during a substitution reaction. Such leaving groups are, for example, halogens or an
activated hydroxyl group, such as a mesylate, tosylate, triflate, and the like. Examples of
leaving groups and references for their preparation are given in "Advanced Organic
Chemistry", J. March, 3rd Edition, Wiley Interscience, pp. 310-316.
The term "protective group PG" is understood to mean a group which makes it
possible to prevent the reactivity of a function group or position during a chemical
reaction which may affect it and which restores the molecule after cleavage according to
methods known to a person skilled in the art.
The term "temporary protective group for amines or alcohols" is understood to
mean the protective groups such as those described in Protective Groups in Organic
Synthesis, Greene T.W. and Wuts P.G.M., published by Wiley Intersciences, 1999, and
in Protecting Groups, Kocienski P.J., 1994, Georg Thieme Verlag.
Mention may be made, for example, of temporary protective groups for amines:
benzyls or carbamates (such as ferf-butoxycarbonyl, cleavable in an acid medium, or
benzyloxycarbonyl, cleavable by hydrogenolysis), temporary protective groups for
carboxylic acids: hydrogenolysable alkyl esters (such as methyl or ethyl or tert-butyl
esters which can be hydrolysed in a basic or acid medium) and benzyl esters, temporary
protective groups for alcohols or phenols, such as tetrahydropyranyl, methyloxymethyl or
methylethoxymethyl, tert-butyl and benzyl ethers, or temporary protective groups for
carbonyl derivatives, such as linear or cyclic acetals, such as, for example, 1,3-dioxan-2-
yl or 1,3-dioxolan-2-yl; and reference may be made to the well known general methods
described in Protective Groups, cited above.
A person skilled in the art will be in the position to choose the appropriate
protective groups according to the circumstances. The compounds of formula (I) can
comprise precursor groups for other functional groups which are generated subsequently
in one or more other stages.
In the general synthetic schemes which follow, the starting compounds and the
reactants, when their method of preparation is not described, are commercially available
or are described in the literature or else can be prepared according to methods which are
described therein or which are known to a person skilled in the art.
The pure enantiomers of the compounds in accordance with the invention can be
obtained from enantiomericaliy pure precursors or else by chiral phase chromatography
or else, when the compounds comprise acid or amine functional groups, by selective
crystallizations of diastereoisomeric salts obtained by reaction of the compounds (I) with
chiral amines or chiral acids respectively.
The compounds of general formula (I) can be obtained according to the following
Schemes 1 to 4. Out of concern for clarity, the R4 group has been chosen as being a
hydrogen, p and p' represent 1 and 2 respectively and the R2 and R3 groups have been
set as indicated in the schemes. However, it is to be understood that R4 can be as
defined in the general formula (I), that R2 and R3 can have the positions indicated in the
general formula (I) and that p and p' can be as defined in the general formula (I).
The synthetic routes described below serve solely as illustration and are under no
circumstances limiting. A person skilled in the art can apply without difficulty the teaching
below to the compounds of formula (I) for which R, R,, R2) R3, R». Ra, Rb, Re, m, n, p, p'
and q are as defined in the general formula (I).
According to Scheme 1, the compound of formula (IV) is obtained by a reductive
amination reaction by reacting a compound of formula (II), in which R' represents a
(C1-C6) alkyl group and R2 is as defined for the compound of formula (I) with a compound
of formula (III) in an acid medium and in the presence of a reducing agent, such as
sodium triacetoxyborohydride. The PG group of the compound of formula (III) is a
protective group for the amine functional group which may advantageously be tert-
butoxycarbonyl (boc). The compound of formula (IV) thus formed is subsequently
acylated, according to methods well known to a person skilled in the art, with an alkyl or
aryl chloroformate to give the compound of formula (V) in which R" represents a (Ci-Ce)
alkyl group or an aryl group which is substituted. A hydrolysis reaction in a basic medium
makes it possible to obtain the compounds of formula (VI) which, by a coupling reaction
with a compound of formula (VII), in which R3 is as defined for the compound of formula
(I), results in the compounds of formula (VIII). An intramolecular cyclization reaction in
the basic medium makes it possible to obtain the quinazolinedione derivatives of formula
(IX). The protective group PG for the amine functional group is subsequently cleaved, for
example in acid medium when PG is a boc, to give the compounds of formula (la) which
give, by an acylation reaction, the compounds of formula (lb).
The compounds of formula (la) are compounds of formula (I) and can act as
intermediate for other compounds of formula (I), such as the compounds of formula (lb).
The compounds of formula (I) for which R2 represents -ORa, Ra being as defined
for the compound of formula (I), correspond to the formula (Id). They can be obtained
from the compounds of formula (X) according to the following Scheme 2. The
compounds of formula (Ic), obtained by a hydrogenolysis reaction on the compounds of
formula (X), are subjected, for example, to an alkylation reaction with an alkylating agent
of type Ra-X, in which Ra is as defined for the compound of formula (I) and X represents
a leaving group (such as a halogen atom, for example), in the presence of a base, such
as caesium carbonate (Cs2C03), or also to a Mitsunobu reaction (Synthesis, 1981, 1)
with an alcohol of type Ra-OH, Ra being as defined for the compound of formula (I), to
give compounds of formula (Id).
The compounds of formula (X) and the compounds of formula (Ic) are compounds
of formula (I) and can act as intermediate for other compounds of formula (I), such as the
compounds of formula (Id).
Alternatively, the compounds of formula (Id) can be obtained by following the
procedure described in Scheme 3.
The compounds of formula (XII) are obtained by a nucleophilic aromatic
substitution reaction involving a compound of formula (XI), in which R' is as defined
above, and an alcohol of type Ra-OH, in which Ra is as defined for the compound of
formula (I), in the presence of a base. The reduction of the nitro group of the compounds
of formula (XII) results in the corresponding anilino derivatives (XIII). A reductive
amination reaction with a compound of formula (III), in which PG is a protective group for
amine functional groups, such as, for example, boc, results in the compounds of formula
(XIV). The compounds of formula (XV) are obtained by reaction of a compound of
formula (XIV) with potassium isocyanate (KNCO) in an acid medium. An intramolecular
cyclization reaction in a basic medium makes it possible to obtain the compounds of
formula (XVI). The protective group PG is cleaved by methods well known to a person
skilled in the art to give the compounds of formula (XVII). An acylation reaction results in
the compounds of formula (XVIII). Finally, the compounds of formula (Id) are obtained
either by an alkylation reaction with a derivative of type (XIX), in which X represents a
leaving group, such as a halogen atom, in the presence of a base, such as, for example,
caesium carbonate, or also by a Mitsunobu reaction with a benzyl alcohol of type (XX). In
the compounds (XIX) and (XX), R3 is as defined above.
Scheme 3
The compounds of formula (le) and (If), in which R2 more particularly represents a
group of type-CH2-NHC(O)Rb, Rb being defined as in the compound of formula (1), can
be prepared according to the following Scheme 4.
It is understood that, in Scheme 3, the R2 group illustrated is of -O-Ra type and is
in the 6 position of the quinoazolinedione structure (see, for example, compound (XVIII))
but that it is also possible to have a second R2 group, as defined in the general formula
(I), in the 7 position of the same quinazolinedione group.
The reduction of the nitro group of the compounds of type (XXI), in which R' and
PG' are as defined above, the PG' group advantageously being boc, results in the
corresponding anilino derivatives (XXII) which, by a reductive amination reaction in which
they react in an acid medium and advantageously in the presence of a reducing agent,
such as sodium triacetoxyborohydride, with a compound of formula (III), in which PG
represents a benzyloxycarbonyl protective group for amines, give compounds of formula
(XXIII). An acylation reaction with an alkyl or aryl chloroformate, in which R" represents a
(C1-C6) alkyl group or an aryl group which is substituted, results in the compounds of
formula (XXIV). The quinazolinedione analogues of formula (XXV) can be obtained by a
hydrolysis reaction in a basic medium and then by a coupling reaction with a compound
of formula (VII), in which R3 is as defined for the compound of formula (I), followed by an
intramolecular cyclization reaction in a basic medium. The PG' group (preferably a boc) is
subsequently cleaved in an acid medium to result in the compounds of formula (XXVI)
which, by acylation, give compounds of formula (XXVII), in which Rb is as defined for the
compound of formula (I). The PG protective group of (XXVII) is cleaved by a
hydrogenolysis reaction to give the compounds of formula (le). Finally, the compounds of
formula (If) are obtained by an acylation reaction on the compounds of formula (le).
It is obvious that a person skilled in the art will be in a position to choose, in the
light of his knowledge and the literature, other appropriate protective groups which make
possible the introduction of all the groups described in the general formula (I).
When the compound of formula (I) comprises a bridged ring, it can be obtained
without distinction by one of the synthetic routes described above.
The following procedures and examples describe the preparation of some
compounds in accordance with the invention. These procedures and examples are not
limiting and serve only to illustrate the present invention.
In the procedures and examples below:
- the mass spectra are produced on a quadrupole spectrometer of Platform LCZ
type (Waters) or of ZQ 4000 type (Waters) in positive electrospray ionization mode;
- the NMR (nuclear magnetic resonance) spectra are produced on a Fourier
transform spectrometer (Bruker) at a temperature of 300°C (exchangeable protons not
recorded);
- s = singlet,
- d = doublet,
- m = multiplet,
- br = broad signal
-1 = triplet,
- q = quartet
- DMSO-d6 = deuterated dimethyl sulphoxide,
- CDCI3 = deuterated chloroform.
The mixtures of solvents are quantified in volumetric ratios.
The NMR spectra and mass spectra confirm the structures of the compounds
obtained according to the examples below.
In the examples which follow, the following abbreviations are used:
ACN: acetonitrile
AcOEt: ethyl acetate
AcOH: acetic acid
DBU: 1,8-diazabicyclo[5.4.0]undec-7-ene
DCM: dichloromethane
DCE: 1,2-dichloroethane
DIAD: diisopropyl azodicarboxylate
DIEA: diisopropylamine
DMF: N,N-dimethylformamide
EtOH: ethanol
HBTU: 0-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate
IBCF: isobutyl chloroformate
MeOH: methanol
NaBH(OAc)3: sodium triacetoxyborohydride
AT: ambient temperature
min: minute
THF: tetrahydrofuran
NEt3: triethylamine
TFA: trifluoroacetic acid
EXAMPLES
The following examples describe the preparation of some compounds in accordance with
the invention. These examples are not limiting and serve only to illustrate the present
invention. The numbers of the compounds in the examples refer to those given in the
table below, in which the chemical structures and the physical properties of a few
compounds in accordance with the invention are illustrated.
EXAMPLE 1: Compound No.°6
Preparation of {[3-(3,4-dimethoxybenzyl)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-
1,2,3,4-tetrahydroquinazolin-6-yl]oxy}acetonitrile
Stage 1.1:
1,1-Dimethylethyl 4-{[4-(benzyloxy)-2-(methoxycarbonyl)phenyl]ami-
no}piperidine-1 -carboxylate
A mixture of 2g of methyl 2-amino-5-(benzyloxy)benzoate, 3.1 g of
1,1-dimethylethyl 4-oxopiperidine-1-carboxylate and 3.29 g of NaBH(OAc)3 in 10 ml of
AcOH is irradiated under a microwave field (Biotage Initiator Sixty) at 110DC for 20 min.
The same reaction is repeated with two other lots of 2 g of methyl 2-amino-5-
(benzyloxy)benzoate. The three reaction media are combined. The combined product is
taken up in AcOEt. The organic phase is washed with water, with a saturated NH4CI
solution and with a saturated NaHC03 solution, dried over Na2SO4 and filtered, and the
solvent is evaporated under reduced pressure. The residue is chromatographed on silica
gel, elution being carried out with an AcOEt/heptane mixture, (5/95, v/v) as far as (30/70,
v/v), to give 10.2 g of the expected product.
Stage 1.2:
1,1-Dimethylethyl 4-{[4-(benzyloxy)-2-(methoxycarbonyl)phenyl][(2-methyl-
propoxy)carbonyl]amino}piperidine-1-carboxylate
A mixture of 2g of 1,1-dimethylethyl 4-{[4-(benzyloxy)-2-
(methoxycarbonyl)phenyl]amino}piperidine-1-carboxylate obtained in stage 1.1, 0.87 ml
of DIEA, 1.78 ml of IBCF and 1 g of NaOH in 10 ml of DCE is irradiated under a
microwave field at 80°C for 30 min. The same reaction is repeated with 4 other lots of 2 g
of 1,1-dimethylethyl 4-{[4-(benzyloxy)-2-(methoxycarbonyl)phenyl]amino}piperidine-1-
carboxylate. The 5 reaction media are combined. The combined product is taken up in
AcOEt and filtered, and the filtrate is evaporated under reduced pressure. The residue is
chromatographed on silica gel, elution being carried out with an AcOEt/heptane mixture,
(10/90, v/v) as far as (50/50, v/v), to give 9.3 g of the expected product.
Stage 1.3:
Sodium salt of 5-(benzyloxy)-2-({1-[(1,1-dimethylethoxy)carbonyl]-piperidin-
4-yl}[(2-methylpropoxy)carbonyl]amino)benzoic acid
A mixture of 9.3 g of 1,1-dimethylethyl 4-{[4-(benzyloxy)-2-
(methoxycarbonyl)phenyl][(2-methylpropoxy)carbonyl]amino}piperidine-1-carboxylate
obtained in stage 1.2 and 34.4 ml of 2N NaOH in 57 ml of MeOH is heated at 100°C for
3h 00. The solution is evaporated under reduced pressure and DCM is added. Drying is
carried out over Na2SO4, filtration is carried out and the solvent is evaporated under
reduced pressure to give 8.7 g of the expected product.
Stage 1.4:
1,1-Dimethylethyl 4-[{4-(benzyloxy)-2-[(3,4-dimethoxybenzyl)carbamoyl]phe-
nyl}(isobutoxycarbonyl)amino]piperidine-1-carboxylate
A mixture of 6g of sodium salt of 5-(benzyloxy)-2-({1-[(1,1-
dimethylethoxy)carbonyl]piperidin-4-yl}[(2-methylpropoxy)carbonyl]amino)benzoic acid
obtained in stage 1.3 and 4.42 g of DIEA in 250 ml of DMF is stirred at AT for 15 min.
6.48 g of HBTU are added and the mixture is left stirring for 30 min. 2.48 g of
veratrylamine are added and the reaction mixture is stirred for 48h 00. It is evaporated
under reduced pressure, the residue is taken up in AcOEt, washed with a saturated
NH4CI solution and with a saturated NaHC03 solution, dried over Na2SO4 and filtered,
and the solvent is evaporated under reduced pressure. The residue is chromatographed
on silica gel, elution being carried out with an AcOEt/heptane mixture, (20/80, v/v) as far
as (60/40, v/v), to give 7.5 g of expected product.
Stage 1.5:
1,1-Dimethylethyl 4-[6-(benzyloxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carboxylate
A mixture of 2.5 g of 1,1-dimethylethyl 4-[{4-(benzyloxy)-2-[(3,4-
dimethoxybenzyl)carbamoyl]phenyl}(isobutoxycarbonyl)amino]piperidine-1-carboxylate
obtained in stage 1.4 and 7.4 g of NaOH in 18.5 ml of DCE is irradiated under a
microwave field at 110°C for 30 min. The same reaction is repeated with 2 other lots of
2.5 g of 1,1-dimethylethyl 4-[{4-(benzyloxy)-2-[(3,4-dimethoxybenzyl)carbamoyl]phenyr}-
(isobutoxycarbonyl)amino]piperidine-1-carboxylate. The 3 reaction media are combined.
The combined product is taken up in DCM, washed with water, dried over Na2SO4 and
filtered, and the solvent is evaporated under reduced pressure to give 6.6 g of expected
product.
Stage 1.6:
A mixture of 3.5 g of 1,1-dimethylethyl 4-[6-(benzyloxy)-3-(3,4-dimethoxybenzyl)-
6-(Benzyloxy)-3-(3,4-dimethoxybenzyl)-1-(piperidin-4-yl)quinazoline-
2,4(1 H,3H)-dione
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carboxylate obtained in stage 1.5
and 25 ml of TFA in 50 ml of DCM is stirred at AT for 2h 00. The mixture is neutralized
with K2C03. It is filtered and the filtrate is evaporated under reduced pressure. The
residue is taken up in DCM and washed with a saturated NaHC03 solution and then with
an 8% NaOH solution. The solution is dried over Na2SO4 and filtered, and the solvent is
evaporated under reduced pressure to give 2.67 g of the expected product.
Stage 1.7:
4-[6-(Benzyloxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-
1(2H)-yl]piperidine-1-carbaldehyde
A mixture of 0.6 g of 6-(benzyloxy)-3-(3,4-dimethoxybenzyl)-1-(piperidin-4-
yl)quinazoline-2,4(1H,3H)-dione obtained in stage 1.6 and 0.113 g of ammonium formate
in 5 ml of ACN is irradiated under a microwave field at 140°C for 1h 00. The mixture is
filtered and the filtrate is evaporated under reduced pressure to give 0.62 g of the
expected product.
Stage 1.8: Compound No. 5:
4-[3-(3,4-Dimethoxybenzyl)-6-hydroxy-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]pi peridine-1 -carbaidehyde
A mixture of 0.618 g of 4-[6-(benzyloxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde obtained in stage 1.7, 0.44 g of
ammonium formate and 0.124 g of Pd/C (10%) in 10 ml of EtOH purged beforehand with
nitrogen is irradiated under a microwave field at 80°C for 2h 00. The mixture is filtered
and the filtrate is evaporated under reduced pressure to give 0.513 g of the expected
product.
Stage 1.9: Compound No. 6
{[3-(3,4-Dimethoxybenzyl)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]oxy}acetonitrile
0.17 g of 4-[3-(3,4-dimethoxybenzyl)-6-hydroxy-2,4-dioxo-3,4-dihydroquinazolin-
1(2H)-yl]piperidine-1-carbaldehyde obtained in stage 1.8 and 0.25 g of Cs2C03 in 3 ml of
DMF are stirred for 15 min at AT. 0.056 g of bromoacetonitrile is added and the reaction
mixture is subsequently irradiated under a microwave field at 100°C for 15 min. It is
filtered and evaporated under reduced pressure. The residue is chromatographed on
silica gel, elution being carried out with an MeOH/DCM mixture, (1/99, v/v) as far as
(4/96, v/v), to give 0.112 g of the expected product.
EXAMPLE 2: Compound No. 3
Preparation of {[1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-
1,2,3,4-tetrahydroquinazolin-6-yl]oxy}acetonitriie
Stage 2.1:
1-(1-Acetylpiperidin-4-yl)-6-(benzyloxy)-3-(3,4-dimethoxybenzyl)quinazoline-
2,4(1 H,3H)-dione
0.14 g of acetyl chloride is added to a mixture of 0.6 g of 6-(benzyloxy)-3-(3,4-
dimethoxybenzyl)-1-(piperidin-4-yl)quinazoline-2,4(1H,3H)-dione obtained according to
stage 1.6 and 0.24 g of NEt3 in 10 ml of DCM cooled to 0°C. The mixture is stirred at AT
overnight. It is washed twice with a saturated NH4CI solution and filtered, and then the
filtrate is evaporated under reduced pressure to give 0.64 g of the expected product.
Stage 2.2: Compound No. 2
1-(1-Acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-6-hydroxyquinazoline-
2,4(1 H,3H)-dione
A mixture of 0.64 g of 1-(1-acetylpiperidin-4-yl)-6-(benzyloxy)-3-(3,4-
dimethoxybenzyl)quinazoline-2,4(1H,3/-/)-dione obtained in stage 2.1, 0.44 g of
ammonium formate and 0.125 g of Pd/C (10%) in 10 ml of EtOH purged beforehand with
nitrogen is irradiated under a microwave field at 80°C for 2h 00. The mixture is filtered
and the filtrate is evaporated under reduced pressure to give 0.48 g of the expected
product.
Stage 2.3: Compound No. 3
{[1-(1-Acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]oxy}acetonitrile
0.12 g of 1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-6-hydroxyquinazoline-
2,4(1 H,3H)-dione obtained in stage 2.2 and 0.172 g of Cs2C03 in 3 ml of DMF are stirred
for 15 min at AT. 0.038 g of bromoacetonitrile is added and the reaction mixture is
subsequently irradiated under a microwave field at 100°C for 15 min. It is filtered and the
filtrate is evaporated under reduced pressure. The residue is chromatographed on silica
gel, elution being carried out with an MeOH/DCM mixture, (1/99, v/v) as far as (4/96, v/v),
to give 0.094 g of the expected product.
EXAMPLE 3: Compound No. 34
Synthesis of 4-[3-(4-chlorobenzyl)-6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
Stage 3.1:
Methyl 5-(2,2-difluoroethoxy)-2-nitrobenzoate
8.53 g of 2,2-difluoroethanol are added to a solution of 17.31 g of methyl 5-fluoro-
2-nitrobenzoate, 9.64 g of NEt3 and 32.71 g of 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-
phosphabicyclo[3.3.3]undecane in 250 ml of anhydrous THF. The mixture is stirred at AT
for 30 min. The solvent is evaporated under reduced pressure. Water is added and
extraction is carried out with AcOEt. The extract is washed with a 1N aqueous HCI
solution, with water and then with a saturated NaCI solution. It is dried over MgSO^ and
filtered, and the solvent is evaporated under reduced pressure to give 21 g of the
expected product.
21 g of methyl 5-(2,2-difluoroethoxy)-2-nitrobenzoate obtained in stage 3.1 and
1 g of Pd/C (10%) in a mixture of 300 ml of AcOEt, 50 ml of EtOH and 5 ml of AcOH are
stirred at AT under a hydrogen atmosphere for 24h 00.
The mixture is filtered and evaporated under reduced pressure to give 18.6 g of
the expected product.
Stage 3.3:
1,1-Dimethylethyl 4-{[4-(2,2-difluoroethoxy)-2-(methoxycarbonyl)phenyl]ami-
no}pi peri di ne-1 -carboxylate
A mixture of 4 g of methyl 2-amino-5-(2,2-difluoroethoxy)benzoate and 6.88 g of
1,1-dimethylethyl 4-oxopiperidine-1-carboxylate obtained in stage 3.2 in 15 ml of AcOH is
heated at 90°C for 10 min. It is allowed to cool to AT and 7.3 g of NaBH(OAc)3 are
added. The mixture is left stirring at AT for 12h 00. It is extracted with AcOEt and the
extract is washed with a saturated K2C03 solution and then with water. It is dried over
MgSO4, filtered and evaporated under reduced pressure to give 6.63 g of the expected
product.
Stage 3.4:
1,1 -Dimethylethyl 4-{carbamoyl[4-(2,2-difluoroethoxy)-2-(methoxycarbonyl)-
phenyl]amino}piperidine-1-carboxylate
1.95 g of potassium isocyanate in solution of 4 ml of water are added to a solution
of 6.63 g of 1,1-dimethylethyl 4-{[4-(2,2-difluoroethoxy)-2-(methoxycarbonyl)phenyl]
amino}piperidine-1-carboxylate obtained in stage 3.3 in 40 ml of AcOH. The mixture is
stirred at AT for 12h 00. It is extracted with AcOEt and the extract is washed with a
saturated K2C03 solution and then with water. It is dried over MgSO4, filtered and
evaporated under reduced pressure to give 6.95 g of the expected product.
Stage 3.5:
1,1-Dimethylethyl 4-[6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-dihydroquinazolin-
1(2H)-yl]piperidine-1-carboxylate
2.5 g of 1,1-dimethylethyl 4-{carbamoyl[4-(2,2-difluoroethoxy)-2-
(methoxycarbonyl)phenyl]amino}piperidine-1-carboxylate obtained in stage 3.4 in solution
in a mixture of 10 ml of dioxane and 5 ml of a 1N aqueous NaOH solution are irradiated
under a microwave field at 130°C for 30 min. Extraction is carried out with AcOEt and the
extract is neutralized with a 1N aqueous HCI solution, washed with water, dried over
MgSO4, filtered and evaporated under reduced pressure. The residue obtained is
triturated in an AcOEt/pentane mixture to give the expected product. The same reaction
is reproduced with 2 other lots of 2.5 g of 1,1-dimethylethyl 4-{carbamoyl[4-(2,2-
difluoroethoxy)-2-(methoxycarbonyl)phenyl]amino}piperidine-1 -carboxylate obtained in
stage 3.4 to give, in total, 5.63 g of expected product.
Stage 3.6:
6-(2,2-Difluoroethoxy)-1-(piperidin-4-yl)quinazoline-2,4(1H,3H)-dione
A solution of 5.63 g of 1,1-dimethylethyl 4-[6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carboxylate obtained in stage 3.5 in 70 ml of
formic acid is stirred at AT for 2h 00. The solvent is evaporated under reduced pressure
to give 6.13 g of the expected product in the form of the formic acid salt.
Stage 3.7:
4-[6-(2,2-Difluoroethoxy)-2,4-dioxo-3,4-dihydroquinazolin-1(2W)-
yl]piperidine-1-carbaldehyde
A mixture of 6.13 g of 6-(2,2-difluoroethoxy)-1-(piperidin-4-yl)quinazoline-
2,4(1 H,3H)-6\one obtained in stage 3.6 and 3.12 g of ammonium formate in 28 ml of
ACN and 28 ml of dioxane is irradiated under a microwave field at 140°C for 1h 00. The
reaction mixture is run into water. The mixture is filtered and the precipitate is washed
with water and then with ether to give 4.47 g of the expected product.
Stage 3.8: Compound No. 34
4-[3-(4-Chlorobenzyl)-6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-dihydroquinazolin-
1 (2H)-y I] piperid i ne-1 -carba Idehyde
A mixture of 0.15 g of 4-[6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-dihydroquinazolin-
1(2H)-yl]piperidine-1-carbaldehyde obtained in stage 3.7, 0.096 g of 1-(bromomethyl)-4-
chlorobenzene and 0.3 g of Cs2C03 in 3 ml of DMF is stirred at AT for 1h 00. AcOEt is
added and washing is carried out with water and then with a saturated NaCI solution. The
organic phase is dried over MgSO4, filtered and evaporated under reduced pressure. The
residue is chromatographed on silica gel, elution being carried out with AcOEt, to give
0.116 g of the expected product.
EXAMPLE 4: Compound No. 49
Synthesis of 4-{3-[3-(cyclopentyloxy)-4-methoxybenzyl]-6-(2,2-difluoro-
ethoxy)-2,4-dioxo-3,4-dihydroquinazolin-1(2W)-yl}piperidine-1-carbaldehyde
0.172 g of DIAD is added to a solution of 0.15 g of 4-[6-(2,2-difluoroethoxy)-2,4-
dioxo-3,44-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]piperidine-1 -carbaldehyde
No. 39:4-t6-(2,2-difluoroethoxy)-3-(3-hydroxy-4-methoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 40:4-t6-(2,2-difluoroethoxy)-3-[3-(2-hydroxyethoxy)-4-methoxybenzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 41:4-[6-(2,2-difluoroethoxy)-3-(3-ethoxy-4-methoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 42:4-[6-(2,2-difluoroethoxy)-3-[4-methoxy-3-(2-methoxyethoxy)benzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 43:4-[6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]azepane-1 -carbaldehyde
No. 47: 4-[6-(2,2-difluoroethoxy)-3-[3-(3-hydroxypropoxy)-4-methoxybenzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 48: 4-[5-chloro-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]piperidine-1-carbaldehyde
No. 49: 4-{3-[3-(cyclopentyloxy)-4-methoxybenzyl]-6-(2,2-difluoroethoxy)-2,4-dioxo-
3,4-dihydroquinazolin-1 (2H)-yl}piperidine-1 -carbaldehyde
No. 50: 2-(5-{[6-(2,2-difluoroethoxy)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,4-
dihydroquinazolin-3(2H)-yl]methyl}-2-methoxyphenoxy)acetamide
No. 51:4-[6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]-3-methylpiperidine-1-carbaldehyde
No. 52: 3-t6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]-8-azabicyclo[3.2.1]octane-8-carbaldehyde
No. 55: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-
1(2H)-yl}piperidine-1-carbaldehyde
No. 56: 4-{3-[4-(cyclopentyloxy)-3-methoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2I4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 57: 4-[3-(3-chlorobenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 58: 4-[3-(4-chlorobenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 59: 4-{3-[3-(cyclopentyloxy)-4-methoxybenzyl]-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 72:4-[3-(3,4-dimethoxybenzyl)-6-(2-hydroxyethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 74: 4-[3-(3,4-dichlorobenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 76:4-{3-[(6-chloropyridin-3-yl)methyl]-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 78: 4-[3-(3-chloro-4-methoxybenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 79:4-[3-(3,4-dimethoxybenzyl)-6-(2-fluoroethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 89: 2-[5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -formylpiperidin-4-yl)-2,4-
dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxyphenoxy]acetamide
No. 90: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-hydroxy-4-methoxybenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 91:4-[3-(3,4-dimethoxybenzyl)-6-ethoxy-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]piperidine-1 -carbaldehyde
No. 97: 4-[5,7-dichloro-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-
1(2H)-yl]piperidine-1-carbaldehyde
No. 102: 4-[7-chloro-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-
1(2H)-yl]piperidine-1-carbaldehyde
No. 108: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-fluoro-4-methoxybenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 111: 4-[6-(difluoromethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 112: 4-[3-(3,4-dimethoxybenzyl)-6-(1-methylethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 114: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-methoxy-3-(1-
methylethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 116: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-(3-methoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 117: 4-{3-[3,5-bis(trifluoromethyl)benzyl]-6-[2-fluoro-1-(fluoromethyl)ethoxy]-
2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-yl}piperidine-1 -carbaldehyde
No. 118: 4-[3-(3-ethoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 124: 4-{3-[3-chloro-4-(2-methoxyethoxy)benzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 130: 4-[3-(3,4-diethoxybenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-
3,4-dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 131:4-[3-(4-ethoxy-3-methoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 133; 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(4-methoxy-3-methylbenzy()-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 134: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-
(trifluoromethyl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 135: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-
(trifluoromethyl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 143: 4-{3-[4-(benzyloxy)-3-methoxybenzyl]-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 145: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-nitrobenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 155: 4-[3-(4-ethoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 158; 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[4-(morpholin-4-ylmethyl)benzyl]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 160:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-(4-(morpholin-4-yl)benzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 165: 4-[3-(biphenyl-4-ylmethyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-
3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 166:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(methylsulphanyl)benzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1 -carbaldehyde
No. 167:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyridin-3-yl)benzyl)-
3,4-dihydroquinazolin-1 (2H)-yl}piperidine-1 -carbaldehyde
No. 170: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-methylbenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 175: 2-t2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]acetamide
No. 178: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-propoxybenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 183: 2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-ciioxo-1,4-dihyclroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
methylacetamide
No. 184: 2-[2-(cyclopentyloxy)-5-({6-t2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1l4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N,N-
dimethylacetamide
No. 185: 2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
methoxy-N-methylacetamide
No. 186: 4-{3-[4-(cyclopentyioxy)-3-ethoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 188;4-{3-[4-(cyclopentyloxy)-3-(1-methylethoxy)benzyl]-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 189: 4-{3-[4-(cyclopentyloxy)-3-propoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 190: 4-{3-[4-(cydopentyloxy)-3-hydroxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 193: 4-{3-[4-(difluoromethoxy)-3-methoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 194: 4-{3-[4-(difluoromethoxy)-3-ethoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 200: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(thiophen-3-yl)-
benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 201: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyridin-4-yl)benzyl)-
34-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 203: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[(1 -methyl-1 H-indol-6-yl)methyl]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 206: 4-{3-[4-(cyclopropylmethoxy)-3-methoxybenzyl]-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No.207:2-[4-<{6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-2f4-
dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxyphenoxy]-N-methylacetamide
No. 212: 4-{6-[2-fIuoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-(1 H-pyrazol-1 -
yl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 213:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyridin-2-yl)benzyl)-
3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 215:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(thiophen-2-yl)-
benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 216: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(quinolin-7-ylmethyl)-
3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 218: 4-{5-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[(6-methoxynaphthalen-2-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 223: 4-{3-[4-(1 H-benzimidazol-1-yl)benzyl]-6-[2-fluoro-1-(fluoromethyl)ethoxy]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 224: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(2-
methylpropoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 226: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(tetrahydrofuran-3-
yloxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 228:4-[3-{4-[(1-benzylpyrrolidin-3-yl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1-
(fIuoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 230: 4-[3-(1-benzothiophen-5-ylmethyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 232: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[3-methoxy-4-(1-
methylethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 233: 4-[3-(3,4-dimethoxybenzyl)-7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 234:4-t3-{4-[(1-acetylpyrrolidin-3-yl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 239: 4-[3-{4-[(4-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 240: 4-[3-{4-[(4-chlorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 242: 4-t3-{4-[(3-chlorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 243: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(3-(thiophen-3-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 245: 4-[3-(4-ethoxy-3-methoxybenzyl)-6-(2-hydroxyethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 246: 4-[3-{4-[2-(2,3-dihydro-1 H-indol-1-yl)-2-oxoethoxy]-3-methoxybenzyl}-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 250: 4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-methoxybenzyl}-6-t2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 251: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(2-oxo-2-(piperidin-
1-yl)ethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 254: 4-{3-[3-ethoxy-4-(thiophen-2-ylmethoxy)benzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 258: 4-[3-(3,4-dimethoxybenzyl)-6-[2-fluoro-1 -(hydroxymethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 263: (2R)-2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]propanoic
acid
No. 264:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(1-methyl-3-(thiophen-2-yl)-1H-
pyrazol-5-yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 270: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(5-methyl-1,2,4-oxadiazol-3-
yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 275: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyrimidin-5-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 276: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(1-methyl-3-phenyl-1H-pyrazol-5-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 278: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-{[6-(1H-pyrazol-1-
yl)pyridin-3-yl]methyl}-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 279: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-[(2-(thiophen-2-
yl)pyrimidin-5-yl)methyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 280: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[4-(1 -methyl-1 H-pyrazol-3-
yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 282: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[4-(3-methyl-1,2,4-oxadiazol-5-
yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 283: [2-(cyclopentyloxy)-5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]aceticacid
No. 285:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(thieno[2,3-b]pyridin-2-
ylmethyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 286: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[(6-phenylpyridin-3-
yl)methyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 287: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[(6-(morpholin-4-yl)pyridin-3-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 289: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-[(6-(thiophen-2-
yl)pyridin-3-yl)methyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 292: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[(1 -methyl-5-phenyl-1 H-pyrazol-3-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 294: 4-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-2,4-dioxo-
1,4-dihydroquinazolin-3(2H)-yl}methyl)biphenyl-2-carbonitrile
No. 295:(2R)-2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-clihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
methylpropanamide
No. 297: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(thiophen-2-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 298: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(morpholin-4-
ylmethyl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 299: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[3-methoxy-4-(piperidin-1 -
ylmethyl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 300:4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 301:2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
ethylacetamide
No. 302: (2S)-2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]propanoic
acid
No. 305:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-(3-methoxy-4-{[(3R)-2-oxo-1-
phenylpyrrolidin-3-yl]oxy}benzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 306: 4-{3-[4-(cyclobutylmethoxy)-3-methoxybenzyi]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 307: 4-{3-[4-(benzyloxy)-3-methoxybenzyl]-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 308: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(4-hydroxy-3-
methoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 309: 4-{3-[4-(cyclopropylmethoxy)-3-methoxybenzyl]-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 310: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-
(2-methylpropoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 311: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[3-methoxy-4-
(1-methylethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 312: 4-[3-(4-ethoxy-3-methoxybenzyl)-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 315: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{[6-(3-
methoxyphenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 316: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{[6-(2-
fluorophenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 317: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{[6-(4-
fluorophenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 318: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{[6-(4-
methoxyphenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 319:4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[(6-(thiophen-2-
yl)pyridin-3-yl)methyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 320: 4-{3-[3-ethoxy-4-(thiophen-2-ylmethoxy)benzyl]-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 321: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[4-(1 -methyl-1 H-pyrazol-
3-yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 322: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyrimidin-5-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 323: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[(1 -methyl-3-(thiophen-2-
yl)-1 H-pyrazol-5-yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-yl}piperidine-1 -
carbaldehyde
No. 324: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(2-oxo-2-
(piperidin-1-yl)ethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 325: 4-[3-{4-[2-(2,3-dihydro-1 H-indol-1 -yl)-2-oxoethoxy]-3-methoxybenzyl}-7-
fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]piperidine-1 -carbaldehyde
No. 326: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(5-methyl-1,2,4-
oxadiazol-3-yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 327: 4-[3-{4-[(3-chlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 328: 4-[3-{[6-(3,5-dichlorophenyl)pyridin-3-yl]methyl}-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 329: 4-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)biphenyl-2-carbonitrile
No. 330: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-(1 H-pyrazol-
1-yl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 331: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-{[6-(3-
fluorophenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 332: 3-[5-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-
yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)pyridin-2-yl]benzonitrile
No. 333:4-[3-(3,4-diethoxybenzyl)-7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 334: 4-[3-{4-[(4-chlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 335: 4-{7-fluoro-6-[2-fluoro-1 -(fluorotnethyl)ethoxy]-3-t4-(morpholin-4-
ylmethyl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 336: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-{[6-(1 H-pyrazol-
1-yl)pyridin-3-yl]methyl}-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 337: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(4-(morpholin-4-yl)-
benzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1 -carbaldehyde
No. 338: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-
propoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 339: 4-{3-[4-(1 H-benzimidazol-1 -yl)benzyl]-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 340: 5-({7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1-formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxybenzonitrile
No. 341: 3-(3,4-dimethoxybenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-7-carbonitrile
No. 342: 4-[3-(4-bromobenzyl)-7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 343:4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-(2-methoxyethoxy)benzyl}-7-fluoro-6-
[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 344: 4-{3-[4-(benzyloxy)benzyl]-7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 345: 4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-ethoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 349:4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-(2-fluoroethoxy)benzyl}-7-fluoro-6-[2-
fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-yl]piperidine-1 -
carbaldehyde
No. 350:4-[3-{4-[(2-chloro-4-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2l4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 351:4-[3-{4-[(2,4-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 352: 4-[3-{4-[(2-chloro-6-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 353: 4-[3-{4-[(2,6-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 354: 4-[3-{4-[(2-chlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-t2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 355: 4-[7-fluoro-3-{4-[(2-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3>4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 357: 2-[(3,4-dichlorobenzyl)oxy]-5-({7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-
1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)benzonitrile
No. 358: 4-[3-{4-[(3,4-dichlorophenoxy)methyl]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 360: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-t4-(2-
phenylethyl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 362: 4-[3-{4-[(4,5-dichloro-2-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 369: 4-[3-{4-[(4-chlorophenoxy)methyl]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 371: 4-[3-{3-chloro-4-[(4-chlorobenzyl)oxy]-5-ethoxybenzyl}-7-fluoro-6-[2-fluoro-
1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 373:4-[3-{3-chloro-4-[(2,4-dichlorobenzyl)oxy]-5-ethoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 375: 4-[7-fluoro-3-{4-[(4-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 376: 4-[3-{4-[(3,5-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 377: 4-[3-(4-{[4-chloro-3-(trifluoromethyl)benzyl]oxy}-3-methoxybenzyl)-7-
fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]piperidine-1-carbaldehyde
No. 379: 4-[3-{4-[(3-chlorophenoxy)methyl]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 380: 4-[3-{4-[(3,5-difluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 381: 4-{3-[4-(benzyloxy)-3-methoxybenzyl]-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 382: 4-[3-{4-[(3-chloro-5-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 383: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-{[4-
(trifluoromethyl)benzyl]oxy}benzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 384: 4-[3-{4-[(2,5-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 385: 4-{[4-({7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -formylpiperidin-4-
yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-
methoxyphenoxy]methyl}benzonitrile
No. 385: 3-{[4-({7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -formylpiperidin-4-
yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-
methoxyphenoxy]methyl}benzonitrile
No. 387:4-[3-{4-t(4-chloro-2-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 388:4-[3-{4-[1-(3,4-dichlorophenyl)ethoxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 389: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{4-[(3-hydroxybenzyl)oxy]-
3-methoxybenzyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 390: 4-[7-fluoro-3-{4-[(3-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 391:4-[3-{4-[(3,4-difluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 392: 4-{3-[4-(5,6-dichloro-1 H-benzimidazol-1-yl)-3-methoxybenzyl]-7-fluoro-6-
[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 393: 4-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenyl 3,4-dichlorobenzenesulphonate
No. 394: 4-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxyphenyl3,4-dichlorobenzene-
sulphonate
No. 403: 3,4-dichloro-N-[4-({7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-clihydroquinazolin-3(2H)-yl}nnethyl)-2-
methoxyphenyl]benzamide;
in the form of the base or of an addition salt with an acid.
15. Compound corresponding to the general formula (I)
in which
— A represents an aryl group or a heteroaryl group;
— R1 represents:
■ a hydrogen atom,
■ -C(O)R in which R is a hydrogen atom, a (C1-C6) alkoxy group, an aryl group, a
(C3-C6) cycloalkyl group or a (C1-C6) alkyl group, the said alkyl optionally being
substituted by:
. one or more hydroxyl group(s),
. a benzyloxy group,
. a (C1-C6) alkoxy group, optionally substituted by an aryl, or
. a (C3-C6) cycloalkyl group,
■ an optionally substituted (C1-C6) alkyl group;
— R2 represents:
■ a hydrogen atom,
■ a halogen atom,
■ a cyano group,
■ a nitro group,
■ a (C1-C6) alkyl group optionally substituted by an -NH2 or else by an
-NHC(O)Rb group, with Rb as defined below,
■ an -ORa group in which Ra represents:
. a hydrogen atom,
. a (C1-C6) alkyl group optionally substituted by one or more halogen
atom(s), by one or more hydroxyl group(s), by an aryl group and/or by one or
more cyano group(s),
. a (C2-C6) alkynyl group,
. an aryl group;
— R3 represents:
■ a hydrogen atom,
■ a halogen atom,
■ a hydroxyl group,
■ a cyano group,
■ an -SCF3 group,
■ a nitro group,
■ an -S(O)0-2-alkyl group, an -S(O)0-2-heterocycloalkyl group, an -O-SO2-aryl
group optionally substituted by one or more halogen atom(s);
■ an -alkylaminoalkyl or -cycloalkylaminoalkyl group, each optionally substituted
on the end alkyl,
■ an optionally substituted sulphonamide group,
■ an aryl group or a heteroaryl group, the said group being monocyclic or
polycyclic and in addition optionally being substituted by a (C1-C6) alkyl group, by
one or more halogen atom(s) or by a (C1-C6) alkoxy group,
■ a heterocycloalkyl group optionally substituted by a (C1-C6) alkyl group,
■ a (C1-C6) alkyl group optionally substituted by:
- one or more halogen atom(s),
- an aryl group which can be substituted by one or more halogen atom(s)
or by one or more hydroxyl group(s),
- a heteroaryl group,
- one or more hydroxyl group(s) which can be substituted by an aryl group
itself optionally substituted by one or more halogen atom(s), or
- a heterocycloalkyl group optionally substituted by a CO(O)Ra group or by
a (C1-C6) alkyl group, with Ra as defined above,
■ a -C(O)NRbRc group, with Rb and Rc as defined below,
■ a -C(O)ORc group or an -O-C(O)ORc group, with Rc as defined below,
■ a (C1-C6) alkoxy group, optionally substituted by
- an aminoalkyl group,
- an aminocycloalkyl group,
- a cycloalkyl group,
- a heterocycloalkyl group,
- a monocyclic or polycyclic heteroaryl group,
- one or more hydroxyl group(s),
- one or more halogen atom(s),
- a (C1-C6) alkoxy group,
- a -C(O)ORc group, with RC as defined below,
- a -C(O)NRbRc group, with Rb and Rc as defined below, and/or
- an aryl group, itself optionally substituted by one or more halogen
atom(s), a cyano group, a (C1-C6) alkoxy group, an -O-haloalkyl group and/or a
haloalkyl group,
■ an -O-cycloalkyl group, an -O-aryl group or an -O-heterocycloalkyl group, each
optionally substituted by
- an aryl group, itself optionally substituted by one or more halogen
atom(s) or by a (C1-C6) alkyl group,
- one or more halogen atom(s), and/or
- a (C1-C6) alkyl group, which can itself be substituted by an aryl group,
■ an -NH-CO-NH-aryl group, an -NH-CO-NH-heteroaryl group or an -NH-CO-
NH-(C1-C6) alkyl group, each optionally being substituted by one or more halogen
atom(s), by a cyano group, by a nitro group, by one or more hydroxyl group(s) or by a
(C1-C6) alkoxy group,
■ an -N-(C1-C6) alkyl group, it being possible for the (C1-C6) alkyl group to be
substituted by
one or more aryl group(s) optionally substituted by one or more halogen atom(s)
and/or by an SO2 group,
■ an -NH-CO-aryl group or an -NH-CO-heteroaryl group, each optionally being
substituted by one or more halogen atom(s);
or else R3 forms, with A, a polycyclic heteroaryl group optionally substituted by a (C1-C6)
alkoxy group or a (C1-C6) alkyl group optionally substituted by an aryl group which can
itself be substituted by one or more halogen atom(s);
— R4 represents a hydrogen atom or a (C1-C6) alkyl group;
— Rb represents:
. a hydrogen atom,
. a (C1-C6) alkyl group optionally substituted by one or more halogen atom(s), by
one or more hydroxyl, cyano, amino, heterocycloalkyl or (C1-C6) alkoxy group(s) or by an
aryl group optionally substituted by one or more halogen atom(s),
. a (C3-C6) cycloalkyl group,
. a (C2-C6) alkynyl group,
. a (C1-C6) alkoxy group,
. an aryl group optionally substituted by one or more halogen atom(s);
— Rc represents a hydrogen atom or a (C1-C6) alkyl group optionally substituted
by one or more halogen atom(s);
or then Rb and Rc form, together with the nitrogen atom to which they are attached, a
polycyclic heteroaryl group or a heterocycloalkyl group;
— m and n represent, independently of one another, the value 0, 1 or 2, it being
understood that m+n<3;
— p and p' represent, independently of one another, the value 1, 2 or 3, it being
understood that, when p is greater than or equal to 2, then the R2 groups are on separate
carbon atoms and can be different from one another and, when p' is greater than or
equal to 2, then the R3 groups are on separate carbon atoms and can be different from
one another;
— q represents the value 0 or 2, it being understood that, when q = 0, then the
nitrogenous heterocyclic group attached to the nitrogen situated in the 1 position of the
2,4-dioxo-1,2,3,4-tetrahydroquinazoline ring system is no longer bridged and is of the
type:
with R1, R4, m and n as defined above,
— r represents the value 0 or 1;
in the form of bases or of addition salts with acids;
intended to treat at least one cardiovascular disease and/or to prevent the
appearance of at least one cardiovascular disease.
16. Compound according to the preceding claim, characterized in that the cardiovascular
diseases are chosen from (i) coronary diseases, (ii) diseases of the cardiac muscle, (iii)
diseases of the heart valves, (iv) diseases of the pericardium, (v) diseases of the heart
rhythm and diseases of cardiac conduction, and (vi) diseases of the vessels.
17. Compound according to either one of Claims 15 and 16, characterized in that the
cardiovascular disease is chosen from myocardial infarction, in particular contractile
cardiac dysfunction resulting from a myocardial infarction, diseases associated with
reperfusion injuries of the cardiac and/or skeletal muscle, pulmonary hypertension,
hepatic fibrosis, post-angioplasty arterial restenosis, with or without fitting a stent,
atherosclerosis and its complications, cardiac insufficiency, dilated cardiopathy and
myocarditis of viral and/or bacterial origin.
18. Compound according to one of Claims 15 to 17, characterized in that:
— A is as defined in Claim 5;
— q, m and n are as defined in Claim 6;
— R2 is as defined in Claim 7, Claim 8 or Claim 9.
19. Compound according to one of Claims 15 to 17, characterized in that:
A is a phenyl, R1 is a -C(O)R group in which R represents a hydrogen atom, q is equal to
0, n and m each have the value 1 and R2 represents -ORa, Ra being as defined in
Claim 1 or Claim 2.
20. Compound according to one of Claims 15 to 17, characterized in that:
A is a phenyl, R1 is a -C(O)R group in which R represents a hydrogen atom, q is equal to
0, n and m each have the value 1, p = 1 and R2 represents a methyl substituted by an
-NH-CO-Rb group, Rb being as defined in Claim 1 or Claim 2.
21. Compound according to one of Claims 15 to 17, characterized in that:
A is a phenyl, R1 is a -C(O)R group in which R represents a hydrogen atom, q is equal to
0, n and m each have the value 1, p is equal to 2, one of the R2 groups is -ORa, Ra
being as defined in Claim 1 or Claim 2, and the other of the R2 groups is a halogen atom.
22. Compound according to one of Claims 15 to 17, characterized in that:
the R2 group is in the 6 position of the 2,4-dioxo-1,2,3,4-tetrahydroquinazoline ring
system and in that there may additionally be an R2 group, identical to or different from the
said R2 group mentioned above, in the 7 position of the 2,4-dioxo-1,2,3,4-
tetrahydroquinazoline ring system, the said compound of formula (I) being in the base,
hydrate or solvate form, in the form of isomers or in the form of their mixtures.
23. Compound according to one of Claims 15 to 17 chosen from:
No. 1: 2-{[3-(3,4-dimethoxybenzyl)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]oxy}propanenitrile
No. 2: 1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-6-hydroxyquinazoline-
2,4(1 H,3H)-dione
No. 3: {[1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]oxy}acetonitrile
No. 4: 2-{[1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]oxy}propanenitrile
No. 5: {[3-(3,4-dimethoxybenzyl)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]oxy}acetonitrile
No. 6: {[3-(3,4-dimethoxybenzyl)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]oxy}acetonithle
No. 11: 4-[3-(3,4-dimethoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-
3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 12: 1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-6-[2-fluoro-1-
(fluoromethyl)ethoxy]quinazoline-2,4(1H,3H)-dione
No. 13: 4-[3-(3,4-dimethoxybenzyl)-2,4-dioxo-6-(2,2,2-trifluoroethoxy)-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 14: 1-(1-acetylpiperidin-4-yl)-6-(2,2-difluoroethoxy)-3-(3,4-
dimethoxybenzyl)quinazoline-2,4(1H,3H)-dione
No. 16: 4-[6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 20: N-{[3-(3,4-dimethoxybenzyl)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]methyl}acetamide
No. 22:1-(1-acetylpiperidin-4-yl)-6-(aminomethyl)-3-(3,4-
dimethoxybenzyl)quinazoline-2,4(1 H,3H)-dione hydrochloride
No. 23: N-{[3-(3,4-dimethoxybenzyl)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]methyl}formamide
No. 24: N-{[1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]methyl}formamide
No. 25: N-{[1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]methyl}acetamide
No. 32:4-[6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]piperidine-1-carbaldehyde
No. 33: 4-[3-(3,4-dichlorobenzyl)-6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 34:4-t3-(4-chlorobenzyl)-6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 35: methyl 4-{[6-(2,2-difluoroethoxy)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,4-
dihydroquinazolin-3(2H)-yl]methyl}benzoate
No. 36: 4-{[6-(2,2-difluoroethoxy)-1 -(1 -formylpiperidin-4-yl)-2,4-dioxo-1,4-
dihydroquinazolin-3(2H)-yl]methyl}benzoicacid
No. 37: 4-{[6-(2,2-difluoroethoxy)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,4-
dihydroquinazolin-3(2H)-yl]methyl}-N-(2-methoxyethyl)benzamide
No. 38: 4-[3-(3,4-dimethoxybenzyl)-6-methyl-2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-
yl]piperidine-1 -carbaldehyde
No. 39: 4-[6-(2,2-difluoroethoxy)-3-(3-hydroxy-4-methoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 40: 4-[6-(2,2-difluoroethoxy)-3-[3-(2-hydroxyethoxy)-4-methoxybenzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 41: 4-[6-(2,2-difluoroethoxy)-3-(3-ethoxy-4-methoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yi]piperidine-1 -carbaldehyde
No. 42: 4-[6-(2,2-difiuoroethoxy)-3-[4-methoxy-3-(2-methoxyethoxy)benzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 43:4-[6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]azepane-1 -carbaldehyde
No. 47: 4-[6-(2,2-difluoroethoxy)-3-[3-(3-hydroxypropoxy)-4-methoxybenzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 48: 4-[5-chloro-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]piperidine-1 -carbaldehyde
No. 49: 4-{3-[3-(cyclopentyloxy)-4-methoxybenzyl]-6-(2,2-difluoroethoxy)-2,4-dioxo-
3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 50: 2-(5-{[6-(2,2-difluoroethoxy)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,4-
dihydroquinazolin-3(2H)-yl]methyl}-2-methoxyphenoxy)acetamide
No. 51: 4-[6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-2(4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]-3-methylpiperidine-1-carbaldehyde
No. 52:3-[6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]-8-azabicyclo[3.2.1]octane-8-carbaldehyde
No. 55: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-
1(2H)-yl}piperidine-1-carbaldehyde
No. 56: 4-{3-[4-(cyclopentyloxy)-3-methoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 57:4-[3-(3-chlorobenzyl)-6-[2-fluoro-1-{fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 58: 4-[3-(4-chlorobenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 59: 4-{3-[3-(cyclopentyloxy)-4-methoxybenzyl]-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 72: 4-[3-(3,4-dimethoxybenzyl)-6-(2-hydroxyethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 74: 4-[3-(3,4-dichlorobenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 76: 4-{3-[(6-chloropyridin-3-yl)methyl]-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 78: 4-[3-(3-chloro-4-methoxybenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 79:4-[3-(3,4-dimethoxybenzyl)-6-(2-fluoroethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 89: 2-[5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-2,4-
dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxyphenoxy]acetamide
No. 90: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-hydroxy-4-methoxybenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 91: 4-[3-(3,4-dimethoxybenzyl)-6-ethoxy-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]piperidine-1 -carbaldehyde
No. 97: 4-[5,7-dichloro-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-
1(2H)-yl]piperidine-1-carbaldehyde
No. 102: 4-[7-chloro-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-
1(2H)-yl]piperidine-1-carbaldehyde
No. 108: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-fluoro-4-methoxybenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 111: 4-[6-(difluoromethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1 -carbaldehyde
No. 112: 4-[3-(3,4-dimethoxybenzyl)-6-(1-methylethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 114: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-methoxy-3-(1-
methylethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 116: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-(3-methoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 117: 4-{3-[3,5-bis(trifluoromethyl)benzyl]-6-[2-fluoro-1-(fluoromethyl)ethoxy]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 118: 4-[3-(3-ethoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 124: 4-{3-[3-chloro-4-(2-methoxyethoxy)benzyl]-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}pipericline-1 -carbaldehyde
No. 130: 4-[3-(3,4-diethoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-
3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 131: 4-[3-(4-ethoxy-3-methoxybenzyl)-6-t2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 133: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(4-methoxy-3-methylbenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 134: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-
(trifluoromethyl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 135: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-
(trifluoromethyl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 143: 4-{3-[4-(benzyloxy)-3-methoxybenzyl]-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 145: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-nitrobenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 155: 4-[3-(4-ethoxybenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 158: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[4-(morpholin-4-ylmethyl)benzyl]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 160: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(4-(morpholin-4-yl)benzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 165: 4-[3-(biphenyl-4-ylmethyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-
3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 166: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[4-(methylsulphanyl)benzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 167:4-{6-t2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyridin-3-yl)benzyl)-
3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 170:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-(3-methoxy-4-methylbenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 175:2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]acetamide
No. 178: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-propoxybenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 183: 2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1-(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
methylacetamide
No. 184: 2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N,N-
dimethylacetamide
No. 185: 2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
methoxy-N-methylacetamide
No. 186: 4-{3-[4-(cyclopentyloxy)-3-ethoxybenzyl]-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 188: 4-{3-[4-(cyclopentyloxy)-3-(1-methylethoxy)benzyl]-6-t2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 189: 4-{3-[4-(cyclopentyloxy)-3-propoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 190: 4-{3-[4-(cyclopentyloxy)-3-hydroxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 193: 4-{3-[4-(difluoromethoxy)-3-methoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 194: 4-{3-[4-(difluoromethoxy)-3-ethoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 200: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(thiophen-3-yl)-
benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 201: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyridin-4-yl)benzyl)-
3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 203: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(1-methyl-1 H-indol-6-yl)methyl]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 206: 4-{3-[4-(cyclopropylmethoxy)-3-methoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 207:2-[4-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-2,4-
dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxyphenoxy]-N-methylacetamide
No. 212:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-(1H-pyrazol-1-
yl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 213: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyridin-2-yl)benzyl)-
3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 215: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(thiophen-2-yl)-
benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 216: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(quinolin-7-ylmethyl)-
3,4-dihydroquinazolin-1 (2H)-yl}piperidine-1 -carbaldehyde
No. 218: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(6-methoxynaphthalen-2-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 223: 4-{3-[4-(1 H-benzimidazol-1-yl)benzyl]-6-[2-fluoro-1-(fluoromethyl)ethoxy]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 224: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(2-
methylpropoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 226: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(tetrahydrofuran-3-
yloxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 228: 4-[3-{4-[(1 -benzylpyrrolidin-3-yl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)6thoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 230: 4-[3-(1 -benzothiophen-5-ylmethyl)-6-[2-fluoro-1 -(fluorometrtyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 232: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[3-methoxy-4-(1 -
methylethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 233: 4-[3-(3,4-dimethoxybenzyl)-7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxyj-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 234:4-[3-{4-[(1-acetylpyrrolidin-3-yl)oxy]-3-nriethoxybenzyl}-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 239:4-[3-{4-[(4-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 240: 4-[3-{4-[(4-chlorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 242: 4-[3-{4-[(3-chlorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoramethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 243: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(3-(thiophen-3-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 245: 4-[3-(4-ethoxy-3-methoxybenzyl)-6-(2-hydroxyethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 246: 4-[3-{4-[2-(2,3-dihydro-1 H-indol-1-yl)-2-oxoethoxy]-3-methoxybenzyl}-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 250: 4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 251: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[3-methoxy-4-(2-oxo-2-(piperidin-
1-yl)ethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 254: 4-{3-[3-ethoxy-4-(thiophen-2-ylmethoxy)benzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 258: 4-[3-(3,4-dimethoxybenzyl)-6-[2-fluoro-1 -(hydroxymethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 263:(2R)-2-t2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
forrnylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]propanoic
acid
No. 264: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(1-methyl-3-(thiophen-2-yl)-1 H-
pyrazol-5-yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 270: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(5-methyl-1,2,4-oxadiazol-3-
yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 275: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyrimidin-5-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 276: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(1-methyl-3-phenyl-1 H-pyrazol-5-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 278:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-{[6-(1H-pyrazol-1-
yl)pyridin-3-yl]methyl}-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 279:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[(2-(thiophen-2-
yl)pyrimidin-5-yl)methyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 280:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(1-methyl-1H-pyrazol-3-
yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 282: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(3-methyl-1,2,4-oxadiazol-5-
yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 283: t2-(cyclopentyloxy)-5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazoliri-3(2H)-yl}methyl)phenoxy]aceticacid
No. 285: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-(thieno[2,3-blpyridin-2-
ylmethyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 286: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-[(6-phenylpyridin-3-
yl)methyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 287: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[(6-(morpholin-4-yl)pyridin-3-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 289: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-[(6-(thiophen-2-
yl)pyridin-3-yl)methyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 292: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(1 -methyl-5-phenyl-1 H-pyrazol-3-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 294: 4-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-2,4-dioxo-
1,4-dihydroquinazolin-3(2H)-yl}methyl)biphenyl-2-carbonitrile
No. 295: (2R)-2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
methylpropanamide
No. 297: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(thiophen-2-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 298: 4-{6-[2-fluoro-1 -(f luoromethyl)ethoxy]-3-[3-methoxy-4-(morpholin-4-
ylmethyl)benzyl]-2,4-clioxo-3,4-dihydroquinazolin-1(2H)-yl}pipericline-1-carbalclehyde
No. 299: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(piperidin-1 -
ylmethyl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 300: 4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fiuoromethyl)ethoxy]-2I4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 301: 2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
ethylacetamide
No. 302: (2S)-2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]propanoic
acid
No. 305: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-{[(3R)-2-oxo-1 -
phenylpyrrolidin-3-yl]oxy}benzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 306: 4-{3-[4-(cyclobutylmethoxy)-3-methoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 307: 4-{3-[4-(benzyloxy)-3-methoxybenzyl]-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 308: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(4-hydroxy-3-
methoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 309: 4-{3-[4-(cyclopropylmethoxy)-3-methoxybenzyl]-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 310: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-
(2-methylpropoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 311: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[3-methoxy-4-
(1-methylethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 312: 4-[3-(4-ethoxy-3-methoxybenzyl)-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 315: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{[6-(3-
methoxyphenyl)pyridin-3-yl]rnethyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 316:4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-{[6-(2-
fluorophenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 317: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{[6-(4-
fluorophenyl)pyridin-3-yl]methyl}-2,4-dioxo-3I4-dihyclroquinazolin-1(2H)-yl}pipericline-1-
carbaldehyde
No. 318:4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-{[6-(4-
methoxyphenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 319: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[(6-(thiophen-2-
yl)pyridin-3-yl)methyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 320: 4-{3-[3-ethoxy-4-(thiophen-2-ylmethoxy)benzyl]-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 321: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[4-(1 -methyl-1 H-pyrazol-
3-yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 322: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyrimidin-5-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 323: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[(1 -methyl-3-(thiophen-2-
yl)-1H-pyrazol-5-yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 324: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(2-oxo-2-
(piperidin-1 -yl)ethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-yl}piperidine-1 -
carbaldehyde
No. 325: 4-[3-{4-[2-(2,3-dihydro-1 H-indol-1 -yl)-2-oxoethoxy]-3-methoxybenzyl}-7-
fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]piperidine-1-carbaldehyde
No. 326: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[4-(5-methyl-1,2,4-
oxadiazol-3-yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 327: 4-[3-{4-[(3-chlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 328:4-[3-{[6-(3,5-dichlorophenyl)pyridin-3-yl]methyl}-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
i No. 329: 4-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)biphenyl-2-carbonitrile
No. 330: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-(1 H-pyrazol-
1 -yl)benzyl]-3,4-dihydroquinazolin-1 (2H)-yl}piperidine-1 -carbaldehyde
No. 331: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{[6-(3-
fluorophenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 332:3-[5-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-
yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)pyridin-2-yl]benzonitrile
No. 333: 4-[3-(3,4-diethoxybenzyl)-7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 334: 4-[3-{4-[(4-chloroben2yl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 335: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(morpholin-4-
ylmethyl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 336: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-{[6-(1 H-pyrazol-
1-yl)pyridin-3-yl]methyl}-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 337: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(4-(morpholin-4-yl)-
benzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 338: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-
propoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 339:4-{3-[4-(1H-benzimidazol-1-yl)benzyl]-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 340: 5-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxybenzonitrile
No. 341: 3-(3,4-dimethoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-y4-dioxo-1.2.3.SAtetrahydroquinazoline-7-carbonitrile
No. 342: 4-[3-(4-bromobenzyl)-7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 343:4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-(2-methoxyethoxy)benzyl}-7-fluoro-6-
[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 344: 4-{3-[4-(benzyloxy)benzyl]-7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 345: 4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-ethoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 349:4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-(2-fluoroethoxy)benzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 350:4-[3-{4-[(2-chloro-4-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 351: 4-[3-{4-[(2,4-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 352:4-[3-{4-[(2-chloro-6-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 353: 4-[3-{4-[(2,6-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihyclroquinazolin-1(2H)-yl]pipericline-1-carbaldehyde
No. 354: 4-[3-{4-[(2-chlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 355: 4-[7-fluoro-3-{4-[(2-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 357: 2-[(3,4-dichlorobenzyl)oxy]-5-({7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-
1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)benzonitrile
No. 358: 4-[3-{4-[(3,4-dich!orophenoxy)methyl]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 360: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-(2-
phenylethyl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 362: 4-[3-{4-[(4,5-dichloro-2-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 369: 4-[3-{4-[(4-chlorophenoxy)methyl]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 371: 4-[3-{3-chloro-4-[(4-chlorobenzyl)oxy]-5-ethoxybenzyl}-7-fluoro-6-[2-fluoro-
1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 373: 4-[3-{3-chloro-4-[(2,4-dichlorobenzyl)oxy]-5-ethoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 375: 4-[7-fluoro-3-{4-[(4-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 376: 4-[3-{4-[(3,5-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 377: 4-[3-(4-{[4-chloro-3-(trifluoromethyl)benzyl]oxy}-3-methoxybenzyl)-7-
fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]piperidine-1 -carbaldehyde
No. 379: 4-[3-{4-[(3-chlorophenoxy)methyl]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 380: 4-[3-{4-f(3,5-difluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-t2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 381:4-{3-[4-(benzyloxy)-3-methoxybenzyl]-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 382:4-[3-{4-t(3-chloro-5-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fiuorc-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-y!]piperidine-1 -
carbaldehyde
No. 383: 4-{7-fluoro-6-[2-f!uoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-{[4-
(trifluoromethyl)benzyl]oxy}ben2yl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 384: 4-[3-{4-[(2,5-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-t2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 385: 4-{[4-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-
yi)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-
methoxyphenoxy]methyl}benzonitrile
No. 386: 3-{[4-({7-fluoro-6-[2-fluoro-1-(fiuoromethyl)ethoxy]-1-(1-formylpiperidin-4-
yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-
methoxyphenoxy]methyl}benzonitrile
No. 387: 4-[3-{4-[(4-chloro-2-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 388: 4-[3-{4-[1-(3,4-dichlorophenyl)ethoxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 389: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{4-[(3-hydroxybenzy!)oxy]-
3-methoxybenzyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 390: 4-[7-fluoro-3-{4-t(3-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fIuoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 391:4-[3-{4-[(3,4-difluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 392:4-{3-[4-(5,6-dichloro-1H-benzimidazol-1-yl)-3-methoxybenzyl]-7-fluoro-6-
[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 393:4-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenyl 3,4-dichlorobenzenesulphonate
No. 394: 4-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxyphenyl 3,4-dichlorobenzene-
sulphonate
No. 403:3,4-dichloro-N-[4-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-
methoxyphenyrjbenzamide;
THERAPEUTIC APPLICATIONS IN THE CARDIOVASCULAR FIELD OF
QUINAZOLINEDIONE DERIVATIVES
A subject-matter of the invention is the use of quinazolinedione derivatives as
medicaments or for manufacturing a medicament intended for the treatment and/or
prevention of at least one cardiovascular disease.
The invention relates more particularly to the use of quinazolinedione derivatives
capable of acting as inhibitors of phosphodiesterase 7 (PDE7), indeed even, for some of
these derivatives, capable of also acting as inhibitors of phosphodiesterase 8 (PDE8), it
being known that it is not ruled out for these same quinazolinedione derivatives also to be
capable of acting via other biological/biochemical routes on the cardiovascular system,
with the aim of treating one or more cardiovascular condition(s) and/or preventing the
appearance of such condition(s).
Phosphodiesterases (PDEs) are intracellular enzymes responsible for the
hydrolysis of cAMP (cyclic adenosine 3',5'-monophosphate) and cGMP (cyclic guanosine
3',5'-monophosphate) secondary messengers to give inactive 5'-monophosphate
nucleotides. cAMP and cGMP play an essential role in cell signalling pathways and are
involved in numerous physiological processes.
The inhibition of phosphodiesterases is reflected by an increase in intracellular
concentrations of cAMP and cGMP, resulting in the specific activation of phosphorylation
pathways involved in varied functional responses. The increase in the intracellular
concentrations of cAMP or of cGMP using selective inhibitors of phosphodiesterases
appears to be a promising approach in the treatment of various diseases (Bender and
Beavo, Pharmacol. Rev., (2006) 58, 488-520). The inhibitors of phosphodiesterases are
thus of interest as therapeutic agents and as pharmacological tools.
To date, eleven families of phosphodiesterases have been identified. They are
distinguished by their primary structure, their substrate specificity and their sensitivity with
regard to various effectors and inhibitors specific for PDEs. Each family is composed of
one or more genes which are expressed in various tissues in the form of splicing variants
(Bender and Beavo, Pharmacol. Rev, (2006) 58, 488-520; Lugnier, Pharmacol.
Therapeut., (2006) 109, 366-398).
PDE4, PDE7 and PDE8 specifically hydrolyse cAMP and PDE5, PDE6 and PDE9
specifically hydrolyse cGMP.
The family PDE7 is represented by the isoforms PDE7A and PDE7B originating
from two distinct genes.
Human PDE7A (Michaeli et al., J. Biol. Chem, (1993) 268, 12925-12932; Han et
al, J. Biol. Chem., (1997) 272, 16152-16157; Wang et al., Biochem. Biophys. Res.
Commun, (2000) 276, 1271-1277) and human PDE7B (Sasaki et al, Biochem. Biophys.
Res. Commun, (2000), 271, 575-583; Gardner et al, Biochem. Biophys. Res. Commun,
(2000) 272, 186-192) selectively hydrolyse cAMP with Michaelis constants (Km) of 0.1 to
0.2 pM and 0.13 to 0.2 uM respectively. The catalytic part of PDE7B exhibits
approximately 67% homology with that of PDE7A.
Three splicing variants are known for PDE7A. PDE7A1 and PDE7A3 are
expressed mainly in the cells of the immune system and of the lungs, while PDE7A2 is
above all expressed in the muscles of the skeleton, the heart and the kidneys. For
PDE7B, three variants have also recently been identified (Giembycz and Smith, Drugs
Future, (2006)31,207-229).
The tissue distribution profiles for PDE7A and PDE7B are very different,
suggesting that these two isoforms have distinct functions from the physiological
viewpoint. PDE7A is copiously expressed in haematopoietic cells, the lungs, the
placenta, the spleen, the muscles of the skeleton, the heart, Leydig cells, the collecting
tubes of the kidneys, and the adrenal glands. Strong expression of PDE7B is detected in
the pancreas, the heart, the thyroid and the muscles of the skeleton (Giembycz and
Smith, Drugs Future, (2006) 31, 207-229; Wang etal., Biochem. Biophys. Res. Commun.
(2000), 276, 1271-1277). Coexpression of the messenger RNAs (mRNAs) of PDE7A and
PDE7B is observed in some tissues. This is the case in the osteoblasts (Ahlstrom et al.,
Cell Mol. Biol. Lett., (2005) 10, 305-319) and in some regions of the brain: several areas
of the cortex, the dentate gyrus, the majority of the components of the olfactory system,
the striatum, numerous nuclei of the thalamus and the pyrimidal cells of the hippocampus
(Miro et al., Synapse, (2001) 40, 201-214; Reyes-lrisarri et al., Neuroscience, (2005) 132,
1173-1185). In contrast, in some areas of the brain, only one of the two isoforms is
expressed. Thus, only the mRNAs of PDE7A are present in many nuclei of the brain
stem. Likewise, the mRNAs of PDE7B are present at high concentrations in the nucleus
accombens and the dorsal motor nucleus of the vagus nerve, while the mRNAs of
PDE7A are not detected there (Miro et al„ Synapse, (2001) 40, 201-214; Reyes-lrisarri et
al., Neuroscience, (2005) 132, 1173-1185).
A subject-matter of the present invention is in particular therapeutic applications of
quinazolinedione derivatives, which can prove to be powerful inhibitors of PDE7, or of
PDE7 and of PDE8, according to the derivatives, or which can act by other biological
routes.
The invention relates to the use of a compound corresponding to the following
general formula (I):
in which
— A represents an aryl group or a heteroaryl group;
— R1represents:
■ a hydrogen atom,
■ -C(O)R in which R is a hydrogen atom, a (C1-C6) alkoxy group, an aryl group, a
(C3-C6) cycloalkyl group or a (C1-C6) alkyl group, the said alkyl optionally being
substituted by:
. one or more hydroxyl group(s),
. a benzyloxy group,
. a (C1-C6) alkoxy group, optionally substituted by an aryl, or
. a (C3-C6) cycloalkyl group,
■ an optionally substituted (C1-C6) alkyl group;
— R2 represents:
■ a hydrogen atom,
■ a halogen atom,
■ a cyano group,
■ a nitro group,
■ a (C1-C6) alkyl group optionally substituted by an -NH2 or else by an
-NHC(O)Rb group, with Rb as defined below,
■ an -ORa group in which Ra represents:
. a hydrogen atom,
. a (C1-C6) alkyl group optionally substituted by one or more halogen
atom(s), by one or more hydroxyl group(s), by an aryl group and/or by one or
more cyano group(s),
. a (C2-C6) alkynyl group,
. an aryl group;
— R3 represents:
■ a hydrogen atom,
■ a halogen atom,
■ a hydroxyl group,
■ a cyano group,
■ an -SCF3 group,
■ a nitro group,
■ an -S(O)0-2-alkyl group, an -S(O)0-2-heterocycloalkyl group, an -O-SO2-aryl
group optionally substituted by one or more halogen atom(s);
■ an -alkylaminoalkyl or -cycloalkylaminoalkyl group, each optionally substituted
on the end alkyl,
■ an optionally substituted sulphonamide group,
■ an aryl group or a heteroaryl group, the said group being monocyclic or
polycyclic and in addition optionally being substituted by a (C1-C6) alkyi group, by
one or more halogen atom(s) or by a (C1-C6) alkoxy group,
■ a heterocycloalkyl group optionally substituted by a (C1-C6) alkyl group,
■ a (C1-C6) alkyl group optionally substituted by:
- one or more halogen atom(s),
- an aryl group which can be substituted by one or more halogen atom(s)
or by one or more hydroxyl group(s),
- a heteroaryl group,
- one or more hydroxyl group(s) which can be substituted by an aryl group
itself optionally substituted by one or more halogen atom(s), or
- a heterocycloalkyl group optionally substituted by a CO(O)Ra group or by
a (C1-C6) alkyl group, Ra being as defined above,
■ a -C(O)NRbRc group, with Rb and Rc being as defined below,
■ a -C(O)ORc group or an -O-C(O)ORc group, with Rc being as defined below,
■ a (C1-C6) alkoxy group, optionally substituted by
- an aminoalkyl group,
- an aminocycloalkyl group,
- a cycloalkyl group,
- a heterocycloalkyl group,
- a monocyclic or polycyclic heteroaryl group,
- one or more hydroxyl group(s),
- one or more halogen atom(s),
- a (C1-C6) alkoxy group,
- a -C(O)ORc group, with Rc being as defined below,
- a -C(O)NRbRc group, with Rb and Rc being as defined below, and/or
-an aryl group, itself optionally substituted by one or more halogen
atom(s), a cyano group, a (C1-C6) alkoxy group, an -O-haloalkyl group and/or a
haloalkyl group,
■ an -O-cycloalkyl group, an -O-aryl group or an -O-heterocycloalkyl group, each
optionally substituted by
-an aryl group, itself optionally substituted by one or more halogen
atom(s) or by a (C1-C6) alkyl group,
- one or more halogen atom(s), and/or
- a (C1-C6) alkyl group, which can itself be substituted by an aryl group,
■ an -NH-CO-NH-aryl group, an -NH-CO-NH-heteroaryl group or an -NH-CO-
NH-(C1-C6) alkyl group, each optionally being substituted by one or more halogen
atom(s), by a cyano group, by a nitro group, by one or more hydroxyl group(s) or by a
(C1-C6) alkoxy group,
■ an -N-(C1-C6) alkyl group, it being possible for the (C1-C6) alkyl group to be
substituted by
one or more aryl group(s) optionally substituted by one or more halogen atom(s)
and/or by an SO2 group,
■ an -NH-CO-aryl group or an -NH-CO-heteroaryl group, each optionally being
substituted by one or more halogen atom(s);
or else R3 forms, with A, a polycyclic heteroaryl group optionally substituted by a (C1-C6)
alkoxy group or a (C1-C6) alkyl group optionally substituted by an aryl group which can
itself be substituted by one or more halogen atom(s);
— R4 represents a hydrogen atom or a (C1-C6)alkyl group;
— Rb represents:
. a hydrogen atom,
. a (C1-C6) alkyl group optionally substituted by one or more halogen atom(s), by
one or more hydroxyl, cyano, amino, heterocycloalkyl or (C1-C6) alkoxy group(s) or by an
aryl group optionally substituted by one or more halogen atom(s),
. a (C3-C6) cycloalkyl group,
. a (C2-C6) alkynyl group,
. a (C1-C6) alkoxy group,
. an aryl group optionally substituted by one or more halogen atom(s);
— Rc represents a hydrogen atom or a (C1-C6) alkyl group optionally substituted
by one or more halogen atom(s);
or then Rb and Rc form, together with the nitrogen atom to which they are attached, a
polycyclic heteroaryl group or a heterocycloalkyl group;
— m and n represent, independently of one another, the value 0, 1 or 2, it being
understood that m+n<3;
— p and p' represent, independently of one another, the value 1, 2 or 3, it being
understood that, when p is greater than or equal to 2, then the R2 groups are on separate
carbon atoms and can be different from one another and, when p' is greater than or
equal to 2, then the R3 groups are on separate carbon atoms and can be different from
one another;
— q represents the value 0 or 2, it being understood that, when q = 0, then the
nitrogenous heterocyclic group attached to the nitrogen situated in the 1 position of the
2,4-dioxo-1,2,3,4-tetrahydroquinazoline ring system is no longer bridged and is of the
type:
with R-1, R4, m and n as defined above,
— r represents the value 0 or 1,
as medicament or for the preparation of a medicament which are intended to treat at
least one cardiovascular disease and/or to prevent the appearance of at least one
cardiovascular disease.
The compounds of general formula (I) can comprise one or more asymmetric
carbons. They can thus exist in the form of enantiomers or of diastereoisomers. These
enantiomers or diastereoisomers, and their mixtures, including racemic mixtures, come
within the invention.
Due to their structure, the compounds of general formula (I) can also exist in the
form of isomers of rotamer or atropisomer type.
The compounds of formula (I) can also exist in the form of bases or addition salts
with acids. Such addition salts come within the invention.
These salts are advantageously prepared with pharmaceutical^ acceptable acids
but the salts of other acids, for example of use in the purification or separation of the
compounds of general formula (I) also come within the invention.
The compounds of general formula (I) can also occur in the crystalline,
amorphous or oily form, these forms coming within the invention.
The compounds of general formula (I) can in addition occur in the form of
hydrates or of solvates, namely in the form of combinations or of associations with one or
more molecules of water or with a solvent. Such hydrates and solvates also come within
the invention.
According to the present invention, the N-oxides of the compounds comprising an
amine also come within the invention.
The compounds of formula (I) in accordance with the invention also comprise
those in which one or more hydrogen, carbon or halogen, in particular chlorine or
fluorine, atoms have been replaced by their radioactive isotopes, for example tritium, in
order to replace hydrogen, or carbon-14, in order to replace carbon-12. Such labelled
compounds are of use in research, metabolism or pharmacokinetic studies or in
biological and pharmacological assays as tools.
In the context of the invention, the following definitions apply:
- in (C1.C6)' the numerical indices determine the possible number of carbon atoms
present in a chain or a ring. Thus, by way of example, C1-C6 represents a carbon chain
which can have from 1 to 6 carbon atoms. Likewise, by way of example, (C1-C5)
represents a carbon chain which can have from 1 to 5 carbon atoms or also (C3-C6) can
represent a saturated carbon ring which can have from 3 to 6 carbon atoms;
-alkoxy: an -O-alkyl group comprising a saturated, linear or branched, aliphatic
chain;
- alkynyl: a mono- or polyunsaturated, linear or branched, aliphatic group comprising,
for example, one or two acetylenic unsaturations. For example, a (C2-C6) alkynyl group
can represent an ethynyl, propynyl, and the like;
- alkyl: a saturated, linear or branched, aliphatic group; for example, a (C1-C6) alkyl
group represents a linear or branched carbon chain of 1 to 6 carbon atoms, in particular
a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl or pentyl;
- aminoalkyl: an -NH(C1-C6) alkyl or also -N((C1-C6) alkyl)2 group;
- aryl: an optionally substituted monocyclic aromatic system comprising from 5 to
14 members per ring, preferably from 5 to 10 members per ring. Mention may be made,
as examples of monocyclic aryl groups, of phenyl or naphthyl; the aryl group can be
substituted by a group which can be one or more halogen atom(s), a hydroxyl group, a
cyano group, a trifluoromethylthio group, a nitro group, an alkyl group, an alkoxy group,
an alkylthio group, a methylsulphonyl group, an alkylaminoalkyl group or
alkylaminocycloalkyl group which is optionally substituted, an alkylaminoalkoxy or
cycloalkylaminoalkoxy group or a sulphonamide group, for example:
- polycyclic aryl: an optionally substituted polycyclic aromatic system comprising from
5 to 14 members per ring, preferably from 5 to 10 members per ring, and comprising
from 2 to 10 rings, at least one of the rings of which is aromatic. Mention may be made,
as examples of polycyclic aryl groups, of aceanthrylene, anthracene, azulene, coronene,
rubicene or naphthalene; the polycyclic aryl group can be substituted by a group which
can be one or more halogen atom(s), a hydroxyl group, a cyano group, a
trifluoromethylthio group, a nitro group, an alkyl group, an alkoxy group, an alkylthio
group, a methylsulphonyl group, an alkylaminoalkyl or alkylaminocycloalkyl group which
is optionally substituted, an alkylaminoalkoxy or cycloalkylaminoalkoxy group or a
sulphonamide group, for example;
- a bridged ring: a bicyclic structure comprising, according to the invention, a
nitrogen atom, in which at least two carbon atoms are connected via a single bond or a
carbon chain which can comprise 2 carbon atoms. By way of example, the
abovementioned ring is of the type:
with q = 1 or 2 and with the other groups and indices as defined above;
- cycloalkyl: a saturated cyclic aliphatic group comprising from 3 to 8 carbon atoms.
Mention may be made, by way of example, of a cyclopropyl, methylcyclopropyl,
cyclobutyl, cyclopentyl or cyclohexyl group;
- halogen: a fluorine, a chlorine, a bromine or an iodine;
- haloalkyl: (C1-C6) alkyl substituted by one to three halogen atom(s);
- heteroaryl: a monocyclic aromatic system comprising from 5 to 14 ring members,
preferably from 5 to 10 ring members, and comprising one to several heteroatoms, such
as nitrogen, oxygen or sulphur atoms. The nitrogen atoms can be in the form of
N-oxides. For example, a monocyclic heterocycle can be a pyran, a pyrazine, a pyrazole,
a pyridazine, a pyridine, a pyrimidine, a pyrrole, an isothiazole, an isoxazole, a furan, an
imidazole, a morpholine, a thiophene, a piperazine, a diazetidine, a dihydropyrrolidine, a
piperidine, an azepine, and the like; a bicyclic heterocycle can be an isoquinoline, a
pteridine, a chroman, and the like; a tricyclic heterocycle can be a phenanthroline, a
xanthene, and the like;
- polycyclic heteroaryl: an optionally substituted polycyclic aromatic system
comprising from 5 to 14 members per ring, preferably from 5 to 10 members per ring,
and comprising from 2 to 10 rings, additionally comprising one to several heteroatoms,
such as nitrogen, oxygen or sulphur atoms, in at least one of the rings, and at least one
of the rings of which is aromatic. Mention may be made, as examples of polycyclic
heteroaryl groups, of indole, benzofuran, benzimidazole, benzothiophene, benzotriazole,
benzothiazole, benzoxazole, quinoline, isoquinoline, indazole, quinazoline, phthalazine,
quinoxaline, naphthyridine, 2,3-dihydro-1H-indole, 2,3-dihydrobenzofuran, 2,3-dihydro-
indene, tetrahydroquinoline, tetrahydroisoquinoline or tetrahydroisoquinazoline;
- a heterocycloalkyl: an optionally substituted saturated ring comprising from 3 to
8 atoms and comprising one to several heteroatoms, such as nitrogen, oxygen or sulphur
atoms, in at least one of the rings, or several heteroatoms which are identical to or
different from one another. For example, a heterocycloalkyl can be a pyrrolidine, a
morpholine, a piperazine, a diazetidine, a dihydropyrrolidine, a piperidine, a piperadine,
an azepan, an imidazolidine, a thiomorpholine, a tetrahydropyran, a tetrahydrothiopyran,
a piperazine, a diazepan, and the like;
- hydroxyl: an -OH group;
- nitro: an -N02 group;
- oxo: a -C(O)- group;
- sulphonamide: group corresponding to the formula SO2-N-alkyl or SO2-N-cyclo-
alkyl, alkyl and cycloalkyl being as defined above;
- trifluoromethylthio is defined by the formula -S-CF3.
Furthermore, it is understood that, in the present description, when an atom or a
group is substituted or optionally substituted by one or more defined group(s) or atom(s),
the substituents can be identical to or different from one another and may be carried, if
appropriate, by the same atom or different atoms.
Mention may be made, among the compounds which are a subject-matter of the
invention, of a group of compounds of formula (I) in which A represents an aryl group, in
particular a phenyl or heteroaryl group, in particular a pyridyl group, and all the other
substituents and indices are as defined in the general formula (I) defined above.
Mention may be made, among the compounds in accordance with the invention, of a
group of compounds of formula (I) in which q = 0, m and n each represents 1, and all the
other substituents and indices are as defined in the general formula (I) defined above.
Mention may be made, among the compounds in accordance with the invention, of a
group of compounds of formula (I) in which R2 represents a (C1-C6) alkyl group, in
particular a methyl, substituted by an -NHC(O)Rb group in which Rb and the other
substituents and indices are as defined for the compound of general formula (I) defined
above.
Mention may be made, among the compounds in accordance with the invention, of a
group of compounds of general formula (I) in which R2 represents an -ORa group, the Ra
group and all the other substituents and indices being as defined in the general formula
(I) defined above.
Mention may be made, among the compounds in accordance with the invention, of a
group of compounds of general formula (I) in which R2 is a halogen atom or a cyano or a
hydrogen or a hydroxyl or a (C1-C6) alkyl optionally substituted by an -NH2, or else by an
-NHC(O)Rb group, Rb and the other substituents and indices being as defined in the
general formula (I) defined above.
Mention may be made, among the compounds in accordance with the invention, of a
group of compounds of general formula (I) in which A is a phenyl, R, is a -C(O)R group in
which R represents a hydrogen atom, q is equal to 0, n and m each have the value 1,
and R2 represents -ORa, Ra and the other substituents and indices being as defined in
the general formula (I) defined above.
Mention may be made, among the compounds in accordance with the invention, of a
group of compounds of general formula (I) in which A is a phenyl, R, is a -C(O)R group in
which R represents a hydrogen atom, q is equal to 0, n and m each have the value 1, p is
equal to 2, one of the R2 groups is -ORa and the other of the R2 groups is a halogen
atom, Ra and the other substituents and indices being as defined in the general formula
(I) defined above.
Mention may be made, among the compounds in accordance with the invention, of a
group of compounds of general formula (I) in which A is a phenyl, R1 is a -C(O)R group in
which R represents a hydrogen atom, q is equal to 0, n and m each have the value 1,
p = 1 and R2 is a methyl substituted by an -NH-CO-Rb group, Rb and the other
substituents and indices being as defined in the general formula (I) defined above.
Advantageously, in the compounds of formula (I), the R2 group is in the 6 position of
the 2,4-dioxo-1,2,3,4-tetrahydroquinazoline ring system. The compounds of formula (I)
can also have an R2 group in the 7 position of the 2,4-dioxo-1,2,3,4-tetrahydroquinazoline
ring system. The R2 groups in the 6 and 7 positions can be identical or different.
Advantageously, in the compounds of formula (I), p is equal to 1 or 2.
The compounds of general formula (I) can be in the base, hydrate or solvate form, in
the form of isomers or in the form of their mixtures.
In a specific form, when p' = 2, then the two R3 groups are in the 3 and 4 positions of
the ring system A and can be different from one another.
The combinations of the groups of compounds in accordance with the invention
mentioned above also come within the invention.
Mention may be made, as examples of preferred compounds in accordance with the
invention, of the following compounds:
No. 1: 2-{[3-(3,4-dimethoxybenzyl)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]oxy}propanenitrile
No. 2: 1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-6-hydroxyquinazoline-
2,4(1 H,3H)-dione
No. 3: {[1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]oxy}acetonitrile
No. 4: 2-{[1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]oxy}propanenitrile
No. 5: {[3-(3,4-dimethoxybenzyl)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]oxy}acetonitrile
No. 11: 4-[3-(3,4-dimethoxybenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-
3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 12:1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-6-[2-fluoro-1-
(fluoromethyl)ethoxy]quinazoline-2,4(1H,3H)-dione
No. 13:4-[3-(3,4-dimethoxybenzyl)-2,4-dioxo-6-(2,2,2-trifluoroethoxy)-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 14: 1-(1-acetylpiperidin-4-yl)-6-(2,2-difluoroethoxy)-3-(3,4-
dimethoxybenzyl)quinazoline-2,4(1H,3H)-dione
No. 16: 4-[6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 20: N-{[3-(3,4-dimethoxybenzyl)-1-(1-formylpiperidir-4--yl)-2,4dioxo-1 ,2,3,4-
tetrahydroquinazolin-6-yl]methyl}acetamide
No. 22: 1-(1-acetylpiperidin-4-yl)-6-(aminomethyl)-3-(3,4-
dimethoxybenzyl)quinazoline-2,4(1 H,3H)-dione hydrochloride
No. 23: N-{[3-(3,4-dimethoxybenzyl)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]methyl}formamide
No. 24: N-{[1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]methyl}formamide
No. 25: N-{[1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]methyl}acetamide
No. 32:4-[6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-
yl]piperidine-1 -carbaldehyde
No. 33:4-[3-(3,4-dichlorobenzyl)-6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 34:4-[3-(4-chlorobenzyl)-6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 35: methyl 4-{[6-(2,2-difluoroethoxy)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,4-
dihydroquinazolin-3(2H)-yl]methyl}benzoate
No. 36: 4-{[6-(2,2-difluoroethoxy)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,4-
dihydroquinazolin-3(2H)-yl]methyl}benzoicacid
No. 37: 4-{[6-(2,2-difluoroethoxy)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,4-
dihydroquinazolin-3(2H)-yl]methyl}-N-(2-methoxyethyl)benzamide
No. 38: 4-t3-(3,4-dimethoxybenzyl)-6-methyl-2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-
yl]piperidine-1 -carbaldehyde
No. 39:4-[6-(2,2-difluoroethoxy)-3-(3-hydroxy-4-methoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 40:4-[6-(2,2-difluoroethoxy)-3-[3-(2-hydroxyethoxy)-4-methoxybenzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 41:4-[6-(2,2-difluoroethoxy)-3-(3-ethoxy-4-methoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 42:4-[6-(2,2-difluoroethoxy)-3-[4-methoxy-3-(2-methoxyethoxy)benzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 43:4-[6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]azepane-1-carbaldehyde
No. 47:4-[6-(2,2-difluoroethoxy)-3-[3-(3-hydroxypropoxy)-4-methoxybenzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 48: 4-[5-chloro-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-
yl]piperidine-1 -carbaldehyde
No. 49:4-{3-[3-(cyclopentyloxy)-4-methoxybenzyl]-6-(2,2-difluoroethoxy)-2,4-dioxo-
3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 50: 2-(5-{[6-(2,2-difluoroethoxy)-1 -(1-formylpiperidin-4-yl)-2,4-dioxo-1,4-
dihydroquinazolin-3(2H)-yl]methyl}-2-methoxyphenoxy)acetamide
No. 51: 4-[6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]-3-methylpiperidine-1-carbaldehyde
No. 52:3-[6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]-8-azabicyclo[3.2.1]octane-8-carbaldehyde
No. 56: 4-{3-[4-(cyclopentyloxy)-3-methoxybenzyl]-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 57: 4-[3-(3-chlorobenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 58:4-[3-(4-chlorobenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 59: 4-{3-[3-(cyclopentyloxy)-4-methoxybenzyl]-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 72: 4-[3-(3,4-dimethoxybenzyl)-6-(2-hydroxyethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 74: 4-[3-(3,4-dichlorobenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 76: 4-{3-[(6-chloropyridin-3-yl)methyl]-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 78: 4-[3-(3-chloro-4-methoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 79: 4-[3-(3,4-dimethoxybenzyl)-6-(2-fluoroethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 89:2-[5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-2,4-
dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxyphenoxy]acetamide
No. 90: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-(3-hydroxy-4-methoxybenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 91: 4-[3-(3,4-dimethoxybenzyl)-6-ethoxy-2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-
yl]piperidine-1 -carbaldehyde
No. 97: 4-[5,7-dichloro-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-
1 (2H}-yl]piperidine-1 -carbaldehyde
No. 102: 4-[7-chloro-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-
1 (2H)-yl]piperidine-1 -carbaldehyde
No. 108: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-fluoro-4-methoxybenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 111: 4-[6-(difluoromethoxy)-3-(3,4-dimethoxybenzyl)-2l4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 112: 4-[3-(3 AdimethoxybenzyO-e-O-methylethoxy^^-dioxo-S^-
dihydroquinazolin-I^HJ-yOpiperidine-l^arbaldehyde
No. 114: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-methoxy-3-(1-
methylethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 116:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-(3-methoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 117: 4-{3-[3,5-bis(trifluoromethyl)benzyl]-6-[2-fluoro-1-(fluoromethyl)ethoxy]-
2,4-dioxo-3>4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 118: 4-[3-(3-ethoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 124:4-{3-[3-chloro-4-(2-methoxyethoxy)benzyl]-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 130:4-[3-(3,4-diethoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-
3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 131:4-[3-(4-ethoxy-3-methoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 133: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(4-methoxy-3-methylbenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 134: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-
(trifluoromethyl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 135: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-
(trifluoromethyl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 143: 4-{3-[4-(benzyloxy)-3-methoxybenzyl]-6-[2-fluoro-1-(fluoromethyl)ethoxy]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 145:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-(3-methoxy-4-nitrobenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 155: 4-[3-(4-ethoxybenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 158: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-t4-(morpholin-4-ylmethyl)benzylj-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 160: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(4-(morpholin-4-yl)benzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 165: 4-[3-(biphenyl-4-ylmethyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-
3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 166:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(methylsulphanyl)benzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 167: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyridin-3-yl)benzyl)-
3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 170: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-methylbenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 175: 2-[2-(cyclopentyloxy)-5-({6-t2-fluoro-1-(fluoromethyl)ethoxy]-1-(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]acetamide
No. 178: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-(3-methoxy-4-propoxybenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 183:2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
methylacetamide
No. 184:2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N,N-
dimethylacetamide
No. 185:2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
methoxy-N-methylacetamide
No. 186: 4-{3-[4-(cyclopentyloxy)-3-ethoxybenzyl]-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 188: 4-{3-[4-(cyclopentyloxy)-3-(1 -methylethoxy)benzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 189: 4-{3-[4-(cyclopentyloxy)-3-propoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 190: 4-{3-[4-(cyclopentyloxy)-3-hydroxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 193: 4-{3-[4-(difluoromethoxy)-3-methoxybenzyl]-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 194: 4-{3-[4-(difluoromethoxy)-3-ethoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 200: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(thiophen-3-yl)-
benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 201: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyridin-4-yl)benzyl)-
3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 203:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(1-methyl-1H-indol-6-yl)methyl]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 206: 4-{3-[4-(cyclopropylmethoxy)-3-methoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidin6-1-carbaldehyde
No. 207: 2-[4-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-2,4-
dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxyphenoxy]-N-methylacetamide
No. 212: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-(1 H-pyrazol-1 -
yl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 213: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyridin-2-yl)benzyl)-
3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 215: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(thiophen-2-yl)-
benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 216: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(quinolin-7-ylmethyl)-
3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 218: 4-{6-t2-fluoro-1-(fluoromethyl)ethoxy]-3-[(6-methoxynaphthalen-2-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 223: 4-{3-[4-(1 H-benzimidazol-1 -yl)benzyl]-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 224: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(2-
methylpropoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 226: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(tetrahydrofuran-3-
yloxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 228: 4-[3-{4-[(1 -benzylpyrrolidin-3-yl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 230: 4-[3-(1-benzothiophen-5-ylmethyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 232: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[3-methoxy-4-(1-
methylethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 233: 4-[3-(3,4-dimethoxybenzyl)-7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 234: 4-[3-{4-[(1 -acetylpyrrolidin-3-yl)oxy]-3-methoxybenzyl}-6-t2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 239: 4-[3-{4-[(4-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 240: 4-[3-{4-[(4-chlorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 242: 4-[3-{4-[(3-chlorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 243:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(3-(thiophen-3-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 245: 4-[3-(4-ethoxy-3-methoxybenzyl)-6-(2-hydroxyethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 246: 4-[3-{4-[2-(2,3-dihydro-1 H-indol-1-yl)-2-oxoethoxy]-3-methoxybenzyl}-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 250: 4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3>4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 251:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[3-methoxy-4-(2-oxo-2-(piperidin-
1-yl)ethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 254: 4-{3-[3-ethoxy-4-(thiophen-2-ylmethoxy)benzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 258:4-[3-(3,4-dimethoxybenzyl)-6-[2-fluoro-1-(hydroxymethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 263: (2R)-2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]propanoic
acid
No. 264:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(1-methyl-3-(thiophen-2-yl)-1H-
pyrazol-5-yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 270: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(5-methyl-1,2,4-oxadiazol-3-
yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 275: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyrimidin-5-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 276: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(1-methyl-3-phenyl-1H-pyrazol-5-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 278: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-{[6-(1H-pyrazol-1-
yl)pyridin-3-yl]methyl}-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 279: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-[(2-(thiophen-2-
yl)pyrimidin-5-yl)methyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 280: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(1-methyl-1H-pyrazol-3-
yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 282: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(3-methyl-1,2,4-oxadiazol-5-
yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 283: [2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1I4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]aceticacid
No. 285: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(thieno[2,3-b]pyridin-2-
ylmethyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 286: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-t(6-phenylpyridin-3-
yl)methyl]-3,4-dihydroquinazoiin-1(2H)-yl}piperidine-1-carbaldehyde
No. 287: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(6-(morpholin-4-yl)pyridin-3-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 289: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[(6-(thiophen-2-
yl)pyridin-3-yl)methyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 292: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(1-methyl-5-phenyl-1 H-pyrazol-3-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 294: 4-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-2,4-dioxo-
1,4-dihydroquinazolin-3(2H)-yl}methyl)biphenyl-2-carbonitrile
No. 295: (2R)-2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
methylpropanamide
No. 297: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(thiophen-2-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 298: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(morpholin-4-
ylmethyl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 299: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[3-methoxy-4-(piperidin-1-
ylmethyl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 300: 4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydraquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 301: 2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
ethylacetamide
No. 302: (2S)-2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]propanoic
acid
No. 305: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-{[(3R)-2-oxo-1-
phenylpyrrolidin-3-yl]oxy}benzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 306: 4-{3-[4-(cyclobutylmethoxy)-3-methoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 307: 4-{3-[4-(benzyloxy)-3-methoxybenzyl]-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 308: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(4-hydroxy-3-
methoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 309: 4-{3-[4-(cyclopropylmethoxy)-3-methoxybenzyl]-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 310: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-
(2-methylpropoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 311: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[3-methoxy-4-
(1-methylethoxy)benzyl]-2,4-dioxo-3,4-dihyclroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 312: 4-[3-(4-ethoxy-3-methoxybenzyl)-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 315: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-{[6-(3-
methoxyphenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 316: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-{[6-(2-
fluorophenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 317: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-{[6-(4-
fluorophenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 318: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{[6-(4-
methoxyphenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 319: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-[(6-(thiophen-2-
yl)pyridin-3-yl)methyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 320: 4-{3-t3-ethoxy-4-(thiophen-2-ylmethoxy)benzyl]-7-fluoro-6-t2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 321: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(1 -methyl-1 H-pyrazol-
3-yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 322:4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyrimidin-5-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 323: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[(1 -methyl-3-(thiophen-2-
yl)-1 H-pyrazol-5-yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-yl}piperidine-1 -
carbaldehyde
No. 324: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(2-oxo-2-
(piperidin-1-yl)ethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 325: 4-[3-{4-[2-(2,3-dihydro-1 H-indol-1-yl)-2-oxoethoxy]-3-methoxybenzyl}-7-
fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]piperidine-1 -carbaldehyde
No. 326: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(5-methyl-1,2,4-
oxadiazol-3-yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 327: 4-[3-{4-[(3-chlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-t2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 328:4-[3-{[6-(3,5-dichlorophenyl)pyridin-3-yl]methyl}-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 329:4-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)biphenyl-2-carbonitrile
No. 330: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-(1 H-pyrazol-
1-yl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 331: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{[6-(3-
fluorophenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 332: 3-[5-({7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -formylpiperidin-4-
yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)pyridin-2-yl]benzonitrile
No. 333:4-[3-(3,4-diethoxybenzyl)-7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 334: 4-[3-{4-[(4-chlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 335: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[4-(morpholin-4-
ylmethyl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 336: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-{[6-(1 H-pyrazol-
1 -yl)pyridin-3-yl]methyl}-3,4-dihydroquinazolin-1 (2H)-yl}piperidine-1 -carbaldehyde
No. 337: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-(4-(morpholin-4-yl)-
benzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 338:4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-(3-methoxy-4-
propoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 339: 4-{3-[4-(1 H-benzimidazol-1 -yl)benzyl]-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 340: 5-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxybenzonitrile
No. 341: 3-(3,4-dimethoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-7-carbonitrile
No. 342: 4-[3-(4-bromobenzyl)-7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 343: 4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-(2-methoxyethoxy)benzyl}-7-fluoro-6-
[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 344: 4-{3-[4-(benzyloxy)benzyl]-7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 345: 4-f3-{4-[(3,4-dichlorobenzyl)oxy]-3-ethoxybenzyl}-7-fluoro-5-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 349:4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-(2-fluoroethoxy)benzyl}-7-fluoro-6-[2-
fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-yl]piperidine-1 -
carbaldehyde
No. 350: 4-[3-{4-[(2-chloro-4-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 351: 4-[3-{4-[(2,4-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 352: 4-[3-{4-[(2-chloro-6-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 353: 4-[3-{4-[(2,6-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 354: 4-[3-{4-[(2-chlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 355: 4-[7-fluoro-3-{4-[(2-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 357: 2-[(3,4-dichlorobenzyl)oxy]-5-({7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-
1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)benzonitrile
No. 358: 4-[3-{4-t(3,4-dichlorophenoxy)methyl]-3-methoxybenzyl}-7-fluoro-6-t2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 360:4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-(2-
phenylethyl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 362:4-[3-{4-[(4,5-dichloro-2-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 369: 4-[3-{4-[(4-chlorophenoxy)methyl]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 371:4-[3-{3-chloro-4-[(4-chlorobenzyl)oxy]-5-ethoxybenzyl}-7-fluoro-6-[2-fluoro-
1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 373: 4-[3-{3-chloro-4-[(2,4-dichlorobenzyl)oxy]-5-ethoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 375: 4-[7-fluoro-3-{4-[(4-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 376: 4-[3-{4-[(3,5-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 377: 4-[3-(4-{[4-chloro-3-(trifluoromethyl)benzyl]oxy}-3-methoxybenzyl)-7-
fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquina2olin-1(2H)-
yl]piperidine-1 -carbaldehyde
No. 379: 4-[3-{4-[(3-chlorophenoxy)methyl]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 380: 4-[3-{4-[(3,5-difluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2)4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 381:4-{3-[4-(benzyloxy)-3-methoxybenzyl]-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 382:4-[3-{4-[(3-chloro-5-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 383: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-{[4-
(trifluoromethyl)benzyl]oxy}benzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 384: 4-[3-{4-[(2,5-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 385: 4-{[4-({7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -formylpiperidin-4-
yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-
methoxyphenoxy]methyl}benzonitrile
No. 386: 3-{[4-({7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -formylpiperidin-4-
yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-
methoxyphenoxy]methyl}benzonitrile
No. 387: 4-[3-{4-[(4-chloro-2-fluorobenzyl)oxy]-3-methoxybenzylf7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 388:4-[3-{4-[1-(3,4-dichlorophenyl)ethoxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 389: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{4-[(3-hydroxybenzyl)oxy]-
3-methoxybenzyl}-2>4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 390: 4-[7-fluoro-3-{4-[(3-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 391: 4-[3-{4-[(3,4-difluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 392: 4-{3-[4-(5,6-dichloro-1H-benzimidazol-1-yl)-3-methoxybenzyl]-7-fluoro-6-
[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 393: 4-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenyl3,4-dichlorobenzenesulphonate
No. 394: 4-({7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxyphenyl3,4-dichloro benzene-
sulphonate
No. 403: 3,4-dichloro-N-[4-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-
methoxyphenyl]benzamide
The compounds in accordance with the invention can be prepared by the methods
illustrated in the following Schemes 1 to 4.
In that which follows, the term "leaving group" is understood to mean a group
which can be easily substituted, with departure of an electron pair, by cleavage of a
heterolytic bond. This group can thus be easily replaced by another group, for example
during a substitution reaction. Such leaving groups are, for example, halogens or an
activated hydroxyl group, such as a mesylate, tosylate, triflate, and the like. Examples of
leaving groups and references for their preparation are given in "Advanced Organic
Chemistry", J. March, 3rd Edition, Wiley Interscience, pp. 310-316.
The term "protective group PG" is understood to mean a group which makes it
possible to prevent the reactivity of a function group or position during a chemical
reaction which may affect it and which restores the molecule after cleavage according to
methods known to a person skilled in the art.
The term "temporary protective group for amines or alcohols" is understood to
mean the protective groups such as those described in Protective Groups in Organic
Synthesis, Greene T.W. and Wuts P.G.M., published by Wiley Intersciences, 1999, and
in Protecting Groups, Kocienski P.J., 1994, Georg Thieme Verlag.
Mention may be made, for example, of temporary protective groups for amines:
benzyls or carbamates (such as ferf-butoxycarbonyl, cleavable in an acid medium, or
benzyloxycarbonyl, cleavable by hydrogenolysis), temporary protective groups for
carboxylic acids: hydrogenolysable alkyl esters (such as methyl or ethyl or tert-butyl
esters which can be hydrolysed in a basic or acid medium) and benzyl esters, temporary
protective groups for alcohols or phenols, such as tetrahydropyranyl, methyloxymethyl or
methylethoxymethyl, tert-butyl and benzyl ethers, or temporary protective groups for
carbonyl derivatives, such as linear or cyclic acetals, such as, for example, 1,3-dioxan-2-
yl or 1,3-dioxolan-2-yl; and reference may be made to the well known general methods
described in Protective Groups, cited above.
A person skilled in the art will be in the position to choose the appropriate
protective groups according to the circumstances. The compounds of formula (I) can
comprise precursor groups for other functional groups which are generated subsequently
in one or more other stages.
In the general synthetic schemes which follow, the starting compounds and the
reactants, when their method of preparation is not described, are commercially available
or are described in the literature or else can be prepared according to methods which are
described therein or which are known to a person skilled in the art.
The pure enantiomers of the compounds in accordance with the invention can be
obtained from enantiomericaliy pure precursors or else by chiral phase chromatography
or else, when the compounds comprise acid or amine functional groups, by selective
crystallizations of diastereoisomeric salts obtained by reaction of the compounds (I) with
chiral amines or chiral acids respectively.
The compounds of general formula (I) can be obtained according to the following
Schemes 1 to 4. Out of concern for clarity, the R4 group has been chosen as being a
hydrogen, p and p' represent 1 and 2 respectively and the R2 and R3 groups have been
set as indicated in the schemes. However, it is to be understood that R4 can be as
defined in the general formula (I), that R2 and R3 can have the positions indicated in the
general formula (I) and that p and p' can be as defined in the general formula (I).
The synthetic routes described below serve solely as illustration and are under no
circumstances limiting. A person skilled in the art can apply without difficulty the teaching
below to the compounds of formula (I) for which R, R,, R2) R3, R». Ra, Rb, Re, m, n, p, p'
and q are as defined in the general formula (I).
According to Scheme 1, the compound of formula (IV) is obtained by a reductive
amination reaction by reacting a compound of formula (II), in which R' represents a
(C1-C6) alkyl group and R2 is as defined for the compound of formula (I) with a compound
of formula (III) in an acid medium and in the presence of a reducing agent, such as
sodium triacetoxyborohydride. The PG group of the compound of formula (III) is a
protective group for the amine functional group which may advantageously be tert-
butoxycarbonyl (boc). The compound of formula (IV) thus formed is subsequently
acylated, according to methods well known to a person skilled in the art, with an alkyl or
aryl chloroformate to give the compound of formula (V) in which R" represents a (Ci-Ce)
alkyl group or an aryl group which is substituted. A hydrolysis reaction in a basic medium
makes it possible to obtain the compounds of formula (VI) which, by a coupling reaction
with a compound of formula (VII), in which R3 is as defined for the compound of formula
(I), results in the compounds of formula (VIII). An intramolecular cyclization reaction in
the basic medium makes it possible to obtain the quinazolinedione derivatives of formula
(IX). The protective group PG for the amine functional group is subsequently cleaved, for
example in acid medium when PG is a boc, to give the compounds of formula (la) which
give, by an acylation reaction, the compounds of formula (lb).
The compounds of formula (la) are compounds of formula (I) and can act as
intermediate for other compounds of formula (I), such as the compounds of formula (lb).
The compounds of formula (I) for which R2 represents -ORa, Ra being as defined
for the compound of formula (I), correspond to the formula (Id). They can be obtained
from the compounds of formula (X) according to the following Scheme 2. The
compounds of formula (Ic), obtained by a hydrogenolysis reaction on the compounds of
formula (X), are subjected, for example, to an alkylation reaction with an alkylating agent
of type Ra-X, in which Ra is as defined for the compound of formula (I) and X represents
a leaving group (such as a halogen atom, for example), in the presence of a base, such
as caesium carbonate (Cs2C03), or also to a Mitsunobu reaction (Synthesis, 1981, 1)
with an alcohol of type Ra-OH, Ra being as defined for the compound of formula (I), to
give compounds of formula (Id).
The compounds of formula (X) and the compounds of formula (Ic) are compounds
of formula (I) and can act as intermediate for other compounds of formula (I), such as the
compounds of formula (Id).
Alternatively, the compounds of formula (Id) can be obtained by following the
procedure described in Scheme 3.
The compounds of formula (XII) are obtained by a nucleophilic aromatic
substitution reaction involving a compound of formula (XI), in which R' is as defined
above, and an alcohol of type Ra-OH, in which Ra is as defined for the compound of
formula (I), in the presence of a base. The reduction of the nitro group of the compounds
of formula (XII) results in the corresponding anilino derivatives (XIII). A reductive
amination reaction with a compound of formula (III), in which PG is a protective group for
amine functional groups, such as, for example, boc, results in the compounds of formula
(XIV). The compounds of formula (XV) are obtained by reaction of a compound of
formula (XIV) with potassium isocyanate (KNCO) in an acid medium. An intramolecular
cyclization reaction in a basic medium makes it possible to obtain the compounds of
formula (XVI). The protective group PG is cleaved by methods well known to a person
skilled in the art to give the compounds of formula (XVII). An acylation reaction results in
the compounds of formula (XVIII). Finally, the compounds of formula (Id) are obtained
either by an alkylation reaction with a derivative of type (XIX), in which X represents a
leaving group, such as a halogen atom, in the presence of a base, such as, for example,
caesium carbonate, or also by a Mitsunobu reaction with a benzyl alcohol of type (XX). In
the compounds (XIX) and (XX), R3 is as defined above.
Scheme 3
The compounds of formula (le) and (If), in which R2 more particularly represents a
group of type-CH2-NHC(O)Rb, Rb being defined as in the compound of formula (1), can
be prepared according to the following Scheme 4.
It is understood that, in Scheme 3, the R2 group illustrated is of -O-Ra type and is
in the 6 position of the quinoazolinedione structure (see, for example, compound (XVIII))
but that it is also possible to have a second R2 group, as defined in the general formula
(I), in the 7 position of the same quinazolinedione group.
The reduction of the nitro group of the compounds of type (XXI), in which R' and
PG' are as defined above, the PG' group advantageously being boc, results in the
corresponding anilino derivatives (XXII) which, by a reductive amination reaction in which
they react in an acid medium and advantageously in the presence of a reducing agent,
such as sodium triacetoxyborohydride, with a compound of formula (III), in which PG
represents a benzyloxycarbonyl protective group for amines, give compounds of formula
(XXIII). An acylation reaction with an alkyl or aryl chloroformate, in which R" represents a
(C1-C6) alkyl group or an aryl group which is substituted, results in the compounds of
formula (XXIV). The quinazolinedione analogues of formula (XXV) can be obtained by a
hydrolysis reaction in a basic medium and then by a coupling reaction with a compound
of formula (VII), in which R3 is as defined for the compound of formula (I), followed by an
intramolecular cyclization reaction in a basic medium. The PG' group (preferably a boc) is
subsequently cleaved in an acid medium to result in the compounds of formula (XXVI)
which, by acylation, give compounds of formula (XXVII), in which Rb is as defined for the
compound of formula (I). The PG protective group of (XXVII) is cleaved by a
hydrogenolysis reaction to give the compounds of formula (le). Finally, the compounds of
formula (If) are obtained by an acylation reaction on the compounds of formula (le).
It is obvious that a person skilled in the art will be in a position to choose, in the
light of his knowledge and the literature, other appropriate protective groups which make
possible the introduction of all the groups described in the general formula (I).
When the compound of formula (I) comprises a bridged ring, it can be obtained
without distinction by one of the synthetic routes described above.
The following procedures and examples describe the preparation of some
compounds in accordance with the invention. These procedures and examples are not
limiting and serve only to illustrate the present invention.
In the procedures and examples below:
- the mass spectra are produced on a quadrupole spectrometer of Platform LCZ
type (Waters) or of ZQ 4000 type (Waters) in positive electrospray ionization mode;
- the NMR (nuclear magnetic resonance) spectra are produced on a Fourier
transform spectrometer (Bruker) at a temperature of 300°C (exchangeable protons not
recorded);
- s = singlet,
- d = doublet,
- m = multiplet,
- br = broad signal
-1 = triplet,
- q = quartet
- DMSO-d6 = deuterated dimethyl sulphoxide,
- CDCI3 = deuterated chloroform.
The mixtures of solvents are quantified in volumetric ratios.
The NMR spectra and mass spectra confirm the structures of the compounds
obtained according to the examples below.
In the examples which follow, the following abbreviations are used:
ACN: acetonitrile
AcOEt: ethyl acetate
AcOH: acetic acid
DBU: 1,8-diazabicyclo[5.4.0]undec-7-ene
DCM: dichloromethane
DCE: 1,2-dichloroethane
DIAD: diisopropyl azodicarboxylate
DIEA: diisopropylamine
DMF: N,N-dimethylformamide
EtOH: ethanol
HBTU: 0-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate
IBCF: isobutyl chloroformate
MeOH: methanol
NaBH(OAc)3: sodium triacetoxyborohydride
AT: ambient temperature
min: minute
THF: tetrahydrofuran
NEt3: triethylamine
TFA: trifluoroacetic acid
EXAMPLES
The following examples describe the preparation of some compounds in accordance with
the invention. These examples are not limiting and serve only to illustrate the present
invention. The numbers of the compounds in the examples refer to those given in the
table below, in which the chemical structures and the physical properties of a few
compounds in accordance with the invention are illustrated.
EXAMPLE 1: Compound No.°6
Preparation of {[3-(3,4-dimethoxybenzyl)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-
1,2,3,4-tetrahydroquinazolin-6-yl]oxy}acetonitrile
Stage 1.1:
1,1-Dimethylethyl 4-{[4-(benzyloxy)-2-(methoxycarbonyl)phenyl]ami-
no}piperidine-1 -carboxylate
A mixture of 2g of methyl 2-amino-5-(benzyloxy)benzoate, 3.1 g of
1,1-dimethylethyl 4-oxopiperidine-1-carboxylate and 3.29 g of NaBH(OAc)3 in 10 ml of
AcOH is irradiated under a microwave field (Biotage Initiator Sixty) at 110DC for 20 min.
The same reaction is repeated with two other lots of 2 g of methyl 2-amino-5-
(benzyloxy)benzoate. The three reaction media are combined. The combined product is
taken up in AcOEt. The organic phase is washed with water, with a saturated NH4CI
solution and with a saturated NaHC03 solution, dried over Na2SO4 and filtered, and the
solvent is evaporated under reduced pressure. The residue is chromatographed on silica
gel, elution being carried out with an AcOEt/heptane mixture, (5/95, v/v) as far as (30/70,
v/v), to give 10.2 g of the expected product.
Stage 1.2:
1,1-Dimethylethyl 4-{[4-(benzyloxy)-2-(methoxycarbonyl)phenyl][(2-methyl-
propoxy)carbonyl]amino}piperidine-1-carboxylate
A mixture of 2g of 1,1-dimethylethyl 4-{[4-(benzyloxy)-2-
(methoxycarbonyl)phenyl]amino}piperidine-1-carboxylate obtained in stage 1.1, 0.87 ml
of DIEA, 1.78 ml of IBCF and 1 g of NaOH in 10 ml of DCE is irradiated under a
microwave field at 80°C for 30 min. The same reaction is repeated with 4 other lots of 2 g
of 1,1-dimethylethyl 4-{[4-(benzyloxy)-2-(methoxycarbonyl)phenyl]amino}piperidine-1-
carboxylate. The 5 reaction media are combined. The combined product is taken up in
AcOEt and filtered, and the filtrate is evaporated under reduced pressure. The residue is
chromatographed on silica gel, elution being carried out with an AcOEt/heptane mixture,
(10/90, v/v) as far as (50/50, v/v), to give 9.3 g of the expected product.
Stage 1.3:
Sodium salt of 5-(benzyloxy)-2-({1-[(1,1-dimethylethoxy)carbonyl]-piperidin-
4-yl}[(2-methylpropoxy)carbonyl]amino)benzoic acid
A mixture of 9.3 g of 1,1-dimethylethyl 4-{[4-(benzyloxy)-2-
(methoxycarbonyl)phenyl][(2-methylpropoxy)carbonyl]amino}piperidine-1-carboxylate
obtained in stage 1.2 and 34.4 ml of 2N NaOH in 57 ml of MeOH is heated at 100°C for
3h 00. The solution is evaporated under reduced pressure and DCM is added. Drying is
carried out over Na2SO4, filtration is carried out and the solvent is evaporated under
reduced pressure to give 8.7 g of the expected product.
Stage 1.4:
1,1-Dimethylethyl 4-[{4-(benzyloxy)-2-[(3,4-dimethoxybenzyl)carbamoyl]phe-
nyl}(isobutoxycarbonyl)amino]piperidine-1-carboxylate
A mixture of 6g of sodium salt of 5-(benzyloxy)-2-({1-[(1,1-
dimethylethoxy)carbonyl]piperidin-4-yl}[(2-methylpropoxy)carbonyl]amino)benzoic acid
obtained in stage 1.3 and 4.42 g of DIEA in 250 ml of DMF is stirred at AT for 15 min.
6.48 g of HBTU are added and the mixture is left stirring for 30 min. 2.48 g of
veratrylamine are added and the reaction mixture is stirred for 48h 00. It is evaporated
under reduced pressure, the residue is taken up in AcOEt, washed with a saturated
NH4CI solution and with a saturated NaHC03 solution, dried over Na2SO4 and filtered,
and the solvent is evaporated under reduced pressure. The residue is chromatographed
on silica gel, elution being carried out with an AcOEt/heptane mixture, (20/80, v/v) as far
as (60/40, v/v), to give 7.5 g of expected product.
Stage 1.5:
1,1-Dimethylethyl 4-[6-(benzyloxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carboxylate
A mixture of 2.5 g of 1,1-dimethylethyl 4-[{4-(benzyloxy)-2-[(3,4-
dimethoxybenzyl)carbamoyl]phenyl}(isobutoxycarbonyl)amino]piperidine-1-carboxylate
obtained in stage 1.4 and 7.4 g of NaOH in 18.5 ml of DCE is irradiated under a
microwave field at 110°C for 30 min. The same reaction is repeated with 2 other lots of
2.5 g of 1,1-dimethylethyl 4-[{4-(benzyloxy)-2-[(3,4-dimethoxybenzyl)carbamoyl]phenyr}-
(isobutoxycarbonyl)amino]piperidine-1-carboxylate. The 3 reaction media are combined.
The combined product is taken up in DCM, washed with water, dried over Na2SO4 and
filtered, and the solvent is evaporated under reduced pressure to give 6.6 g of expected
product.
Stage 1.6:
A mixture of 3.5 g of 1,1-dimethylethyl 4-[6-(benzyloxy)-3-(3,4-dimethoxybenzyl)-
6-(Benzyloxy)-3-(3,4-dimethoxybenzyl)-1-(piperidin-4-yl)quinazoline-
2,4(1 H,3H)-dione
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carboxylate obtained in stage 1.5
and 25 ml of TFA in 50 ml of DCM is stirred at AT for 2h 00. The mixture is neutralized
with K2C03. It is filtered and the filtrate is evaporated under reduced pressure. The
residue is taken up in DCM and washed with a saturated NaHC03 solution and then with
an 8% NaOH solution. The solution is dried over Na2SO4 and filtered, and the solvent is
evaporated under reduced pressure to give 2.67 g of the expected product.
Stage 1.7:
4-[6-(Benzyloxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-
1(2H)-yl]piperidine-1-carbaldehyde
A mixture of 0.6 g of 6-(benzyloxy)-3-(3,4-dimethoxybenzyl)-1-(piperidin-4-
yl)quinazoline-2,4(1H,3H)-dione obtained in stage 1.6 and 0.113 g of ammonium formate
in 5 ml of ACN is irradiated under a microwave field at 140°C for 1h 00. The mixture is
filtered and the filtrate is evaporated under reduced pressure to give 0.62 g of the
expected product.
Stage 1.8: Compound No. 5:
4-[3-(3,4-Dimethoxybenzyl)-6-hydroxy-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]pi peridine-1 -carbaidehyde
A mixture of 0.618 g of 4-[6-(benzyloxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde obtained in stage 1.7, 0.44 g of
ammonium formate and 0.124 g of Pd/C (10%) in 10 ml of EtOH purged beforehand with
nitrogen is irradiated under a microwave field at 80°C for 2h 00. The mixture is filtered
and the filtrate is evaporated under reduced pressure to give 0.513 g of the expected
product.
Stage 1.9: Compound No. 6
{[3-(3,4-Dimethoxybenzyl)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]oxy}acetonitrile
0.17 g of 4-[3-(3,4-dimethoxybenzyl)-6-hydroxy-2,4-dioxo-3,4-dihydroquinazolin-
1(2H)-yl]piperidine-1-carbaldehyde obtained in stage 1.8 and 0.25 g of Cs2C03 in 3 ml of
DMF are stirred for 15 min at AT. 0.056 g of bromoacetonitrile is added and the reaction
mixture is subsequently irradiated under a microwave field at 100°C for 15 min. It is
filtered and evaporated under reduced pressure. The residue is chromatographed on
silica gel, elution being carried out with an MeOH/DCM mixture, (1/99, v/v) as far as
(4/96, v/v), to give 0.112 g of the expected product.
EXAMPLE 2: Compound No. 3
Preparation of {[1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-
1,2,3,4-tetrahydroquinazolin-6-yl]oxy}acetonitriie
Stage 2.1:
1-(1-Acetylpiperidin-4-yl)-6-(benzyloxy)-3-(3,4-dimethoxybenzyl)quinazoline-
2,4(1 H,3H)-dione
0.14 g of acetyl chloride is added to a mixture of 0.6 g of 6-(benzyloxy)-3-(3,4-
dimethoxybenzyl)-1-(piperidin-4-yl)quinazoline-2,4(1H,3H)-dione obtained according to
stage 1.6 and 0.24 g of NEt3 in 10 ml of DCM cooled to 0°C. The mixture is stirred at AT
overnight. It is washed twice with a saturated NH4CI solution and filtered, and then the
filtrate is evaporated under reduced pressure to give 0.64 g of the expected product.
Stage 2.2: Compound No. 2
1-(1-Acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-6-hydroxyquinazoline-
2,4(1 H,3H)-dione
A mixture of 0.64 g of 1-(1-acetylpiperidin-4-yl)-6-(benzyloxy)-3-(3,4-
dimethoxybenzyl)quinazoline-2,4(1H,3/-/)-dione obtained in stage 2.1, 0.44 g of
ammonium formate and 0.125 g of Pd/C (10%) in 10 ml of EtOH purged beforehand with
nitrogen is irradiated under a microwave field at 80°C for 2h 00. The mixture is filtered
and the filtrate is evaporated under reduced pressure to give 0.48 g of the expected
product.
Stage 2.3: Compound No. 3
{[1-(1-Acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]oxy}acetonitrile
0.12 g of 1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-6-hydroxyquinazoline-
2,4(1 H,3H)-dione obtained in stage 2.2 and 0.172 g of Cs2C03 in 3 ml of DMF are stirred
for 15 min at AT. 0.038 g of bromoacetonitrile is added and the reaction mixture is
subsequently irradiated under a microwave field at 100°C for 15 min. It is filtered and the
filtrate is evaporated under reduced pressure. The residue is chromatographed on silica
gel, elution being carried out with an MeOH/DCM mixture, (1/99, v/v) as far as (4/96, v/v),
to give 0.094 g of the expected product.
EXAMPLE 3: Compound No. 34
Synthesis of 4-[3-(4-chlorobenzyl)-6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
Stage 3.1:
Methyl 5-(2,2-difluoroethoxy)-2-nitrobenzoate
8.53 g of 2,2-difluoroethanol are added to a solution of 17.31 g of methyl 5-fluoro-
2-nitrobenzoate, 9.64 g of NEt3 and 32.71 g of 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-
phosphabicyclo[3.3.3]undecane in 250 ml of anhydrous THF. The mixture is stirred at AT
for 30 min. The solvent is evaporated under reduced pressure. Water is added and
extraction is carried out with AcOEt. The extract is washed with a 1N aqueous HCI
solution, with water and then with a saturated NaCI solution. It is dried over MgSO^ and
filtered, and the solvent is evaporated under reduced pressure to give 21 g of the
expected product.
21 g of methyl 5-(2,2-difluoroethoxy)-2-nitrobenzoate obtained in stage 3.1 and
1 g of Pd/C (10%) in a mixture of 300 ml of AcOEt, 50 ml of EtOH and 5 ml of AcOH are
stirred at AT under a hydrogen atmosphere for 24h 00.
The mixture is filtered and evaporated under reduced pressure to give 18.6 g of
the expected product.
Stage 3.3:
1,1-Dimethylethyl 4-{[4-(2,2-difluoroethoxy)-2-(methoxycarbonyl)phenyl]ami-
no}pi peri di ne-1 -carboxylate
A mixture of 4 g of methyl 2-amino-5-(2,2-difluoroethoxy)benzoate and 6.88 g of
1,1-dimethylethyl 4-oxopiperidine-1-carboxylate obtained in stage 3.2 in 15 ml of AcOH is
heated at 90°C for 10 min. It is allowed to cool to AT and 7.3 g of NaBH(OAc)3 are
added. The mixture is left stirring at AT for 12h 00. It is extracted with AcOEt and the
extract is washed with a saturated K2C03 solution and then with water. It is dried over
MgSO4, filtered and evaporated under reduced pressure to give 6.63 g of the expected
product.
Stage 3.4:
1,1 -Dimethylethyl 4-{carbamoyl[4-(2,2-difluoroethoxy)-2-(methoxycarbonyl)-
phenyl]amino}piperidine-1-carboxylate
1.95 g of potassium isocyanate in solution of 4 ml of water are added to a solution
of 6.63 g of 1,1-dimethylethyl 4-{[4-(2,2-difluoroethoxy)-2-(methoxycarbonyl)phenyl]
amino}piperidine-1-carboxylate obtained in stage 3.3 in 40 ml of AcOH. The mixture is
stirred at AT for 12h 00. It is extracted with AcOEt and the extract is washed with a
saturated K2C03 solution and then with water. It is dried over MgSO4, filtered and
evaporated under reduced pressure to give 6.95 g of the expected product.
Stage 3.5:
1,1-Dimethylethyl 4-[6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-dihydroquinazolin-
1(2H)-yl]piperidine-1-carboxylate
2.5 g of 1,1-dimethylethyl 4-{carbamoyl[4-(2,2-difluoroethoxy)-2-
(methoxycarbonyl)phenyl]amino}piperidine-1-carboxylate obtained in stage 3.4 in solution
in a mixture of 10 ml of dioxane and 5 ml of a 1N aqueous NaOH solution are irradiated
under a microwave field at 130°C for 30 min. Extraction is carried out with AcOEt and the
extract is neutralized with a 1N aqueous HCI solution, washed with water, dried over
MgSO4, filtered and evaporated under reduced pressure. The residue obtained is
triturated in an AcOEt/pentane mixture to give the expected product. The same reaction
is reproduced with 2 other lots of 2.5 g of 1,1-dimethylethyl 4-{carbamoyl[4-(2,2-
difluoroethoxy)-2-(methoxycarbonyl)phenyl]amino}piperidine-1 -carboxylate obtained in
stage 3.4 to give, in total, 5.63 g of expected product.
Stage 3.6:
6-(2,2-Difluoroethoxy)-1-(piperidin-4-yl)quinazoline-2,4(1H,3H)-dione
A solution of 5.63 g of 1,1-dimethylethyl 4-[6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carboxylate obtained in stage 3.5 in 70 ml of
formic acid is stirred at AT for 2h 00. The solvent is evaporated under reduced pressure
to give 6.13 g of the expected product in the form of the formic acid salt.
Stage 3.7:
4-[6-(2,2-Difluoroethoxy)-2,4-dioxo-3,4-dihydroquinazolin-1(2W)-
yl]piperidine-1-carbaldehyde
A mixture of 6.13 g of 6-(2,2-difluoroethoxy)-1-(piperidin-4-yl)quinazoline-
2,4(1 H,3H)-6\one obtained in stage 3.6 and 3.12 g of ammonium formate in 28 ml of
ACN and 28 ml of dioxane is irradiated under a microwave field at 140°C for 1h 00. The
reaction mixture is run into water. The mixture is filtered and the precipitate is washed
with water and then with ether to give 4.47 g of the expected product.
Stage 3.8: Compound No. 34
4-[3-(4-Chlorobenzyl)-6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-dihydroquinazolin-
1 (2H)-y I] piperid i ne-1 -carba Idehyde
A mixture of 0.15 g of 4-[6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-dihydroquinazolin-
1(2H)-yl]piperidine-1-carbaldehyde obtained in stage 3.7, 0.096 g of 1-(bromomethyl)-4-
chlorobenzene and 0.3 g of Cs2C03 in 3 ml of DMF is stirred at AT for 1h 00. AcOEt is
added and washing is carried out with water and then with a saturated NaCI solution. The
organic phase is dried over MgSO4, filtered and evaporated under reduced pressure. The
residue is chromatographed on silica gel, elution being carried out with AcOEt, to give
0.116 g of the expected product.
EXAMPLE 4: Compound No. 49
Synthesis of 4-{3-[3-(cyclopentyloxy)-4-methoxybenzyl]-6-(2,2-difluoro-
ethoxy)-2,4-dioxo-3,4-dihydroquinazolin-1(2W)-yl}piperidine-1-carbaldehyde
0.172 g of DIAD is added to a solution of 0.15 g of 4-[6-(2,2-difluoroethoxy)-2,4-
dioxo-3,44-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]piperidine-1 -carbaldehyde
No. 39:4-t6-(2,2-difluoroethoxy)-3-(3-hydroxy-4-methoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 40:4-t6-(2,2-difluoroethoxy)-3-[3-(2-hydroxyethoxy)-4-methoxybenzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 41:4-[6-(2,2-difluoroethoxy)-3-(3-ethoxy-4-methoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 42:4-[6-(2,2-difluoroethoxy)-3-[4-methoxy-3-(2-methoxyethoxy)benzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 43:4-[6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]azepane-1 -carbaldehyde
No. 47: 4-[6-(2,2-difluoroethoxy)-3-[3-(3-hydroxypropoxy)-4-methoxybenzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 48: 4-[5-chloro-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]piperidine-1-carbaldehyde
No. 49: 4-{3-[3-(cyclopentyloxy)-4-methoxybenzyl]-6-(2,2-difluoroethoxy)-2,4-dioxo-
3,4-dihydroquinazolin-1 (2H)-yl}piperidine-1 -carbaldehyde
No. 50: 2-(5-{[6-(2,2-difluoroethoxy)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,4-
dihydroquinazolin-3(2H)-yl]methyl}-2-methoxyphenoxy)acetamide
No. 51:4-[6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]-3-methylpiperidine-1-carbaldehyde
No. 52: 3-t6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]-8-azabicyclo[3.2.1]octane-8-carbaldehyde
No. 55: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-
1(2H)-yl}piperidine-1-carbaldehyde
No. 56: 4-{3-[4-(cyclopentyloxy)-3-methoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2I4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 57: 4-[3-(3-chlorobenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 58: 4-[3-(4-chlorobenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 59: 4-{3-[3-(cyclopentyloxy)-4-methoxybenzyl]-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 72:4-[3-(3,4-dimethoxybenzyl)-6-(2-hydroxyethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 74: 4-[3-(3,4-dichlorobenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 76:4-{3-[(6-chloropyridin-3-yl)methyl]-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 78: 4-[3-(3-chloro-4-methoxybenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 79:4-[3-(3,4-dimethoxybenzyl)-6-(2-fluoroethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 89: 2-[5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -formylpiperidin-4-yl)-2,4-
dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxyphenoxy]acetamide
No. 90: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-hydroxy-4-methoxybenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 91:4-[3-(3,4-dimethoxybenzyl)-6-ethoxy-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]piperidine-1 -carbaldehyde
No. 97: 4-[5,7-dichloro-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-
1(2H)-yl]piperidine-1-carbaldehyde
No. 102: 4-[7-chloro-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-
1(2H)-yl]piperidine-1-carbaldehyde
No. 108: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-fluoro-4-methoxybenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 111: 4-[6-(difluoromethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 112: 4-[3-(3,4-dimethoxybenzyl)-6-(1-methylethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 114: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-methoxy-3-(1-
methylethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 116: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-(3-methoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 117: 4-{3-[3,5-bis(trifluoromethyl)benzyl]-6-[2-fluoro-1-(fluoromethyl)ethoxy]-
2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-yl}piperidine-1 -carbaldehyde
No. 118: 4-[3-(3-ethoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 124: 4-{3-[3-chloro-4-(2-methoxyethoxy)benzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 130: 4-[3-(3,4-diethoxybenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-
3,4-dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 131:4-[3-(4-ethoxy-3-methoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 133; 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(4-methoxy-3-methylbenzy()-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 134: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-
(trifluoromethyl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 135: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-
(trifluoromethyl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 143: 4-{3-[4-(benzyloxy)-3-methoxybenzyl]-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 145: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-nitrobenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 155: 4-[3-(4-ethoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 158; 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[4-(morpholin-4-ylmethyl)benzyl]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 160:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-(4-(morpholin-4-yl)benzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 165: 4-[3-(biphenyl-4-ylmethyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-
3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 166:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(methylsulphanyl)benzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1 -carbaldehyde
No. 167:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyridin-3-yl)benzyl)-
3,4-dihydroquinazolin-1 (2H)-yl}piperidine-1 -carbaldehyde
No. 170: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-methylbenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 175: 2-t2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]acetamide
No. 178: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-propoxybenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 183: 2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-ciioxo-1,4-dihyclroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
methylacetamide
No. 184: 2-[2-(cyclopentyloxy)-5-({6-t2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1l4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N,N-
dimethylacetamide
No. 185: 2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
methoxy-N-methylacetamide
No. 186: 4-{3-[4-(cyclopentyioxy)-3-ethoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 188;4-{3-[4-(cyclopentyloxy)-3-(1-methylethoxy)benzyl]-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 189: 4-{3-[4-(cyclopentyloxy)-3-propoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 190: 4-{3-[4-(cydopentyloxy)-3-hydroxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 193: 4-{3-[4-(difluoromethoxy)-3-methoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 194: 4-{3-[4-(difluoromethoxy)-3-ethoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 200: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(thiophen-3-yl)-
benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 201: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyridin-4-yl)benzyl)-
34-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 203: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[(1 -methyl-1 H-indol-6-yl)methyl]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 206: 4-{3-[4-(cyclopropylmethoxy)-3-methoxybenzyl]-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No.207:2-[4-<{6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-2f4-
dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxyphenoxy]-N-methylacetamide
No. 212: 4-{6-[2-fIuoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-(1 H-pyrazol-1 -
yl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 213:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyridin-2-yl)benzyl)-
3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 215:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(thiophen-2-yl)-
benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 216: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(quinolin-7-ylmethyl)-
3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 218: 4-{5-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[(6-methoxynaphthalen-2-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 223: 4-{3-[4-(1 H-benzimidazol-1-yl)benzyl]-6-[2-fluoro-1-(fluoromethyl)ethoxy]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 224: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(2-
methylpropoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 226: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(tetrahydrofuran-3-
yloxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 228:4-[3-{4-[(1-benzylpyrrolidin-3-yl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1-
(fIuoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 230: 4-[3-(1-benzothiophen-5-ylmethyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 232: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[3-methoxy-4-(1-
methylethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 233: 4-[3-(3,4-dimethoxybenzyl)-7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 234:4-t3-{4-[(1-acetylpyrrolidin-3-yl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 239: 4-[3-{4-[(4-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 240: 4-[3-{4-[(4-chlorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 242: 4-t3-{4-[(3-chlorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 243: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(3-(thiophen-3-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 245: 4-[3-(4-ethoxy-3-methoxybenzyl)-6-(2-hydroxyethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 246: 4-[3-{4-[2-(2,3-dihydro-1 H-indol-1-yl)-2-oxoethoxy]-3-methoxybenzyl}-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 250: 4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-methoxybenzyl}-6-t2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 251: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(2-oxo-2-(piperidin-
1-yl)ethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 254: 4-{3-[3-ethoxy-4-(thiophen-2-ylmethoxy)benzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 258: 4-[3-(3,4-dimethoxybenzyl)-6-[2-fluoro-1 -(hydroxymethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 263: (2R)-2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]propanoic
acid
No. 264:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(1-methyl-3-(thiophen-2-yl)-1H-
pyrazol-5-yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 270: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(5-methyl-1,2,4-oxadiazol-3-
yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 275: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyrimidin-5-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 276: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(1-methyl-3-phenyl-1H-pyrazol-5-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 278: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-{[6-(1H-pyrazol-1-
yl)pyridin-3-yl]methyl}-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 279: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-[(2-(thiophen-2-
yl)pyrimidin-5-yl)methyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 280: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[4-(1 -methyl-1 H-pyrazol-3-
yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 282: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[4-(3-methyl-1,2,4-oxadiazol-5-
yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 283: [2-(cyclopentyloxy)-5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]aceticacid
No. 285:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(thieno[2,3-b]pyridin-2-
ylmethyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 286: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[(6-phenylpyridin-3-
yl)methyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 287: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[(6-(morpholin-4-yl)pyridin-3-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 289: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-[(6-(thiophen-2-
yl)pyridin-3-yl)methyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 292: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[(1 -methyl-5-phenyl-1 H-pyrazol-3-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 294: 4-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-2,4-dioxo-
1,4-dihydroquinazolin-3(2H)-yl}methyl)biphenyl-2-carbonitrile
No. 295:(2R)-2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-clihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
methylpropanamide
No. 297: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(thiophen-2-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 298: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(morpholin-4-
ylmethyl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 299: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[3-methoxy-4-(piperidin-1 -
ylmethyl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 300:4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 301:2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
ethylacetamide
No. 302: (2S)-2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]propanoic
acid
No. 305:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-(3-methoxy-4-{[(3R)-2-oxo-1-
phenylpyrrolidin-3-yl]oxy}benzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 306: 4-{3-[4-(cyclobutylmethoxy)-3-methoxybenzyi]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 307: 4-{3-[4-(benzyloxy)-3-methoxybenzyl]-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 308: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(4-hydroxy-3-
methoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 309: 4-{3-[4-(cyclopropylmethoxy)-3-methoxybenzyl]-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 310: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-
(2-methylpropoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 311: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[3-methoxy-4-
(1-methylethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 312: 4-[3-(4-ethoxy-3-methoxybenzyl)-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 315: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{[6-(3-
methoxyphenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 316: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{[6-(2-
fluorophenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 317: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{[6-(4-
fluorophenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 318: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{[6-(4-
methoxyphenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 319:4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[(6-(thiophen-2-
yl)pyridin-3-yl)methyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 320: 4-{3-[3-ethoxy-4-(thiophen-2-ylmethoxy)benzyl]-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 321: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[4-(1 -methyl-1 H-pyrazol-
3-yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 322: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyrimidin-5-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 323: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[(1 -methyl-3-(thiophen-2-
yl)-1 H-pyrazol-5-yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-yl}piperidine-1 -
carbaldehyde
No. 324: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(2-oxo-2-
(piperidin-1-yl)ethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 325: 4-[3-{4-[2-(2,3-dihydro-1 H-indol-1 -yl)-2-oxoethoxy]-3-methoxybenzyl}-7-
fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]piperidine-1 -carbaldehyde
No. 326: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(5-methyl-1,2,4-
oxadiazol-3-yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 327: 4-[3-{4-[(3-chlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 328: 4-[3-{[6-(3,5-dichlorophenyl)pyridin-3-yl]methyl}-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 329: 4-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)biphenyl-2-carbonitrile
No. 330: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-(1 H-pyrazol-
1-yl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 331: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-{[6-(3-
fluorophenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 332: 3-[5-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-
yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)pyridin-2-yl]benzonitrile
No. 333:4-[3-(3,4-diethoxybenzyl)-7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 334: 4-[3-{4-[(4-chlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 335: 4-{7-fluoro-6-[2-fluoro-1 -(fluorotnethyl)ethoxy]-3-t4-(morpholin-4-
ylmethyl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 336: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-{[6-(1 H-pyrazol-
1-yl)pyridin-3-yl]methyl}-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 337: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(4-(morpholin-4-yl)-
benzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1 -carbaldehyde
No. 338: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-
propoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 339: 4-{3-[4-(1 H-benzimidazol-1 -yl)benzyl]-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 340: 5-({7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1-formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxybenzonitrile
No. 341: 3-(3,4-dimethoxybenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-7-carbonitrile
No. 342: 4-[3-(4-bromobenzyl)-7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 343:4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-(2-methoxyethoxy)benzyl}-7-fluoro-6-
[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 344: 4-{3-[4-(benzyloxy)benzyl]-7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 345: 4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-ethoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 349:4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-(2-fluoroethoxy)benzyl}-7-fluoro-6-[2-
fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-yl]piperidine-1 -
carbaldehyde
No. 350:4-[3-{4-[(2-chloro-4-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2l4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 351:4-[3-{4-[(2,4-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 352: 4-[3-{4-[(2-chloro-6-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 353: 4-[3-{4-[(2,6-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 354: 4-[3-{4-[(2-chlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-t2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 355: 4-[7-fluoro-3-{4-[(2-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3>4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 357: 2-[(3,4-dichlorobenzyl)oxy]-5-({7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-
1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)benzonitrile
No. 358: 4-[3-{4-[(3,4-dichlorophenoxy)methyl]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 360: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-t4-(2-
phenylethyl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 362: 4-[3-{4-[(4,5-dichloro-2-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 369: 4-[3-{4-[(4-chlorophenoxy)methyl]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 371: 4-[3-{3-chloro-4-[(4-chlorobenzyl)oxy]-5-ethoxybenzyl}-7-fluoro-6-[2-fluoro-
1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 373:4-[3-{3-chloro-4-[(2,4-dichlorobenzyl)oxy]-5-ethoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 375: 4-[7-fluoro-3-{4-[(4-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 376: 4-[3-{4-[(3,5-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 377: 4-[3-(4-{[4-chloro-3-(trifluoromethyl)benzyl]oxy}-3-methoxybenzyl)-7-
fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]piperidine-1-carbaldehyde
No. 379: 4-[3-{4-[(3-chlorophenoxy)methyl]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 380: 4-[3-{4-[(3,5-difluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 381: 4-{3-[4-(benzyloxy)-3-methoxybenzyl]-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 382: 4-[3-{4-[(3-chloro-5-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 383: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-{[4-
(trifluoromethyl)benzyl]oxy}benzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 384: 4-[3-{4-[(2,5-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 385: 4-{[4-({7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -formylpiperidin-4-
yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-
methoxyphenoxy]methyl}benzonitrile
No. 385: 3-{[4-({7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -formylpiperidin-4-
yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-
methoxyphenoxy]methyl}benzonitrile
No. 387:4-[3-{4-t(4-chloro-2-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 388:4-[3-{4-[1-(3,4-dichlorophenyl)ethoxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 389: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{4-[(3-hydroxybenzyl)oxy]-
3-methoxybenzyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 390: 4-[7-fluoro-3-{4-[(3-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 391:4-[3-{4-[(3,4-difluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 392: 4-{3-[4-(5,6-dichloro-1 H-benzimidazol-1-yl)-3-methoxybenzyl]-7-fluoro-6-
[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 393: 4-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenyl 3,4-dichlorobenzenesulphonate
No. 394: 4-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxyphenyl3,4-dichlorobenzene-
sulphonate
No. 403: 3,4-dichloro-N-[4-({7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-clihydroquinazolin-3(2H)-yl}nnethyl)-2-
methoxyphenyl]benzamide;
in the form of the base or of an addition salt with an acid.
15. Compound corresponding to the general formula (I)
in which
— A represents an aryl group or a heteroaryl group;
— R1 represents:
■ a hydrogen atom,
■ -C(O)R in which R is a hydrogen atom, a (C1-C6) alkoxy group, an aryl group, a
(C3-C6) cycloalkyl group or a (C1-C6) alkyl group, the said alkyl optionally being
substituted by:
. one or more hydroxyl group(s),
. a benzyloxy group,
. a (C1-C6) alkoxy group, optionally substituted by an aryl, or
. a (C3-C6) cycloalkyl group,
■ an optionally substituted (C1-C6) alkyl group;
— R2 represents:
■ a hydrogen atom,
■ a halogen atom,
■ a cyano group,
■ a nitro group,
■ a (C1-C6) alkyl group optionally substituted by an -NH2 or else by an
-NHC(O)Rb group, with Rb as defined below,
■ an -ORa group in which Ra represents:
. a hydrogen atom,
. a (C1-C6) alkyl group optionally substituted by one or more halogen
atom(s), by one or more hydroxyl group(s), by an aryl group and/or by one or
more cyano group(s),
. a (C2-C6) alkynyl group,
. an aryl group;
— R3 represents:
■ a hydrogen atom,
■ a halogen atom,
■ a hydroxyl group,
■ a cyano group,
■ an -SCF3 group,
■ a nitro group,
■ an -S(O)0-2-alkyl group, an -S(O)0-2-heterocycloalkyl group, an -O-SO2-aryl
group optionally substituted by one or more halogen atom(s);
■ an -alkylaminoalkyl or -cycloalkylaminoalkyl group, each optionally substituted
on the end alkyl,
■ an optionally substituted sulphonamide group,
■ an aryl group or a heteroaryl group, the said group being monocyclic or
polycyclic and in addition optionally being substituted by a (C1-C6) alkyl group, by
one or more halogen atom(s) or by a (C1-C6) alkoxy group,
■ a heterocycloalkyl group optionally substituted by a (C1-C6) alkyl group,
■ a (C1-C6) alkyl group optionally substituted by:
- one or more halogen atom(s),
- an aryl group which can be substituted by one or more halogen atom(s)
or by one or more hydroxyl group(s),
- a heteroaryl group,
- one or more hydroxyl group(s) which can be substituted by an aryl group
itself optionally substituted by one or more halogen atom(s), or
- a heterocycloalkyl group optionally substituted by a CO(O)Ra group or by
a (C1-C6) alkyl group, with Ra as defined above,
■ a -C(O)NRbRc group, with Rb and Rc as defined below,
■ a -C(O)ORc group or an -O-C(O)ORc group, with Rc as defined below,
■ a (C1-C6) alkoxy group, optionally substituted by
- an aminoalkyl group,
- an aminocycloalkyl group,
- a cycloalkyl group,
- a heterocycloalkyl group,
- a monocyclic or polycyclic heteroaryl group,
- one or more hydroxyl group(s),
- one or more halogen atom(s),
- a (C1-C6) alkoxy group,
- a -C(O)ORc group, with RC as defined below,
- a -C(O)NRbRc group, with Rb and Rc as defined below, and/or
- an aryl group, itself optionally substituted by one or more halogen
atom(s), a cyano group, a (C1-C6) alkoxy group, an -O-haloalkyl group and/or a
haloalkyl group,
■ an -O-cycloalkyl group, an -O-aryl group or an -O-heterocycloalkyl group, each
optionally substituted by
- an aryl group, itself optionally substituted by one or more halogen
atom(s) or by a (C1-C6) alkyl group,
- one or more halogen atom(s), and/or
- a (C1-C6) alkyl group, which can itself be substituted by an aryl group,
■ an -NH-CO-NH-aryl group, an -NH-CO-NH-heteroaryl group or an -NH-CO-
NH-(C1-C6) alkyl group, each optionally being substituted by one or more halogen
atom(s), by a cyano group, by a nitro group, by one or more hydroxyl group(s) or by a
(C1-C6) alkoxy group,
■ an -N-(C1-C6) alkyl group, it being possible for the (C1-C6) alkyl group to be
substituted by
one or more aryl group(s) optionally substituted by one or more halogen atom(s)
and/or by an SO2 group,
■ an -NH-CO-aryl group or an -NH-CO-heteroaryl group, each optionally being
substituted by one or more halogen atom(s);
or else R3 forms, with A, a polycyclic heteroaryl group optionally substituted by a (C1-C6)
alkoxy group or a (C1-C6) alkyl group optionally substituted by an aryl group which can
itself be substituted by one or more halogen atom(s);
— R4 represents a hydrogen atom or a (C1-C6) alkyl group;
— Rb represents:
. a hydrogen atom,
. a (C1-C6) alkyl group optionally substituted by one or more halogen atom(s), by
one or more hydroxyl, cyano, amino, heterocycloalkyl or (C1-C6) alkoxy group(s) or by an
aryl group optionally substituted by one or more halogen atom(s),
. a (C3-C6) cycloalkyl group,
. a (C2-C6) alkynyl group,
. a (C1-C6) alkoxy group,
. an aryl group optionally substituted by one or more halogen atom(s);
— Rc represents a hydrogen atom or a (C1-C6) alkyl group optionally substituted
by one or more halogen atom(s);
or then Rb and Rc form, together with the nitrogen atom to which they are attached, a
polycyclic heteroaryl group or a heterocycloalkyl group;
— m and n represent, independently of one another, the value 0, 1 or 2, it being
understood that m+n<3;
— p and p' represent, independently of one another, the value 1, 2 or 3, it being
understood that, when p is greater than or equal to 2, then the R2 groups are on separate
carbon atoms and can be different from one another and, when p' is greater than or
equal to 2, then the R3 groups are on separate carbon atoms and can be different from
one another;
— q represents the value 0 or 2, it being understood that, when q = 0, then the
nitrogenous heterocyclic group attached to the nitrogen situated in the 1 position of the
2,4-dioxo-1,2,3,4-tetrahydroquinazoline ring system is no longer bridged and is of the
type:
with R1, R4, m and n as defined above,
— r represents the value 0 or 1;
in the form of bases or of addition salts with acids;
intended to treat at least one cardiovascular disease and/or to prevent the
appearance of at least one cardiovascular disease.
16. Compound according to the preceding claim, characterized in that the cardiovascular
diseases are chosen from (i) coronary diseases, (ii) diseases of the cardiac muscle, (iii)
diseases of the heart valves, (iv) diseases of the pericardium, (v) diseases of the heart
rhythm and diseases of cardiac conduction, and (vi) diseases of the vessels.
17. Compound according to either one of Claims 15 and 16, characterized in that the
cardiovascular disease is chosen from myocardial infarction, in particular contractile
cardiac dysfunction resulting from a myocardial infarction, diseases associated with
reperfusion injuries of the cardiac and/or skeletal muscle, pulmonary hypertension,
hepatic fibrosis, post-angioplasty arterial restenosis, with or without fitting a stent,
atherosclerosis and its complications, cardiac insufficiency, dilated cardiopathy and
myocarditis of viral and/or bacterial origin.
18. Compound according to one of Claims 15 to 17, characterized in that:
— A is as defined in Claim 5;
— q, m and n are as defined in Claim 6;
— R2 is as defined in Claim 7, Claim 8 or Claim 9.
19. Compound according to one of Claims 15 to 17, characterized in that:
A is a phenyl, R1 is a -C(O)R group in which R represents a hydrogen atom, q is equal to
0, n and m each have the value 1 and R2 represents -ORa, Ra being as defined in
Claim 1 or Claim 2.
20. Compound according to one of Claims 15 to 17, characterized in that:
A is a phenyl, R1 is a -C(O)R group in which R represents a hydrogen atom, q is equal to
0, n and m each have the value 1, p = 1 and R2 represents a methyl substituted by an
-NH-CO-Rb group, Rb being as defined in Claim 1 or Claim 2.
21. Compound according to one of Claims 15 to 17, characterized in that:
A is a phenyl, R1 is a -C(O)R group in which R represents a hydrogen atom, q is equal to
0, n and m each have the value 1, p is equal to 2, one of the R2 groups is -ORa, Ra
being as defined in Claim 1 or Claim 2, and the other of the R2 groups is a halogen atom.
22. Compound according to one of Claims 15 to 17, characterized in that:
the R2 group is in the 6 position of the 2,4-dioxo-1,2,3,4-tetrahydroquinazoline ring
system and in that there may additionally be an R2 group, identical to or different from the
said R2 group mentioned above, in the 7 position of the 2,4-dioxo-1,2,3,4-
tetrahydroquinazoline ring system, the said compound of formula (I) being in the base,
hydrate or solvate form, in the form of isomers or in the form of their mixtures.
23. Compound according to one of Claims 15 to 17 chosen from:
No. 1: 2-{[3-(3,4-dimethoxybenzyl)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]oxy}propanenitrile
No. 2: 1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-6-hydroxyquinazoline-
2,4(1 H,3H)-dione
No. 3: {[1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]oxy}acetonitrile
No. 4: 2-{[1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]oxy}propanenitrile
No. 5: {[3-(3,4-dimethoxybenzyl)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]oxy}acetonitrile
No. 6: {[3-(3,4-dimethoxybenzyl)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]oxy}acetonithle
No. 11: 4-[3-(3,4-dimethoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-
3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 12: 1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-6-[2-fluoro-1-
(fluoromethyl)ethoxy]quinazoline-2,4(1H,3H)-dione
No. 13: 4-[3-(3,4-dimethoxybenzyl)-2,4-dioxo-6-(2,2,2-trifluoroethoxy)-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 14: 1-(1-acetylpiperidin-4-yl)-6-(2,2-difluoroethoxy)-3-(3,4-
dimethoxybenzyl)quinazoline-2,4(1H,3H)-dione
No. 16: 4-[6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 20: N-{[3-(3,4-dimethoxybenzyl)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]methyl}acetamide
No. 22:1-(1-acetylpiperidin-4-yl)-6-(aminomethyl)-3-(3,4-
dimethoxybenzyl)quinazoline-2,4(1 H,3H)-dione hydrochloride
No. 23: N-{[3-(3,4-dimethoxybenzyl)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]methyl}formamide
No. 24: N-{[1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]methyl}formamide
No. 25: N-{[1-(1-acetylpiperidin-4-yl)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-1,2,3,4-
tetrahydroquinazolin-6-yl]methyl}acetamide
No. 32:4-[6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]piperidine-1-carbaldehyde
No. 33: 4-[3-(3,4-dichlorobenzyl)-6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 34:4-t3-(4-chlorobenzyl)-6-(2,2-difluoroethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 35: methyl 4-{[6-(2,2-difluoroethoxy)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,4-
dihydroquinazolin-3(2H)-yl]methyl}benzoate
No. 36: 4-{[6-(2,2-difluoroethoxy)-1 -(1 -formylpiperidin-4-yl)-2,4-dioxo-1,4-
dihydroquinazolin-3(2H)-yl]methyl}benzoicacid
No. 37: 4-{[6-(2,2-difluoroethoxy)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,4-
dihydroquinazolin-3(2H)-yl]methyl}-N-(2-methoxyethyl)benzamide
No. 38: 4-[3-(3,4-dimethoxybenzyl)-6-methyl-2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-
yl]piperidine-1 -carbaldehyde
No. 39: 4-[6-(2,2-difluoroethoxy)-3-(3-hydroxy-4-methoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 40: 4-[6-(2,2-difluoroethoxy)-3-[3-(2-hydroxyethoxy)-4-methoxybenzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 41: 4-[6-(2,2-difluoroethoxy)-3-(3-ethoxy-4-methoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yi]piperidine-1 -carbaldehyde
No. 42: 4-[6-(2,2-difiuoroethoxy)-3-[4-methoxy-3-(2-methoxyethoxy)benzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 43:4-[6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]azepane-1 -carbaldehyde
No. 47: 4-[6-(2,2-difluoroethoxy)-3-[3-(3-hydroxypropoxy)-4-methoxybenzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 48: 4-[5-chloro-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]piperidine-1 -carbaldehyde
No. 49: 4-{3-[3-(cyclopentyloxy)-4-methoxybenzyl]-6-(2,2-difluoroethoxy)-2,4-dioxo-
3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 50: 2-(5-{[6-(2,2-difluoroethoxy)-1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,4-
dihydroquinazolin-3(2H)-yl]methyl}-2-methoxyphenoxy)acetamide
No. 51: 4-[6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-2(4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]-3-methylpiperidine-1-carbaldehyde
No. 52:3-[6-(2,2-difluoroethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]-8-azabicyclo[3.2.1]octane-8-carbaldehyde
No. 55: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-
1(2H)-yl}piperidine-1-carbaldehyde
No. 56: 4-{3-[4-(cyclopentyloxy)-3-methoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 57:4-[3-(3-chlorobenzyl)-6-[2-fluoro-1-{fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 58: 4-[3-(4-chlorobenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 59: 4-{3-[3-(cyclopentyloxy)-4-methoxybenzyl]-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 72: 4-[3-(3,4-dimethoxybenzyl)-6-(2-hydroxyethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 74: 4-[3-(3,4-dichlorobenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 76: 4-{3-[(6-chloropyridin-3-yl)methyl]-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 78: 4-[3-(3-chloro-4-methoxybenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 79:4-[3-(3,4-dimethoxybenzyl)-6-(2-fluoroethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 89: 2-[5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-2,4-
dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxyphenoxy]acetamide
No. 90: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-hydroxy-4-methoxybenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 91: 4-[3-(3,4-dimethoxybenzyl)-6-ethoxy-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]piperidine-1 -carbaldehyde
No. 97: 4-[5,7-dichloro-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-
1(2H)-yl]piperidine-1-carbaldehyde
No. 102: 4-[7-chloro-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-
1(2H)-yl]piperidine-1-carbaldehyde
No. 108: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-fluoro-4-methoxybenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 111: 4-[6-(difluoromethoxy)-3-(3,4-dimethoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1 -carbaldehyde
No. 112: 4-[3-(3,4-dimethoxybenzyl)-6-(1-methylethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 114: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-methoxy-3-(1-
methylethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 116: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-(3-methoxybenzyl)-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 117: 4-{3-[3,5-bis(trifluoromethyl)benzyl]-6-[2-fluoro-1-(fluoromethyl)ethoxy]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 118: 4-[3-(3-ethoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 124: 4-{3-[3-chloro-4-(2-methoxyethoxy)benzyl]-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}pipericline-1 -carbaldehyde
No. 130: 4-[3-(3,4-diethoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-
3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 131: 4-[3-(4-ethoxy-3-methoxybenzyl)-6-t2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 133: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(4-methoxy-3-methylbenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 134: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-
(trifluoromethyl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 135: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-
(trifluoromethyl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 143: 4-{3-[4-(benzyloxy)-3-methoxybenzyl]-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 145: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-nitrobenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 155: 4-[3-(4-ethoxybenzyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-
dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 158: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[4-(morpholin-4-ylmethyl)benzyl]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 160: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(4-(morpholin-4-yl)benzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 165: 4-[3-(biphenyl-4-ylmethyl)-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-
3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 166: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[4-(methylsulphanyl)benzyl]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 167:4-{6-t2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyridin-3-yl)benzyl)-
3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 170:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-(3-methoxy-4-methylbenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 175:2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]acetamide
No. 178: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-propoxybenzyl)-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 183: 2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1-(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
methylacetamide
No. 184: 2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N,N-
dimethylacetamide
No. 185: 2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
methoxy-N-methylacetamide
No. 186: 4-{3-[4-(cyclopentyloxy)-3-ethoxybenzyl]-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 188: 4-{3-[4-(cyclopentyloxy)-3-(1-methylethoxy)benzyl]-6-t2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 189: 4-{3-[4-(cyclopentyloxy)-3-propoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 190: 4-{3-[4-(cyclopentyloxy)-3-hydroxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 193: 4-{3-[4-(difluoromethoxy)-3-methoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 194: 4-{3-[4-(difluoromethoxy)-3-ethoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 200: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(thiophen-3-yl)-
benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 201: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyridin-4-yl)benzyl)-
3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 203: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(1-methyl-1 H-indol-6-yl)methyl]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 206: 4-{3-[4-(cyclopropylmethoxy)-3-methoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 207:2-[4-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-2,4-
dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxyphenoxy]-N-methylacetamide
No. 212:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-(1H-pyrazol-1-
yl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 213: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyridin-2-yl)benzyl)-
3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 215: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(thiophen-2-yl)-
benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 216: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(quinolin-7-ylmethyl)-
3,4-dihydroquinazolin-1 (2H)-yl}piperidine-1 -carbaldehyde
No. 218: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(6-methoxynaphthalen-2-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 223: 4-{3-[4-(1 H-benzimidazol-1-yl)benzyl]-6-[2-fluoro-1-(fluoromethyl)ethoxy]-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 224: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(2-
methylpropoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 226: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(tetrahydrofuran-3-
yloxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 228: 4-[3-{4-[(1 -benzylpyrrolidin-3-yl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)6thoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 230: 4-[3-(1 -benzothiophen-5-ylmethyl)-6-[2-fluoro-1 -(fluorometrtyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 232: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[3-methoxy-4-(1 -
methylethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 233: 4-[3-(3,4-dimethoxybenzyl)-7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxyj-
2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 234:4-[3-{4-[(1-acetylpyrrolidin-3-yl)oxy]-3-nriethoxybenzyl}-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 239:4-[3-{4-[(4-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 240: 4-[3-{4-[(4-chlorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 242: 4-[3-{4-[(3-chlorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoramethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 243: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(3-(thiophen-3-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 245: 4-[3-(4-ethoxy-3-methoxybenzyl)-6-(2-hydroxyethoxy)-2,4-dioxo-3,4-
dihydroquinazolin-1 (2H)-yl]piperidine-1 -carbaldehyde
No. 246: 4-[3-{4-[2-(2,3-dihydro-1 H-indol-1-yl)-2-oxoethoxy]-3-methoxybenzyl}-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 250: 4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 251: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[3-methoxy-4-(2-oxo-2-(piperidin-
1-yl)ethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 254: 4-{3-[3-ethoxy-4-(thiophen-2-ylmethoxy)benzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 258: 4-[3-(3,4-dimethoxybenzyl)-6-[2-fluoro-1 -(hydroxymethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 263:(2R)-2-t2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
forrnylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]propanoic
acid
No. 264: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(1-methyl-3-(thiophen-2-yl)-1 H-
pyrazol-5-yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 270: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(5-methyl-1,2,4-oxadiazol-3-
yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 275: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyrimidin-5-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 276: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(1-methyl-3-phenyl-1 H-pyrazol-5-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 278:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-{[6-(1H-pyrazol-1-
yl)pyridin-3-yl]methyl}-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 279:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[(2-(thiophen-2-
yl)pyrimidin-5-yl)methyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 280:4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(1-methyl-1H-pyrazol-3-
yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 282: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(3-methyl-1,2,4-oxadiazol-5-
yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 283: t2-(cyclopentyloxy)-5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazoliri-3(2H)-yl}methyl)phenoxy]aceticacid
No. 285: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-(thieno[2,3-blpyridin-2-
ylmethyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 286: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-[(6-phenylpyridin-3-
yl)methyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 287: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[(6-(morpholin-4-yl)pyridin-3-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 289: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-[(6-(thiophen-2-
yl)pyridin-3-yl)methyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 292: 4-{6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[(1 -methyl-5-phenyl-1 H-pyrazol-3-
yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 294: 4-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-2,4-dioxo-
1,4-dihydroquinazolin-3(2H)-yl}methyl)biphenyl-2-carbonitrile
No. 295: (2R)-2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
methylpropanamide
No. 297: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(thiophen-2-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 298: 4-{6-[2-fluoro-1 -(f luoromethyl)ethoxy]-3-[3-methoxy-4-(morpholin-4-
ylmethyl)benzyl]-2,4-clioxo-3,4-dihydroquinazolin-1(2H)-yl}pipericline-1-carbalclehyde
No. 299: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(piperidin-1 -
ylmethyl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 300: 4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fiuoromethyl)ethoxy]-2I4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 301: 2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]-N-
ethylacetamide
No. 302: (2S)-2-[2-(cyclopentyloxy)-5-({6-[2-fluoro-1 -(fluoromethyl)ethoxy]-1 -(1 -
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenoxy]propanoic
acid
No. 305: 4-{6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-{[(3R)-2-oxo-1 -
phenylpyrrolidin-3-yl]oxy}benzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 306: 4-{3-[4-(cyclobutylmethoxy)-3-methoxybenzyl]-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 307: 4-{3-[4-(benzyloxy)-3-methoxybenzyl]-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 308: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(4-hydroxy-3-
methoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 309: 4-{3-[4-(cyclopropylmethoxy)-3-methoxybenzyl]-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 310: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-
(2-methylpropoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 311: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[3-methoxy-4-
(1-methylethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 312: 4-[3-(4-ethoxy-3-methoxybenzyl)-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 315: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{[6-(3-
methoxyphenyl)pyridin-3-yl]rnethyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 316:4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-{[6-(2-
fluorophenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 317: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{[6-(4-
fluorophenyl)pyridin-3-yl]methyl}-2,4-dioxo-3I4-dihyclroquinazolin-1(2H)-yl}pipericline-1-
carbaldehyde
No. 318:4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-{[6-(4-
methoxyphenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 319: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[(6-(thiophen-2-
yl)pyridin-3-yl)methyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 320: 4-{3-[3-ethoxy-4-(thiophen-2-ylmethoxy)benzyl]-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 321: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[4-(1 -methyl-1 H-pyrazol-
3-yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 322: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-(4-(pyrimidin-5-
yl)benzyl)-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 323: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[(1 -methyl-3-(thiophen-2-
yl)-1H-pyrazol-5-yl)methyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 324: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[3-methoxy-4-(2-oxo-2-
(piperidin-1 -yl)ethoxy)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-yl}piperidine-1 -
carbaldehyde
No. 325: 4-[3-{4-[2-(2,3-dihydro-1 H-indol-1 -yl)-2-oxoethoxy]-3-methoxybenzyl}-7-
fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]piperidine-1-carbaldehyde
No. 326: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-[4-(5-methyl-1,2,4-
oxadiazol-3-yl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 327: 4-[3-{4-[(3-chlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 328:4-[3-{[6-(3,5-dichlorophenyl)pyridin-3-yl]methyl}-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
i No. 329: 4-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)biphenyl-2-carbonitrile
No. 330: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-(1 H-pyrazol-
1 -yl)benzyl]-3,4-dihydroquinazolin-1 (2H)-yl}piperidine-1 -carbaldehyde
No. 331: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{[6-(3-
fluorophenyl)pyridin-3-yl]methyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 332:3-[5-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-
yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)pyridin-2-yl]benzonitrile
No. 333: 4-[3-(3,4-diethoxybenzyl)-7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 334: 4-[3-{4-[(4-chloroben2yl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 335: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-3-[4-(morpholin-4-
ylmethyl)benzyl]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 336: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-{[6-(1 H-pyrazol-
1-yl)pyridin-3-yl]methyl}-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 337: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(4-(morpholin-4-yl)-
benzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 338: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-
propoxybenzyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 339:4-{3-[4-(1H-benzimidazol-1-yl)benzyl]-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 340: 5-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxybenzonitrile
No. 341: 3-(3,4-dimethoxybenzyl)-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-y4-dioxo-1.2.3.SAtetrahydroquinazoline-7-carbonitrile
No. 342: 4-[3-(4-bromobenzyl)-7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 343:4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-(2-methoxyethoxy)benzyl}-7-fluoro-6-
[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 344: 4-{3-[4-(benzyloxy)benzyl]-7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-2,4-
dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 345: 4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-ethoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 349:4-[3-{4-[(3,4-dichlorobenzyl)oxy]-3-(2-fluoroethoxy)benzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 350:4-[3-{4-[(2-chloro-4-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 351: 4-[3-{4-[(2,4-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 352:4-[3-{4-[(2-chloro-6-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 353: 4-[3-{4-[(2,6-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihyclroquinazolin-1(2H)-yl]pipericline-1-carbaldehyde
No. 354: 4-[3-{4-[(2-chlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 355: 4-[7-fluoro-3-{4-[(2-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 357: 2-[(3,4-dichlorobenzyl)oxy]-5-({7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-
1-(1-formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)benzonitrile
No. 358: 4-[3-{4-[(3,4-dich!orophenoxy)methyl]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 360: 4-{7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3-[4-(2-
phenylethyl)benzyl]-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 362: 4-[3-{4-[(4,5-dichloro-2-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 369: 4-[3-{4-[(4-chlorophenoxy)methyl]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 371: 4-[3-{3-chloro-4-[(4-chlorobenzyl)oxy]-5-ethoxybenzyl}-7-fluoro-6-[2-fluoro-
1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 373: 4-[3-{3-chloro-4-[(2,4-dichlorobenzyl)oxy]-5-ethoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 375: 4-[7-fluoro-3-{4-[(4-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 376: 4-[3-{4-[(3,5-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 377: 4-[3-(4-{[4-chloro-3-(trifluoromethyl)benzyl]oxy}-3-methoxybenzyl)-7-
fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-
yl]piperidine-1 -carbaldehyde
No. 379: 4-[3-{4-[(3-chlorophenoxy)methyl]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 380: 4-[3-{4-f(3,5-difluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-t2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 381:4-{3-[4-(benzyloxy)-3-methoxybenzyl]-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 382:4-[3-{4-t(3-chloro-5-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fiuorc-1 -(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1 (2H)-y!]piperidine-1 -
carbaldehyde
No. 383: 4-{7-fluoro-6-[2-f!uoro-1 -(fluoromethyl)ethoxy]-3-(3-methoxy-4-{[4-
(trifluoromethyl)benzyl]oxy}ben2yl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 384: 4-[3-{4-[(2,5-dichlorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-t2-fluoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 385: 4-{[4-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-
yi)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-
methoxyphenoxy]methyl}benzonitrile
No. 386: 3-{[4-({7-fluoro-6-[2-fluoro-1-(fiuoromethyl)ethoxy]-1-(1-formylpiperidin-4-
yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-
methoxyphenoxy]methyl}benzonitrile
No. 387: 4-[3-{4-[(4-chloro-2-fluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 388: 4-[3-{4-[1-(3,4-dichlorophenyl)ethoxy]-3-methoxybenzyl}-7-fluoro-6-[2-
fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-
carbaldehyde
No. 389: 4-{7-fluoro-6-[2-fluoro-1 -(fluoromethyl)ethoxy]-3-{4-[(3-hydroxybenzy!)oxy]-
3-methoxybenzyl}-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-carbaldehyde
No. 390: 4-[7-fluoro-3-{4-t(3-fluorobenzyl)oxy]-3-methoxybenzyl}-6-[2-fIuoro-1 -
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 391:4-[3-{4-[(3,4-difluorobenzyl)oxy]-3-methoxybenzyl}-7-fluoro-6-[2-fluoro-1-
(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl]piperidine-1-carbaldehyde
No. 392:4-{3-[4-(5,6-dichloro-1H-benzimidazol-1-yl)-3-methoxybenzyl]-7-fluoro-6-
[2-fluoro-1-(fluoromethyl)ethoxy]-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}piperidine-1-
carbaldehyde
No. 393:4-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)phenyl 3,4-dichlorobenzenesulphonate
No. 394: 4-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-formylpiperidin-4-yl)-
2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-methoxyphenyl 3,4-dichlorobenzene-
sulphonate
No. 403:3,4-dichloro-N-[4-({7-fluoro-6-[2-fluoro-1-(fluoromethyl)ethoxy]-1-(1-
formylpiperidin-4-yl)-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}methyl)-2-
methoxyphenyrjbenzamide;
A subject-matter of the present invention is the use of compounds of formula (I)
in the base, hydrate or solvate form or in the form of their mixtures, as medicaments or
for the preparation of medicaments intended for the treatment of at least one
cardiovascular disease and/or to prevent the appearance of at least one cardiovascular
disease.