PYRAZOLOQUINOLINONE DERIVATIVES, PREPARATION THEREOF AND
THERAPEUTIC USE THEREOF
The present invention relates to pyrazoloquinolinone derivatives, to their preparation and
to their therapeutic use.
The compounds according to the present invention are reversible and selective
inhibitors of type-2 methionine aminopeptidase (MetAP2).
MetAP2 is a ubiquitous cytosol-based metalloprotease involved in polypeptide
catabolism.
MetAP2 catalyses the cleavage of methionine residues located at the N-terminal
end of proteins newly synthesized by the cell (Bradshaw R.A. et al., TIBS, 1998,
23, 263-267). Cleavage of the N-terminal methionine residues is an important step
in the maturation of many proteins and polypeptides. It enables the cell to
continue the usual post-translational modifications (myristoylation, palmitoylation,
etc.), and then to degrade these same proteins. However, MetAP2 can only
cleave this residue on condition that the second residue is of smaller size and
uncharged.
MetAP2 is active when the active site contains two divalent metal atoms such as
Co(ll) or Mn(ll) (Li X., Chang Y.H., Biochem. Biophys. Res. Commun. 227, 1996,
152-159). Studies have moreover made it possible to establish that human
MetAP2 quite probably uses manganese as physiological metal ion (Wang J. et
al., Biochemistry 2003, 42, 5035-5042).
Another function of MetAP2 is combination with a protein translation factor, elF2
(eukaryotic initiation factor 2), thus preventing its phosphorylation (Datta et al.,
1988; Li and Chang, 1996). It has been shown that the phosphorylation of elF2
results in inhibition of overall protein synthesis in eukaryotic cells. By binding to
elF2, MetAP2 protects the phosphorylation site (Datta, 2000; Kimball, 1999;
Pestova et al., 2001). However, inhibitors of MetAP2 activity do not affect the

capacity of MetAP2 to block the phosphorylation of elF2 (Griffith, 1997), which
suggests that the two functions are independent.
A MetAP2 isoform exists: MetAPI. These two isoforms are distinguished by the
presence of an additional helical domain of about 60 residues within the C-
terminal domain of MetAP2. Eukaryotes possess the two forms. A mutation of the
two forms is lethal to the eukaryotic cell. This result underlines the interest in
identifying inhibitors that are selective towards MetAP2. On the other hand, when
only one isoform is mutated, growth reduction is observed (Li X. and Chang Y.H.,
Proc. Natl. Acad. Sci. 1995, 92, 12357-12361). These results confirm that
methionine aminopeptidase (MAP) function is essential for cell growth and this
activity cannot be relayed by a route independent of MetAPs.
Two types of MetAP2 inhibitor also exist: reversible inhibitors and irreversible
inhibitors. Certain known irreversible inhibitors are fumagillin, TNP-470 and
ovalicin. At the molecular level, TNP-470, just like fumagillin and ovalicin, binds
covalently and irreversibly to MetAP2 (Griffith E.C. et a/., Chem. Biol. 1997, 4,
461-471).
MetAP2 has been identified as being the target of a family of anti-angiogenic
agents derived from fumagillin, described as powerful irreversible MetAP2
inhibitors. The causal link between the inhibition of MetAP2 and the resulting
inhibition of endothelial cell proliferation and of neovascularization is clearly
established (Griffith E.C. etal., Chem. Biol. 1998, 95, 15183-15188).
At the cellular level, the target proteins of MetAP2 are still at the present time very
scarcely known. One of them is glyceraldehyde-3-phosphate dehydrogenase. A
defect in the synthesis of this enzyme has been observed during treatment of
endothelial cells with TNP-470. Recent studies support the hypothesis that the
anti-MetAP2 activity of TNP-470 is the source of its anti-angiogenic activity.
It has been shown that irreversible MetAP2 inhibitors play a role in the treatment
of pulmonary and hepatic fibroses. Fibrosis is the abnormal formation of scar

tissues following a tissue lesion and leads to chronic and progressive impairment
of the affected organs, which may result in serious dysfunction of the affected
organ. Many causes of fibrosis may exist, but in the majority of cases the cause of
the affliction remains unknown and the lesions are difficult to detect. Aggregates
of activated fibroblasts and myofibroblasts develop, which constitute the start of
numerous fibrotic foci. When the lesions are formed, they are irreversible and
cannot be eliminated. Treatments are thus directed towards slowing down the
evolution of the complaint and of improving the symptoms. In this context,
irreversible MetAP2 inhibitors have shown on in vivo models a reduction of
pulmonary and hepatic fibrosis. However, substantial toxicity of these irreversible
inhibitors has been demonstrated (Kruger E.A., Exp. Opinion Invest. Drugs, 2000;
Satchi-Fainaro R. et al., Nature Medicine, 2004).
One subject of the present invention is compounds corresponding to formula (I)

in which:
R1 represents:
• -(C1-C4)alkyl
• -(C1-C4)haloalkyl
R2 represents:
• a group:


• a group:

• a group: -A -X
R3 represents:
• -H
• halogen
• -(C1-C6)alkyl
• a cyano group
• -CO2H
• -CONH2
A represents:
• an aryl or heteroaryl group
X is absent or represents:
• halogen
• a cyano group
• an oxo group
• -(CH2)nOH
• -(C1-C6) haloalkyl
• -(C1-C6)alkyl
• -(C1-C6)alkoxy
• -CHOH-aryl
• heterocycle
• heteroaryl
• -(C1-C6)alkyl-heterocycle
• -(C1-C6)alkyl-heteroaryl
• -(C1-C6)alkyl-CO0Ra
• -(C1-C6)alkyl-NRaRb
• -heteroaryl-(CH2)n-NRaRb

• -(CH2)n-NRa-C(0)-Rb
• -NRaRb
• -NRa-(CH2)n-0-Rb
• -NRa-heterocycle
• -NRa-aryl
• -NRa-C(0)-(CH2)n-NRaRb
• -NRaC(0)-(C1-C6)alkyl
• -NRa-C(0)-(C1-C6)alkyl-aryl
• -NRa-C(0)-(CH2)n-0-Rb
• -NRa-S02-(CH2)n-aryl
• -NRa-S02-(CH2)n-NRaRb
• -NRa-S02-Rb
• -NRa-S02-aryl-0-aryl
• -NRa-S02-aryl-(CH2)n-NRb-C(0)-Rb
• -COORa

• -CONRaRb
• -C(0)-NRa-(CH2)n-0-Rb
• -C(0)-NRa-aryl-C(0)-NRaRb
• -C(0)-NRa-(CH2)n-NRaRb
• -C(0)-NRa-(CH2)n-heteroaryl
• -0-(CH2)n-NRaRb
• -O-heterocycle
• -CO-heterocycle
• -CO-heteroaryl
• -S02NRaRb
• -S02-heterocycle
Ra and Rb represent, independently:
• -H
• -(C1-C6)alkyl
n represents 0, 1, 2 or 3.
The compounds of formula (I) may comprise one or more asymmetric carbon atoms.
They may thus exist in the form of enantiomers or diastereoisomers. These enantiomers

and diastereoisomers, and also mixtures thereof, including racemic mixtures, form part of
the invention.
The compounds of formula (I) may exist in the form of tautomers. These tautomeric forms
form part of the invention.
The compounds of formula (I) may exist in the form of bases or salified with acids or
bases, especially pharmaceutical^ acceptable acids or bases. Such addition salts form
part of the invention.
These salts are advantageously prepared with pharmaceutical^ acceptable acids, but the
salts of other acids that are useful, for example, for purifying or isolating the compounds
of formula (I) also form part of the invention.
The compounds of formula (I) may also exist in the form of hydrates, i.e. in the form of
associations or combinations with one or more water molecules. Such hydrates also form
part of the invention.
In the context of the present invention, and unless otherwise mentioned in the text, the
following definitions apply:
- a halogen atom: a fluorine, a chlorine, a bromine or an iodine;
- an alkyl group: a linear, branched or cyclic saturated aliphatic group. The alkyl
group may be substituted with one or more alkoxy groups. Examples that may be
mentioned include methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl,
cyclohexyl, etc. groups;

- an alkoxy group: a radical -O-alkyl in which the alkyl group is as defined
previously; an example that will be mentioned is methoxy;
- a haloalkyl group: an alkyl group as defined above substituted with 1 to 5
halogen atoms, as defined previously. Examples that will be mentioned are
trifluoromethyl, trifluoroethyl, etc. groups;
- a cyano group: a group CN;
- an oxo group: a radical containing a double-bonded oxygen atom in the form =0;
this group may substitute an aryl, heteroaryl or heterocyclic group
as in the following example:

- an aryl group: a cyclic aromatic group comprising between 5 and 10 carbon
atoms, this group possibly being fused with a heterocycle such as a morpholine
(compound 56). An example of an aryl group that may be mentioned is the phenyl group;
the aryl group may be substituted with one or more halogen atoms or (C1-C6)alkyl, (C1-
C6)alkoxy, NRaRb, OH, C(0)-(C1-C6)alkyl or oxo groups;
- a heteroaryl group: a cyclic aromatic group comprising between 5 and 10 carbon
atoms and comprising between 1 and 5 heteroatoms, such as nitrogen, oxygen or sulfur.
The heteroaryl group may comprise an /V-oxide group. Examples of heteroaryl groups
that may be mentioned include pyridine, 2-pyridyl, 4-pyridyl, 3-pyridyl, pyrazole,
thiophene, indole, pyrimidine, imidazole, furan, indazole, tetrazole, benzoxazine, oxazole,
quinoline, triazole and oxadiazole groups; the heteroaryl group may be substituted with
one or more halogen atoms or (C1-C6)alkyl, (C1-C6)alkoxy, NRaRb, OH, C(0)-(C1-
C6)alkyl or oxo groups;
- a heterocycle: an optionally bridged cyclic alkyl group comprising from 4 to 9
atoms forming this ring, 1 or 2 of which are heteroatoms, such as oxygen, nitrogen or
sulfur. Mention may be made especially of pyrrolidine, piperazine, piperidine, morpholine,
oxazepane, diazepane and azetidine groups; the heterocyclic group may be substituted
with one or more halogen atoms or (C1-C6)alkyl, (C1-C6)alkoxy, NRaRb, OH, C(0)-(C1-
C6)alkyl or oxo groups.
Among the compounds that are subjects of the invention, mention may be made of a first
group of compounds of formula (I) in which R3 represents H or a halogen atom, more
particularly chlorine, the definition of the other substituents remaining unchanged.
Another group of compounds that are subjects of the invention is formed by the
compounds of formula (I) in which R1 represents a (C1-C4)alkyl group, more particularly
an ethyl group, or a (C1-C4)haloalkyl group, more particularly a trifluoroethyl group, the
definition of the other substituents remaining unchanged.
Another group of compounds that are subjects of the invention is formed by the
compounds of formula (I) in which R2 represents a group: -A-X with A representing an
aryl or heteroaryl group and X being absent or representing a heterocycle, NRaRb, (C1-
C6)alkyl, a halogen, more particularly chlorine or fluorine, a cyano, NRa-S02-Rb or CO-
heterocyclic group; the definition of the other substituents remaining unchanged.
The combinations of the abovementioned groups of compounds of the invention also
form part of the invention as embodiments according to the invention.

Another group of compounds that are subjects of the invention is formed by the
compounds of formula (I) with the exception of the following compounds:
- compound 2: 7-(2-aminopyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 12: 7-[2-(morpholin-4-ylcarbonyl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 14: 7-(2-morpholin-4-ylphenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 16: 7-(2-morpholin-4-ylmethylphenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 19: 7-[4-(4-methylpiperazin-1-yl)phenyI]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4/-/-pyrazolo[4,3-c]quinolin-4-one;
- compound 23: 7-(4-diethylaminophenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 30: 7-[4-(piperazin-1-yl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 32: 7-(4-dimethylaminophenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 42: 7-(2-{5-[(propan-2-ylamino)methyl]furan-2-yl}phenyl)-5-(2,2,2-
trifluoroethyl)-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 66: 7-[6-(piperazin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 68: 7-[2-(4-methylpiperazin-1-yl)pyrid-4-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;

- compound 70: 7-[2-(piperazin-1-yl)pyrid-4-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 83: 7-[6-(morpholin-4-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 95: 7-(6-aminopyrid-3-yl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 113: isopropyl 2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-y[]benzoate;
- compound 114: cyclopropanecarboxylic acid {2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-
dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]phenyl}amide;
- compound 115: 7-[2-(1-methyl-1H-imidazole-2-carbonyl)phenyl]-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;

- compound 116: 7-(4-cyclopentylpyrimidin-5-yl)-5-(2,2,2-trifluoroethyl)-1,5-clihyclro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 117: 7-(4-cyclohexylpyrimidin-5-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 118: 7-(2-propylaminomethylphenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 119: 2-methoxy-W-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]phenyl}acetamide;
- compound 120: A/-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]phenyl}isobutyramide;
- compound 121: A/-{4-methyl-2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]phenyl}propionamide;
- compound 123: 7-[4-methyl-2-(piperidin-4-yloxy)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 124: 7-[2-(1,4-diazepan-1-ylmethyl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 125: ethyl 2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinoiin-7-yl]benzoate;

- compound 126: 7-(2-aminophenyl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 127: 7-(2-piperazin-1-ylphenyl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 172: 7-[2-(morpholin-4-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 174: 7-(2-cyclopropylaminopyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 178: methyl 2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]nicotinoate;
- compound 181: 7-[2-(4-fluorophenylamino)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 196: 8-chloro-7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 204: 2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]benzoic acid;
- compound 209: 7-{2-[(4-methyl-1,4-diazepan-1-yl)carbonyl]phenyl}-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 210: 7-{2-[(4-methylpiperazin-1-yl)carbonyl]phenyl}-5-(2,2,2-trifluoroethyl)-

1,5-dihydro-4H-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 212: A/-(3-dimethylaminopropyl)-2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-
dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]benzamide;
- compound 214: 2-[4-oxo-5-(2I2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]-/S/-[2-(pyrid-4-yl)ethyl]benzamide;
- compound 218: 2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1/-/-pyrazolo[4,3-
c]quinolin-7-yl]-A/-(pyrid-3-ylmethyl)benzamide;
- compound 219: /V-ethyl-2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1/-/-pyrazolo[4,3-
c]quinolin-7-yl]-/S/-(pyrid-4-ylmethyl)benzamide;
- compound 223: A/-{3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyrid-2-yl}acetamide;
- compound 224: 3-dimethylamino-A/-{2-[4-oxo-5-(2,2,2-trifluoroethyI)-4,5-dihydro-
2H,4H-pyrazolo[4,3-c]quinolin-7-yl]phenyl}propionamide;
- compound 225: 4-(dimethylamino)-A/-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]phenyl}butanamide;
- compound 230: 2-(3-chlorophenyl)-N-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-3-yl}acetamide;
- compound 231: 2-(2,4-dichlorophenyl)-N-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-
1H-pyrazolo[4,3-c]quinolin-7-yl]pyrid-3-yl}acetamide;
- compound 232: A/-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-2H-pyrazolo[4,3-
c]quinolin-7-yl]phenyl}methanesulfonamide;

- compound 233: 2-(dimethylamino)-/V-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]phenyl}ethanesulfonamide;
- compound 234: /V-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]phenyl}-1-phenylmethanesulfonamide;
- compound 235: 3-chloro-/S/-{2-[4-oxo-5-(2,2>2-trifluoroethyl)-4,5-dihydro-1 H-
pyrazolo[4,3-c]quinoIin-7-yl]phenyl}benzenesulfonamide;
- compound 236: /V-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyrid-3-yl}methanesulfonamide;
- compound 237: A/-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyrid-3-yl}-1-phenylmethanesulfonamide;
- compound 238: 3-chloro-A/-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-3-yl}benzenesulfonamide;
- compound 240: A/-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1 H-pyrazolo[4,3-
c]quinolin-7-yl]pyrid-3-yl}-2-phenoxybenzenesulfonamide.

Among the compounds of formula (I) that are subjects of the invention, mention may be
made especially of the following compounds:
- compound 1: 7-(pyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 2: 7-(2-aminopyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 3: 7-(2-fluorophenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 4: 5-ethyl-7-pyrid-2-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 5: 5-ethyl-7-(4-fluorophenyl)-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 6: 7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 7: 5-ethyl-7-pyrid-4-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 8: 7-(2-dimethylaminophenyl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 9: A/-(3-dimethylaminopropyl)-4-(5-ethyl-4-oxo-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl)benzamide;
- compound 10: 5-ethyl-7-(4-piperazin-1-ylphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 11: 5-ethyl-7-[4-(4-methylpiperazin-1-yl)phenyl]-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 12: 7-[2-(morpholin-4-ylcarbonyl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;

- compound 13: A/-(2-dimethylaminoethyl)-4-(5-ethyl-4-oxo-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl)benzamide;
- compound 14: 7-(2-morpholin-4-ylphenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 15: 7-[4-(1-dimethylaminoethyl)phenyl]-5-ethyl-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
i - compound 16: 7-(2-morpholin-4-ylmethylphenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4/-/-pyrazolo[4,3-c]quinolin-4-one;
- compound 17: 5-ethyl-7-(2-morpholin-4-ylmethylphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 18: 5-ethyl-7-[4-(piperazine-1-carbonyl)phenyl]-1,5-dihydro-4H-
i pyrazolo[4,3-c]quinolin-4-one;
- compound 19: 7-[4-(4-methylpiperazin-1-yl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4/-/-pyrazolo[4,3-c]quinolin-4-one;

- compound 20: 5-ethyl-7-(2-piperazin-1-ylpyrimidin-5-yl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 21: 5-ethyl-7-[4-(4-methylpiperazine-1-carbonyl)phenyl]-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 22: 5-ethyl-7-[4-(1-pyrrolidin-1-yl-ethyl)phenyl]-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 23: 7-(4-diethylaminophenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 24: 7-(4-amino-2-methyiphenyl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 25: 7-(4-morpholin-4-ylphenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 26: 5-ethyl-7-(4-morpholin-4-ylphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 27: 5-(5-ethyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl)-2-fluoro-
A/-methylbenzamide;
- compound 28: 5-ethyl-7-(2-fluoro-5-methoxyphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 29: 7-[3-chloro-4-(morpholine-4-carbonyl)phenyl]-5-ethyl-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 30: 7-[4-(piperazin-1-yl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 31: 5-ethyl-7-[2-(4-methylpiperazin-1-yl)pyrimidin-5-yI]-1,5-dihydro-4H-
pyrazolo[4,3-c]q uinolin-4-one;
- compound 32: 7-(4-dimethylaminophenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 33: 2-chloro-4-(5-ethyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-
yl)benzamide;
- compound 34: 5-ethyl-7-(1H-indazol-5-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 35: A/-ethyl-3-(5-ethyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-
yl)benzamide;
- compound 36: 5-(5-ethyl-4-oxo-4,5-dihydro-1/-/-pyrazolo[4,3-c]quinolin-7-yl)-2-fluoro-
benzamide;
- compound 37: A/-(2-dimethylaminoethyl)-3-(5-ethyl-4-oxo-4,5-dihydro-1/-/-
pyrazolo[4,3-c]quinolin-7-yl)benzamide;
- compound 38: A/-[4-(5-ethyl-4-oxo-4,5-dihydro-1/-/-pyrazolo[4,3-c]quinolin-7-

yl)benzyl]acetamide;
- compound 39: 3-(5-ethyl-4-oxo-4,5-dihydro-1/-/-pyrazolo[4,3-c]quinolin-7-yl)-A/-(2-
methoxyethyl)benzamide;
- compound 40: 7-(3-hydroxyphenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 41: 7-(2-chloro-3-fluoropyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 42: 7-(2-{5-[(propan-2-ylamino)methyl]furan-2-yl}phenyl)-5-(2,2,2-
trifluoroethyl)-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 43: A/-[2-(5-ethyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-
yl)phenyl]methanesulfonamide;
- compound 44: 7-(2-aminophenyl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 45: 5-ethyl-7-(3-morpholin-4-ylphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 46: A/-[2-(5-ethyl-4-oxo-4,5-dihydro-1/-/-pyrazolo[4,3-c]quinolin-7-
yl)phenyl]acetamide;
- compound 47: 5-ethy!-7-(2-hydroxyphenyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinoiin-4-
one;
- compound 48: 5-ethyl-7-[4-(morpholine-4-sulfonyl)phenyl]-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 49: 7-(2-hydroxymethyl-4-methoxyphenyl)-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 50: 5-ethyl-7-(3-pyrazol-1-ylphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 51: 5-ethyl-7-(1 H-indol-5-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 52: 5-(5-ethyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl)-
thiophene-2-carbonitrile;
- compound 53: 7-(3-chloro-2-hydroxyphenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 54: 5-ethyl-7-(2-hydroxy-3-methoxyphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 55: methyl 3-amino-4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]benzoate;
- compound 56: 5-ethyl-7-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-7-yl)-1,5-dihydro-
4/-/-pyrazolo[4,3-c]quinolin-4-one;
- compound 57: 7-(2,5-dichloropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1>5-dihydro-4H-

pyrazolo[4,3-c]quinolin-4-one;
- compound 58: 7-(2-chloro-5-methoxyphenyl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 59: A/-(3-dimethylaminopropyl)-3-(5-ethyl-4-oxo-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl)benzamide;
- compound 60: 5-ethyl-7-(4-fluoro-2-hydroxyphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 61: 5-ethyl-7-(2-fluoro-4-methoxyphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 62: 7-(4-aminomethylphenyl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 63: 5-ethyl-7-(2-fluoro-3-methoxyphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 64: 7-(2-dimethylaminomethylphenyl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 65: 4-(5-ethyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl)benzoic
acid;
- compound 66: 7-[6-(piperazin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5Hdihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 67: 5-ethyl-7-[6-(piperazin-1-yl)pyrid-3-yl]-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;

- compound 68: 7-[2-(4-methylpiperazin-1-yl)pyrid-4-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 69: 5-ethyl-7-[2-(4-methylpiperazin-1-yl)pyrid-4-yl]-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 70: 7-[2-(piperazin-1-yl)pyrid-4-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 71: 5-ethyl-7-(2-piperazin-1-ylpyrid-4-yl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 72: 7-(2-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 73: 5-ethyl-7-(2-methylpyrid-3-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 74: 7-(2-chloro-6-methylpyrid-3-yl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 75: 7-(2-chloro-6-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 76: 7-(2-chloropyrid-4-yl)-5-(2)2,2-trifluoroethy[)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 77: 7-(2-fluoropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 78: 5-ethyl-7-(2-fluoropyrid-3-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 79: 7-(6-chloro-2-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 80: 7-(2-methoxypyrid-3-yl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 81: 5-ethyl-7-(2-methoxypyrid-3-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-
4-one;
- compound 82: 7-(6-chloro-4-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 83: 7-[6-(morpholin-4-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 84: 7-[6-(3-dimethylaminopropoxy)pyrid-3-yl]-5-ethyl-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 85: 5-ethyl-7-quinolin-8-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 86: 7-(6-chloropyrid-2-yl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-cJquinolin-4-one;

- compound 87: 5-ethyl-7-quinolin-6-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinoIin-4-one;
- compound 88: 7-(6-chloropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 89: 7-(6-chloro-5-methylpyrid-3-y[)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 90: 5-ethyl-7-(3-fluoropyrid-4-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 91: 7-(3-chloropyrid-4-yl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 92: 5-ethyl-7-(6-fluoro-5-methylpyrid-3-yl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 93: 7-(2-ethoxypyrid-3-yl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 94: 5-ethyI-7-(5-methoxypyrid-3-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-
4-one;
- compound 95: 7-(6-aminopyrid-3-yl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-

one;
- compound 96: 5-ethyl-7-pyrid-3-yl-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 97: 7-(2-chloro-6-isopropylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 98: 7-(5-chloro-2-methoxypyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 99: 7-(pyrid-3-yloxy)-5-(2,2I2-trifluoroethyl)-2,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 100: 5-ethyl-7-(pyrid-3-yloxy)-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 101: 7-(pyrid-3-ylamino)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-cJquinolin-4-one;
- compound 102: 5-(2,2-difluoroethyl)-7-pyrid-4-yl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 103: 5-cyclopropylmethyl-7-pyrid-4-yl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 104: 5-propyl-7-pyrid-4-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 105: 5-(2,2-difluorocyclopropylmethyl)-7-pyrid-4-yl-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 106: 5-(2-fluoroethyl)-7-pyrid-4-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-
4-one;
- compound 107: 5-isopropyl-7-pyrid-4-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 108: 5-cyclopropyl-7-pyrid-4-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;

- compound 109: 8-fluoro-7-pyrid-2-yl-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 110: 7-(2-chloropyrid-3-yl)-8-methyl-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 111: 7-(2-chloropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 112: 7-[2-(dimethylamino)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 113: isopropyl 2-[4-oxo-5-(2,2l2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]benzoate;
- compound 114: cyclopropanecarboxylic acid {2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-
dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]phenyl}amide;
- compound 115: 7-[2-(1-methyl-1H-imidazole-2-carbonyl)phenyl]-5-(2t2,2-

trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 116: 7-(4-cyclopentylpyrimidin-5-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 117: 7-(4-cyclohexylpyrimidin-5-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinoiin-4-one;
- compound 118: 7-(2-propylaminomethylphenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 119: 2-methoxy-/\/-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]phenyl}acetamide;
- compound 120: A/-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]phenyl}isobutyramide;
- compound 121: /V-{4-methyl-2-[4-oxo-5-(2,2,2-trifluoroethy!)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]phenyl}propionamide;
- compound 122: A/-isopropyl-2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]benzamide;
- compound 123: 7-[4-methyl-2-(piperidin-4-yloxy)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 124: 7-[2-(1,4-diazepan-1-ylmethyl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 125: ethyl 2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]benzoate;
- compound 126: 7-(2-aminophenyl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 127: 7-(2-piperazin-1-ylphenyl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 128: 7-(6-methoxypyrid-3-yl)-5-(2,2I2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 129: 7-(5-chloro-2-fluoropyrid-3-yl)-5-(2l2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 130: A/-{5-methyl-3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-yl}acetamide;
- compound 131: 7-[2-(2-hydroxy-ethyl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 132: 7-(2-amino-5-fluoropyrid-3-yi)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 133: 7-[2-(pyrrolidine-1-sulfonyl)phenyl]-5-(2,2,2-trifIuoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;

- compound 134: A/-isopropyl-2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]benzenesulfonamide;
- compound 135: 7-(2-fluoro-5-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 136: W,/V-diethyl-2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]benzenesulfonamide;
- compound 137: 7-(6-amino-4-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 138: 7-(6-methoxy-2-methylpyrid-3-y[)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 139: 7-(5-methyl-6-[1,2,4]triazol-4-ylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 140: 7-(4-methyl-6-[1,2,4]triazol-4-ylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 141: 7-[6-(morpholine-4-carbonyl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 142: 7-(6-amino-2-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 143: 7-(4-ethylpyrimidin-5-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 144: methyl {2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]phenyl}acetate;
- compound 145: 7-(4-methoxypyrid-2-yl)-5-(2,2l2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 146: 7-(4-propylpyrimidin-5-yl)-5-(2,2,2-trifiuoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 147: /V-{6-methyl-5-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-yl}propionamide;
- compound 148: 7-(2-oxazol-5-ylphenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 149: 7-(4-dimethylamino-2-methoxypyrimidin-5-yl)-5-(2,2,2-trifluoroethyl)-
1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 150: 7-[2-(5-ethyl-[1,2,4]oxadiazol-3-yl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 151: A/-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]benzyl}acetamide;
- compound 152: 7-[5-(hydroxyphenylmethyl)pyrid-2-yl]-5-(2,2,2-trifluoroethyl)-1,5-

dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 153: 6-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyridine-2-carbonitrile;
- compound 154: 7-(6-hydroxymethylpyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 155: 7-[3-(2-dimethylaminoethoxy)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 156: methyl 2-[4-oxo-5-(2,2l2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]benzoate;
- compound 157: 7-(5-hydroxymethylpyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 158: 7-(2-methoxypyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 159: 7-(2-[1,2,4]triazol-1-ylmethylphenyl)-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 160: 7-(4-phenylpyrimidin-5-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 161: 7-(6-methoxy-4-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 162: 7-(4-isopropylpyrimidin-5-yl)-5-(2,2,2-trifiuoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 163: 7-(6-fluoropyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 164: methyl 6-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyridine-2-carboxylate;
- compound 165: 7-(5-fluoropyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 166: 7-[2-(4-methylpiperazin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 167: 7-(3-aminopyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 168: 7-(2,6-dimethylpyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 169: 7-(3-chloropyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 170: methyl 3-[4-oxo-5-(2,2)2-trifluoroethyl)-4,5-dihydro-1/-/-pyrazolo[4I3-
c]quinolin-7-yl]pyridine-2-carboxylate;

compound 171: 7-(6-methylpyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
compound 172: 7-[2-(morpholin-4-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
compound 173: 5-(2,2,2-trifluoroethyl)-7-(2-trifluoromethylpyrid-3-yi)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
compound 174: 7-(2-cyclopropylaminopyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
compound 175: 5-(2,2,2-trifluoroethyl)-7-(3-trifluoromethylpyrid-2-yl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
■ compound 176: 3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyridine-2-carbonitrile;
■ compound 177: 2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1/-/-pyrazolo[4,3-
c]quinolin-7-yl]pyridine-3-carbonitrile;
• compound 178: methyl 2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]nicotinoate;
- compound 179: 7-(2-propoxypyrid-3-yl)-5-(2,2,2-trifluoroethy|)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 180: 7-(3-hydroxypyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 181: 7-[2-(4-fluorophenylamino)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 182: 7-(2-methylaminophenyl)-5-(2,2,2-trifluoroethyi)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 183: 7-(2-ethoxypyrid-3-yl)-5-(2,2,2-trifluoroethy!)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 184: 7-(2-isopropoxypyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 185: 7-(5-chloro-2-methoxypyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 186: 7-(2-methylpyrid-4-yl)-5-(2,2,2-trifiuoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 187: 7-(4-methylpyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 188: 7-(6-morpholin-4-ylpyrid-2-yl)-5-(2,2,2-trifluoroethy|)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 189: 7-(4-methylaminophenyl)-5-(2,2,2-trifluoroethyi)-1,5-dihydro-4H-

pyrazolo[4,3-c]quinolin-4-one;
- compound 190: 5-(2,2,2-trifluoroethyl)-7-(6-trifluoromethylpyrid-3-yl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 191: y-Ce-methoxypyrid^-yO-S-CZ^^-trifluoroethyO-I.S-dihydro^H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 192: 7-[4-(2H-tetrazol-5-yl)phenyl]-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 193: 7-(3,5-dichloropyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 194: 8-chloro-7-(pyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 195: 8-bromo-7-pyrid-2-yl-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 196: 8-chloro-7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 197: 8-bromo-7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 198: 8-chloro-5-ethyl-7-pyrid-4-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-
4-one;
- compound 199: 8-chloro-7-(2-chloropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 200: 8-methyl-7-pyrid-2-yl-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 201: 4-oxo-7-pyrid-4-yl-5-(2,2,2-trifluoroethyl)-4,5-dihydro-2H,4H-
pyrazolo[4,3-c]quinoline-8-carbonitrile;
- compound 202: 4-oxo-7-pyrid-4-yl-5-(2,2,2-trifluoroethyl)-4,5-dihydro-2H,4H-
pyrazoio[4,3-c]quinoline-8-carboxylicacid;
- compound 203: 3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyridine-2-carboxylicacid;

- compound 204: 2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]benzoic acid;
- compound 205: 4-oxo-7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-4,5-dihydro-2H-
pyrazolo[4,3-c]quinoline-8-carboxamide;
- compound 206: 7-[2-(morpholin-4-ylcarbonyl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 207: A/-[2-(dimethylamino)ethyl]-A/-methyl-2-[4-oxo-5-(2,2,2-trifluoroethyl)-
4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]benzamide;

- compound 208: A/-(2-dimethylaminoethyl)-A/-ethyl-2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-
dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]benzamide;
- compound 209: 7-{2-[(4-methyl-1 Adiazepan-l-yOcarbonylJphenylJ-S-^^-
trifluoroethyO-I^Kiihydro^H-pyrazolo^.S-cJquinolin^-one;
- compound 210: 7-{2-[(4-methytpiperazin-1-yl)carbonyl]phenyl}-5-(2I2)2-trifluoroethyl)-
1,5-dihydro-4H-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 211: /V-(3-carbamoylphenyl)-2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-
1H-pyrazolo[4,3-c]quinolin-7-yl]benzamide;
- compound 212: A/-(3-dimethylaminopropyl)-2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-
dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]benzamide;
- compound 213: A/,A/-dimethyl-3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyridine-2-carboxamide;
- compound 214: 2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]-A/-[2-(pyrid-4-yl)ethyl]benzamide;
- compound 215: A/-[2-(dimethylamino)ethyl]-N-methyl-3-[4-oxo-5-(2,2,2-trifluoroethyl)-
4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]pyridine-2-carboxamide;
- compound 216: 7-[2-(1,4-oxazepan-4-ylcarbonyl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 217: /V-methyl-3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yllpyridine-2-carboxamide;
- compound 218: 2-[4-oxo-5-(2,2!2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yI]-A/-(pyrid-3-ylmethyl)benzamide;

- compound 219: /Sf-ethyl-2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]-A/-(pyrid-4-ylmethyl)benzamide;
- compound 220: 3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyridine-2-carboxamide;
- compound 221: N-[2-(dimethylamino)ethyl]-/S/-ethyl-3-[4-oxo-5-(2,2,2-trifluoroethyl)-
4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]pyridine-2-carboxamide;
- compound 222: 7-[2-((2S)6R)-2,6-dimethylmorpholine-4-carbonyl)pyrid-3-yl]-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 223: /V-{3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1/-/-pyrazolo[4,3-
c]quinolin-7-yl]pyrid-2-yl}acetamide;
- compound 224: 3-dimethylamino-A/-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-
2H,4H-pyrazolo[4,3-c]quinolin-7-yl]phenyl}propionamide;
- compound 225: 4-(dimethylamino)-/V-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]phenyl}butanamide;
- compound 226: A/-{4-[4-oxo-5-(2,2l2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-

c]quinolin-7-yl]pyrid-3-yl}acetamide;
- compound 227: A/-{3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyrid-2-yl}cyclopropanecarboxamide;
- compound 228: 2-methoxy-A/-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1 H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-3-yl}-2-phenylacetamide;
- compound 229: A/^-^-oxo-S^^^-trifluoroethyO^.S-dihydro-IH-pyrazolo^.S-
c]quinolin-7-yl]pyrid-3-yl}-2-phenylpropionamide;
- compound 230: 2-(3-chlorophenyl)-N-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-3-yl}acetamide;
- compound 231: 2-(2,4-dichlorophenyl)-N-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-
1H-pyrazolo[4,3-c]quinolin-7-yl]pyrid-3-yl}acetamide;
- compound 232: A/-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-2H-pyrazolo[4,3-
c]quinolin-7-yl]phenyl}methanesulfonamide;
- compound 233: 2-(dimethylamino)-A/-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pheny!}ethanesulfonamide;
- compound 234: A/-{2-[4-oxo-5-(2,2T2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]phenyl}-1-phenylmethanesulfonamide;
- compound 235: 3-chloro-/\/-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]phenyl}benzenesulfonamide;
- compound 236: A/-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyrid-3-yl}methanesulfonamide;

- compound 237: A/-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyrid-3-yl}-1-phenylmethanesulfonamide;
- compound 238: 3-chloro-A/-{4-[4-oxo-5-(2,2,2-trifiuoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-3-yl}benzenesulfonamide;
- compound 239: A/-(4-methoxy-3-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-3-ylsulfamoyl}benzyl)acetamide;
- compound 240: A/-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyrid-3-yl}-2-phenoxybenzenesulfonamide;
- compound 241: A/-methyl-/\/-{3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-yl}acetamide;
- compound 242: /\/-methyl-/\/-{3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-yl}cyclopropanecarboxamide;
- compound 243: 7-[2-(methylamino)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 244: 7-[2-(1,4-diazepan-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;

- compound 245: 7-(3,4,5!6-tetrahydro-2H-[1,2']bipyridinyl-3'-yl)-5-(2,2,2-trifluoroethyl)-
2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 246: 7-[2-(3-hydroxypyrrolidin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 247: 7-[2-(3,4-dihydroxypyrrolidin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-
2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 248: 7-[2-(dimethylamino)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 249: 7-{2-[ethyl(methyl)amino]pyrid-3-yl}-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 250: 7-{2-[(2-hydroxyethyl)(methyl)amino]pyrid-3-yl}-5-(2,2,2-trifluoroethyl)-
1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 251: 7-[2-(pyrrolidin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 252: 7-[2-(1,4-oxazepan-4-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 253: 7-[2-(3-oxopiperazin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 254: 7-[2-(azetidin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 255: 7-{2-[(2-methoxyethyl)methylamino]pyrid-3-yl}-5-(2,2,2-trifluoroethyl)-
2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;

- compound 256: 7-[2-(4-acetylpiperazin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-2,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 257: 7-[2-(diethylamino)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 258: 7-[2-(cyclobutylamino)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4/-/-pyrazolo[4,3-c]quinolin-4-one;
- compound 259: 7-[2-(2,6-dimethylmorpholin-4-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-2,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 260: 7-[2-(4-cyclopropylpiperazin-1-yl)pyrid-4-yl]-5-(2,2,2-trifluoroethyl)-
2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 261: 7-(2-cyclohexylaminopyrid-3-yl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 262: 7-[2-(isopropylmethylamino)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-2,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 263: 7-(2-cyclopentylaminopyrid-3-yl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-

4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 264: 7-(6-pyrrolidin-1-ylpyrid-2-yl)-5-(2,2,2-trifiuoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 265: 7-[6-(2,6-dimethylmorpholin-4-yl)pyrid-2-yl]-5-(2,2,2-trifluoroethyl)-2,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 266: 7-{2-[cyclohexyl(methyl)amino]pyrid-3-yl}-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 267: 7-[2-(4-cyclopropylpiperazin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-
2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 268: 7-[3-(4-cyclopropylpiperazin-1-yl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 269: 7-[2-(4-acetyl-1,4-diazepan-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 270: 7-[2-(4-methyl-1,4-diazepan-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-
1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 271: 7-[2-(4-cyclopropyl-[1,4]diazepan-1-yl)pyrid-3-yl]-5-(2,2,2-
trifluoroethyl)-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 272: 7-[2-(3-fluoropyrrolidin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-2,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 273: 7-[2-(4-fluoropiperidin-1-yl)pyrid-3-yi]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;

- compound 274: 7-(2-hydroxypyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 275: 7-(1-oxypyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 276: 7-(1-oxypyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
in the form of the base or of an acid-addition salt, and also in hydrate form.
Among the compounds of formula (I) that are subjects of the invention, mention may be
made especially of the following compounds:
- compound 1: 7-(pyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 3: 7-(2-fluorophenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 4: 5-ethyl-7-pyrid-2-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one

- compound 5: 5-ethyl-7-(4-fluorophenyl)-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 6: 7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 7: 5-ethyl-7-pyrid-4-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 8: 7-(2-dimethylaminophenyl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 9: N-(3-dimethylaminopropyl)-4-(5-ethyl-4-oxo-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl)benzamide;
- compound 10: 5-ethyl-7-(4-piperazin-1-ylphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 11: 5-ethyl-7-[4-(4-methylpiperazin-1-yl)phenyl]-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 13: A/-(2-dimethylaminoethyl)-4-(5-ethyl-4-oxo-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl)benzamide;
- compound 15: 7-[4-(1-dimethylaminoethyl)phenyl]-5-ethyl-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 17: 5-ethyl-7-(2-morpholin-4-ylmethylphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 18: 5-ethyl-7-[4-(piperazine-1-carbonyl)phenyl]-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 20: 5-ethyl-7-(2-piperazin-1-ylpyrimidin-5-yl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;

- compound 21: 5-ethyl-7-[4-(4-methylpiperazine-1-carbonyl)phenyl]-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 22: 5-ethyl-7-[4-(1-pyrrolidin-1-yl-ethyl)phenyl]-1,5-dihydro-4H-
pyrazolo[4,3-c]quino!in-4-one;
- compound 24: 7-(4-amino-2-methylphenyl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 25: 7-(4-morpholin-4-ylphenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 26: 5-ethyl-7-(4-morpholin-4-ylphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 27: 5-(5-ethyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl)-2-fluoro-
A/-methylbenzamide;
- compound 28: 5-ethyl-7-(2-fluoro-5-methoxyphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 29: 7-[3-chloro-4-(morpholine-4-carbonyl)phenyl]-5-ethyl-1,5-dihydro-4H-

pyrazolo[4,3-c]quinolin-4-one;
- compound 31: 5-ethyl-7-[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 33: 2-chloro-4-(5-ethyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-
yl)benzamide;
- compound 34: 5-ethyl-7-(1H-indazol-5-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 35: A/-ethyl-3-(5-ethyl-4-oxo-4,5-dihydro-1/-/-pyrazolo[4,3-c]quinolin-7-
yl)benzamide;
- compound 36: 5-(5-ethyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl)-2-fluoro-
benzamide;
- compound 37: W-(2-dimethylaminoethyl)-3-(5-ethyl-4-oxo-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl)benzamide;
- compound 38: A/-[4-(5-ethyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-
yl)benzyl]acetamide;
- compound 39: 3-(5-ethyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl)-A/-(2-
methoxyethyl)benzamide;
- compound 40: 7-(3-hydroxyphenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 41: 7-(2-chloro-3-fluoropyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 43: N-[2-(5-ethyl-4-oxo-4,5-dihydro-1/-/-pyrazolo[4,3-c]quinoiin-7-
yl)phenyl]methanesulfonamide;
- compound 44: 7-(2-aminophenyl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;

- compound 45: 5-ethyl-7-(3-morpholin-4-ylphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 46: A/-[2-(5-ethyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-
yl)phenyl]acetamide;
- compound 47: 5-ethyl-7-(2-hydroxyphenyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 48: 5-ethyl-7-[4-(morpholine-4-sulfonyl)phenyl]-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 49: 7-(2-hydroxymethyl-4-methoxyphenyl)-5-(2,2,2-trifIuoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 50: 5-ethyl-7-(3-pyrazol-1-ylphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;

- compound 51: 5-ethyl-7-(1 H-indol-5-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 52: 5-(5-ethyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yI)-
thiophene-2-carbonitrile;
- compound 53: 7-(3-chloro-2-hydroxyphenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 54: 5-ethyl-7-(2-hydroxy-3-methoxyphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 55: methyl 3-amino-4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]benzoate;
- compound 56: 5-ethyl-7-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-7-yl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 57: 7-(2,5-dichloropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 58: 7-(2-chloro-5-methoxyphenyl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 59: /V-(3-dimethylaminopropyl)-3-(5-ethyl-4-oxo-4,5-dihydro-1/-/-
pyrazolo[4,3-c]quinolin-7-yl)benzamide;
- compound 60: 5-ethyl-7-(4-fluoro-2-hydroxyphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;

- compound 61: 5-ethyl-7-(2-fluoro-4-methoxyphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 62: 7-(4-aminomethylphenyl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 63: 5-ethyl-7-(2-fluoro-3-methoxyphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 64: 7-(2-dimethylaminomethylphenyl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 65: 4-(5-ethyl-4-oxo-4,5-dihydro-1/-/-pyrazolo[4,3-c]quinolin-7-yl)benzoic
acid;
- compound 67: 5-ethyl-7-[6-(piperazin-1-yl)pyrid-3-yl]-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-ong;
- compound 69: 5-ethyl-7-[2-(4-methylpiperazin-1-yl)pyrid-4-yl]-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 71: 5-ethyl-7-(2-piperazin-1-ylpyrid-4-yl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 72: 7-(2-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 73: 5-ethyl-7-(2-methylpyrid-3-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 74: 7-(2-chloro-6-methylpyrid-3-yl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 75: 7-(2-chloro-6-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 76: 7-(2-chloropyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 77: 7-(2-fluoropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 78: 5-ethyl-7-(2-fluoropyrid-3-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 79: 7-(6-chloro-2-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 80: 7-(2-methoxypyrid-3-yl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 81: 5-ethyl-7-(2-methoxypyrid-3-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-
4-one;
- compound 82: 7-(6-chloro-4-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 84: 7-[6-(3-dimethylaminopropoxy)pyrid-3-yl]-5-ethyl-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 85: 5-ethyl-7-quinolin-8-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 86: 7-(6-chloropyrid-2-yl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 87: 5-ethyl-7-quinolin-6-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 88: 7-(6-chloropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 89: 7-(6-chloro-5-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
compound 90: 5-ethyl-7-(3-fluoropyrid-4-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 91: 7-(3-chloropyrid-4-yl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 92: 5-ethyl-7-(6-fluoro-5-methylpyrid-3-yl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 93: 7-(2-ethoxypyrid-3-yl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-

one;
- compound 94: 5-ethyl-7-(5-methoxypyrid-3-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-
4-one;
- compound 96: 5-ethyl-7-pyrid-3-yl-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 97: 7-(2-chloro-6-isopropylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 98: 7-(5-chloro-2-methoxypyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 99: 7-(pyrid-3-yloxy)-5-(2,2>2-trifluoroethyl)-2,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 100: 5-ethyl-7-(pyrid-3-yloxy)-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 101: 7-(pyrid-3-ylamino)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 102: 5-(2,2-difluoroethyl)-7-pyrid-4-yl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 103: 5-cyclopropylmethyl-7-pyrid-4-yl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 104: 5-propyl-7-pyrid-4-yl-1,5-dihydro-4H-pyrazoio[4,3-c]quinolin-4-one;
- compound 105: 5-(2,2-difluorocyclopropylmethyl)-7-pyrid-4-yl-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 106: 5-(2-fluoroethyl)-7-pyrid-4-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-
4-one;

- compound 107: 5-isopropyl-7-pyrid-4-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 108: 5-cyclopropyl-7-pyrid-4-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quino!in-4-
one;
- compound 109: 8-fluoro-7-pyrid-2-yl-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 110: 7-(2-chloropyrid-3-yl)-8-methyl-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 111: 7-(2-chloropyrid-3-yl)-5-(2>2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 112: 7-[2-(dimethylamino)phenyl]-5-(2,2,2-trifluoroethyl)-1>5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 122: /V-isopropyl-2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]benzamide;
- compound 128: 7-(6-methoxypyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1>5-dihydro-4H-

pyrazolo[4,3-c]quinolin-4-one;
- compound 129: 7-(5-chloro-2-fluoropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihyclro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 130: W-{5-methyl-3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-yl}acetamide;
- compound 131: 7-[2-(2-hydroxy-ethyl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 132: 7-(2-amino-5-fluoropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 133: 7-[2-(pyrrolidine-1-sulfonyl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 134: A/-isopropyl-2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]benzenesulfonamide;
- compound 135: 7-(2-fluoro-5-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 136: A/,A/-diethyl-2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]benzenesulfonamide;
- compound 137: 7-(6-amino-4-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 138: 7-(6-methoxy-2-methylpyrid-3-yl)-5-(2,2,2-trifluoroethy[)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;

- compound 139: 7-(5-methyl-6-[1,2,4]triazol-4-ylpyrid-3-yl)-5-(2,2,2-trifluoroethy[)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 140: 7-(4-methy!-6-[1,2,4]triazol-4-ylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 141: 7-[6-(morphorme-4-carbonyl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 142: 7-(6-amino-2-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 143: 7-(4-ethylpyrimidin-5-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 144: methyl {2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]phenyl}acetate;
- compound 145: 7-(4-methoxypyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 146: 7-(4-propylpyrimidin-5-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 147: N-{6-methyl-5-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-yl}propionamide;
- compound 148: 7-(2-oxazol-5-ylphenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 149: 7-(4-dimethylamino-2-methoxypyrimidin-5-yl)-5-(2,2,2-trifluoroethyl)-
1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 150: 7-[2-(5-ethyl-[1,2,4]oxadiazol-3-yl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 151: W-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]benzyI}acetamide;
- compound 152: 7-[5-(hydroxyphenylmethyl)pyrid-2-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 153: 6-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyridine-2-carbonitrile;
- compound 154: 7-(6-hydroxymethylpyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 155: 7-[3-(2-dimethylaminoethoxy)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 156: methyl 2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]benzoate;

- compound 157: 7-(5-hydroxymethylpyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 158: 7-(2-methoxypyrid-4-y!)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 159: 7-(2-[1,2,4]triazol-1-ylmethylphenyl)-5-(2,2,2-trifluoroethyl)-1I5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 160: 7-(4-phenylpyrimidin-5-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 161: 7-(6-methoxy-4-methylpyhd-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 162: 7-(4-isopropylpyrimidin-5-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 163: 7-(6-fluoropyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 164: methyl 6-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyridine-2-carboxylate;
- compound 165: 7-(5-fluoropyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-

pyrazolo[4,3-c]quinoIin-4-one;
- compound 166: 7-[2-(4-methylpiperazin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1I5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 167: 7-(3-aminopyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazoio[4,3-c]quinolin-4-one;
- compound 168: 7-(2,6-dimethylpyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 169: 7-(3-chloropyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1I5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 170: methyl 3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyridine-2-carboxylate;
- compound 171: 7-(6-methylpyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 173: 5-(2,2,2-trifluoroethyl)-7-(2-trifluoromethylpyrid-3-yl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 175: 5-(2,2,2-trifluoroethyl)-7-(3-trifluoromethylpyrid-2-yl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinoIin-4-one;
- compound 176: 3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyridine-2-carbonitrile;
- compound 177: 2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1/-/-pyrazolo[4,3-
c]quinolin-7-yl]pyridine-3-carbonitrile;
- compound 179: 7-(2-propoxypyrid-3-yl)-5-(2,2>2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]q uinolin-4-one;
- compound 180: 7-(3-hydroxypyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 182: 7-(2-methylaminophenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 183: 7-(2-ethoxypyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 184: 7-(2-isopropoxypyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 185: 7-(5-chloro-2-methoxypyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 186: 7-(2-methylpyrid-4-yl)-5-(2,2,2-trifIuoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 187: 7-(4-methylpyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 188: 7-(6-morpholin-4-ylpyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 189: 7-(4-methylaminophenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 190: 5-(2,2,2-trifluoroethy[)-7-(6-trifluoromethylpyrid-3-yl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 191: 7-(6-methoxypyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 192: 7-[4-(2H-tetrazol-5-yl)phenyl]-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 193: 7-(3,5-dichloropyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 194: 8-chloro-7-(pyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 195: 8-bromo-7-pyrid-2-yl-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 197: 8-bromo-7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 198: 8-chloro-5-ethyl-7-pyrid-4-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-
4-one;
- compound 199: 8-chloro-7-(2-chloropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 200: 8-methyl-7-pyrid-2-yl-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 201: 4-oxo-7-pyrid-4-yI-5-(2,2,2-trifluoroethyl)-4,5-dihydro-2H,4H-
pyrazolo[4,3-c]quinoline-8-carbonitrile;

- compound 202: 4-oxo-7-pyrid-4-yl-5-(2,2,2-trifluoroethyl)-4,5-dihydro-2H,4H-
pyrazolo[4,3-c]quinoline-8-carboxylic acid;
- compound 203: 3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1 H-pyrazolo[4,3-
c]quinolin-7-yl]pyridine-2-carboxyIicacid;
- compound 204: 2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]benzoic acid;
- compound 205: 4-oxo-7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-4,5-dihyciro-2/-/-
pyrazolo[4,3-c]quinoline-8-carboxamide;
- compound 206: 7-[2-(morpholin-4-ylcarbonyl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 207: A/-[2-(dimethylamino)ethyl]-/V-methyl-2-[4-oxo-5-(2,2,2-trifluoroethyl)-

4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]benzamide;
- compound 208: A/-(2-dimethylaminoethyl)-A/-ethyl-2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-
dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]benzamide;
- compound 211: A/-(3-carbamoylphenyl)-2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-
1H-pyrazolo[4,3-c]quinolin-7-yl]benzamide;
- compound 213: A/,A/-dimethyl-3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7ryl]pyridine-2-carboxamide;
- compound 215: A/-[2-(dimethylamino)ethyl]-A/-methyl-3-[4-oxo-5-(2,2,2-trifluoroethyl)-
4,5-dihydro-1/-/-pyrazolo[4,3-c]quinolin-7-yl]pyridine-2-carboxamide;
- compound 216: 7-[2-(1,4-oxazepan-4-ylcarbonyl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 217: A/-methyl-3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyridine-2-carboxamide;
- compound 220: 3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyridine-2-carboxamide;
- compound 221: A/-[2-(dimethylamino)ethyl]-A/-ethyl-3-[4-oxo-5-(2,2,2-trifluoroethyl)-
4,5-dihydro-1/-/-pyrazolo[4,3-c]quinolin-7-yl]pyridine-2-carboxamide;
- compound 222: 7-[2-((2S,6f?)-2,6-dimethylmorpholine-4-carbonyl)pyrid-3-yl]-5-(2,2>2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 226: A/-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyrid-3-yl}acetamide;

- compound 227: A/-{3-[4-oxo-5-(2,2,2-trifluoroethyl)-4I5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyrid-2-yl}cyclopropanecarboxamide;
- compound 228: 2-methoxy-W-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1 H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-3-yl}-2-phenylacetamide;
- compound 229: A/-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1 H-pyrazolo[4,3-
c]quinolin-7-yl]pyrid-3-yl}-2-phenylpropionamide;
- compound 238: 3-chloro-/V-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinoIin-7-yl]pyrid-3-yl}benzenesulfonamide;
- compound 239: A/-(4-methoxy-3-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1 H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-3-ylsulfamoyl}benzyl)acetamide;
- compound 241: /V-methyl-A/-{3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-yl}acetamide;
- compound 242: A/-methyl-A/-{3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-yl}cyclopropanecarboxamide;
- compound 243: 7-[2-(methylamino)pyrid-3-yl]-5-(2,2I2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

compound 244: 7-[2-(1,4-diazepan-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
compound 245: 7-(3,4,5,6-tetrahydro-2H-[112,]bipyridinyl-3'-y[)-5-(2,2,2-trifluoroethyl)-
2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
compound 246: 7-[2-(3-hydroxypyrrolidin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
■ compound 247: 7-[2-(3,4-dihydroxypyrrolidin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethy!)-
2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
■ compound 248: 7-[2-(dimethylamino)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
■ compound 249: 7-{2-[ethyl(methyl)amino]pyrid-3-yl}-5-(2,2,2-trifluoroethyl)-1I5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;

- compound 250: 7-{2-[(2-hydroxyethyl)(methyl)amino]pyrid-3-yl}-5-(2,2,2-trifluoroethy!)-
1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 251: 7-[2-(pyrrolidin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 252: 7-[2-(1,4-oxazepan-4-yl)pyrid-3-yl]-5-(2,2I2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 253: 7-[2-(3-oxopiperazin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 254: 7-[2-(azetidin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 255: 7-{2-[(2-methoxyethyl)methylamino]pyrid-3-yl}-5-(2,2,2-trifluoroethyl)-
2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 256: 7-[2-(4-acetylpiperazin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-2,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 257: 7-[2-(diethylamino)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 258: 7-[2-(cyclobutylamino)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 259: 7-[2-(2,6-dimethylmorpholin-4-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-2,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 260: 7-[2-(4-cyclopropylpiperazin-1-yl)pyrid-4-yl]-5-(2,2,2-trifluoroethyl)-
2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 261: 7-(2-cyclohexylaminopyrid-3-yl)-5-(2,2,2-thfluoroethyl)-2,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 262: 7-[2-(isopropylmethylamino)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-2,5-

dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 263: 7-(2-cyclopentylaminopyrid-3-yl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 264: 7-(6-pyrrolidin-1-ylpyrid-2-yl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 265: 7-[6-(2,6-dimethylmorpholin-4-yl)pyrid-2-yl]-5-(2,2,2-trifluoroethyl)-2,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 266: 7-{2-[cyclohexyl(methyl)amino]pyrid-3-y!}-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 267: 7-[2-(4-cyclopropylpiperazin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-
2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 268: 7-[3-(4-cyclopropylpiperazin-1-yl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 269: 7-[2-(4-acetyl-1,4-diazepan-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 270: 7-[2-(4-methyl-1,4-diazepan-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-
1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 271: 7-[2-(4-cyclopropyl-[1,4]diazepan-1-yl)pyrid-3-yl]-5-(2,2,2-
trifluoroethyl)-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 272: 7-[2-(3-fluoropyrrolidin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-2,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 273: 7-[2-(4-fluoropiperidin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;

- compound 274: 7-(2-hydroxypyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 275: 7-(1-oxypyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 276: 7-(1-oxypyrid-4-y!)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
in the form of the base or of an acid-addition salt, and also in hydrate form.
Among the compounds of formula (I) that are subjects of the invention, mention may be
made especially of the following compounds:
- compound 1: 7-(pyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 2: 7-(2-aminopyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 6: 7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihyclro-4H-pyra2olo[4,3-
c]quinolin-4-one;
- compound 19: 7-[4-(4-methylpiperazin-1-yl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4/-/-pyrazolo[4,3-c]quinolin-4-one;
- compound 67: 5-ethyl-7-[6-(piperazin-1-yl)pyrid-3-yl]-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 68: 7-[2-(4-methylpiperazin-1-yl)pyrid-4-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 69: 5-ethyl-7-[2-(4-methylpiperazin-1-yl)pyrid-4-yl]-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 72: 7-(2-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 74: 7-(2-chloro-6-methylpyrid-3-yl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 75: 7-(2-chloro-6-methylpyrid-3-yl)-5-(2,2,2-trifiuoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 76: 7-(2-chloropyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 77: 7-(2-fluoropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 79: 7-(6-chloro-2-methylpyrid-3-yl)-5-(2I2,2-trifluoroethy[)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 83: 7-[6-(morpholin-4-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 88: 7-(6-chloropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 111: 7-(2-chloropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 168: 7-(2,6-dimethylpyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 169: 7-(3-chloropyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 171: 7-(6-methylpyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quino!in-4-one;
- compound 172: 7-[2-(morpholin-4-yl)pyrid-3-yI]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 176: 3-[4-oxo-5-(2T2,2-trifluoroethyl)-4,5-dihydro-1f/-pyrazolo[4,3-

c]quinolin-7-yl]pyridine-2-carbonitrile;
- compound 186: 7-(2-methylpyrid-4-y!)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 196: 8-chloro-7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 199: 8-chloro-7-(2-chloropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 209: 7-{2-[(4-methyl-1,4-diazepan-1-yl)carbonyl]phenyl}-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 232: A/-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-2H-pyrazolo[4,3-
c]quinolin-7-yl]phenyl}methanesulfonamide;
- compound 248: 7-[2-(dimethylamino)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 251: 7-[2-(pyrrolidin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 257: 7-[2-(diethylamino)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 273: 7-[2-(4-fluoropiperidin-1-yl)pyrid-3-yl]-5-(2>2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
in the form of the base or of an acid-addition salt, and also in hydrate form.
Among the compounds of formula (I) that are subjects of the invention, mention may be
made especially of the following compounds:
- compound 1: 7-(pyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 6: 7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinoiin-4-one;
- compound 67: 5-ethyl-7-[6-(piperazin-1-yl)pyrid-3-yl]-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 69: 5-ethyl-7-[2-(4-methylpiperazin-1-yl)pyrid-4-yl]-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 72: 7-(2-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quino!in-4-one;
- compound 74: 7-(2-chloro-6-methylpyrid-3-yl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 75: 7-(2-chloro-6-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 76: 7-(2-chloropyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4tf-
pyrazoio[4,3-c]quinolin-4-one;
- compound 77: 7-(2-fluoropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 79: 7-(6-chloro-2-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 88: 7-(6-chloropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 111: 7-(2-chloropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 168: 7-(2,6-dimethylpyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 169: 7-(3-chloropyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 171: 7-(6-methylpyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 176: 3-[4-oxo-5-(2,2,2-trifluoroethy[)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyridine-2-carbonitrile;
- compound 186: 7-(2-methylpyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 199: 8-chloro-7-(2-chloropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 248: 7-[2-(dimethylamino)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 251: 7-[2-(pyrrolidin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 257: 7-[2-(diethylamino)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4tf-
pyrazolo[4,3-c]quinolin-4-one;
- compound 273: 7-[2-(4-fluoropiperidin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
in the form of the base or of an acid-addition salt, and also in hydrate form.
In the text hereinbelow, the term "protecting group PG" means a group that can, firstly,
protect a reactive function such as a pendent hydroxyl or amine during a synthesis and,
secondly, regenerate the intact reactive function at the end of the synthesis. Examples of
protecting groups and of protection and deprotection methods are given in "Protective

Groups in Organic Synthesis", Greene etal., 3rd Edition (John Wiley & Sons, Inc., New
York).
In the text hereinbelow, the term "leaving group LG" means a group that can be readily
cleaved from a molecule by breaking a heterolytic bond, with loss of an electron pair. This
group may thus be readily replaced with another group during a substitution reaction, for
example. Such leaving groups are, for example, halogens or an activated hydroxyl group
such as a mesyl, tosyl, triflate, acetyl, etc. Examples of leaving groups and references for
preparing them are given in "Advanced Organic Chemistry", J. March, 3rd Edition, Wiley
Interscience, pp. 310-316.
In accordance with the invention, the compounds of general formula (I) may be prepared
according to the processes that follow.
Unless otherwise mentioned, R1, R2 and R3 are as defined previously.
Unless otherwise mentioned, the group Hal represents a bromine, iodine or chlorine
atom, more particularly a bromine or iodine atom.
Scheme 1: preparation of an intermediate 1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one of formula (VI)

Scheme 1 illustrates the synthesis of the key intermediate of formula (VI). The reaction of
a 4-hydroxyquinolin-2(1H)-one derivative of formula (II) [obtained according to or after
adaptation of the processes described in Bioorganic & Medicinal Chemistry, 2005, 13(4),
1069-1081] with A/,A/-dimethylformamide dimethyl acetal (DMFDMA) gives the enamine
of formula (III) [according to an adaptation of the process described in Tetrahedron, 2004,

60(39), 8633-8644]. Treatment of compound (III) with POCI3 at room temperature in an
inert solvent such as DMF gives the derivative 4-chloro-2-oxo-1,2-dihydroquinoline-3-
carbaldehyde of formula (IV) after aqueous work-up. The term "room temperature" means
a temperature of between 5 and 25°C. Condensation of hydrazine with the chloro-
aldehyde of formula (IV) generates 1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one of
formula (V) in a solvent such as DMF, THF or ethanol, working at a temperature between
room temperature and 100°C and preferably by heating to 80°C. The pyrazole may be
selectively protected with a protecting group that is stable in basic medium such as SEM
or THP to give the intermediate of formula (VI).
F
H
As indicated in Scheme 2, the compounds of formula (I) in which the group R2 is -O-
pyridine or -NH-pyridine or -A-X as defined previously, and with the exception of the
case where R3 represents -CO2H, may be obtained according to the following routes:
- route A: 1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one of formula (VI) may be alkylated
with an electrophile R1-E in which E is a good leaving group such as a halogen or a
triflate, in the presence of a base such as sodium hydride, potassium terf-butoxide or
sodium, potassium or caesium carbonate, in an inert solvent such as DMF or THF, at
room temperature or by heating to 80°C. The /V-alkyl compound of formula (VII) is
predominant and its O-alkyl isomer is obtained in an amount of up to 30% depending on
the electrophile and the base used.
The halogenated derivative of formula (VII) may be engaged:
'< - either in an organometallic coupling reaction catalysed with palladium, for example
PdCI2(dppf), either with boronic acids or esters or with tin derivatives, in the presence
or absence of a phosphine ligand and/or of a weak base in a solvent such as DMF, by

heating to between 80 and 150°C, to give the compounds of formula (VIII) with R2
being a group -A-X-;
- or in a coupling reaction with hydroxypyridine or aminopyridine derivatives catalysed
with copper in the presence or absence of a ligand and/or of a weak base, to give the
compounds of formula (VIII) with R2 being a group -O-pyridine or-NH-pyridine.
Finally, the compounds of formula (I) are obtained after deprotection of the pyrazole of
the compounds of formula (VIII) under suitable conditions according to the protecting
group PG. For example, when PG represents SEM or THP in the compounds of formula
(VIII), a treatment in acidic medium, for example with TFA or anhydrous dilute HCI,
makes it possible to obtain the compounds of formula (I).
- route B: the halogenated derivative of formula (VI) may be engaged in an
organometallic coupling reaction either with boronic acids or esters or tin derivatives,
or with hydroxypyridine or aminopyridine derivatives with R2 being a group -A-X or
-O-pyridine or -NH-pyridine, respectively, to give a compound of formula (IX), which
may then be alkylated with an electrophile R1-E in the presence of a base as
described in route A above.
Scheme 3 (route C): preparation of an intermediate 1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one of formula (XIV) and production of the compounds of formula (I)

An alternative to the introduction of the substituent R1 by A/-alkylation of the
intermediates of formula (VI) or (IX) with an electrophile R1-E (see routes A and B above)
consists in introducing the group R1 via substitution of the fluorine atom of the
compounds of formula (X), with the exception of the cases where R3 represents a

fluorine atom, via the amine R1-NH2 as described in J. Med. Chem., 2008, 51(6), 1925-
1944, or by reductive amination with the aldehyde R1-CHO of the anilines of formula (XI),
as indicated in Scheme 3. The compounds of formula (XII) obtained are converted into
compounds of formula (XIII) according to the processes described for preparing the
compounds of formula (II). The processes for converting the compounds of formula (II)
into compounds of formula (V) are used for converting the compounds of formula (XIII)
into compounds of formula (XIV). The compounds of formula (I) are obtained directly from
the compounds of formula (XIV) via:
- either an organometallic coupling reaction catalysed with palladium, for example
with PdCI2(dppf), either with boronic acids or esters or with tin derivatives in the presence
of a phosphine ligand and/or a weak base in a solvent such as DMF with heating to
between 80 and 150°C. The compounds of formula (I) are thus obtained with R2 being a
group -A-X.
- or a coupling reaction with hydroxypyridine or aminopyridine derivatives
catalysed with copper in the presence of a ligand and/or a weak base, to give the
compounds of formula (I) with R2 being a group -O-pyridine or-NH-pyridine.
Scheme 4 (route D): preparation of an intermediate 1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one of formula (VII) via an intramolecular Heck reaction

Scheme 4 illustrates an alternative route for the synthesis of the compound of formula
(VII), which intermediate may be used as described in Scheme 2 for preparing the
compounds of formula (I). The anilines of formula (XV) react with an acid chloride of
formula (XVI) comprising a protecting group that is stable in basic medium such as SEM
or THP in the presence of a base such as fBuOK or NaH in a solvent such as THF or
DMF, at room temperature, to give the amide of formula (XVII). The amide of formula
(XVII) may be alkylated with an electrophilic group R1-E in which E is a good leaving
group such as a halogen or a triflate, in the presence of a base such as sodium hydride,
potassium terf-butoxide or sodium, potassium or caesium carbonate, in an inert solvent
such as DMF or THF, at room temperature or by heating up to 80°C. The /V-alkyl
compound of formula (XVIII) predominantly obtained versus its O-alkyl isomer is then
engaged in an intramolecular Heck reaction catalysed with palladium, for example with

Pd(PPh3)4, in the presence of a weak base such as triethylamine or potassium acetate, in
a solvent such as DMF, while heating to between 60 and 120°C to give the protected 1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one of formula (VII).
Scheme 5 (route E): alternative to the preparation of the compounds of formula (I)
via the intermediates of formulae (VII) and (XIV)

The halogenated derivatives of formula (VII) or (XIV) obtained according to the processes
described in Schemes 2, 3 and 4 may be converted into the boronic acid or ester of
formula (XIX) or (XX), respectively, via a palladium-catalysed coupling reaction with a
diborane derivative, for example pinacol diborane. The boronic acid or ester of formula
(XIX) or (XX) for which R represents a hydrogen atom or the two groups R are carbon
atoms bonded together and optionally substituted with one or more (C1-C4) alkyl groups
may be engaged in a palladium-catalysed Suzuki coupling reaction with aromatic
compounds R2-E bearing a leaving group E such as a halogen, for instance chlorine,
bromine or iodine, or a triflate group, to give, respectively, the compounds of formula
(VIII) that allow preparation of the compounds of formula (I) as described previously, or
directly the compound of formula (I).
Scheme 6 (route F): functionalization in position 8 of the 1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-ones with R3 representing a halogen

As indicated in Scheme 6, the regioselective introduction of a halogen atom into position
8 of the 1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one compounds of formula (V) or (VI) or
(VII) or (VIII) or (IX) or (XIV) or (I) when R3 is a hydrogen, may be performed via an
aromatic electrophilic substitution reaction with reagents such as, for example, NBS or

NCS in the presence or absence of a catalyst such as palladium, for example Pd(OAc)2,
in the presence or absence of an acid such as dry acetic acid, with heating from 60 to
120°C.
Scheme 7 (route G): functionalization in position 8 of the 1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-ones with R3 representing -Me or -CN

When R3 is a chlorine or bromine atom, the halogenated derivative of formula (VIII) or
(IX) or (I) may be engaged in a palladium-catalysed coupling reaction with tetramethyltin
to give the compound of formula (VIII) or (IX) or (I) with R3 being a methyl group, or
alternatively with zinc cyanide to give the compound of formula (VIII) or (IX) or (I) with R3
being a nitrile group.
When X and/or R3 contains or represents a cyano group, it may be hydrolysed to a group
-COORa with Ra being H or a primary amide, according to processes that are well known
to those skilled in the art (route H).
When X contains or represents a group -COORa with Ra other than H, it may be
converted by saponification into a group -COORa with Ra being H (route I).
When X and/or R3 contains or represents a group -COORa with Ra being H, it may be
coupled, after activation, to an amine or to ammonium bicarbonate or to a heterocycle or
to a heteroaryl comprising an -NH function, to give a group -CONRaRb with Ra=Rb=H for
R3 and/or a group -CONRaRb, -C(0)-NRa-(CH2)n-0-Rb, -C(0)-NRa-aryl-C(0)-NRaRb,
-C(0)-NRa-(CH2)n-NRaRb, -C(0)-NRa-(CH2)n-heteroaryl, -CO-heterocycle or -CO-
heteroaryl for X (route J).
When X contains or represents a group -NRaRb with Rb being H, it may be coupled with
an activated carboxylic acid derivative in the presence of a weak base, to give a group
-NRaC(0)-(C1-C6)alkyl, -NRa-C(0)-(CH2)n-NRaRb, -NRa-C(0)-aryl, -NRa-C(0)-(C1-
C6)alkyl-aryl or -NRa-C(0)-(CH2)n-0-Rb (route K).

When X contains or represents a group -NRaRb with Rb being H, it may react with a
sulfonyl chloride in the presence of a weak base to give a group -NRa-S02-(CH2)n-aryl,
-NRa-S02-(CH2)n-NRaRb, -NRa-S02-Rb, -NRa-S02-aryl-0-aryl or -NRa-S02-aryl-
(CH2)n-NRa-C(O)-Rb (route L).
When X contains or represents a group -NRaC(O)-(C1-C6)alkyl, -NRa-C(O)-(CH2)n-
NRaRb, -NRa-C(O)-aryl, -NRa-C(O)-(C1-C6)alkyl-aryl, -NRa-C(O)-(CH2)n-0-Rb, -NRa-
S02-(CH2)n-aryl, -NRa-S02-(CH2)n-NRaRb, -NRa-S02-Rb, -NRa-S02-aryl-0-aryl or
-NRa-S02-aryl-(CH2)n-NRb-C(O)-Rb with Ra being a hydrogen, it may react with an
electrophile of formula (C1-C6)alkyl-LG (LG being a leaving group) in the presence of a
base to give a group -NRaC(O)-(C1-C6)alkyl, -NRa-C(O)-(CH2)n-NRaRb, -NRa-C(O)-
aryl, -NRa-C(O)-(C1-C6)alkyl-aryl, -NRa-C(O)-(CH2)n-0-Rb, -NRa-S02-(CH2)n-aryl,
-NRa-S02-(CH2)n-NRaRb, -NRa-S02-Rb, -NRa-S02-aryl-0-aryl or -NRa-S02-aryl-
(CH2)n-NRb-C(O)-Rb in which Ra represents -(C1-C6)alkyl (route M).
When X is a halogen, it may be substituted with an amine in the presence or absence of
a palladium(O) or copper(l) catalyst, in the presence or absence of a base, to give the
compounds in which X represents a group -NRaRb, -NRa-(CH2)n-0-Rb, -NRa-
heterocycle or -NRa-aryl (route N).
When X contains a primary or secondary amine function, it may be engaged in a
reductive amination reaction with an aldehyde in the presence of a reducing agent of
hydride type, to give the corresponding amine (route O).
When X contains a hydroxyl function, it may be engaged in a fluorination reaction (route
P)-
When X represents a group -(C1-C6)alkoxy, it may be engaged in a hydrolysis reaction to
give a group -O-Ra with Ra being H (route Q).
When A represents a heteroaryl, for instance a pyridine, it may be oxidized to give the N-
oxide analogue of the heteroaryl (route R).
In Schemes 1-7, the starting compounds and the reagents, when their preparation
method is not described, are commercially available or described in the literature, or else

may be prepared according to methods that are described therein or that are known to
those skilled in the art.
According to another of its aspects, a subject of the invention is also compounds of
formulae (II) to (XX). These compounds are useful as intermediates for synthesizing
compounds of formula (I), and more particularly the intermediates (III), (IV), (V), (VI), (VII),
(VIII), (IX), (XIII), (XIV), (XVII), (XVIII), (XIX) and (XX).
The examples that follow describe the preparation of certain compounds in accordance
with the invention. The examples are not limiting, but serve merely to illustrate the
present invention. The table hereinbelow illustrates the chemical structures and physical
properties of a number of compounds according to the invention.
The following abbreviations and empirical formulae are used:
EtOAc ethyl acetate
Cul copper iodide
DCM dichloromethane
DCE dichloroethane
DHP dihydropyranyl
DMF A/,/V-dimethylformamide
DMSO dimethyl sulfoxide
EtOH ethanol
HCI hydrogen chloride
HPLC high-performance liquid chromatography
LCMS liquid chromatography/mass spectrometry
MeOH methanol
MeTHF 2-methyltetrahydrofuran
MHz MegaHertz
NaH sodium hydride
NaCI sodium chloride
NaBH4 sodium borohydride
NaHCO3 sodium hydrogen carbonate
Na2S04 sodium sulfate
NBS A/-bromosuccinimide
NCS A/-chlorosuccinimide
NMP /V-methyl-2-pyrrolidone

PdCI2(dppf) [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II)
Pd(PPh3)4 tetrakis(triphenylphosphine)palladium(O)
Pd((j-Br)(tBu3P)]2 di-u-bromobis(tri-terf-butylphosphine)dipalladium(l)
Pd(OAc)2 palladium(ll) acetate
POCI3 phosphoryl chloride
tBuOK potassium terf-butoxide
TFA trifluoroacetic acid
THF tetrahydrofuran
THP tetrahydropyranyl
SEM 2-(trimethylsilyl)ethoxy]methyl
Zn(CN)4 zinc cyanide
°C degrees Celsius
min minute(s)
mL millilitre(s)
mmol millimole(s)
ppm parts per million
In the text hereinbelow:
- the proton magnetic resonance spectra (1H NMR), as described below, are recorded at
400 MHz or 500 MHz in DMSO-d6, using the DMSO-d6 peak as reference. The chemical
shifts 6 are expressed in parts per million (ppm). The signals observed are expressed as
follows: s = singlet; d = doublet; t = triplet; m = multiplet or br. s. = broad singlet;
- the LCMS characteristics, as described below, successively indicated the high-
performance liquid chromatography analytical method used and detailed below (A to J),
the MH+ peak identified by mass spectrometry and the retention time of the compound,
expressed in minutes.
* Method A
Instrument: HPLC line of the type 1100 (Agilent) or Alliance (Waters); simple quadrupole
mass spectrometer of the type MSD (Agilent) orZQ (Waters)
Column: Symmetry C18 3.5 urn (2.1 x 50 mm) Waters
Solvent A: H20 + 0.005% TFA; Solvent B: CH3CN + 0.005% TFA
Flow rate: 0.4 mL/min
Gradient A/B: 100/0 (tO min) to 0/100 (t10 min) to 0/100 (t15 min)
Detection: UV 220 nm
Ionization: eiectrospray positive mode ESI+

* Method B: Method A with change of gradient A/B
Gradient A/B: 100/0 (tO min) to 0/100 (t30 min) to 0/100 (t35 min)
* Method C
Instrument: HPLC line of the type 1100 (Agilent) or Alliance (Waters); simple quadrupole
mass spectrometer of the type MSD (Agilent) or ZQ (Waters)
Column: X Terra C18 3.5 urn (2.1 x 50 mm) Waters
Solvent A: H20 + NH4OAc 10 mM pH 7; Solvent B: CH3CN
Flow rate: 0.4 mL/min
Gradient A/B: 100/0 (tO min) to 10/90 (t10 min) to 10/90 (t15 min)
Detection: UV 220 nm
Ionization: electrospray positive mode ESI+
* Method D
Instrument: UPLC Acquity line (Waters); SQD mass spectrometer (Waters)
Column: BEH- C18 (2.1 x 50 mm) 1.7 urn (Waters); column temp.: 55°C
Solvent A: H20 +0.02% HCOOH; Solvent B: CH3CN +0.02% HCOOH
Flow rate: 1 mL/min
Gradient A/B: 98/2 (tO min) to 2/98 (t4 min) to 2/98 (t4.5 min)
Detection: UV 220 nm
Ionization: electrospray positive mode ESI+
* Method E
Instrument: HPLC line of the type 1100 (Agilent) or Alliance (Waters); simple quadrupole
mass spectrometer of the type MSD (Agilent) or ZQ (Waters)
Column: Luna C18(2)-HST Phenomenex (30 x 2 mm) 2.5 urn; column temp.: 50°C
Solvent A: H20 + 0.05% TFA; Solvent B: CH3CN + 0.035% TFA
Flow rate: 1 mL/min
Gradient A/B: 100/0 (tO min) to 0/100 (t2.5 min) to 0/100 (t3.5 min)
Detection: UV 220 nm
Ionization: electrospray positive mode ESI+
* Method F
Instrument: HPLC line of the type 1100 (Agilent) or Alliance (Waters); simple quadrupole
mass spectrometer of the type MSD (Agilent) or ZQ (Waters)
Column: Symmetry C18 (50 x 2.1 mm) 3.5 urn (Waters); column temp.: 40°C
Solvent A: H2Q + 0.05% TFA; Solvent B: CH3CN + 0.035% TFA

Flow rate: 0.5 mL/min
Gradient A/B: 100/0 (tO min) to 0/100 (t7 min)
Detection: UV 220 nm
Ionization: electrospray positive mode ESI+
* Method G
Instrument: UPLC Acquity line (Waters), SQD mass spectrometer (Waters)
Column: BEH C18 (50x2.1 mm) 1.7 urn (Waters); column temp.: 55°C
Solvent A: H20 + 0.05% TFA; Solvent B: CH3CN + 0.035% TFA
Flow rate: 0.8 mL/min
Gradient A/B: 98/2 (tO min) to 0/100 (t2.4 min) to 0/100 (t3 min)
Detection: UV 220 nm
Ionization: electrospray positive mode ESI+
* Method H
Instrument: Waters UPLC
Column: BEH C18 (2.1x50 mm) 1.7 urn
Solvent A: H20 + 0.05% HCO2H; Solvent B: CH3CN + 0.035% HCO2H
Flow rate: 0.9 mL/min
Gradient A/B: 95/5 (tO min) to 5/95 (t1.1 min) to 5/95 (t1.7 min)
Detection: 220 nM
Ionization: electrospray positive mode ESI+
* Method H': Method H with change of eluents
Solvent A: H20 + 0.1% HCO2H; Solvent B: CH3CN + 0.08% HCO2H
Gradient A/B: 95/5 (tO min) to 5/95 (t1.1 min) to 5/95 (t1.7 min)
* Method I
Instrument: Waters UPLC
Column: Waters XBridge C18 (4.6x50 mm) 2.5 urn
Solvent A: H20 + 0.1% HCO2H; Solvent B: CH3CN + 0.08% HCO2H
Gradient A/B: 97/3 (tO min) to 40/60 (t3.5 min) to 2/98 (t4 min) to 2/98 (t5 min)
Detection: 220 nM
Ionization: electrospray positive mode ESI+
* Method l': Method H with change of eluents
Solvent A: H20 + 0.05% TFA; Solvent B: CH3CN + 0.05% TFA

Gradient A/B: 95/5 (tO min) to 95/5 (t0.3 min) to 5/95 (t3.5 min) to 5/95 (t4 min)
* Method J
Instrument: Waters UPLC
Column: Jsphere (33x2.1 mm) 4 urn
Solvent A: H20 + 0.05% TFA; Solvent B: CH3CN + 0.05% TFA
Gradient A/B: 98/2 (tO min) to 98/2 (t1 min) to 5/95 (t5 min) to 5/95 (t6.25 min)
Detection: 220 nM
Ionization: electrospray positive mode ESI+
Example 1: 7-(pyrid-2-v0-5-(2.2.2-trifluoroethvn-1.5-dihvdro-4tf-pvrazolor4.3-
c]quinolin-4-one hydrochloride (compound 1)
Step 1.1. (3E,Z)-7-bromo-3-[(dimethylamino)methylidene]quinollne-2,4(1H,3H)-dlone
In a three-necked flask, A/,A/-dimethylformamide dimethyl acetal (103 mL, 0.77 mol) is
added to a suspension of 7-bromo-4-hydroxyquinolin-2(1H)-one (12.3 g, 51.2 mmol) in
250 mL of toluene. The reaction mixture is stirred for 24 hours at 80°C, and then cooled
to room temperature and filtered. The solid obtained is washed with toluene and dried
under vacuum to give 13.5 g of (3E,Z)-7-bromo-3-[(dimethylamino)methylidene]quinoline-
2,4(1 H,3H)-dione in the form of a beige-coloured solid (yield: 89%).
LCMS (Method C): MH+ = 295.0, RT = 5.86 min
Step 1.2. 7-bromo-4-chloro-2-oxo-1,2-dihydroquinoline-3-carbaldehyde
Phosphoryl chloride (1.9 mL, 20.3 mmol) is added dropwise to a suspension of (3E,Z)-7-
bromo-3-[(dimethylamino)methylidene]quinoline-2,4(1H,3H)-dione (5 g, 16.9 mmol) in
50 mL of DMF at 0°C. The reaction mixture is stirred for 4 hours at room temperature and
then poured into ice-water. The precipitate formed is filtered off and dried under vacuum
to give 4.6 g of 7-bromo-4-chloro-2-oxo-1,2-dihydroquinoline-3-carbaldehyde in the form
of a yellow solid (yield: 81 %).
LCMS (Method A): MH+ = 288.0, RT = 6.38 min
Step 1.3. 7-bromo-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one
To a solution of 7-bromo-4-chloro-2-oxo-1,2-dihydroquinoline-3-carbaldehyde (8.0 g,
27.9 mmol) in 150 mL of DMF at 80°C is added hydrazine hydrate (2 mL, 33.5 mmol) at
80°C. The reaction medium is stirred for 24 hours at 80°C and then cooled to room
temperature and filtered. The solid obtained is washed with diisopropyl ether and dried to

give 5.3 g of 7-bromo-1,5-dihydro-4H-pyrazolo[4,3-c]quinoiin-4-one in the form of a pale
yellow powder (yield: 72%).
LCMS (Method A): MH+ = 264.1, RT = 5.27 min
Step 1.4. 7-bromo-1-(tetrahydro-2H-pyran-2-yI)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one and 7-bromo-2-(tetrahydro-2H-pyran-2-yl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one
To a solution of 7-bromo-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one (17.95 g
67.97 mmol) in 1L ofDMF are added 3,4-dihydro-2H-pyran (18.6 mL, 204 mmol) and
para-toluenesulfonic acid (1.29 g, 6.80 mmol) at room temperature. The reaction medium
is stirred at room temperature for 72 hours and then poured into saturated NaHCO3 and
extracted with EtOAc. The organic phase is washed with saturated NaCI solution and
dried over Na2S04, filtered and concentrated to dryness to give a brown solid. The solid is
taken up in diisopropyl ether and, after filtering off, 18.8 g of an orange-coloured powder
(yield: 71%) are obtained.
LCMS (Method A): MH+ = 350.1, RT = 5.28 min
Step 1.5. 7-bromo-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one and of 7-bromo-2-(tetrahydro-2H-pyran-2-yl)-5-
(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one
To a suspension of 7-bromo-1-(tetrahydro-2H-pyran-2-yl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one and 7-bromo-2-(tetrahydro-2H-pyran-2-yl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one (17.3 g, 49.7 mmol) in 170 mL of anhydrous MeTHF at 70°C is added t-
BuOK (11.2 g, 99.4 mmol) portionwise. After stirring for 15 minutes at 70°C, 2,2,2-
trifluoroethyl trifluoromethanesulfonate (14.4 mL, 99.4 mmol) is added dropwise. The
reaction medium is stirred for 2 hours at 70°C after addition of 180 mL of anhydrous
MeTHF. After 2 hours, a further portion of f-BuOK (11.14 g, 49.7 mmol) and of 2,2,2-
trifluoroethyl trifluoromethanesulfonate (7.2 mL, 49.7 mmol) is added at 70°C. The
reaction medium is stirred for 2 hours 30 minutes at 70°C. The reaction medium is
concentrated and the residue is taken up in DCM. The solution is washed with water and
then with saturated NaCI solution, dried over Na2S04, filtered and concentrated to
dryness to give a brown solid, which is taken up in a diisopropyl ether/acetone mixture
(2/1) and stirred for 16 hours to give 12.1 g of a white powder (yield: 57%).
LCMS (Method E): MH+ = 347.9, RT = 5.27 min

Step 1.6. 7-(pyrid-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-2,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-(pyrid-2-yl)-2-(tetrahydro-2H-pyran-
2-yl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one
To a suspension of 7-bromo-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-bromo-2-(tetrahydro-2/-/-pyran-2-yl)-5-
(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one (1.0 g, 2.32 mmol) in
20 m!_ of anhydrous DMF contained in a microwave reactor under nitrogen are added 2-
pyridyltri-n-butylstannane (1.21 mL, 3.02 mmol) and the catalyst Pd(M3u3P)2 (356 mg,
0.7 mmol). The reactor is sealed and the reaction medium is stirred for 10 minutes at
120°C under microwave irradiation. The mixture is concentrated to dryness and taken up
in EtOAc. The solution is washed with saturated NaHCO3 solution, saturated aqueous
NaCI solution, dried over Na2S04, filtered and concentrated to dryness to give a beige-
coloured solid. After purification by flash chromatography on silica (DCM/EtOH: 95/5 to
85/15), 0.38 g of a white powder is obtained (yield: 38%).
LCMS (Method A): MH+ = 429.2, RT = 8.14 min
Step 1.7. 7-(pyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one hydrochloride
To a solution of 7-(pyrid-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-2,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-(pyrid-2-yl)-2-(tetrahydro-2H-pyran-2-yl)-
5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one (60 mg, 0.14 mmol)
in 1 mL of DCM is added a 4M solution of anhydrous hydrogen chloride in dioxane
(350 uL, 1.40 mmol). After stirring for 1 hour at room temperature, the suspension is
filtered and the solid is dried under vacuum to give 59 mg of 7-(pyrid-2-yl)-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one in the form of a beige-
coloured powder (hydrochloride, 0.88 H20; quantitative yield).
LCMS (Method A): MH+ = 345.0, RT = 6.63 min
1H NMR (400 MHz, DMSO-d6): 5 ppm 8.79 (dd, 1 H) 8.47 (br. s., 1 H) 8.39 (s, 1 H) 8.35
(d, 1 H) 8.26 (d, 1 H) 8.14 (dd, 1 H) 8.10 (t, 1 H) 7.51 - 7.58 (m, 1 H) 5.47 (d, 1 H) 5.42 (d,
1 H)

Example 2: 7-(2-aminopyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one hydrochloride (compound 2)
Step 2.1. 7-(3-aminopyrid-4-yl)-1 -(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifIuoroethyI)-
1,5-dihydro-4W-pyrazolo[4,3-c]quinolin-4-one
7-Bromo-1-(tetrahydro-2H-pyran-2-yl)-5-(2>2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one and 7-bromo-2-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one (9.7g, 19.4 mmol), potassium carbonate (5.3 g,
38.4 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrid-2-amine (4.82 g,
21.9 mmol), 14 ml_ of anhydrous DMF, 1.8 mL of degassed water, and the catalyst
PdCI2(dppf) (0.79 g, 0.96 mmol) are successively introduced into a microwave reactor
under argon. The reactor is sealed and the mixture is stirred for 10 minutes at 130°C
under microwave irradiation. The mixture is diluted with EtOAc, poured into saturated
aqueous NaHCO3 solution and stirred for 30 minutes. The precipitate is filtered off and
washed with water and then taken up in isopropanol. After filtering off and drying, 7.58 g
of a grey powder are obtained (yield: 88%).
LCMS (Method D): MH+ = 444.2, RT = 0.87 min
Step 2.2. 7-(2-aminopyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one hydrochloride
The product is obtained according to the procedure described in Step 1.7. by treating 7-
(3-aminopyrid-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one with anhydrous HCI in dioxane (4 M), in the form of a beige-
coloured powder (hydrochloride, 2 H20; yield 89%).
LCMS (Method A): MH+ = 360.1, RT = 4.83 min
1H NMR (400 MHz, DMSO-d6): 5 ppm 14.22 (br. s., 1 H) 8.20-8.60 (m, 2 H) 8.11 (dd, 1 H)
7.95 (dd, 1 H) 7.87 (s, 1 H) 7.80 (br. s., 2 H) 7.50 (d, 1 H) 7.06 (dd, 1 H) 5.35 (d, 1 H)
5.31 (d, 1 H)
Example 3: 7-(pyrid-3-yloxy)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4W-pyrazolo[4,3-
c]quinolin-4-one hydrochloride (compound 99)
Step 3.1. 7-bromo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one and 7-bromo-2-{[2-(trimethylsilyl)ethoxy]methyl}-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one
To a suspension of 7-bromo-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one [described in
Step 1.3.] (1.49g, 5.64 mmol) in 30 mL of anhydrous DMF is added caesium carbonate

(2.0 g, 6.21 mmol) and [2-(chloromethoxy)ethyI](trimethyl)silane (10 mL, 56.4 mmol)
dropwise. The reaction mixture is stirred at room temperature for 16 hours under nitrogen
and then poured into water and extracted with a THF/EtOAc mixture (50/50). The organic
phase is washed with saturated aqueous NaCI solution, dried over Na2S04, filtered and
concentrated to dryness. The residue obtained is purified by flash chromatography on
silica (DCM/MeOH: 100/0 to 98/2) to give 1.45 g of a yellow solid (yield: 61%).
LCMS (Method A): MH+ = 396.1, RT = 8.77 min
Step 3.2. 7-bromo-5-(2,2,2-trifluoroethyl)-1 -{[2-(trimethylsilyl)ethoxy]methyl}-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and7-bromo-5-(2,2,2-trifluoroethyl)-2-{[2-
(trimethylsilyl)ethoxy]methyl}-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one
To a suspension of 7-bromo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one, 7-bromo-2-{[2-(trimethylsilyl)ethoxy]methyl}-1,5-dihydro-
4/-/-pyrazolo[4,3-c]quinolin-4-one (10.0g, 25.4 mmol) and caesium carbonate (24.8 g,
76.1 mmol) in 130 mL of MeTHF heated to 60°C is added 2,2,2-trifluoroethyl
trifluoromethanesulfonate (5.5 mL, 38.0 mmol) dropwise. The mixture is stirred at 60°C
for 3 hours. The reaction medium is cooled and concentrated to dryness. The residue
obtained is taken up in water, filtered and dried. After purification by flash
chromatography (cyclohexene/EtOAc: 90/10 to 50/50), 6.67 g of a white powder are
obtained (yield: 55%).
LCMS (Method A): MH+ = 476.3, RT = 10.64 min
Step 3.3. 7-(pyrid-3-yloxy)-5-(2,2,2-trifluoroethyl)-1 -{[2-(trimethylsilyl)ethoxy]-
methyl}-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-(pyrid-3-yloxy)-5-(2,2,2-
trifluoroethyl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one
7-Bromo-1-[2-(trimethylsilyl)ethoxy]-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-
bromo-2-[2-(trimethylsilyl)ethoxy]-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one (0.2 g,
0.42 mmol), 3-hydroxypyridine (0.12 g, 1.26 mmol), the catalyst Cul (80 mg, 0.42 mmol),
the ligand 1,1,1-tris(hydroxymethyl)ethane (50 mg, 0.42 mmol), caesium carbonate
(0.55 g, 1.68 mmol), 0.4 mL of anhydrous DMF and 1.5 mL of dioxane are successively
introduced into a reactor under argon. The reactor is sealed and the mixture is stirred
vigorously for 17 hours at 110°C. After cooling, the mixture is filtered off through Celite
and washed with EtOAc. The solution is washed with water and with saturated aqueous
NaCI solution, dried over Na2S04 and concentrated to dryness to give 195 mg of a brown
gum, which is used in the next step.
LCMS (Method E): MH+ = 491.4, RT = 2.36 min

Step 3.4. 7-(pyrid-3-yloxy)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one hydrochloride
A suspension of 7-(pyrid-3-yloxy)-5-(2,2,2-trifluoroethyl)-1-{[2-(trimethylsilyl)ethoxy]-
methyl}-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-(pyrid-3-yloxy)-5-(2,2,2-
trifluoroethyl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one (0.19 g, 0.39 mmol) in 10 mL of anhydrous hydrogen chloride dissolved in dioxane
(4M) is stirred at room temperature for 18 hours. The suspension is filtered and the solid
is washed with DCM and then purified by flash chromatography on a C18 reverse phase
(H20/MeCN: 100/0 to 0/100). The gum obtained is dissolved in molar hydrochloric acid
solution and then concentrated to dryness to give 78 mg of a white powder (1.2
hydrochloride, 1.15 H20; yield: 58%).
LCMS (Method A): MH+ = 361.2, RT = 6.65 min
1H NMR (400 MHz, DMSO-d6): 5 ppm 8.66 (d, 1 H) 8.56 (d, 1 H) 8.41 (s, 1 H) 8.30 (d,
1 H) 7.84 (d, 1 H) 7.73 (dd, 1 H) 7.62 (s, 1 H) 7.19 (dd, 1 H) 5.27 (d, 1 H) 5.23 (d, 1 H)
Example 4: 5-(2,2-difluoroethyl)-7-(pyrid-4-yl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one hydrochloride (compound 102)
Step 4.1. 7-(pyrid-4-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one and 7-(pyrid-4-yl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-
1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one
To a solution of 7-bromo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one and 7-bromo-2-{[2-(trimethylsilyl)ethoxy]methyl}-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one [described in Step 3.1.] (18.2 g, 46.2 mmol) in 150 mL of
DMF placed in a microwave reactor are successively added 4-(4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)pyridine (11.4 g, 55.4 mmol), aqueous 2M K3P04 solution (47 mL,
92.4 mmol) and the catalyst PdCI2(dppf) (1.88 g, 2.31 mmol) under nitrogen. The reactor
is sealed and the reaction mixture is stirred for 20 minutes at 150°C under microwave
irradiation. After concentrating the reaction mixture, purification by flash chromatography
on silica (DCM/MeOH: 0/100 to 95/5) gives 12.4 g of 7-(pyrid-4-yl)-1-[2-
(trimethylsilyl)ethoxy]-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-(pyrid-4-yl)-2-
[2-(trimethylsilyl)ethoxy]-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one in the form of a
white solid (yield: 54%).
LCMS (Method A) MH+ = 393.2, RT = 6.60 and 6.74 min (isomers of pyrazole protected
with the SEM group)

Step 4.2. 5-(2,2-difluoroethyl)-7-(pyrid-4-yl)-1 -{[2-(trimethylsilyI)ethoxy]methyl}-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-oneand5-(2,2-difluoroethyl)-7-(pyrid-4-yl)-2-
{[2-(trimethylsilyl)ethoxy]methyl}-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one
To a solution of 7-(pyrid-4-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,5-dihyciro-4H-
pyrazolo[4,3-c]quinolin-4-one and 7-(pyrid-4-yl)-2-{[2-(trimethylsilyl)ethoxyJmethyl}-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one (0.40 g, 1.0 mmol) in 8 mL of DMF is added
caesium carbonate (0.66 g, 2.04 mmol) and 2,2-difluoroethyl trifluoromethanesulfonate
(0.33 mL, 2.55 mmol). The mixture is stirred for 24 hours at room temperature, and then
poured into water and extracted with EtOAc. The organic phase is washed with saturated
aqueous NaCI solution, dried over Na2S04, filtered and concentrated to dryness. After
purification on silica by flash chromatography (DCM/EtOH: 100/0 to 95/5), 108 mg of an
orange-coloured solid are obtained (yield: 23%).
LCMS (Method A) MH+= 457.3, RT = 6.94 min
Step 4.3. 5-(2,2-difluoroethyl)-7-(pyrid-4-yl)-1,5-dihydro-4W-pyrazolo[4,3-c]quinolin-
4-one hydrochloride
To a solution of 5-(2,2-difluoroethyl)-7-(pyrid-4-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 5-(2,2-difluoroethyl)-7-(pyrid-4-yl)-2-{[2-
(trimethylsilyl)ethoxy]methyl}-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one (100 mg,
0.22 mmol) in 2 mL of DCM is added a 4M solution of anhydrous hydrogen chloride in
dioxane (1.10 mL, 4.38 mmol) at room temperature. After stirring at room temperature for
24 hours, the mixture is filtered. The solid obtained is taken up in isopropanol, filtered off
and dried under vacuum to give 74 mg of a white powder (hydrochloride, yield: 94%).
LCMS (Method A): MH+ = 327.0, RT = 4.86
1H NMR (400 MHz, DMSO-d6): 5 ppm 8.96 - 9.03 (m, 2 H) 8.37 - 8.56 (m, 4 H) 8.19 (s,
1 H) 7.98 (d, 1 H) 6.43 (tt, 1 H) 5.04 (td, 2 H)
Example 5: 5-(propan-2-yl)-7-(pyrid-4-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one hydrochloride (compound 107)
Step 5.1. 4-bromo-2-(propan-2-ylamlno)benzoic acid
Isopropylamine (134.9 g, 2.28 mol), 10 mL of f-butanol and 4-bromo-2-fluorobenzoic acid
(10 g, 45.7 mmol), added portionwise, are mixed together in a microwave reactor. The
reactor is sealed and the mixture is stirred for 45 minutes at 150°C under microwave
irradiation. The colourless solution is cooled and poured into ice-water, and glacial acetic

acid is then added. The white precipitate formed is filtered off, washed with water and
dried under vacuum. 7.9 g of a white solid are obtained (yield: 67%).
LCMS (Method A) MH+ = 257.1, RT = 8.11 min
Step 5.2. 4-bromo-2-[(3-ethoxy-3-oxopropanoyl)(propan-2-yl)amino]benzoic acid
To a solution of 4-bromo-2-(propan-2-ylamino)benzoic acid (6.8 g, 26.64 mmol) in
260 ml_ of DCM is added triethylamine (4 ml_, 31.6 mmol), followed by dropwise addition
of ethyl malonate chloride (4.0 ml_, 31. mmol). The mixture is stirred for 2 hours at room
temperature, and then poured into molar hydrochloric acid solution and extracted with
EtOAc. The organic phase is washed with water and with saturated aqueous NaCI
solution, dried over Na2S04 and concentrated to dryness. 7.15 g of a pale yellow solid are
obtained (yield: 72%).
LCMS (Method A): MH+ = 372.1, RT = 7.42 min
Step 5.3. ethyl 7-bromo-2,4-dioxo-1-(propan-2-yl)-1,2,3,4-tetrahydroquinoline-3-
carboxylate
To a solution of 4-bromo-2-[(3-ethoxy-3-oxopropanoyl)(propan-2-yl)amino]benzoic acid
(6.2 g,16.7 mmol) in 170 mL of DCE is added triethylamine (3.5 ml_, 25.1 mmol), followed
by addition of thionyl chloride (1.45 mL, 20.6 mmol) at 0°C. After stirring at room
temperature for 3 hours, the reaction medium is diluted with DCM and washed with
aqueous HCI solution (1M). The organic phase is washed with saturated aqueous
NaHCO3 solution and saturated aqueous NaCI solution, dried over Na2S04 and
concentrated to dryness. The oil obtained is purified by flash chromatography
(toluene/EtOAc: 100/0 to 90/10) to give 2.23 g of a white solid (yield: 52%).
LCMS (Method A) MH+ = 354.2, RT = 9.58 min
Step 5.4. 7-bromo-4-hydroxy-1-(propan-2-yl)quinolin-2(1H)-one
A suspension of ethyl 7-bromo-2,4-dioxo-1-(propan-2-yl)-1,2,3,4-tetrahydroquinoline-3-
carboxylate (1.5 g, 4.23 mmol) in sodium hydroxide (2M solution, 32 mL, 64 mmol) is
heated to reflux. The reaction medium becomes homogeneous and, after 3 hours, a
suspension is once again observed. 6 mL of NMP are added to homogenize, and the
resulting mixture is then refluxed for 12 hours. The solution cooled to room temperature is
poured into 6M hydrochloric acid solution to give a white precipitate, which is filtered off.
After rinsing with water and drying the precipitate under vacuum, 1.1 g of a white solid are
obtained (yield: 91%).
LCMS (Method A) MH+ = 284.1 RT = 6.99 min

Step 5.5. (3£,Z)-7-bromo-3-[(dimethylamino)methylidene]-1 -(propan-2-yl)quinoline-
2,4(1 H,3H)-dione
As described in Step 1.1., to a solution of 7-bromo-4-hydroxy-1-(propan-2-yI)quinolin-
2(1H)-one (1.2 g, 4.25 mmol) in 43 mL of toluene is added A/,A/-dimethylformamide
dimethyl acetal (8.8 mL, 63.8 mmol). The solution is heated at 80°C for 8 hours. The
resulting mixture is concentrated to dryness to give a pale yellow solid, which is taken up
in diisopropyl ether. After filtering off, 321 mg of a white solid are obtained (yield: 92%).
LCMS (Method A) MH+ = 338.1, RT = 8.39 min
Step 5.6. 7-bromo-4-chloro-2-oxo-1 -(propan-2-yl)-1,2-dihydroquinoline-3-
carbaldehyde
As described in Step 1.2., to a solution of (3E,Z)-7-bromo-3-[(dimethylamino)methyl-
idene]-1-(propan-2-yl)quinoline-2,4(1H,3H)-dione (1.32 g, 3.9 mmol) in 10 mL of DMF is
added dropwise POCI3 (0.44 mL, 4.70 mmol) at 0°C. The solution is stirred for 3 hours at
room temperature and then poured into ice-water to give a precipitate. After filtering off
and drying the precipitate under vacuum, 1.2 g of a yellow solid are obtained (yield: 93%).
LCMS (Method A) MH+= 327.1, RT = 7.29 min
Step 5.7. 7-bromo-5-(propan-2-yl)-1,5-dihydro-4f/-pyrazolo[4,3-c]quinolin-4-one
As described in Step 1.3., to a solution of 7-bromo-4-chloro-2-oxo-1-(propan-2-yl)-1,2-
dihydroquinoline-3-carbaldehyde (1.0 g, 3.08 mmol) in 30 mL of DMF at 0°C is added
hydrazine hydrate (0.19 mL, 3.70 mmol). After stirring for 8 hours at room temperature,
the reaction mixture is poured into water. The orange-coloured precipitate formed is
filtered off and washed with water and then dried under vacuum to give 859 mg of an
orange-coloured solid (yield: 73%).
LCMS (Method A) MH+= 306.1, RT = 6.88 min
Step 5.8. 5-(propan-2-yl)-7-(pyrid-4-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one
To a solution of 7-bromo-5-(propan-2-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one
(0.25 g, 0.82 mmol) in 8 mL of DMF placed in a microwave reactor are added caesium
carbonate (0.8 g 2.5 mmol), 4-(4,4,5,5-tetramethyl-1I3,2-dioxaborolan-2-yl)pyridine
(0.25 g 1.22 mmol) and the catalyst PdCI2(dppf) (60 mg, 0.08 mmol). The reactor is
sealed and the mixture is stirred for 20 minutes at 150°C under microwave irradiation.
The reaction medium is diluted with an EtOAcfTHF mixture (50/50) and washed with
water and then with saturated aqueous NaCI solution. The organic phase is dried over
Na2S04 and concentrated to dryness. After purification by flash chromatography
(DCM/MeOH: 100/0 to 90/10), 45 mg of a white solid are obtained (yield: 19%).

LCMS (Method A): MH+= 305.2, RT = 4.98 min
1H NMR (400 MHz, DMSO-d6): 5 ppm 8.92 (d, 2 H) 8.23 - 8.44 (m, 4 H) 8.11 (s, 1 H) 7.90
(d, 1 H) 5.48 (br. s., 1 H)1.64(d, 6 H)
Example 6: 8-fluoro-7-(pyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one hydrochloride (compound 109)
Step 6.1.1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole-4-carboxylic acid
To a suspension of 1 H-pyrazole-4-carboxylic acid (50 g, 446 mmol) in 500 mL of DMF
are added para-toluenesulfonic acid (8.48 g, 44 mmol) and DHP (132 mL, 1561 mmol).
The reaction medium turns yellow and then black after stirring at room temperature for
20 hours. The reaction mixture is poured into saturated aqueous NaHCO3 solution and
extracted with EtOAc. The aqueous phase is acidified to pH 3 by adding 6M hydrochloric
acid solution. The precipitate formed is filtered off and washed with water and then dried
under vacuum at 50°C to give 61.2 g of a white powder (yield: 70%).
LCMS (Method D): MH+= 197.1, RT = 0.60 min
Step 6.2.1-(tetrahydro-2W-pyran-2-yl)-1H-pyrazole-4-carboxylic acid fluoride
To a solution of 1-(tetrahydro-2/-/-pyran-2-yl)-1H-pyrazole-4-carboxylic acid (31.7 g,
61 mmol) in 650 mL of DCM at 0°C are added pyridine (77 mL, 0.97 mol) and cyanogen
fluoride (41 mL, 0.48 mmol) dropwise. The reaction medium is stirred for 4 hours at room
temperature, poured into saturated aqueous NaHCO3 solution and extracted with DCM.
The organic phase is washed with water and then with saturated aqueous NaCI solution,
dried over Na2S04, filtered and concentrated to dryness to give 29.1 g of a brown oil
(yield: 91%).
LCMS (Method D): [M+NH4]+= 216.6, RT = 0.95 min
Step 6.3. W-(5-chloro-4-fluoro-2-iodophenyl)-1 -(tetrahydro-2H-pyran-2-yl)-1 H-
pyrazole-4-carboxamide
Potassium f-butoxide (12.52 g, 111.6 mmol) is added at room temperature to a solution of
5-chloro-4-fluoro-2-iodoaniline (5.0 g, 22.3 mmol) in 250 mL of anhydrous THF under
nitrogen. After stirring for 15 minutes, a solution of 1-(tetrahydro-2H-pyran-2-yl)-1H-
pyrazole-4-carboxylic acid fluoride (5.67 g, 24.6 mmol) in 30 mL of anhydrous THF is
added dropwise. The reaction mixture is stirred for 4 hours at room temperature and then
poured into saturated aqueous NaHCO3 solution and extracted with EtOAc. The organic
phase is washed with saturated aqueous NaCI solution, dried over Na2S04 and
concentrated to dryness. After purification by flash chromatography on silica

(cyclohexene/EtOAc: 95/5 to 80/20), a red solid is obtained, which is purified by flash
chromatography on amine phase (DCM) to give 2.84 g of a white solid (yield: 31%).
LCMS (Method E): MH+= 404.0, RT = 2.29 min
Step 6.4. A/-(5-chloro-4-fluoro-2-iodophenyl)-1 -(tetrahydro-2H-pyran-2-yl)-W-(2,2,2-
trifIuoroethyl)-1H-pyrazole-4-carboxamide
To a solution of /V-(5-chloro-4-fluoro-2-iodophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-
pyrazole-4-carboxamide (1.26 g, 3.13 mmol) in 55 mL of anhydrous MeTHF heated to
65°C are added potassium f-butoxide (421 mg, 3.76 mmol) and 2,2,2-trifluoroethyl
trifluoromethanesulfonate (0.54 mL, 3.76 mmol). The reaction mixture is stirred for
2 hours at 65°C, and then cooled, poured into saturated aqueous NaHCO3 solution and
extracted with EtOAc. The organic phase is washed with saturated aqueous NaCI
solution, dried over Na2S04 and concentrated to dryness. After purification by flash
chromatography on silica (DCM/EtOAc: 100/0 to 95/5), 2.32 g of an orange-coloured solid
are obtained (yield: 73%).
LCMS (Method G): MH+= 404.0, RT = 1.82 min
Step 6.5. 7-chloro-8-fluoro-2-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one
The catalyst Pd(PPh3)4 (630 mg, 0.55 mmol) and potassium acetate (890 mg, 9.0 mmol)
are added to a solution of A/-(5-chloro-4-fluoro-2-iodophenyl)-1-(tetrahydro-2H-pyran-2-
yl)-/V-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carboxamide (2.2 g, 4.5 mmol) in 10 mL of
anhydrous DMF placed in a microwave reactor under nitrogen. The reactor is sealed and
the reaction mixture is stirred for 15 minutes at 90°C under microwave irradiation. A
further amount of catalyst Pd(PPh3)4 (630 mg, 0.55 mmol) and of potassium acetate
(890 mg, 9.0 mmol) are added to the reaction medium, which is stirred for 15 minutes at
110°C under microwave irradiation. The mixture is cooled, poured into water and
extracted with EtOAc. The organic phase is washed with saturated aqueous NaCI
solution, dried over Na2S04 and concentrated to dryness. After purification by flash
chromatography on silica (DCM/EtOAc: 100/0 to 95/5) and then (cyclohexene/EA: 90/10)
and DCM (100%), 260 mg of a white solid are obtained (yield: 57%).
LCMS (Method G): MH+ = 403.9, RT = 2.59 min
Step 6.6. 8-11uoro-7-(pyrid-2-yl)-2-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-
1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one
According to the process described in Step 1.6., 2-pyridyltri-n-butylstannane (4.40 mL,
11.5 mmol) and the catalyst Pd(fBu3P)2 (199 mg, 0.39 mmol) are added to a solution of 7-

chloro-8-fluoro-2-(tetrahydro-2H-pyran-2-yI)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one (526 mg, 1.30 mmol) in 10 mL of anhydrous DMF under
nitrogen placed in a microwave reactor. The reactor is sealed and the reaction mixture is
stirred for 20 minutes at 130°C under microwave irradiation. The mixture is poured into
saturated aqueous NaHCO3 solution and extracted with EtOAc. The organic phase is
washed with water, with saturated aqueous NaCI solution, dried over Na2S04 and
concentrated to dryness. After purification by flash chromatography on silica
(cyclohexene/EtOAc: 90/10 to 70/30 and then DCM/acetone: 98/2 to 90/10), 72 mg of a
white powder are obtained (yield: 12%).
LCMS (Method E): MH+ = 447.0, RT = 2.44 min
Step 6.7. 8-fluoro-7-(pyrid-2-yl)-5-(2,2,2-trifluoroethyI)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one hydrochloride
The product is obtained according to the procedure described in Step 1.7. by treating 8-
fluoro-7-(pyrid-2-yl)-2-(tetrahydro-2/-/-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one with HCI in dioxane (4M). It is in the form of a white powder
(hydrochloride; yield 75%).
LCMS (Method D): MH+ = 363.1, RT = 1.69 min
1H NMR (500 MHz, DMSO-d6): 5 ppm 8.81 - 8.83 (m, 1 H) 8.52 (br. s., 1 H) 8.21 (d, 1 H)
8.13 (d, 1 H)8.03(td, 1 H) 7.90- 7.93 (m, 1 H) 7.52 (ddd, 1 H) 5.35 (d, 1H)5.32(d, 1H)
Example 7: 7-(2-chloropyrid-3-yl)-5-(2,2,2-trif!uoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one (compound 111)
Step 7.1.1-(tetrahydro-2W-pyran-2-yl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 2-
(tetrahydro-2H-pyran-2-yl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one
To a suspension of 7-bromo-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-bromo-2-(tetrahydro-2H-pyran-2-yl)-5-
(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one [described in Step 1.5.]
(8.0 g, 18.6 mmol) in 200 mL of DMF is added pinacol diborane (18.9 g, 74.4 mmol). The
mixture is heated to 60°C under nitrogen, followed by addition of potassium acetate
(4.6 g, 46.5 mmol) and the catalyst PdCI2(dppf) (3.04 g, 3.72 mmol). The solution is
heated for 3 hours at60°C, and then cooled to room temperature and poured into
saturated aqueous NaHCO3 solution. After extraction with EtOAc, the organic phase is

washed with saturated aqueous NaCI solution, dried over Na2S04 and concentrated to
dryness. A black oil is obtained, to which is added diisopropyl ether, leading to the
formation of a black solid. After filtering and concentrating the filtrate, a yellow oil is
obtained, which is taken up in a petroleum ether (40-65°C)/diisopropyl ether mixture,
leading to precipitation of a pale yellow solid. After filtering off and drying the precipitate
under vacuum, 5.10 g of a pale yellow solid are obtained (first crop).
The filtrate is concentrated. Saturated aqueous NaHCO3 solution and 10% THF are
added to the yellow oil obtained. The mixture is stirred vigorously at room temperature for
12 hours and then acidified with molar hydrochloric acid solution, and extracted with
EtOAc. The organic phase is washed with saturated aqueous NaCI solution, dried over
Na2S04 and concentrated to dryness to give a yellow solid, which is taken up in
petroleum ether. After filtering off and drying under vacuum, 1.44 g of a white solid are
obtained (second crop).
The two crops are combined and taken up in diisopropyl ether. After filtering off and
drying, 6.54 g of a white powder are obtained (yield: 74%).
LCMS (Method F): MH+ = 478.0, RT = 2.80 min
Step 7.2. 7-(2-chloropyrid-3-yI)-1 -(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-
1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-(2-chloropyrid-3-yl)-2-
(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4W-pyrazolo[4,3-
c]quinolin-4-one
To a solution of 1-(tetrahydro-2H-pyran-2-yl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 2-(tetrahydro-
2H-pyran-2-yl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one (100 mg, 0.1 mmol) in 3 ml_ of DMF under
nitrogen at 95°C are added the catalyst PdCI2(dppf) (17 mg, 0.02 mmol), caesium
carbonate (136 mg, 0.42 mmol), 0.5 ml_ of degassed water and 3-bromo-2-chloropyridine
(40 mg, 0.21 mmol). The reaction mixture is stirred for 1.5 hours 95°C under nitrogen,
cooled to room temperature, concentrated and taken up in EtOAc. The solution is washed
i with water and then with saturated aqueous NaCI solution, dried over Na2S04, filtered
and concentrated to dryness to give a black wax. After purification by flash
chromatography on silica (DCM/EtOH: 100/0 to 95/5), 38 mg of a yellow solid are
obtained (yield = 79%).
LCMS (Method G): MH+ = 463.3, RT = 1.66 min
Step 7.3. 7-(2-chIoropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one

To a solution of 7-(2-chloropyrid-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-
1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-(2-chloropyrid-3-yl)-2-(tetrahydro-2H-
pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one (1.6 g,
3.46 mmol) in 34 mL of DCM, is added a 4M solution of hydrogen chloride in dioxane
(8.5 mL, 34.6 mmol). The mixture is stirred for 3 hours at room temperature and
concentrated to dryness. After purification by flash chromatography on amine phase
(DCM/EtOH: 100/0 to 90/10), 189 mg of a white solid are obtained (yield = 15%).
LCMS (Method A): MH+ = 379.2, RT = 6.91 min
1H NMR (400 MHz, DMSO-d6): 5 ppm 8.51 (dd, 1 H) 8.47 (br. s., 1 H) 8.29 (d, 1 H) 7.95
(dd, 1 H) 7.90 (s, 1 H) 7.61 (dd, 1 H) 7.53 (d, 1 H) 5.36 (d, 1 H) 5.31 (dd, 1 H)
Example 8: 8-chloro-7-(pyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one hydrochloride (compound 194)
Step 8.1.8-chloro-7-(pyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dlhydro-4H-pyrazolo[4,3-
c]quinolin-4-one
To a suspension of 7-(pyrid-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-2,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-(pyrid-2-yl)-2-(tetrahydro-2H-pyran-2-yl)-
5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one [described in Step
1.5.] (1.6 g, 3.73 mmol) in 32 mL of acetic acid is added /V-chlorosuccinimide (2.49 g,
18.67 mmol). The reaction mixture is stirred for 3 hours at 80°C, cooled to room
temperature and concentrated to dryness to give a yellow solid, which is dissolved in
DCM. The solution is washed with saturated aqueous NaHCO3 solution and then with
saturated aqueous NaCI solution, dried over Na2S04, filtered and concentrated to give a
yellow solid. The solid is taken up in DCM. After filtering off and drying, 542 mg of a white
solid are obtained (yield: 35%).
LCMS (Method A): MH+ = 379.2, RT = 6.93 min
Step 8.2. 8-chloro-7-(pyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one hydrochloride
To a solution of 8-chloro-7-(pyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one (532 mg, 1.40 mmol) in a DCM/MeOH mixture (50/50) is added a 4M
solution of hydrogen chloride in dioxane (3.5 mL, 14.1 mmol). The suspension is stirred at
room temperature and then filtered and dried under vacuum to give 420 mg of a white
powder (hydrochloride, 0.06 H20; yield: 72%)
LCMS (Method A): MH+ = 379.2, RT = 6.91 min

1H NMR (400 MHz, DMSO-d6): 5 ppm 8.77 - 8.83 (m, 1 H) 8.52 (br. s., 1 H) 8.40 (s, 1 H)
8.06 (td, 1 H) 7.96 (s, 1 H) 7.77 (d, 1 H) 7.54 - 7.59 (m, 1 H) 5.35 (d, 1 H) 5.30 (d, 1 H)
Example 9: 8-bromo-7-(pyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one hydrochloride (compound 195)
Step 9.1. 8-bromo-7-(pyrid-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trlfluoroethyl)-
1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 8-bromo-7-(pyrld-2-yl)-2-
(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4W-pyrazolo[4,3-
c]quinolin-4-one
To a solution of 7-(pyrid-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-2,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-(pyrid-2-yl)-2-(tetrahydro-2H-pyran-2-yl)-
5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one [described in Step
1.5.] (100 mg, 0.23 mmol) in 2 ml_ of acetonitrile placed in a microwave reactor under
nitrogen are added A/-bromosuccinimide (50 mg, 0.28 mmol) and the catalyst Pd(OAc)2
(2.6 mg, 0.01 mmol). The reactor is sealed and the reaction mixture is stirred
for 15 minutes at 100°C under microwave irradiation under nitrogen. Since the reaction is
incomplete, further /V-bromosuccinimide (17 mg, 0.1 mmol) and catalyst Pd(OAc)2
(2.6 mg, 0.01 mmol) are added to the reaction mixture, which is stirred for a further
10 minutes at 100°C under microwave irradiation. The mixture is diluted in EtOAc, and
the solution is washed with water and then with saturated aqueous NaCI solution, dried
over Na2S04, filtered and concentrated to dryness. After purification by flash
chromatography on silica (DCM/EtOAc: 90/10 to 80/20), 72 mg of a yellow solid are
obtained (yield: 43%).
LCMS (Method A): MH+ = 507.0, RT = 8.88 min
Step 9.2. 8-bromo-7-(pyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one hydrochloride
The product is obtained according to the procedure described in Step 1.7. by treating 8-
bromo-7-(pyrid-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one and 8-bromo-7-(pyrid-2-yl)-2-(tetrahydro-2H-pyran-2-yl)-5-
(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one with 4M HCI in dioxane,
in the form of a white powder (hydrochloride, 0.4 H20; yield 94%).
LCMS (Method A): MH+ = 425.2, RT = 7.00 min
1H NMR (400 MHz, DMSO-d6): 5 ppm 8.77 - 8.84 (m, 1 H) 8.58 (s, 1 H) 8.51 (br. s., 1 H)
8.04 - 8.17 (m, 1 H) 7.93 (s, 1 H) 7.75 (dd, 1 H) 7.56 - 7.65 (m, 1 H) 5.33 (d, 1 H) 5.29 (d,
1 H)

Example 10: 4-oxo-7-(pvrid-4-vl)-5-(2.2.2-trifluoroethvn-4.5-dihvdro-2H-pyrazolor4.3-
c]quinoline-8-carbonitrile hydrochloride (compound 201)
Step 10.1. 4-oxo-7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1 -{[2-(trimethylsilyl)ethoxy]-
methyl}-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline-8-carbonitrile and 4-oxo-7-(pyrid-4-
yO-S^^^-trifluoroethyO^^^-ttrimethylsilylJethoxylmethylM.S-dihydro^W-
pyrazolo[4,3-c]quinoline-8-carbonitrile
8-Bromo-7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-2,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one [obtained according to the protocols described
in Step 4.2. with 2,2,2-trifluoroethyi trifluoromethanesulfonate and Step 9.1.] (1.0 g,
1.88 mmol), zinc cyanide (0.66 g, 5.64 mmol), the catalyst Pd(PPh3)4 (390 mg,
0.34 mmol) and 16 mL of anhydrous DMF are successively introduced into a microwave
reactor under nitrogen. The reactor is sealed and the mixture is stirred vigorously for 10
minutes at 180°C under microwave irradiation. After cooling, the mixture is poured into
saturated aqueous NaHCO3 solution. After extraction with EtOAc, the organic phase is
washed with saturated aqueous NaCI solution, dried over Na2S04 and concentrated to
dryness. After purification by flash chromatography on silica (diisopropyl ether/EtOAc:
90/10 to 20/80 and then diisopropyl ether/EtOAc: 50/50), 342 mg of a white powder are
obtained (yield: 36%).
LCMS (Method A): MH+ = 500.0, RT = 8.59 min
Step 10.2. 4-oxo-7-(pyrJd-4-yl)-5-(2,2,2-trifluoroethyl)-4,5-dihydro-2H-pyrazolo[4,3-
c]quinoline-8-carbonitrile hydrochloride
The product is obtained according to the procedure described in Step 4.3. starting with 4-
oxo-7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-4,5-dihydro-
2H-pyrazolo[4,3-c]quinoline-8-carbonitrile and 4-oxo-7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-
2-{[2-(trimethylsilyl)ethoxy]methyl}-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline-8-carbonitrile,
in the form of a white powder (1.8 hydrochloride; yield 15%).
LCMS (Method C): MH+ = 369.9, RT = 6.82 min
1H NMR (400 MHz, DMSO-d6): 5 ppm 8.92 (d, 2 H) 8.80 (s, 1 H) 8.61 (br. s, 1 H) 8.08 (s,
1 H) 7.90 (d, 2 H) 5.47 (d, 1 H) 5.43 (d, 1H)
Example 11: 4-oxo-7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-4,5-dihydro-2H-pyrazolo[4,3-
c]quinoline-8-carboxylic acid hydrochloride (compound 202)

A solution of 4-oxo-7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1-{[2-(trimethylsilyl)ethoxy]-
methyl}-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline-8-carbonitrile and 4-oxo-7-(pyrid-4-yl)-5-
(2I2,2-trifluoroethyl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-415-dihydro-2H-pyrazolo[4,3-
c]quinoline-8-carbonitrile [described in Step 10.1] (0.23 g, 0.46 mmol) in a mixture of
5 mL of acetic acid and 5 mL of concentrated hydrochloric acid is stirred for 80 minutes at
160°C. The mixture is concentrated to dryness. The brown residue obtained is taken up
in MeOH and precipitated from ethyl ether. After filtering off and drying under vacuum,
182 mg of a beige-coloured powder are obtained (hydrochloride, 2.8 H20; yield: 93%).
LCMS (Method A): MH+ = 389.0, RT = 4.37 min
1H NMR (400 MHz, DMSO-d6): 5 ppm 13.33 (br. s., 1 H) 8.88 - 8.97 (m, 3 H) 8.55 (br. s.,
1 H) 7.96 (d, 2 H) 7.81 (s, 1 H) 5.40 (d, 1 H) 5.36 (d, 1 H)
Example 12: 3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-
7-yl]pyridine-2-carboxylic acid hydrochloride (compound 203)
Step 12.1. 3-[4-oxo-1-(tetrahydro-2W-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-4,5-dihydro-
1H-pyrazolo[4,3-c]quinolin-7-yl]pyridine-2-carboxylic acid and 3-[4-oxo-2-
(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyridine-2-carboxylic acid
Sodium hydroxide (1M) (3.1 mL, 3.1 mmol) is added to a solution of methyl 3-[4-oxo-1-
(tetrahydro-2/-/-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-
7-yl]pyridine-2-carboxylate [obtained via the process described in Step 7.2.] (1.0 g,
2.06 mmol) in 15 mL of DMSO at 40°C. The reaction mixture is stirred for 15 minutes at
40°C and then poured into water and acidified with 30 mL of 0.1M hydrochloric acid
solution to reach pH = 3-4. After extraction with EtOAc, the organic phase is washed with
saturated NaCI solution, dried over Na2S04 and concentrated to dryness to give 890 mg
of a white solid (yield: 92%).
LCMS (Method A): MH+ = 473.1, RT = 6.73 min
i Step 12.2. 3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-
yl]pyridine-2-carboxylic acid hydrochloride
To a solution of 3-[4-oxo-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-4,5-dihydro-
1H-pyrazolo[4,3-c]quinolin-7-yl]pyridine-2-carboxylic acid and 3-[4-oxo-2-(tetrahydro-2H-
pyran-2-yl)-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]pyridine-2-
! carboxylic acid (50 mg, 0.11 mmol) in 1 mL of DCM is added a 4M solution of hydrogen
chloride in dioxane (0.26 mL, 1.06 mmol). After stirring at room temperature for 1 hour,

the reaction mixture is filtered. The solid is washed with DCM and dried under vacuum to
give 42 mg of a white powder (hydrochloride; yield: 93%).
LCMS (Method E): MH+ = 389.0, RT = 1.58 min
1H NMR (400 MHz, DMSO-d6): 5 ppm 8.68 (dd, 1 H) 8.46 (s, 1 H) 8.26 (d, 1 H) 7.99 (dd,
1 H) 7.81 (s, 1 H) 7.70 (dd, 1 H) 7.42 (dd, 1 H) 5.35 (d, 1 H) 5.30 (d, 1 H)
Example 13: 4-oxo-7-(pvrid-4-vl)-5-(2,2,2-trifluoroethvl)-4,5-dihvdro-2H-pyrazolo[4,3-
c]quinoline-8-carboxamide (compound 205)
A mixture of 4-oxo-7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-4,5-dihydro-2H-pyrazolo[4,3-
c]quinoline-8-carboxylic acid [Example 11] (38 mg, 0.10 mmol), ammonium bicarbonate
(46 mg, 0.59 mmol) and di-terf-butyl dicarbonate (47 mg, 0.22 mmol) in 1 mL of
pyridine/EtOAc (1/1) is stirred at room temperature under nitrogen for 16 hours and then
concentrated to dryness. After purification by preparative HPLC on a C18 reverse phase
[eluent A: H2O/0.1M CH3COONH4 (90/10); eluent B: CH3CN/0.1M CH3COONH4 (90/10);
gradient A/B: 95/5 to 50/50], 3 mg of a white powder are obtained (8%).
LCMS (Method C): MH+ = 388.0, RT = 5.78 min
1H NMR (500 MHz, DMSO-d6): 5 ppm 14.37 (br. s., 1 H) 8.65 - 8.68 (m, 2 H) 8.47 (br. s.,
1 H) 8.36 (s, 1 H) 7.99 (s, 1 H) 7.77 (s, 1 H) 7.53 (br. s., 1 H) 7,48 - 7.50 (m, 2 H) 5.43 (d,
1 H) 5.39 (d, 1 H)
Example 14: 7-[2-(morpholin-4-ylcarbonyl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one hydrochloride (compound 206)
Step 14.1. 7-[2-(morpholin-4-ylcarbonyl)pyrid-3-yl]-1-(tetrahydro-2H-pyran-2-yl)-5-
(2,2,2-trifluoroethyI)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-[2-
(morpholin-4-ylcarbonyl)pyrid-3-yl]-2-(tetrahydro-2W-pyran-2-yl)-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one
To a solution of 3-[4-oxo-1-(tetrahydro-2/-/-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-4,5-dihydro-
1H-pyrazolo[4,3-c]quinolin-7-yl]pyridine-2-carboxylic acid and 3-[4-oxo-2-(tetrahydro-2H-
pyran-2-yl)-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1/-/-pyrazolo[4,3-c]quinolin-7-yl]pyridine-2-
carboxylic acid [described in Step 12.1.] (100 mg, 0.21 mmol) in 5 mL of anhydrous THF
at room temperature under nitrogen are successively added triethylamine (60 uL,
0.53 mmol), PyBOP® (132 mg, 0.25 mmol) and, after stirring for 10 minutes, morpholine
(22 to uL, 22 mg, 0.25 mmol). The solution is stirred for 3 hours, poured into saturated
aqueous NaHCO3 solution and extracted with EtOAc. The organic phase is washed with
saturated aqueous NaCI solution, dried over Na2S04, and concentrated to dryness. After

purification by flash chromatography (DCM/EtOH: 100/0 to 95/5), 46 mg of a white solid
are obtained (yield: 36%).
LCMS (Method A): MH+ = 542.1, RT = 7.18 min
Step 14.2. 7-[2-(morpholin-4-ylcarbonyl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one hydrochloride
The product is obtained according to the procedure described in Step 1.7. starting with 7-
[2-(morpholin-4-ylcarbonyl)pyrid-3-yl]-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-
1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-[2-(morpholin-4-ylcarbonyl)pyrid-3-yl]-
2-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one, in the form of a white powder (hydrochloride, 0.7 H20; yield 78%).
LCMS (Method A): MH+ = 458.1, RT = 5.95 min
1H NMR (400 MHz, DMSO-d6): 6 ppm 8.68 (dd, 1 H) 8.49 (br. s., 1 H) 8.28 (d, 1 H) 8.03
(dd, 1 H) 7.81 (s, 1 H) 7.66 (dd, 1 H) 7.46 (dd, 1 H) 5.33 (d, 1 H) 5.29 (d, 1 H) 3.45 - 3.52
(m, 2 H) 3.33 - 3.41 (m, 2 H) 3.05 - 3.11 (m, 2 H) 2.98 - 3.04 (m, 2 H)
Example 15: /V-{3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyrid-2-yl}acetamide hydrochloride (compound 223)
Step 15.1 N-{3-[4-oxo-1 -(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-4,5-
dihydro-1 H-pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-yl}acetamide and W-{3-[4-oxo-2-
(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyrid-2-yl}acetamide
Acetic anhydride (1.28 ml_, 13.5 mmol) is added to a solution of 7-(2-aminopyrid-3-yl)-1-
(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-
4-one and 7-(2-aminopyrid-3-yl)-2-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one [described in Step 2.1.] (3.0 g, 6.77 mmol) in
34 mL of pyridine heated to 80°C. After stirring at 80°C for 2.5 hours, the reaction
medium is cooled and concentrated to dryness. After purification by flash
chromatography on silica (DCM/EtOAc: 100/0 to 70/30), 2.1 g of a white powder are
obtained (yield 63%).
LCMS (Method A): MH+ = 486.2, RT = 6.69 min
Step 15.2. W-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1 H-pyrazolo[4,3-
c]quinolin-7-yl]pyrid-3-yl}acetamide hydrochloride
The product is obtained according to the procedure described in Step 3.4. starting with
W-{3-[4-oxo-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-

pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-yl}acetamide and A/-{3-[4-oxo-2-(tetrahydro-2/-/-pyran-
2-yl)-5-(2I2,2-trifluoroethyl)-4,5-dihydro-1/-/-pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-
yl}acetamide, in the form of a white powder (hydrochloride, 1.5 H20; yield 66%).
LCMS (Method A): MH+ = 402.0, RT = 5.56 min
1H NMR (400 MHz, DMSO-d6): 5 ppm 10.34 (s, 1 H) 8.52 (dd, 1 H) 8.44 (s, 1 H) 8.28 (d,
1 H) 8.05 (dd, 1 H) 7.82 (s, 1 H) 7.54 (dd, 1 H) 7.48 (dd, 1 H) 5.33 (d, 1 H) 5.29 (d, 1 H)
1.91 (s, 3H)
Example 16: W-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-2H-pyra2olo[4,3-
c]quinolin-7-yl]phenyl}methanesulfonamide (compound 232)
Step 16.1. A/-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-1 -{[2-(trimethylsilyl)ethoxy]methyl}-4,5-
dihydro-2W-pyrazolo[4,3-c]quinolin-7-yl]phenyl}methanesulfonamide and A/-{2-[4-
oxo-5-(2,2,2-trifluoroethyl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-4,5-dihydro-2H-
pyrazolo[4,3-c]quinolin-7-yl]phenyl}methanesulfonamide
Methanesulfonyl chloride (33 uL, 0.41 mmol) is added to a solution of 7-(2-aminophenyl)-
5-(2,2,2-trifluoroethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-2,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one and 7-(2-aminophenyl)-5-(2,2,2-trifluoroethyl)-2-{[2-(trimethylsilyl)-
ethoxy]methyl}-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one [obtained according to the
process described in Step 7.2. starting with 2-chloroaniline and 7-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)-5-(2,2,2-trifluoroethyl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-2,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one obtained according to the process described in
Step 7.1. starting with 7-bromo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one and 7-bromo-2-{[2-(trimethylsilyl)ethoxy]methyl}-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one described in Step 3.1.] (0.20 g, 0.41 mmol) in
2 mL of pyridine at room temperature. After stirring for 1 hour, the reaction medium is
poured into molar hydrochloric acid solution and extracted with EtOAc. The organic
phase is washed with water, dried over Na2S04 and concentrated to dryness. After
purification by flash chromatography on silica (cyclohexene/EtOAc: 100/0 to 50/50),
195 mg of a white powder are obtained (yield: 84%).
LCMS (Method A): MH+ = 567.0, RT = 9.70 min
Step 16.2. W-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-2H-pyrazolo[4,3-
c]quinolin-7-yl]phenyl}methanesulfonamide
The product is obtained according to the procedure described in Step 4.3. starting with A/-
{2-[4-oxo-5-(2,2,2-trifluoroethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-4,5-dihydro-2H-
pyrazolo[4,3-c]quinolin-7-yl]phenyl}methanesulfonamide and A/-{2-[4-oxo-5-(2,2,2-

trifluoroethyl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-4,5-dihydro-2H-pyrazolo[4,3-c]quih'oIin-7-
yl]phenyl}methanesulfonamide, in the form of a white powder (yield 74%).
LCMS (Method B): MH+ = 437.1, RT = 13.31 min
1H NMR (400 MHz, DMSO-d6): 5 ppm 14.29 (br. s., 1 H) 9.08 (br. s., 1 H) 8.39 (br. s, 1 H)
8.24 (d, 1 H) 7.79 (s, 1 H) 7.37 - 7.56 (m, 5 H) 5.35 (d, 1 H) 5.33 (d, 1 H) 2.74 (s, 3 H)
Example 17: W-methyl-W-{3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihyclro-1 H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-yl}acetamide hydrochloride (compound 241)
Step 17.1. A/-methyl-W-{3-[4-oxo-1 -(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-
4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-yl}acetamlde and W-methyl-A/-
{3-[4-oxo-2-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-4J5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-yl}acetamide
A/-{3-[4-Oxo-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-yl}acetamide and A/-{3-[4-oxo-2-(tetrahydro-2/-/-pyran-
2-yl)-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-
yljacetamide [described in Step 15.1] (0.69 g, 1.43 mmol) and methyl iodide (0.27 mL,
4.33 mmol) are successively added to sodium hydride (60% suspension in oil, 0.17 g,
4.33 mmol) in 16 mL of anhydrous DMF under nitrogen at room temperature. After stirring
for 15 minutes, the reaction mixture is poured into molar potassium hydrogen sulfate
solution and extracted with EtOAc. The organic phase is washed with water and with
saturated aqueous NaCI solution, dried over Na2S04 and concentrated to dryness. After
purification by flash chromatography on silica (DCM /EtOAc: 100/0 to 50/50), 0.57 g of a
white powder is obtained (yield: 80%).
LCMS (Method A): MH+ = 500.3, RT = 1.16 min
Step 17.2. A/-methyl-W-{3-[4-oxo-5-(2)2,2-trifluoroethyl)-4J5-dihydro-1 H-pyrazolo[4,3-
c]quinolin-7-yI]pyrid-2-yl}acetamide hydrochloride
The product is obtained according to the procedure described in Step 1.7. starting with A/-
methyl-A/-{3-[4-oxo-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-yl}acetamide and A/-methyl-W-{3-[4-oxo-2-(tetrahydro-
2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-
yljacetamide, in the form of a white powder (hydrochloride, 1 H20; yield 58%).
LCMS (Method A): MH+ = 416.1, RT = 6.15 min
1H NMR (400 MHz, DMSO-d6): 5 ppm 8.62 (d, 1 H) 8.46 (br. s., 1 H) 8.26 (d, 1 H) 8.03 (d,
1 H) 7.82 (s, 1 H) 7.63 (dd, 1 H) 7.38 (d, 1 H) 5.27 - 5.41 (m, 2 H) 2.97 (s, 3 H) 1.70 (s, 3
H)

Example 18: 7-[2-(1,4-diazepan-1 -yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one hydrochloride (compound 244)
Step 18.1. 7-[2-(1,4-diazepan-1 -yl)pyrid-3-yl]-1 -(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-[2-(1,4-diazepan-
1-yl)pyrid-3-yl]-2-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one
A solution of 7-(2-fluoropyrid-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-(2-fluoropyrid-3-yl)-2-(tetrahydro-2H-
pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one (1.0 g,
2.16 mmol) in 11 ml_ of homopiperazine is heated for 4 hours at 180°C under microwave
irradiation in a sealed reactor. The solution is cooled to room temperature and poured
into water. The white precipitate formed is filtered off and purified by flash
chromatography on silica (DCM/EtOH: 100/0 to 70/30). 745 mg of a white solid are
obtained (yield: 66%).
LCMS (Method A): MH+ = 527.4, RT = 5.90 min
Step 18.2. 7-[2-(1,4-diazepan-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one hydrochloride
The product is obtained according to the procedure described in Step 1.7. starting with 7-
[2-(1,4-diazepan-1 -yl)pyrid-3-yl]-1 -(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-[2-(1,4-diazepan-1-yl)pyrid-3-yl]-2-
(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-
4-one, in the form of a white powder (hydrochloride, 1 H20; yield 75%).
LCMS (Method A): MH+ = 443.2, RT = 5.13 min
1H NMR (400 MHz, DMSO-d6): 5 ppm 8.90 (br. s., 2 H) 8.44 (br. s., 1 H) 8.28 (d, 1 H)
8.24 (dd, 1 H) 7.80 (s, 1 H) 7.68 (d, 1 H) 7.47 (dd, 1 H) 7.05 (dd, 1 H) 5.35 (d, 1 H) 5.31
(d, 1 H) 3.58 - 3.62 (m, 2 H) 3.13 - 3.24 (m, 4 H) 2.98 - 3.06 (m, 2 H) 1.80 -1.89 (m, 2 H)
Example 19: 7-[2-(piperidin-1 -yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one hydrochloride (compound 245)
Step 19.1. 7-[2-(piperidin-1 -yl)pyrid-3-yl]-1 -(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-[2-(piperidin-1-
yl)pyrid-3-yl]-2-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4W-
pyrazolo[4,3-c]quinolin-4-one

A solution of 7-(2-fluoropyrid-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-(2-fluoropyrid-3-yl)-2-(tetrahydro-2H-
pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one (0.4 g,
0.896 mmol) and cyclohexylamine (0.76 g, 8.96 mmo!) in 5 mL of NMP is heated for
2 hours at 185°C in a sealed reactor under microwave irradiation. The reaction mixture is
poured into water and extracted with EtOAc. The organic phase is washed with saturated
aqueous NaCI solution, dried over Na2S04 and concentrated to dryness. After purification
by flash chromatography on silica (DCM/EtOH: 100/0 to 90/10), 232 mg of product are
obtained in the form of a solid (yield: 51%).
LCMS (Method E): MH+ = 512.1, RT = 2.01 min
Step 19.2. 7-[2-(piperidin-1 -yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one hydrochloride
The product is obtained according to the procedure described in Step 1.7. starting with 7-
[2-(piperidin-1 -yl)pyrid-3-yl]-1 ~(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-[2-(piperidin-1-yl)pyrid-3-yl]-2-(tetrahydro-
2/-/-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one, in the
form of a white powder (hydrochloride, 1.3 H20; yield 86%).
LCMS (Method A): MH+ = 428.2, RT = 6.13 min
1H NMR (250 MHz, DMSO-d6): 5 ppm 8.46 (s, 1 H) 8.31 (d, 1 H) 8.23 (dd, 1 H) 7.83 -
7.98 (m, 2 H) 7.62 (d, 1 H) 7.23 (dd, 1 H) 5.35 (d, 1 H) 5.30 (d, 1 H) 3.15 (br. s., 4 H) 1.46
(br. s.,6H)
Example 20: 7-[2-(4-cyclopropylpipera2in-1-yl)pyrid-3-yl]-5-(2,2,2-trif!uoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one hydrochloride (compound 267)
Step 20.1. 7-[2-(4-cyclopropylpiperazin-1 -yl)pyrid-3-yl]-1 -(tetrahydro-2H-pyran-2-yl)-
5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-[2-(4-
cyclopropylpiperazin-1-yl)pyrid-3-yl]-2-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one
7-(2-Chloropyrid-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one and 7-(2-chloropyrid-3-yl)-2-(tetrahydro-2H-pyran-2-yl)-5-
(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one [described in Step 7.2.]
(0.4 g, 0.86 mmol), sodium fe/t-butoxide (0.83 g, 8.64 mmol), 1-cyclopropylpiperazine
(0.69 g, 3.46 mmol), 9 mL of anhydrous DMF and the catalyst [Pd(u-Br)(tBu3P)]2 (0.14 g,
0.18 mmol) are successively introduced into a microwave reactor under argon. The
reactor is sealed and the mixture is stirred for 30 minutes at 100°C under microwave
irradiation. The mixture is cooled and adsorbed onto silica. After purification by flash

chromatography on silica (DCM/EtOAc: 100/0 to 50/50), 75 mg of a yellow powder are
obtained (yield: 16%).
LCMS (Method E): MH+ = 553.0, RT = 1.92 min
Step 20.2. 7-[2-(4-cyclopropylpiperazin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one hydrochloride
The product is obtained according to the procedure described in Step 1.7. starting with 7-
[2-(4-cyclopropylpiperazin-1-yl)pyrid-3-yl]-1-(tetrahydro-2/-/-pyran-2-yl)-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-[2-(4-cyclopropyl-
piperazin-1-yl)pyrid-3-yl]-2-(tetrahydro-2/-/-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one, in the form of a white powder (3 hydrochloride, 3H20;
yield 70%).
LCMS (Method A): MH+ = 469.2, RT = 5.32 min
1H NMR (250 MHz, DMSO-d6): 5 ppm 10.57 (br. s., 1 H) 8.46 (br. s., 1 H) 8.28 - 8.33 (m,
2 H) 7.88 (s, 1 H) 7.71 - 7.75 (m, 2 H) 7.19 (dd, 1 H) 5.38 (d, 1 H) 5.34 (d, 1 H) 3.53 (d,
2 H) 3.38 (d, 2 H) 3.03 - 3.24 (m, 4 H) 2.85 (br. s., 1 H) 1.04 (br. s., 2 H) 0.70 - 0.78 (m,
2H)
Example 21: 7-[2-(4-methyl-1,4-diazepan-1 -yI)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one hydrochloride (compound 270)
Step 21.1. 7-[2-(4-methyl-1,4-diazepan-1 -yl)pyrid-3-yl]-1 -(tetrahydro-2H-pyran-2-yl)-
5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-[2-(4-
methyl-1,4-diazepan-1-yl)pyrid-3-yl]-2-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one
To a solution of 7-[2-(1,4-diazepan-1-yl)pyrid-3-yl]-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-[2-(1,4-diazepan-1 -
yl)pyrid-3-yl]-2-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one [described in Step 18.1] (0.2 g, 0.38 mmol) in 17 mL of
MeOH is added formaldehyde (0.356 mL, 3.80 mmol) and the solution is stirred at room
temperature for 1 hour. NaBH4 (72 mg, 1.90 mmol) is added portionwise at 0°C, and
evolution of gas is observed. The reaction mixture is stirred at room temperature for
3 hours and then poured into water and extracted with EtOAc. The organic phase is
washed with saturated aqueous NaCI solution, dried over Na2S04 and concentrated to
dryness. The white solid obtained is taken up in diisopropyl ether and, after filtering off,
142 mg of product are obtained in the form of a white powder (yield: 70%).
LCMS (Method C): MH+ = 541.2, RT = 7.68 min

Step 21.2. 7-[2-(4-methyl-1,4-diazepan-1 -yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one hydrochloride
The product is obtained according to the procedure described in Step 1.7. starting with 7-
[2-(4-methyl-1,4-diazepan-1 -yl)pyrid-3-yl]-1 -(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-[2-(4-m ethyl-1,4-
diazepan-1-yl)pyrid-3-yl]-2-(tetrahydro-2H-pyran-2-yl)-5-(2>2,2-trifluoroethyl)-1,5-dihydro-
4/-/-pyrazolo[4,3-c]quinolin-4-one, in the form of a white powder (2 hydrochloride, 5.5
H20; yield: 28%).
LCMS (Method A): MH+ = 457.2, RT = 5.21 min
1H NMR (250 MHz, DMSO-d6): 5 ppm 9.61 (br. s., 1 H) 8.40 (br. s., 1 H) 8.18 - 8.29 (m,
2 H) 7.76 (s, 1 H) 7.64 (dd, 1 H) 7.45 (d, 1 H) 7.01 (dd, 1 H) 5.26 - 5.42 (m, 2 H) 2.91 -
4.04 (m, 8 H) 2.73 - 2.80 (m, 3 H) 1.90 (br. s., 2 H)
Example 22: 7-[2-(4-cyclopropyl-1,4-diazepan-1 -yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-
1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one hydrochloride (compound 271)
Step 22.1. 7-[2-(4-cyclopropyl-1,4-diazepan-1 -yl)pyrid-3-yl]-1 -(tetrahydro-2H-pyran-
2-yl)-5-(2,2,2-trifluoroethyI)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-[2-
(4-cyclopropyl-1,4-diazepan-1-yl)pyrid-3-yl]-2-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one
To a solution of 7-[2-(1,4-diazepan-1-yl)pyrid-3-yl]-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-[2-(1,4-diazepan-1-
yl)pyrid-3-yl]-2-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1I5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one [described in Step 18.1] (0.1 g, 0.19 mmol) dissolved in
8 mL of MeOH is added (l-methoxycyclopropoxy)trimethylsilane (36.5 mg, 0.23 mmol).
The mixture is stirred for 30 minutes at room temperature, followed by addition of
NaBH3CN (24 mg, 0.38 mmol). Evolution of gas is observed, and the mixture is stirred for
72 hours. The resulting mixture is poured into aqueous solution, extracted with EtOAc,
washed with saturated aqueous NaCI solution, dried over anhydrous Na2S04, filtered and
concentrated to dryness. 85 mg of a white solid are obtained (yield: 78%).
LCMS (Method A): MH+ = 567.1, RT = 6.11 min
Step 22.2. 7-[2-(4-cyclopropyM ,4-diazepan-1 -yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-
1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one hydrochloride
The product is obtained according to the procedure described in Step 1.7. starting with 7-
[2-(4-cyclopropyl-1,4-diazepan-1 -yl)pyrid-3-yl]-1 -(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-[2-(4-cyclopropyl-1,4-

diazepan-1-yl)pyrid-3-y[]-2-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one, in the form of a white powder (hydrochloride, 3.6 H20;
yield 57%).
LCMS (Method A): MH+ = 483.2, RT = 5.36 min
1H NMR (250 MHz, DMSO-d6): 5 ppm 9.95 (br. s., 1 H) 8.44 (br. s., 1 H) 8.19 - 8.29 (m,
2 H) 7.77 (s, 1 H) 7.66 (dd, 1 H) 7.46 (d, 1 H) 7.02 (dd, 1 H) 5.33 (q, 2 H) 3.54 (br. s., 2 H)
3.12 - 3.47 (m, 4 H) 3.06 (br. s., 2 H) 2.88 (br. s., 1 H) 1.96 (br. s., 2 H) 1.00 - 1.06 (m,
2 H) 0.72 - 0.84 (m, 2 H)
Example 23: 7-[2-(3-fluoropyrrolidin-1-yI)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one (compound 272)
Step 23.1. 7-[2-(3-fluoropyrrolidin-1-yl)pyrid-3-yl]-1-(tetrahydro-2H-pyran-2-yI)-5-
(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-[2-(3-
fluoropyrrolidin-1-yl)pyrid-3-yl]-2-(tetrahydro-2W-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-
1,5-dihydro-4W-pyrazolo[4,3-c]quinolin-4-one
To a solution of diethylaminosulfur trifluoride (32 mg, 0.20 mmol) in 4 mL of DCM cooled
to -70°C is added 7-[2-(3-hydroxypyrrolidin-1-yl)pyrid-3-yl]-1-(tetrahydro-2H-pyran-2-yl)-5-
(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-[2-(3-
hydroxypyrrolidin-1-yl)pyrid-3-yl]-2-(tetrahydro-2/-/-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one [obtained according to the process described in
Step 18.1. starting with pyrrolidin-3-ol] (85 mg, 0.17 mmol) dissolved in 3 mL of DCM.
The mixture is stirred for 2 hours at room temperature, saturated aqueous NaHCO3
solution is then added and the resulting mixture is extracted with DCM. The organic
phase is washed with saturated aqueous NaCI solution, dried over Na2S04 and
concentrated to dryness. After purification by flash chromatography on silica (DCM/EtOH:
100/0 to 90/10), 38 mg of a white solid are obtained (yield: 43%).
LCMS (Method E): MH+ = 516.1, RT = 1.89 min
Step 23.2. 7-[2-(3-fluoropyrroIidin-1 -yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one hydrochloride
The product is obtained according to the procedure described in Step 1.7. starting with 7-
[2-(3-fluoropyrrolidin-1-yl)pyrid-3-yl]-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-
1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-[2-(3-fluoropyrrolidin-1-yl)pyrid-3-yl]-
2-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one, in the form of a white powder (hydrochloride, H20; yield 47%).
LCMS (Method A): MH+ = 432.1, RT = 5.50 min

1H NMR (250 MHz, DMSO-d6): 5 ppm 8.45 (br. s., 1 H) 8.26 (d, 1 H) 8.17 (dd, 1 H) 7.82
(s, 1 H) 7.76 (br. s., 1 H) 7.41 (d, 1 H) 7.02 (br. s., 1 H) 5.15 - 5.39 (m, 3 H) 3.18 - 3.48
(m, 4 H) 1.83-2.22 (m, 2 H)
Example 24: 7-(2-hydroxypyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one (compound 274)
Step 24.1. 7-(2-methoxypyrid-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-(2-methoxypyrid-
3-yl)-2-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one
To a solution of 7-bromo-1-(tetrahydro-2H-pyran-2-yl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one and 7-bromo-3-(tetrahydro-2/-/-pyran-2-yl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one [described in Step 1.4.] (0.40 g, 0.93 mmol) dissolved in 10 mL of DMF
placed in a microwave reactor are added 2-methoxy-3-pyridineboronic acid (0.284 g,
1.86 mmol), Cs2CO3 (1.2g, 3.72 mmol), 1 mL of degassed water and the catalyst
PdCI2(dppf) (0.159 mg, 0.2 mmol). The reactor is sealed and the mixture is stirred at
110°C under microwave irradiation for 10 minutes under nitrogen. The reaction mixture is
cooled, poured into water and extracted with EtOAc. The organic phase is washed with
saturated aqueous NaCI solution, dried over Na2S04 and concentrated to dryness. After
purification by flash chromatography on silica (DCM/EtOH: 100/0 to 90/10), 103 mg of a
yellow solid are obtained (yield: 24%).
LCMS (Method A): MH+ = 459.2, RT = 9.04 min
Step 24.2. 7-(2-hydroxypyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one
To a solution of 7-(2-methoxypyrid-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-(2-methoxypyrid-3-yl)-
2-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one (90 mg, 0.20 mmol) in a DCM/MeOH mixture (50/50) is added a 4M
solution of hydrogen chloride in anhydrous dioxane (2 mL, 2.45 mmol). The solution is
stirred at room temperature for 10 days and then poured into diisopropyl ether. The
precipitate formed is filtered off and washed with EtOH. 52 mg of a white solid are
obtained (yield: 65%).
LCMS (Method A): MH+ = 361.0, RT = 5.91 min
1H NMR (250 MHz, DMSO-d6): 5 ppm 14.30 (br. s., 1 H) 11.92 (br. s., 1 H) 8.20 - 8.80 (m,
1 H) 8.17 (d, 1 H) 8.08 (br. s., 1 H) 7.85 (d, 2 H) 7.48 (d, 1 H) 6.38 (t, 1 H) 5.31 (q, 2 H)

Example 25: 7-(1 -oxidopyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one hydrochloride (compound 275)
Step 25.1. 7-(1 -oxidopyrld-2-yl)-1 -(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-
1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-(1 -oxidopyrid-2-yl)-2-
(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one
mefa-Chloroperbenzoic acid (585 mg, 2.62 mmol) is added at 0°C to a suspension of 7-
(pyrid-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one and 7-(pyrid-2-yl)-2-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-
trifluoroethyl)-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one (280 mg, 0.65 mmol) in 5 m!_
of DCM. The mixture is stirred for 3 hours at room temperature. After purification by flash
chromatography on amine phase (DCM/EtOAc: 95/5 to 80/20 and then DCM/EtOH: 95/5),
120 mg of a white powder are obtained (yield: 43%).
LCMS (Method A): MH+= 445.2, RT = 6.69 min
Step 25.2. 7-(1 -oxidopyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one hydrochloride
The product is obtained according to the procedure described in Step 1.7. by treating 7-
(1 -oxidopyrid-2-yl)-1 -(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one and 7-(1 -oxidopyridin-2-yl)-2-(tetrahydro-2H-pyran-2-yl)-5-
(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one with 4M HCI in dioxane,
in the form of a white powder (hydrochloride, 1 H20; yield 99%).
LCMS (Method A): MH+ = 361.2, RT = 5.53 min
1H NMR (250 MHz, DMSO-d6): 5 ppm 8.48 (br. s., 1 H) 8.39 - 8.43 (m, 1 H) 8.27 (d, 1 H)
8.15 (s, 1 H) 7.92 (d, 1 H) 7.70 - 7.76 (m, 1 H) 7.46 - 7.52 (m, 2 H) 5.36 (d, 1 H) 5.31 (d,
1 H)
The table that follows illustrates the chemical structures and the physical properties of a
number of compounds according to the invention. In this table:
- Me, Et, Pr, c-Pr and i-Pr represent, respectively, methyl, ethyl, propyl, cyclopropyl and
isopropyl groups;
- in the "salt" column 7" represents a compound in free base form, whereas "HCI"
represents a compound in hydrochloride form and "TFA" represents a compound in the
form of the trifluoroacetic acid salt.

The compounds according to the invention underwent biochemical studies in order to
determine their capacity to inhibit the enzyme methionine-aminopeptidase2 (enzymatic
test on isolated enzyme). The inhibitory activity of the compounds was then validated on
a cell test (test of in vitro proliferation of HUVEC cells induced with FGF-2 (fibroblast
growth factor 2)).
MetAP2 enzymatic screening test
For the enzymatic test, human MetAP2 protein was obtained from a culture supernatant
of insect cells (sf9) infected with MetAP2 recombinant baculovirus.
Before performing the experiment, dialysis of the MetAP2 supernatant is performed over
24 hours at 4°C in a buffer (10 mM Hepes, 100 mM KCI, 10% glycerol, pH 7.4) in the
presence of EDTA (1 mM) over the first 12 hours.
The dialysis supernatant is recovered and manganese, used as cofactor, is added to a
final concentration of 300 uM.
The enzymatic test is a test in two steps.
In a first step, it consists in placing in contact the compound according to the invention,
the dialysed MetAP2 protein and the substrate (Met-Pro-Arg-pNa peptide synthesized by
Neosystem), the AMerminal methionine of which can be cleaved with MetAP2, and which
bears at the C-terminal end a para-nitroaniline (pNa) chromophore, which can itself be
released by another peptidase only when the A/-terminal methionine has been cleaved
beforehand.

Consequently, the second step consists in reacting the peptides cleaved in the preceding
step with a second peptidase in order to release the chromophore. The peptidase used in
this second step is cathepsin, which comes from the TagZyme "DAPase" kit (Quiagen,
34366).
The MetAP2 activity is proportional to the amount of para-nitroaniline released, which is
measured by absorbance at 405 nm.
The IC50 values for the compounds of the invention are generally less than 550 nM,
more particularly between 1 and 550 nM and even more particularly between 1 and
100 nM and/or show inhibition at 100 nM of greater than or equal to 34%, as indicated in
the table below:

In order to determine the selectivity of the compounds of the invention towards the protein
MetAPI, an enzymatic test on the isolated enzyme is performed. The MetAPI
recombinant protein was produced in Escherichia coli.
The MetAPI enzymatic test is based on the same principle as the MetAP2 test.
The MetAPI activity is proportional to the amount of para-nitroaniline released, which is
measured by absorbance at 405 nm.
The compounds of the invention show no activity at 10 uM.
Test of in vitro proliferation of HUVEC cells induced with fibroblast growth factor 2
(FGF-2).
It has been demonstrated that an angiogenesis inhibitor, fumagillin, is capable of
selectively inhibiting the proliferation of endothelial cells (Wang J. et a/., J. Cell. Bioch.
2000, vol. 77, 465-473). Consequently, the compounds of the invention that show good
activity in the MetAP2 enzymatic test were evaluated in a test of in vitro proliferation of
HUVEC cells induced with FGF-2.
Human venous endothelial cells HUVEC (promocell, C-12200) are seeded at a rate of
5000 cells per well in 96-well plates (Biocoat collagen I cellware, Becton Dickinson
354650) in 200 ul of EBM medium (Clonetics C3121) with 2% FCS (foetal calf serum)
and hEGF (epidermal growth factor humain) at 10 ug/ml and then incubated for 24 hours
at 37°C in the presence of CO2. The medium is then aspirated and replaced with 200 ul
of deprivation medium RPMI1640 (Invitrogen, 31872-025) supplemented with 0.5% FCS,
2 mM glutamine, 2 mM sodium pyruvate 1x (Invitrogen, 11360-039) and NEAA (non-
essential amino acids) 1x (Invitrogen, 11140-035). The cells are then placed in contact
with the compound according to the invention and FGF-2 in a proportion of 1 ng/ml (R&D
System, 133-FB-025). After incubation for 48 hours, the medium is aspirated and
replaced with the deprivation medium RPMI1640 mentioned previously. A second
stimulation is then performed. The cells are again incubated at 37°C in the presence of
CO2. After incubation for 72 hours, the medium is again aspirated and 100 pi of Cell Titer-
GLO™ Luminescent Cell Viability Assay (Promega, G7571) are added over 10 minutes.
The amount of ATP present in the cells, measured using a luminometer, is proportional to
the number cells per well corresponding to the cell proliferation.

The IC50 values for the compounds of the invention are generally less than 900 nM,
more particularly between 150 and 900 nM and even more particularly between 100 and
350 nM, as indicated, for example, for the compounds below:



It thus appears that the compounds according to the invention have inhibitory activity on
MetAP2.
The compounds according to the invention may thus be used for the preparation of
medicaments, in particular medicaments for preventing or treating any pathology in which
MetAP2 is involved, more particularly those indicated below.
The compounds according to the invention may also be used for preventing or treating
any pathology in which MetAP2 is involved, more particularly those indicated below.
Thus, according to another of its aspects, a subject of the invention is medicaments that
comprise a compound of formula (I), or an addition salt thereof with a pharmaceutically
acceptable acid, or alternatively a hydrate of the compound of formula (I).
Thus, the compounds according to the invention may be used, in man or animals, in the
treatment or prevention of pulmonary and hepatic fibrosis.
The compounds according to the invention may also be used in the treatment or
prevention of pathologies involving a reactivation of angiogenesis, such as diabetic
retinopathy, age-related macular degeneration (ARMD) and psoriasis.
The compounds according to the invention may also be used in the treatment or
prevention of any carcinoma having a substantial degree of vascularization, such as lung,
breast, prostate, oesophageal, pancreatic, liver, colon or kidney carcinomas or
carcinomas that induce metastases, such as colon, breast, liver and stomach

carcinomas, and melanomas. These compounds may be used in monotherapy or
combination with radiotherapy or chemotherapy.
The compounds according to the invention may also be used in antitumour treatment,
alone or in combination with chemotherapy or solid tumours, such as pancreatic, breast,
prostate, colon or kidney tumours, neuroblastomas and Kaposi's sarcoma.
The compounds according to the invention may also be used in the treatment or
prevention of hepatocarcinomas, cholangiocarcinoma and also malignant mesothelioma,
pancreatic cancer, haemoangioma, endometriosis, arthritis and in particular rheumatoid
arthritis, autoimmune diseases, obesity and microsporidiosis.
According to another of its aspects, the present invention relates to pharmaceutical
compositions comprising, as active principle, a compound according to the invention.
These pharmaceutical compositions contain an effective dose of at least one compound
according to the invention, or a pharmaceutically acceptable salt of the said compound,
and also at least one pharmaceutically acceptable excipient.
The said excipients are chosen, according to the pharmaceutical form and the desired
mode of administration, from the usual excipients known to those skilled in the art.
In the pharmaceutical compositions of the present invention for oral, sublingual,
subcutaneous, intramuscular, intravenous, topical, local, intratracheal, intranasal,
transdermal or rectal administration, the active principle of formula (I) above, or the salt
thereof, may be administered in unit administration form, as a mixture with standard
pharmaceutical excipients, to man and animals for the prevention or treatment of the
above disorders or diseases.
The appropriate unit administration forms include oral-route forms such as tablets, soft or
hard gel capsules, powders, granules and oral solutions or suspensions, sublingual,
buccal, intratracheal, intraocular, intranasal or inhalation administration forms, topical,
parenteral such as transdermal, subcutaneous, intramuscular or intravenous
administration forms, rectal administration forms and implants. For topical application, the
compounds according to the invention may be used in creams, gels, ointments or lotions.
By way of example, a unit administration form of a compound according to the invention
in tablet form may comprise the following components:

Compound according to the invention 50.0 mg
Mannitol 223.75 mg
Croscaramellose sodium 6.0 mg
Cornstarch 15.0 mg
Hydroxypropylmethylcellulose 2.25 mg
Magnesium stearate 3.0 mg
The dose of active principle administered per day may range from 0.01 to 100 mg/kg and
preferentially 0.02 to 50 mg/kg, in one or more dosage intakes. In general, the daily dose
of the compound of the invention will be the lowest effective dose of the compound that is
capable of producing a therapeutic effect.
There may be particular cases in which higher or lower dosages are appropriate; such
dosages do not depart from the scope of the invention. According to the usual practice,
the dosage that is appropriate for each patient is determined by the doctor according to
the mode of administration and the weight and response of the said patient.
According to another of its aspects, the present invention also relates to a method for
treating the pathologies indicated above, which comprises the administration, to a patient,
of an effective dose of a compound according to the invention, or a pharmaceutically
acceptable salt thereof.

CLAIMS
1. Compound corresponding to formula (I):

in which:
R1 represents:
• -(C1-C4)alkyl
• -(C1-C4)haloalkyl
R2 represents:
• a group:

• a group:

• a group: -A -X
R3 represents:
• -H
• halogen
• -(C1-C6)alkyl
• a cyano group

• -CO2H
• -CONH2
A represents:
• an aryl or heteroaryl group
X is absent or represents:
• halogen
• a cyano group
• an oxo group
• -(CH2)nOH
• -(C1-C6)haloalkyl
• -(C1-C6)alkyl
• -(C1-C6)alkoxy
• -(CH2)n-aryl
• -CHOH-aryl
• heterocycle
• heteroaryl
• -(C1-C6)alkyl-heterocycle
• -(C1-C6)alkyl-heteroaryl
• -(C1-C6)alkyl-COORa

• -(C1-C6)alkyl-NRaRb
• -heteroaryl-(CH2)n-NRaRb
• -(CH2)n-NRa-C(O)-Rb
• -NRaRb
• -NRa-(CH2)n-O-Rb
• -NRa-heterocycle
• -NRa-aryl
• -NRa-C(O)-(CH2)n-NRaRb
• -NRa-C(O)-aryl
• -NRaC(O)-(C1-C6)alkyl
• -NRa-C(O)-(C1-C6)alkyl-aryl
• -NRa-C(O)-(CH2)n-O-Rb
• -NRa-SO2-(CH2)n-aryl
• -NRa-SO2-(CH2)n-NRaRb
• -NRa-SO2-Rb

• -NRa-SO2-aryl-O-aryl
• -NRa-SO2-aryl-(CH2)n-NRb-C(O)-Rb
• -COORa
• -CONRaRb
• -C(O)-NRa-(CH2)n-O-Rb
• -C(O)-NRa-aryl-C(O)-NRaRb
• -C(O)-NRa-(CH2)n-NRaRb
• -C(O)-NRa-(CH2)n-heteroaryl
• -O-(CH2)n-NRaRb
• -O-heterocycle
• -CO-heterocycle
• -CO-heteroaryl
• -SO2NRaRb
• -SO2-heterocycle
Ra and Rb represent, independently:
• -H
• -(C1-C6)alkyl
n represents 0,1, 2 or 3
in the form of the base or of an acid-addition salt, and also in hydrate form.
2. Compound of formula (I) according to: Claim 1, characterized in that R3 represents H or
a halogen, more particularly chlorine; in the form of the base or of an acid-addition salt,
and also in hydrate form.
3. Compound of formula (I) according to either of Claims 1 and 2, characterized in that R1
-represents an ethyl or a trifluoroethyl; in the form of the base or of an acid-addition salt,
and also in hydrate form.
4. Compound of formula (I) according to one of Claims 1 to 3, characterized in that R2
represents a group -A -X with A which represents an aryl or heteroaryl group and X which
is absent or represents a heterocycle, NRaRb, (C1-C6)alkyl, a halogen, more particularly
chlorine or fluorine, a cyano group, NRa-SO2-Rb, CO-heterocycle; in the form of the base
or of an acid-addition salt, and also in hydrate form.

5. Compound of formula (I) according to any one of the preceding claims, chosen
from the following compounds:
- compound 1: 7-(pyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 2: 7-(2-aminopyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 3: 7-(2-fluorophenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 4: 5-ethyl-7-pyrid-2-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 5: 5-ethyl-7-(4-fluorophenyl)-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 6: 7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 7: 5-ethyl-7-pyrid-4-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 8: 7-(2-dimethylaminophenyi)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 9: N-(3-dimethylaminopropyl)-4-(5-ethyl-4-oxo-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl)benzamide;
- compound 10: 5-ethyl-7-(4-piperazin-1-ylphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 11: 5-ethyl-7-[4-(4-methylpiperazin-1-yl)phenyl]-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 12: 7-[2-(morpholin-4-ylcarbonyl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 13: N-(2-dimethylaminoethyl)-4-(5-ethyl-4-oxo-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl)benzamide;
- compound 14: 7-(2-morpholin-4-ylphenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 15: 7-[4-(1-dimethylaminoethyl)phenyl]-5-ethyl-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 16: 7-(2-morpholin-4-ylmethylphenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 17: 5-ethyl-7-(2-morpholin-4-ylmethylphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 18: 5-ethyl-7-[4-(piperazine-1-carbonyl)phenyl]-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 19: 7-[4-(4-methylpiperazin-1-yl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-

4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 20: 5-ethyl-7-(2-piperazin-1-ylpyrimidin-5-yl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 21: 5-ethyl-7-[4-(4-methylpiperazine-1-carbonyl)phenyl]-1,5-dihydro-4H-
pyrazo!o[4,3-c]quinolin-4-one;
- compound 22: 5-ethyl-7-[4-(1-pyrrolidin-1-yl-ethyl)phenyl]-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 23: 7-(4-diethylaminophenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 24: 7-(4-amino-2-methylphenyl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 25: 7-(4-morpholin-4-ylphenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazoio[4,3-c]quinolin-4-one
- compound 26: 5-ethyl-7-(4-morpholin-4-ylphenyI)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 27: 5-(5-ethyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl)-2-fluoro-
N-methylbenzamide;
- compound 28: 5-ethyl-7-(2-fluoro-5-methoxyphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 29: 7-[3-chloro-4-(morpholine-4-carbonyl)pheny!]-5-ethyl-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 30: 7-[4-(piperazin-1-yl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 31: 5-ethyl-7-[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 32: 7-(4-dimethylaminophenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 33: 2-chloro-4-(5-ethyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-
yl)benzamide;
- compound 34: 5-ethyl-7-(1H-indazol-5-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 35: N-ethyl-3-(5-ethyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-
yl)benzamide;
- compound 36: 5-(5-ethyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl)-2-fluoro-
benzamide;
- compound 37: N-(2-dimethylaminoethyl)-3-(5-ethyl-4-oxo-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl)benzamide;

- compound 38: N-[4-(5-ethyl-4-oxo-4,5-dihydro-1H-pyra2olo[4,3-c]quinolin-7-
yl)benzyl]acetamide;
- compound 39: 3-(5-ethyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl)-N-(2-
methoxyethyl)benzamide;
- compound 40: 7-(3-hydroxyphenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 41: 7-(2-chloro-3-fluoropyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 42: 7-(2-{5-[(propan-2-ylamino)methyl]furan-2-yl}phenyl)-5-(2,2,2-
trifluoroethyl)-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 43: N-[2-(5-ethyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-
yl)phenyl]methanesulfonamide;
- compound 44: 7-(2-aminophenyl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 45: 5-ethyl-7-(3-morpholin-4-yiphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 46: N-[2-(5-ethyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-
yl)phenyl]acetamide;
- compound 47: 5-ethyl-7-(2-hydroxyphenyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 48: 5-ethyl-7-[4-(morphoiine-4-sulfonyl)phenyl]-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 49: 7-(2-hydroxymethyl-4-methoxyphenyl)-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 50: 5-ethyl-7-(3-pyrazol-1-ylphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinoiin-4-one;
- compound 51: 5-ethyl-7-(1 H-indol-5-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 52: 5-(5-ethyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl)-
thiophene-2-carbonitrile;
- compound 53: 7-(3-chloro-2-hydroxyphenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 54: 5-ethyl-7-(2-hydroxy-3-methoxyphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 55: methyl 3-amino-4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]benzoate;
- compound 56: 5-ethyl-7-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-7-yl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;

- compound 57: 7-(2,5-dichloropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihyclro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 58: 7-(2-chloro-5-methoxyphenyl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 59: N-(3-dimethylaminopropyl)-3-(5-ethyl-4-oxo-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl)benzamide;
- compound 60: 5-ethyl-7-(4-fluoro-2-hydroxyphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 61: 5-ethyl-7-(2-fluoro-4-methoxyphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 62: 7-(4-aminomethylphenyl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 63: 5-ethyl-7-(2-fluoro-3-methoxyphenyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 64: 7-(2-dimethylaminomethylphenyl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinoiin-4-one;
- compound 65: 4-(5-ethyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl)benzoic
acid;
- compound 66: 7-[6-(piperazin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 67: 5-ethyl-7-[6-(piperazin-1-yl)pyrid-3-yl]-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 68: 7-[2-(4-methylpiperazin-1-yl)pyrid-4-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 69: 5-ethyl-7-[2-(4-methylpiperazin-1-yl)pyrid-4-yl]-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 70: 7-[2-(piperazin-1-yl)pyrid-4-y!]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 71: 5-ethyl-7-(2-piperazin-1-ylpyrid-4-yl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 72: 7-(2-methy[pyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 73: 5-ethyl-7-(2-methylpyrid-3-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 74: 7-(2-chioro-6-methylpyrid-3-yl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 75: 7-(2-chloro-6-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-

pyrazolo[4,3-c]quinolin-4-one;
- compound 76: 7-(2-chloropyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 77: 7-(2-fluoropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 78: 5-ethyl-7-(2-fluoropyrid-3-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 79: 7-(6-chloro-2-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 80: 7-(2-methoxypyrid-3-yl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 81: 5-ethyl-7-(2-methoxypyrid-3-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-
4-one;
- compound 82: 7-(6-chloro-4-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 83: 7-[6-(morpholin-4-y[)pyrid-3-yl]-5-(2,2,2-trifiuoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 84: 7-[6-(3-dimethylaminopropoxy)pyrid-3-yl]-5-ethyl-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 85: 5-ethyl-7-quinolin-8-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 86: 7-(6-chloropyrid-2-yl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 87: 5-ethyl-7-quinolin-6-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 88: 7-(6-chloropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 89: 7-(6-chloro-5-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 90: 5-ethyl-7-(3-fluoropyrid-4-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 91: 7-(3-chloropyrid-4-yl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 92: 5-ethyl-7-(6-fluoro-5-methylpyrid-3-yl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 93: 7-(2-ethoxypyrid-3-yl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 94: 5-ethyl-7-(5-methoxypyrid-3-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-
4-one;

- compound 95: 7-(6-aminopyrid-3-yl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 96: 5-ethyl-7-pyrid-3-yl-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 97: 7-(2-chloro-6-isopropylpyrid-3-yI)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 98: 7-(5-chloro-2-methoxypyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 99: 7-(pyrid-3-yloxy)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 100: 5-ethyl-7-(pyrid-3-yloxy)-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 101: 7-(pyrid-3-ylamino)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 102: 5-(2,2-difluoroethyl)-7-pyrid-4-yl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 103: 5-cyclopropylmethyl-7-pyrid-4-yi-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 104: 5-propyl-7-pyrid-4-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 105: 5-(2,2-difluorocyclopropylmethyl)-7-pyrid-4-yl-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 106: 5-(2-fluoroethyl)-7-pyrid-4-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-
4-one;
- compound 107: 5-isopropyl-7-pyrid-4-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 108: 5-cyclopropyl-7-pyrid-4-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one;
- compound 109: 8-fluoro-7-pyrid-2-yl-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 110: 7-(2-chloropyrid-3-yl)-8-methyl-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 111: 7-(2-chloropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 112: 7-[2-(dimethylamino)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 113: isopropyl 2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]benzoate;
- compound 114: cyclopropanecarboxylic acid {2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-
dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]phenyl}amide;

- compound 115: 7-[2-(1-methyl-1H-imidazole-2-carbonyl)phenyl]-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 116: 7-(4-cyclopentylpyrimidin-5-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 117: 7-(4-cyclohexy!pyrimidin-5-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 118: 7-(2-propylaminomethylphenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 119: 2-methoxy-N-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]phenyl}acetamide;
- compound 120: N-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]phenyl}isobutyramide;
- compound 121: N-{4-methyl-2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]phenyl}propionamide;
- compound 122: N-isopropyl-2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]benzamide;
- compound 123: 7-[4-methyl-2-(piperidin-4-yloxy)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 124: 7-[2-(1,4-diazepan-1-ylmethyl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;

- compound 125: ethyl 2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]benzoate;
- compound 126: 7-(2-aminophenyl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 127: 7-(2-piperazin-1-ylphenyl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 128: 7-(6-methoxypyrid-3-y[)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 129: 7-(5-chloro-2-fluoropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 130: N-{5-methyl-3-[4-oxo-5-(2>2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyhd-2-yl}acetamide;
- compound 131: 7-[2-(2-hydroxy-ethyl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 132: 7-(2-amino-5-fluoropyrid-3-yl)-5-(2l2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 133: 7-[2-(pyrrolidine-1-sulfonyl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-

4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 134: N-isopropyl-2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]benzenesulfonamide;
- compound 135: 7-(2-fluoro-5-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 136: N,N-diethyl-2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]benzenesuifonamide;
- compound 137: 7-(6-amino-4-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 138: 7-(6-methoxy-2-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 139: 7-(5-methyl-6-[1,2,4]triazo!-4-ylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 140: 7-(4-methyl-6-[1,2,4]triazol-4-ylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 141: 7-[6-(morpholine-4-carbonyl)pyrid-3-yl]-5-(2,2,2-trifluoroethyi)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 142: 7-(6-amino-2-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 143: 7-(4-ethylpyrimidin-5-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 144: methyl {2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]phenyl}acetate;
- compound 145: 7-(4-methoxypyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 146: 7-(4-propylpyrimidin-5-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 147: N-{6-methyl-5-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-yl}propionamide;
- compound 148: 7-(2-oxazol-5-ylphenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 149: 7-(4-dimethylamino-2-methoxypyrimidin-5-yl)-5-(2,2,2-trifluoroethyl)-
1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 150: 7-[2-(5-ethyl-[1,2,4]oxadiazol-3-yl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 151: N-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]benzyl}acetamide;

- compound 152: 7-[5-(hydroxyphenylmethyl)pyrid-2-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 153: 6-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyridine-2-carbonitrile;
- compound 154: 7-(6-hydroxymethylpyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 155: 7-[3-(2-dimethylaminoethoxy)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 156: methyl 2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]benzoate;
- compound 157: 7-(5-hydroxymethylpyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 158: 7-(2-methoxypyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 159: 7-(2-[1,2,4]triazol-1-ylmethylphenyl)-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 160: 7-(4-phenylpyrimidin-5-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 161: 7-(6-methoxy-4-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;

- compound 162: 7-(4-isopropylpyrimidin-5-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 163: 7-(6-fluoropyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 164: methyl 6-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyridine-2-carboxylate;
- compound 165: 7-(5-fluoropyrid-2-yl)-5-(2,2,2-thfluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 166: 7-[2-(4-methylpiperazin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 167: 7-(3-aminopyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 168: 7-(2,6-dimethylpyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 169: 7-(3-chloropyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 170: methyl 3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-

c]quinolin-7-yl]pyridine-2-carboxylate;
- compound 171: 7-(6-methylpyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 172: 7-[2-(morpholin-4-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 173: 5-(2,2,2-trifluoroethyl)-7-(2-trifluoromethylpyrid-3-yl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 174: 7-(2-cyclopropylaminopyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 175: 5-(2,2,2-trifluoroethyl)-7-(3-trifluoromethylpyrid-2-yl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 176: 3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyridine-2-carbonitrile;
- compound 177: 2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyridine-3-carbonitrile;
- compound 178: methyl 2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]nicotinoate;
- compound 179: 7-(2-propoxypyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 180: 7-(3-hydroxypyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 181: 7-[2-(4-fluorophenylamino)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 182: 7-(2-methylaminophenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 183: 7-(2-ethoxypyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 184: 7-(2-isopropoxypyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 185: 7-(5-chloro-2-methoxypyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 186: 7-(2-methylpyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 187: 7-(4-methylpyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 188: 7-(6-morpholin-4-ylpyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 189: 7-(4-methylaminophenyl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinoIin-4-one;
- compound 190: 5-(2,2,2-trifluoroethyl)-7-(6-trifluoromethylpyrid-3-yl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 191: 7-(6-methoxypyrid-2-yl)-5-(2,2,2-trifIuoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 192: 7-[4-(2H-tetrazol-5-yl)phenyl]-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 193: 7-(3,5-dichloropyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 194: 8-chloro-7-(pyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 195 8-bromo-7-pyrid-2-yl-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 196: 8-chloro-7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 197: 8-bromo-7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 198: 8-chloro-5-ethyl-7-pyrid-4-yl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-
4-one;
- compound 199: 8-chloro-7-(2-chloropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-bne;

- compound 200: 8-methyl-7-pyrid-2-yl-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 201: 4-oxo-7-pyrid-4-yl-5-(2,2,2-trifluoroethyl)-4,5-dihydro-2H,4H-
pyrazolo[4,3-c]quinoline-8-carbonitrile;
- compound 202: 4-oxo-7-pyrid-4-yl-5-(2,2,2-trifluoroethyl)-4,5-dihydro-2HI4H-
pyrazolo[4,3-c]quinoline-8-carboxylic acid;
- compound 203: 3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyridine-2-carboxyiic acid;
- compound 204: 2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1 H-pyrazolo[4,3-
c]quinolin-7-yl]benzoic acid;
- compound 205: 4-oxo-7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-4,5-dihydro-2H-
pyrazolo[4,3-c]quinoline-8-carboxamide;
- compound 206: 7-[2-(morpholin-4-ylcarbonyl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 207: N-[2-(dimethylamino)ethyl]-N-methyl-2-[4-oxo-5-(2,2,2-trifluoroethyl)-

4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]benzamide;
- compound 208: N-(2-dimethylaminoethyl)-N-ethyl-2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-
dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]benzamide;
- compound 209: 7-{2-[(4-methyl-1,4-diazepan-1-yl)carbonyl]phenyl}-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 210: 7-{2-[(4-methylpiperazin-1-yl)carbonyl]phenyl}-5-(2,2,2-trifluoroethyl)-
1,5-dihydro-4H-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 211: N-(3-carbamoylphenyl)-2-[4-oxo-5-(2,2,2-trifiuoro6thyl)-4,5-dihydro-
1H-pyrazolo[4,3-c]quinolin-7-yl]benzamide;
- compound 212: N-(3-dimethylaminopropyl)-2-[4-oxo-5-(2,2,2-trifiuoroethyl)-4,5-
dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]benzamide;
- compound 213: N,N-dimethyl-3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyridine-2-carboxamide;
- compound 214: 2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]-N-[2-(pyrid-4-yl)ethyl]benzamide;
- compound 215: N-[2-(dimethylamino)ethyl]-N-methyl-3-[4-oxo-5-(2,2,2-trifluoroethyl)-
4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]pyridine-2-carboxamide;
- compound 216: 7-[2-(1,4-oxazepan-4-ylcarbonyl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 217: N-methyl-3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyridine-2-carboxamide;
- compound 218: 2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinoIin-7-yl]-N-(pyrid-3-ylmethyl)benzamide;
- compound 219: N-ethyl-2-[4-oxo-5-(2,2,2-trifluoroethy[)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]-N-(pyrid-4-ylmethyl)benzamide;

- compound 220: 3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyridine-2-carboxamide;
- compound 221: N-[2-(dimethylamino)ethyl]-N-ethyl-3-[4-oxo-5-(2,2,2-trifluoroethyl)-
4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-7-yl]pyridine-2-carboxamide;
- compound 222: 7-[2-((2S,6R)-2,6-dimethylmorpholine-4-carbony[)pyrid-3-yl]-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 223: N-{3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyrid-2-yl}acetamide;
- compound 224: 3-dimethylamino-N-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-
2H,4H-pyrazolo[4,3-c]quinolin-7-yl]phenyl}propionamide;
- compound 225: 4-(dimethylamino)-N-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]phenyl}butanamide;

- compound 226: N-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyrid-3-yl}acetamide;
- compound 227: N-{3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyrid-2-yl}cyclopropanecarboxamide;
- compound 228: 2-methoxy-N-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1 H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-3-yl}-2-phenylacetamide;
- compound 229: N-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyrid-3-yl}-2-phenylpropionamide;
- compound 230: 2-(3-chlorophenyl)-N-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-3-yl}acetamide;
- compound 231: 2-(2,4-dichlorophenyl)-N-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-
1H-pyrazolo[4,3-c]quinolin-7-yl]pyrid-3-yl}acetamide;
- compound 232: N-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-2H-pyrazolo[4,3-
c]quinolin-7-yl]phenyl}methanesulfonamide;
- compound 233: 2-(dimethylamino)-N-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]phenyl}ethanesuifonamide;
- compound 234: N-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]phenyl}-1-phenylmethanesulfonamide;
- compound 235: 3-chloro-N-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]phenyl}benzenesulfonamide;

- compound 236: N-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyrid-3-yl}methanesulfonamide;
- compound 237: N-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyrid-3-yl}-1-phenylmethanesulfonamide;
- compound 238: 3-chloro-N-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-3-yl}benzenesulfonamide;
- compound 239: N-(4-methoxy-3-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-3-ylsulfamoyl}benzyl)acetamide;
- compound 240: N-{4-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyrid-3-yl}-2-phenoxybenzenesulfonamide;
- compound 241: N-methyl-N-{3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-yl}acetamide;
- compound 242: N-methyl-N-{3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-
pyrazolo[4,3-c]quinolin-7-yl]pyrid-2-yl}cyclopropanecarboxamide;
- compound 243: 7-[2-(methylamino)pyrid-3-yll-5-(2,2,2-trifluoroethyi)-1,5-dihydro-4H-
pyrazolo[4,3-c]quino!in-4-one;
- compound 244: 7-[2-(1,4-diazepan-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-

4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 245: 7-(3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-3'-yI)-5-(2,2,2-trifluoroethyl)-
2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 246: 7-[2-(3-hydroxypyrrolidin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethy[)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 247: 7-[2-(3,4-dihydroxypyrrolidin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-
2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 248: 7-[2-(dimethylamino)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 249: 7-{2-[ethyl(methyl)amino]pyrid-3-yl}-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 250: 7-{2-[(2-hydroxyethyl)(methyl)amino]pyrid-3-yl}-5-(2,2,2-trifluoroethyl)-
1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 251: 7-[2-(pyrrolidin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 252: 7-[2-(1,4-oxazepan-4-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyi)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 253: 7-[2-(3-oxopiperazin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 254: 7-[2-(azetidin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 255: 7-{2-[(2-methoxyethyl)methylamino]pyrid-3-yl}-5-(2,2,2-trifluoroethyl)-
2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 256: 7-[2-(4-acetylpiperazin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-2,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;

- compound 257: 7-[2-(diethyiamino)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 258: 7-[2-(cyclobutylamino)pyrid-3-yl]-5-(2,2,2-trifiuoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 259: 7-[2-(2,6-dimethylmorpholin-4-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-2,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 260: 7-[2-(4-cyclopropylpiperazin-1-yl)pyrid-4-yl]-5-(2,2,2-trifluoroethyl)-
2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 261: 7-(2-cyclohexylaminopyrid-3-yl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-
4H-pyrazoIo[4,3-c]quinolin-4-one;
- compound 262: 7-[2-(isopropylmethylamino)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-2,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;

- compound 263: 7-(2-cyclopentylaminopyrid-3-yl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 264: 7-(6-pyrrolidin-1-ylpyrid-2-yl)-5-(2,2,2-trifluoroethyl)-2,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 265: 7-[6-(2,6-dimethylmorpholin-4-yl)pyrid-2-yl]-5-(2,2,2-trifluoroethyl)-2,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 266: 7-{2-[cyclohexyl(methyl)amino]pyrid-3-yl}-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 267: 7-[2-(4-cyclopropylpiperazin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-
2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 268: 7-[3-(4-cyclopropylpiperazin-1-yl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 269: 7-[2-(4-acetyl-1,4-diazepan-1 -yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 270: 7-[2-(4-methyl-1,4-diazepan-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-
1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 271: 7-[2-(4-cyclopropyl-[1,4]diazepan-1-yl)pyrid-3-yl]-5-(2,2,2-
trifluoroethyl)-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 272: 7-[2-(3-fluoropyrrolidin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-2,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;

- compound 273: 7-[2-(4-fluoropiperidin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 274: 7-(2-hydroxypyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 275: 7-(1-oxypyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 276: 7-(1-oxypyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
in the form of the base or of an acid-addition salt, and also in hydrate form.
6. Compound of formula (I) according to any one of the preceding claims, chosen from
the following compounds:
- compound 1: 7-(pyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 2: 7-(2-aminopyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 6: 7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-

c]quinolin-4-one;
- compound 19: 7-[4-(4-methylpiperazin-1-yl)phenyl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-
4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 67: 5-ethyl-7-[6-(piperazin-1-yl)pyrid-3-yl]-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 68: 7-[2-(4-methylpiperazin-1-yl)pyrid-4-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 69: 5-ethyl-7-[2-(4-methylpiperazin-1-yl)pyrid-4-yl]-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 72: 7-(2-methylpyrid-3-yi)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 74: 7-(2-chloro-6-methylpyrid-3-yl)-5-ethyl-1,5-dihydro-4H-pyrazolo[4,3-
c]quinolin-4-one;
- compound 75: 7-(2-chloro-6-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 76: 7-(2-chloropyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 77: 7-(2-fluoropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 79: 7-(6-chloro-2-methylpyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 83: 7-[6-(morpholin-4-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 88: 7-(6-chloropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 111: 7-(2-chloropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 168: 7-(2,6-dimethylpyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;

- compound 169: 7-(3-chloropyrid-2-yl)-5-(2l2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 171: 7-(6-methylpyrid-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 172: 7-[2-(morpholin-4-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 176: 3-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-
c]quinolin-7-yl]pyridine-2-carbonitrile;

- compound 186: 7-(2-methylpyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 196: 8-chloro-7-(pyrid-4-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 199: 8-chloro-7-(2-chloropyrid-3-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 209: 7-{2-[(4-methyl-1,4-diazepan-1-yl)carbonyl]phenyl}-5-(2,2,2-
trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
- compound 232: N-{2-[4-oxo-5-(2,2,2-trifluoroethyl)-4,5-dihydro-2H-pyrazolo[4,3-
c]quinolin-7-yl]phenyl}methanesulfonamide;
- compound 248: 7-[2-(dimethylamino)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 251: 7-[2-(pyrrolidin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 257: 7-[2-(diethylamino)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-
pyrazolo[4,3-c]quinolin-4-one;
- compound 273: 7-[2-(4-fluoropiperidin-1-yl)pyrid-3-yl]-5-(2,2,2-trifluoroethyl)-1,5-
dihydro-4H-pyrazolo[4,3-c]quinolin-4-one;
in the form of the base or of an acid-addition salt, and also in hydrate form.
7. Compound of formula (III):

in which R3 is as defined in Claim 1 and Hal represents a halogen atom; in the form of
the base or of an acid-addition salt, and also in hydrate form.
8. Compound of formula (IV):


in which R3 is as defined in Claim 1 and Hal represents a halogen atom; in the form of
the base or of an acid-addition salt, and also in hydrate form.
9. Compound of formula (V):

in which R3 is as defined in Claim 1 and Hal represents a halogen atom; in the form of
the base or of an acid-addition salt, and also in hydrate form.
10. Compound of formula (VI):

in which R3 is as defined in Claim 1, Hal represents a halogen atom and PG represents a
protecting group; in the form of the base or of an acid-addition salt, and also in hydrate
form.
11. Compound of formula (VII):

in which R1 and R3 are as defined in Claim 1, Hal represents a halogen atom and PG
represents a protecting group; in the form of the base or of an acid-addition salt, and also
in hydrate form.
12. Compound of formula (VIII):


in which R1, R2 and R3 are as defined in Claim 1 and PG represents a protecting group;
in the form of the base or of an acid-addition salt, and also in hydrate form.
13. Compound of formula (IX):

in which R2 is as defined in Claim 1, R3 represents -H, a halogen, -(C1-C6)alkyl, a cyano
group or -CONH2 and PG represents a protecting group; in the form of the base or of an
acid-addition salt, and also in hydrate form.
14. Compound of formula (XIII):

in which R1 is as defined in Claim 1, Hal represents a halogen atom and R3 represents
-H, a halogen chosen from chlorine, bromine and iodine, -(C1-C6)alkyl, a cyano group,
-CO2H or -CONH2; in the form of the base or of an acid-addition salt, and also in hydrate
form.
15. Compound of formula (XIV):


(XIV)
in which R1 and R3 are as defined in Claim 1 and Hal represents a halogen atom; in the
form of the base or of an acid-addition salt, and also in hydrate form.
16. Compound of formula (XVII):

in which R3 is as defined in Claim 1, Hal represents a halogen atom and PG represents a
protecting group; in the form of the base or of an acid-addition salt, and also in hydrate
form.
17. Compound of formula (XVIII):

in which R1 and R3 are as defined in Claim 1, Hal represents a halogen atom and PG
represents a protecting group; in the form of the base or of an acid-addition salt, and also
in hydrate form.
18. Compound of formula (XIX):

in which R1 and R3 are as defined in Claim 1 and R represents a hydrogen atom or both
the groups R are carbon atoms bonded together and optionally substituted with one or
more groups (C1-C4) alkyl; in the form of the base or of an acid-addition salt, and also in
hydrate form.
19. Compound of formula (XX):


in which R1 and R3 are as defined in Claim 1 and R represents a hydrogen atom or both
the groups R are carbon atoms bonded together and optionally substituted with one or
more groups (C1-C4) alkyl and PG represents a protecting group; in the form of the base
or of an acid-addition salt, and also in hydrate form.
20. Medicament, characterized in that it comprises a compound of formula (I) according
to any one of Claims 1 to 6, or an addition salt of this compound with a pharmaceutical^
acceptable acid.
21. Pharmaceutical composition, characterized in that it comprises a compound of
formula (I) according to any one of Claims 1 to 6, or a pharmaceutically acceptable salt of
this compound, and also at least one pharmaceutically acceptable excipient.
22. Compound of general formula (I) as defined in any one of Claims 1 to 6, for its use as
a medicament.
23. Compound of general formula (I) as defined in any one of Claims 1 to 6, for the
preparation of a medicament for preventing or treating pulmonary and hepatic fibrosis;
pathologies involving a reactivation of angiogenesis, such as diabetic retinopathy, age-
related macular degeneration (ARMD) and psoriasis; any carcinoma with a substantial
degree of vascularization, such as lung, breast, prostate, oesophageal, pancreatic, liver,
colon or kidney carcinoma or any carcinoma inducing metastases, such as colon, breast,
liver or stomach carcinomas, and melanomas; solid tumours, such as pancreatic, breast,
prostate, colon or kidney tumours, neuroblastomas and Kaposi's sarcoma;
hepatocarcinomas; cholangiocarcinoma; malignant mesothelioma; pancreatic cancer;
haemoangioma; endometriosis; arthritis and in particular rheumatoid arthritis; obesity;
autoimmune diseases; microsporidiosis.
24. Use of a compound of formula (I) according to any one of Claims 1 to 6, for the
preparation of a medicament for preventing or treating pulmonary and hepatic fibrosis;
pathologies involving a reactivation of angiogenesis, such as diabetic retinopathy, age-

related macular degeneration (ARMD) and psoriasis; any carcinoma with a substantial
degree of vascularization, such as lung, breast, prostate, oesophageal, pancreatic, liver,
colon or kidney carcinoma or any carcinoma inducing metastases, such as colon, breast,
liver or stomach carcinomas, and melanomas; solid tumours, such as pancreatic, breast,
prostate, colon or kidney tumours, neuroblastomas and Kaposi's sarcoma;
hepatocarcinomas; cholangiocarcinoma; malignant mesothelioma; pancreatic cancer;
haemoangioma; endometriosis; arthritis and in particular rheumatoid arthritis; obesity;
autoimmune diseases; microsporidiosis.
25. Use of a compound of formula (I) according to any one of Claims 1 to 6, in
monotherapy or in combination with radiotherapy or chemotherapy.

The invention relates to compounds corresponding to formula (I)

in which R1, R2 and R3 are as defined in Claim 1, and also to the process for
preparing them and to their therapeutic use.