The present invention relates to novel substituted N-(3-fluoropropyl)-pyrrolidine compounds, the processes for their preparation, as well as the therapeutic uses thereof, in particular as anticancer agents via selective antagonism and degradation of estrogen receptors.

The Estrogen Receptors (ERs) belong to the steroid/nuclear receptor superfamily involved in the regulation of eukaryotic gene expression, cellular proliferation and differentiation in target tissues. ERs are in two forms: the estrogen receptor alpha (ERa) and the estrogen receptor beta (ER3) respectively encoded by the ESR1 and the ESR2 genes. ERa and ER3 are ligand-activated transcription factors which are activated by the hormone estrogen (the most potent estrogen produced in the body is 173-estradiol). In the absence of hormone, ERs are largely located in the cytosol of the cell. When the hormone estrogen binds to ERs, ERs migrate from the cytosol to the cell nucleus, form dimers and then bind to specific genomic sequences called Estrogen Response Elements (ERE). The DNA ER complex interacts with co-regulators to modulate the transcription of target genes.

ERa is mainly expressed in reproductive tissues such as uterus, ovary, breast, bone and white adipose tissue. Abnormal ERa signaling leads to development of a variety of diseases, such as cancers, metabolic and cardiovascular diseases, neurodegenerative diseases, inflammation diseases and osteoporosis.

ERa is expressed in not more than 10% of normal breast epithelium but approximately 50-80% of breast tumors. Such breast tumors with high level of ERa are classified as ERa-positive breast tumors. The etiological role of estrogen in breast cancer is well established and modulation of ERa signaling remains the mainstay of breast cancer treatment for the majority ERa-positive breast tumors. Currently, several strategies for inhibiting the estrogen axis in breast cancer exist, including: 1 - blocking estrogen synthesis by aromatase inhibitors that are used to treat early and advanced ERa-positive breast cancer patients; 2- antagonizing estrogen ligand binding to ERa by tamoxifen which is used to treat ERa-positive breast cancer patients in both pre- and postmenopausal settings; 3- antagonizing and downregulating ERa levels by fulvestrant, which is used to treat breast cancer in patients that have progressed despite endocrine therapies such as tamoxifen or aromatase inhibitors.

Although these endocrine therapies have contributed enormously to reduction in breast cancer development, about more than one-third of ERa-positive patients display de-novo resistance or develop resistance over time to such existing therapies. Several mechanisms have been described to explain resistance to such hormone therapies. For example, hypersensitivity of ERa to low estrogen level in treatment with aromatase inhibitors, the switch of tamoxifen effects from antagonist to agonist effects in tamoxifen treatments or multiple growth factor receptor signaling pathways. More recently proposed, acquired mutations in ERa occurring after initiation of hormone therapies may play a role in treatment failure and cancer progression. Certain mutations in ERa, particularly those identified in the Ligand Binding Domain (LBD), result in the ability to bind to DNA in the absence of ligand and confer hormone independence in cells harboring such mutant receptors.

Most of the endocrine therapy resistance mechanisms identified rely on ERa-dependent activity. One of the new strategies to counterforce such resistance is to shut down the ERa signaling by removing ERa from the tumor cells using Selective Estrogen Receptors Degraders (SERDs). Clinical and preclinical data showed that a significant number of the resistance pathways can be circumvented by the use SERDs.

There is still a need to provide SERDs with good degradation efficacy.

The objective of the present invention is to provide novel compounds able to selectively antagonize and degrade the estrogen receptors (SERDs compounds), for use in cancer treatment.

The present invention relates to the compounds of the formula (l-A):

wherein:

- R1 and R2 represent independently a hydrogen atom or a deuterium atom;

- A represents an oxygen or nitrogen atom (namely, A represents a group of formula -O- or -NH-); and

- SERM-F represents a selective estrogen receptor modulator fragment, i.e. a molecule having a selective antagonist activity for estrogen receptors, said SERM-F comprising an aryl or heteroaryl group linked to the adjacent "A" group.

In another embodiment, the present invention relates to the compounds of the formula (l-A) above wherein:

- R1 and R2 represent independently a hydrogen atom or a deuterium atom;

- A represents an oxygen or nitrogen atom (namely, A represents a group of formula -O- or -NH-); and

- SERM-F represents a selective estrogen receptor modulator fragment, i.e. a molecule having a selective antagonist activity for estrogen receptors, said SERM-F comprising an aryl or heteroaryl group linked to the adjacent "A" group;

with the proviso that the compounds of formula (l-B) below are excluded:

wherein, in formula (l-B):

R1 and R2 represent independently a hydrogen atom or a deuterium atom;

R3 represents a hydrogen atom, a -COOH group, a -OH group or a -OPO(OH)2 group;

R4 represents a hydrogen atom or a fluorine atom;

R5 represents a hydrogen atom or a -OH group;

wherein:

■ at least one of R3 or R5 is different from a hydrogen atom;

■ when R3 represents a -COOH group, a -OH group or a -OPO(OH)2 group, then R5 represents a hydrogen atom;

■ when R5 represents a -OH group, then R3 and R4 represent hydrogen atoms;

R6 is selected from:

■ a phenyl group or a heteroaryl group comprising 3 to 9 carbon atoms and comprising from 1 to 3 heteroatoms independently selected from oxygen, nitrogen and sulphur, said phenyl and heteroaryl groups being unsubstituted or substituted with 1 to 3 substituents independently selected from: a (CrC6)-alkyl group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms; a halogen atom; a -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms; a cyano group; a sulphur group substituted with 5 fluorine atoms or (CrC6)-alkyl groups substituted with two or more (such as 2 or 3) fluorine atoms; a sulfonyl-(Ci- C6)-alkyl group wherein said (CrC6)-alkyl group are unsubstitued or substituted with two or more (such as 2 or 3) fluorine atoms; a silane group substituted with 3 (CrC6)-alkyl groups; an amine group unsubstituted or substituted with one or more (such as 1 or 2) (d-C6)-alkyl groups; an amide group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl groups; a heterocycloalkyi group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen or sulphur; or a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur and being unsubstituted or substituted with an oxo group; and

■ a cycloalkyl group or a heterocycloalkyi group comprising 4 to 9 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen or sulphur, said cycloalkyl or heterocycloalkyi groups being saturated or partially saturated and being unsubstituted or substituted with 1 to 4 substituents independently selected from:

a fluorine atom; a -OH group; a (CrC6)-alkyl group; a -COOR7 group wherein R7 is a (CrC6)-alkyl group; or an oxo group.

In another embodiment, the present invention relates to the compounds of the formula (l-A) above wherein:

- R1 and R2 represent independently a hydrogen atom or a deuterium atom;

- A represents an oxygen or nitrogen atom (namely, A represents a group of formula -O- or -NH-); and

- SERM-F represents a selective estrogen receptor modulator fragment (i.e. a molecule having a selective antagonist activity for estrogen receptors) selected from the following structures (al), (bll), (clll) and (dIV), provided that when A represents a nitrogen atom then SERM-F represents the structure (al):

wherein:

B, D, E and G represent independently carbon (=CH-) or nitrogen (N) atoms;

- n is an integer selected from 0 and 1 ;

- X represents -CH2-, -0-, -S-, -SO- or -S02-;

when n = 1 and X = CH2, then at least one of A, B, D, E or G is a nitrogen atom; R3 represents a hydrogen atom or an -OH, -COOH or -OPO(OH)2 group;

R4 represents a hydrogen, fluorine or chlorine atom or a methyl group;

- R5 represents a hydrogen, fluorine or chlorine atom, or a methyl or -OH group; wherein R3 and R5 do not simultaneously represent -OH groups or hydrogen atoms;

R6 is selected from:

■ a phenyl group, which is unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms or -OH groups; a halogen atom; an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms, (Ci-C6)-alkoxy or heterocycloalkyl groups; a cyano group; a sulphur group substituted with 5 fluorine atoms or with a (CrC6)-alkyl group substituted with two or more (such as 2 or 3) fluorine atoms; a sulfonyl-(CrC6)-alkyl group wherein said (CrC6)-alkyl group is unsubstituted or substituted with two or more (such as 2 or 3) fluorine atoms; a silane group substituted with three (CrC6)-alkyl groups; an amine group unsubstituted or substituted with one or more (such as 1 or 2) (d-C6)-alkyl groups; an amide group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl or (CrC6)-alkoxy groups; a heterocycloalkyl group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur; a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur and being unsubstituted or substituted with an oxo group; a -S02NH2 group; a -COOH group; a -O-cycloalkyl group; a -O-heterocycloalkyl group; and a -OCD3 group;

■ a heteroaryl group comprising 3 to 9 carbon atoms and comprising between 1 to 3 heteroatoms independently selected from oxygen, nitrogen and sulphur, said

heteroaryl group being unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms; a halogen atom; an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms; a cyano group; a sulphur group substituted with 5 fluorine atoms or with a (CrC6)-alkyl group substituted with two or more (such as 2 or 3) fluorine atoms; a sulfonyl-(CrC6)-alkyl group wherein said (C C6)-alkyl group is unsubstituted or substituted with two or more (such as 2 or 3) fluorine atoms; a silane group substituted with three (CrC6)-alkyl groups; an amine group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl groups; an amide group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl or (CrC6)-alkoxy groups; a heterocycloalkyi group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur; a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur and being unsubstituted or substituted with an oxo group; a -COO-(CrC6)-alkyl group; and an oxo group;

■ a cycloalkyl group comprising 4 to 9 carbon atoms, which is saturated or partially saturated, and which is unsubstituted or substituted with 1 to 4 substituents independently selected from:

a fluorine atom; an -OH group; a (CrC6)-alkyl group; a -COOR7 group wherein R7 is a (CrC6)-alkyl group; and an oxo group; and

■ a heterocycloalkyi group comprising 4 to 9 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur, said heterocycloalkyi group being saturated or partially saturated and being unsubstituted or substituted with 1 to 4 substituents independently selected from:

a fluorine atom; an -OH group; a (CrC6)-alkyl group; a -COOR7 group wherein R7 is a (CrC6)-alkyl group; and an oxo group.

In another embodiment, the invention relates to the compounds of formula (Γ):

wherein R1 , R2, R3, R4, R5, R6, A, B, D, E, G, X and n are as defined above. The compounds of formula (Γ) correspond to the compounds of formula (l-A) as described above, wherein the fragment SERM-F corresponds to the formula (al) above.

The compounds of the invention, namely the compounds of formulae (l-A) and (Γ) as defined above, contain one or more asymmetric carbon atoms, more particularly one asymmetric carbon atom on the pyrrolydinyl group. They may therefore exist in the form of enantiomers. These enantiomers form part of the invention. In particular, the carbon 3 of the pyrrolidinyl group linked to the A moiety in formulae (l-A) and (Γ) above may be in the absolute configuration (R) or (S). The carbon 3 of the pyrrolidinyl group is advantageously in the absolute configuration (S).

Hence, the invention also includes the compounds of formula (I), wherein R1 , R2, R3, R4, R5, R6, A, B, D, E, G, ) or (l-A) above:

The compounds of the invention may be present as well under tautomeric forms and are part of the invention.

The compounds of the invention may exist in the form of bases, acids, zwitterion or of addition salts with acids or bases. Such addition salts, bases, acids and zwitterion are part of the invention. Mention may be made for example of hydrochloride salts.

These salts may be prepared with pharmaceutically acceptable acids or bases, although the salts of other acids or bases useful, for example, for purifying or isolating the compounds of the invention also form part of the invention.

In the context of the present invention, the terms below have the following definitions unless otherwise mentioned throughout the specification:

- a halogen atom: a fluorine, a chlorine, a bromine or an iodine atom;

- an oxo: a "=0" group;

- a cyano group: a "-C≡N" group;

- an amine group: a nitrogen atom unsubstituted (-NH2) or substituted with one or more (CrC6)-alkyl groups;

- an amide group: a -C(0)NRR' or -NH-CO-R" group, wherein R represents a hydrogen atom or a (CrC6)-alkyl group, R' represents a hydrogen atom or a (Ci-C6)-alkoxy group, and R" represents a (CrC6)-alkyl or (d-C6)-alkoxy group;

- a silane group: a silicon atom substituted with 3 (CrC6)-alkyl groups;

- an alkyl group: a linear or branched saturated hydrocarbon-based aliphatic group comprising, unless otherwise mentioned, from 1 to 6 carbon atoms (noted "(Ci-C6)-alkyl").

By way of examples, mention may be made of, but not limited to: methyl (Me), ethyl (Et), propyl, n-propyl, isopropyl (iPr), butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl and isohexyl groups, and the like;

- an alkoxy group: an -O-alkyl group where the alkyl group is as previously defined. By way of examples, mention may be made of, but not limited to: methoxy (-OMe), ethoxy

(-OEt), propoxy, isopropoxy (O-iPr), linear, secondary or tertiary butoxy, isobutoxy, pentoxy or hexoxy groups, and the like;

- a cycloalkyl group: a cyclic alkyl group comprising, unless otherwise mentioned, from 3 to 6 carbon atoms, saturated or partially unsaturated and unsubstituted or substituted. By way of examples, mention may be made of, but not limited to: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexen groups, and the like;

- a heterocycloalkyl group: a cyclic alkyl group comprising, unless otherwise mentioned, from 3 to 6 carbon atoms and containing 1 or 2 heteroatoms such as oxygen, nitrogen and sulphur. Such nitrogen atom may be substituted by an oxygen atom in order to form a -N-0 bond. Such -N-0 bond can be in a form of a N-oxide (-N+-0"). Such heterocycloalkyl group may be saturated or partially saturated, unsubstituted or substituted, and may be monocyclic or bicyclic.

By way of examples of monocyclic heterocycloalkyi groups, mention may be made of, but not limited to: tetrahydropyridinyl, dihydropyridinyl, dihydropyranyl, tetrahydropyranyl groups, and the like.

A bicyclic heterocycloalkyi group means: a phenyl or monocyclic heteroaryl group fused to a monocyclic heterocycloalkyi group as defined above. By way of examples of bicyclic heterocycloalkyi groups, mention may be made of, but not limited to: tetrahydroquinolinyl, indolinyl, indolinone (also named oxindolyl), benzodioxolyl, dihydrobenzodioxinyl (also named benzodioxanyl, such as benzo-1 ,4-dioxanyl), dihydrobenzoxazinyl (such as 3,4-dihydro-1 ,4-benz[1 ,4]oxazine), benzofuranyl, 2,3-dihydrobenzofuranyl, 5,6-dihydro-2H-pyranyl and dihydroazaindolinyl (also named 2,3-dihydro-1 H-pyrrolo[2,3-b]pyridinyl) groups, all optionally substituted as above indicated, and the like.

- A heteroaryl group: a cyclic aromatic group containing between 4 and 9 carbon atoms and containing between 1 and 3 heteroatoms, such as nitrogen, oxygen and sulphur. Such nitrogen atom may be substituted by an oxygen atom in order to form a -N-O bond. Such -N-0 bond can be in a form of a N-oxide (-N+-0"). Said heteroaryl group may be monocyclic or bicyclic. By way of examples of heteroaryl groups, mention may be made of, but not limited to: isoxazole, pyridine (or pyridinyl), pyrimidine (or pyrimidinyl), benzotriazole, benzoxazole, benzimidazole, benzoxadiazole, benzothiazole, benzothiadiazole, benzofuran, indole (also named indolyl), quinolyl, indazole, benzisoxazole, benzisothiazole and thiazolyl groups, and the like;

- A zwitterion: a globally neutral molecule with a positive and a negative electrical charge and having an acid group and a basic group. By way of examples, mention may be made of, but not limited to compounds of the present inventions having R3 which represents a -COOH group or an -OPO(OH)2 group.

In an embodiment, in the compounds of the invention, R1 and R2 both represent hydrogen atoms.

The invention is therefore directed to the compounds of formula (l-A-1 ) and (1-1 ) below, wherein SERM-F, A, B, D, E, G, X, n, R3, R4, R5 and R6 are as defined above:

In an embodiment of the compounds of formula (l-A-1 ), (1-1 ), (Γ) and (I), when R5 represents an -OH group, then R3 and R4 advantageously represent hydrogen atoms.

In another embodiment, in the compounds of formula (I) and (Γ), A represents an oxygen atom. The invention therefore includes the compounds of formula (I-2) below, wherein X, n, R1 , R2, R3, R4, defined in formula (I) above:

In the compounds of formula (I-2), R1 and R2 advantageously represent hydrogen atoms.

In an embodiment of the compounds of formula (I-2), B, D, E and G represent carbon atoms.

In another embodiment of the compounds of formula (1-2), one or two of B, D, E and G represent nitrogen atoms.

In another embodiment of the compounds of formula (1-2), D represents a nitrogen atom and B, E and G represent carbon atoms.

In another embodiment of the compounds of formula (1-2), E and D represent nitrogen atoms, and B and G represent carbon atoms.

In another embodiment of the compounds of formula (1-2), E and B represent nitrogen atoms, and D and G represent carbon atoms.

In another embodiment of the compounds of formula (1-2), G and B represent nitrogen atoms, and D and E represent carbon atoms.

In another embodiment, in the compounds of formula (1-2) R6 is as defined above.

In the formula (1-2), (l-A-1 ) and (1-1 ), as well as in the formula (Γ) and (I) described above, R6 is advantageously selected from:

■ a phenyl group, which is unsubstituted or substituted with 1 , 2 or 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms or -OH groups (such as methyl, ethyl, tert-butyl, -C(Me)2OH, -CH2F, -CHF2 or -CF3); a halogen atom (such as fluorine or chlorine); an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms, (CrC6)-alkoxy or heterocycloalkyl (such as pyrrolidinyl) groups (such as -OMe, -OEt, -O-iPr, -OCH2F, -OCHF2, -OCF3 group, -0-(CH2)2-OCH3 and -0-(CH2)2-pyrrolidin-1 -yl); a sulphur group substituted with a (CrC6)-alkyl group substituted with two or more (such as 2 or 3) fluorine atoms (such as a -SCF3 group); a sulfonyl-(CrC6)-alkyl group (such as a -S02Me group); an amine group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl groups (such as a -NHEt or -N(Et)2 group); an amide group substituted with a (C C6)-alkoxy group (such as a group -CO-NH-OMe); a -S02NH2 group; a -COOH group; a -O-cycloalkyl group (such as a -O-cyclopropyl group); a -O-heterocycloalkyl group (such as a -O-oxetanyl group); and a -OCD3 group;

■ a heteroaryl group selected from an indole (more particularly indol-4-yl, indol-5-yl or indol-6-yl), pyridinyl (more particularly pyridin-3-yl or pyridin-4-yl), benzofuran, isoxazole (more particularly isoxazol-4-yl), quinolyl (more particularly quinolin-6-yl) and thiazolyl (more particularly thiazol-5-yl) group, said heteroaryl group being unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group (such as methyl, ethyl or tert-butyl); a halogen atom (such as fluorine); an -OH group; a (CrC6)-alkoxy group (such as -OMe or -OEt); an amine group; an amide group substituted with a (CrC6)-alkoxy group (such as a group -NH-COO-alkyl, in particular -NH-COO(tert-butyl)); and

■ a heterocycloalkyl group selected from an indolinyl (more particularly indolin-5-yl or indolin-6-yl), dihydroazaindolinyl (more particularly 2,3-dihydro-1 H-pyrrolo[2,3-b]pyridin-5-yl), dihydrobenzodioxinyl (more particularly 2,3-dihydro-1 ,4-benzodioxin-6-yl), benzodioxolyl (more particularly benzo[1 ,3]dioxolyl), 2,3-dihydrobenzofuranyl, dihydrobenzoxazinyl (more particularly dihydrobenzoxazin-6-yl and

dihydrobenzoxazin-7-yl) and 5,6-dihydro-2H-pyranyl group, the said heterocycloalkyl group being unsubstituted or substituted with 1 to 4 substituents independently selected from:

a fluorine atom; a (CrC6)-alkyl group (such as Me or Et); a -COOR7 group wherein R7 is a (CrC6)-alkyl group (such as a -CO-Me or -COO(tert-butyl) group); and an oxo group.

More specifically, when R6 represents a heteroaryl group, the said heteroaryl is advantageously selected from the following ones:

thiazol-5-yl pyridin-4-yl pyridin-3-yl

More specifically, when R6 represents a heterocycloalkyl group, said heterocycloalkyl is advantageously selected from the following ones:

5,6-dihydro-2H-pyranyl group

In another embodiment, in the compounds of formula (I), A represents an oxygen atom, B, D, E and G represent carbon atoms, n = 0 and X represents -CH2-.

The invention therefore includes the compounds of formula (1-3) below, wherein R1 , R2, R3, R4, R5 and R6 are as defined in formula (I) above:

In the compounds of formula (I-3), R1 and R2 advantageously represent hydrogen atoms.

In an embodiment of the compounds of formula (1-3), R4 represents a hydrogen atom, and one of R3 or R5 represents an -OH group while the other of R3 or R5 represents a hydrogen atom.

In another embodiment of the compounds of formula (1-3), R6 is selected from:

- a phenyl group, which is unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more fluorine atoms or -OH groups; a halogen atom; an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more fluorine atoms; a cyano group; a sulphur group substituted with 5 fluorine atoms or with a (CrC6)-alkyl group substituted with two or more (such as 2 or 3) fluorine atoms; a sulfonyl-(CrC6)-alkyl group wherein said (CrC6)-alkyl group is unsubstituted or substituted with two or more fluorine atoms; a silane group substituted with 3 (CrC6)-alkyl groups; an amine group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl groups; an amide group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl or (CrC6)-alkoxy groups; a heterocycloalkyi group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur; a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur and being unsubstituted or substituted with an oxo group; a group -S02NH2; a group -O-heterocycloalkyl; or a group -OCD3;

- a heteroaryl group comprising 3 to 9 carbon atoms and comprising between

1 to 3 heteroatoms independently selected from oxygen, nitrogen and sulphur, said heteroaryl group being unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more fluorine atoms; a halogen atom; an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more fluorine atoms; a cyano group; a sulphur group substituted with 5 fluorine atoms or with a (CrC6)-alkyl group substituted with two or more (such as 2 or 3) fluorine atoms; a sulfonyl-(CrC6)-alkyl group wherein said (CrC6)-alkyl group is unsubstituted or substituted with two or more fluorine atoms; a silane group substituted with 3 (CrC6)-alkyl groups; an amine group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl groups; an amide group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl or (CrC6)-alkoxy groups; a heterocycloalkyi group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur; a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur and being unsubstituted or substituted with an oxo group; a -COO-(Ci-C6)-alkyl group; or an oxo group; or

■ a heterocycloalkyi group comprising 4 to 9 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur, the said heterocycloalkyi group being saturated or partially saturated and being unsubstituted or substituted with 1 to 4 substituents independently selected from:

a fluorine atom; an -OH group; a (CrC6)-alkyl group; a -COOR7 group wherein R7 is a (CrC6)-alkyl group; and an oxo group.

In another embodiment of the compounds of formula (I-3), R6 is selected from:

■ a phenyl group, which is substituted with 1 or 2 substituents independently selected from:

a (CrC6)-alkyl group (such as a tert-butyl group); a halogen atom (such as fluorine or chlorine); an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms (such as a -OCF3 group); a sulphur group substituted with a (CrC6)-alkyl group substituted with two or more (such as 2 or 3) fluorine atoms (such as a -SCF3 group);

■ a heteroaryl group selected from a pyridinyl (more particularly pyridinyl-4-yl) and an indole group, the said heteroaryl group being unsubstituted or substituted with 1 to 3 halogen atoms (such as fluorine); and

■ a 5,6-dihydro-2H-pyranyl group.

In another embodiment, in the compounds of formula (I), A represents an oxygen atom, B, D, E and G represent carbon atoms, n = 0 and X represents -S- or -SO-.

The invention therefore includes the compounds of formula (I-4) below, wherein R1 , R2, R3, R4, R5 and R6 are as defined in formula (I) above:

In the compounds of formula (I-4), R1 and R2 advantageously represent hydrogen atoms.

In an embodiment of the compounds of formula (I-4), R4 and R5 represent hydrogen atoms and R3 represents a group of formula -OH, -COOH or -OPO(OH)2.

In another embodiment, in formula (I-4) R3 represents a hydroxyl group.

In another embodiment, in formula (I-4) R6 is selected from:

■ a phenyl group, which is unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms or -OH groups; a halogen atom; an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms, (Ci-C6)-alkoxy or heterocycloalkyl groups; a cyano group; a sulphur group substituted with 5 fluorine atoms or with a (CrC6)-alkyl group substituted with two or more (such as 2 or 3) fluorine atoms; a sulfonyl-(CrC6)-alkyl group wherein the said (CrC6)-alkyl group is unsubstituted or substituted with two or more (such as 2 or 3) fluorine atoms; a silane group substituted with three (CrC6)-alkyl groups; an amine group unsubstituted or substituted with one or more (such as 1 or 2) (d-C6)-alkyl groups; an amide group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl or (CrC6)-alkoxy groups; a heterocycloalkyl group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur; a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur and being unsubstituted or substituted with an oxo group; a -S02NH2 group; a -COOH group; a -O-cycloalkyl group; a -O-heterocycloalkyl group; and a -OCD3 group;

■ a heteroaryl group comprising 3 to 9 carbon atoms and comprising between 1 to 3 heteroatoms independently selected from oxygen, nitrogen and sulphur, the said heteroaryl group being unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms; a halogen atom; an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms; a cyano group; a sulphur group substituted with 5 fluorine atoms or with a (CrC6)-alkyl group substituted with two or more (such as 2 or 3) fluorine atoms; a sulfonyl-(CrC6)-alkyl group wherein said (C C6)-alkyl group is unsubstituted or substituted with two or more (such as 2 or 3) fluorine atoms; a silane group substituted with three (CrC6)-alkyl groups; an amine group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl groups; an amide group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl or (CrC6)-alkoxy groups; a heterocycloalkyl group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur; a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur and being unsubstituted or substituted with an oxo group; a -COO-(CrC6)-alkyl group; and an oxo group; and

■ a heterocycloalkyl group comprising 4 to 9 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur, said

heterocycloalkyi group being saturated or partially saturated and being unsubstituted or substituted with 1 to 4 substituents independently selected from:

a fluorine atom; an -OH group; a (CrC6)-alkyl group; a -COOR7 group wherein R7 is a (CrC6)-alkyl group; and an oxo group.

In another embodiment, in formula (I-4) R6 is selected from:

■ a phenyl group substituted with 1 , 2 or 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms or -OH groups (such as methyl, ethyl, tert-butyl, -C(Me)2OH, -CH2F or -CHF2); a halogen atom (such as fluorine or chlorine); a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms (such as -OMe, -OEt, -OCH2F, -OCHF2 or -OCF3); a sulphur group substituted with a (CrC6)-alkyl group, which alkyl group is substituted with 2 to 3 fluorine atoms (such as a -SCF3 group); an amine group unsubstituted or substituted with one or two (CrC6)-alkyl groups (such as a -N(Et)2 group); a -S02NH2 group; a -O-heterocycloalkyl group (such as a -O-oxetanyl group); or a -OCD3 group;

■ a heteroaryl group selected from an indole, pyridinyl (more particularly pyridin-3-yl or pyridin-4-yl), quinolyl and thiazolyl group, said heteroaryl group being unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group (such as methyl, ethyl or tert-butyl) unsubstituted or substituted with 1 or 2 fluorine atoms; a halogen atom (such as fluorine or chlorine); an -OH group; a (C C6)-alkoxy group (such as -OMe or -OEt) unsubstituted or substituted with one or more (such as 1 , 2 o 3) fluorine atoms; an amine group; an amide group substituted by a (C C6)-alkoxy group (such as a group -NH-COO-alkyl, in particular -NH-COO(tert-butyl)); and

■ a heterocycloalkyi group selected from an indolinyl (more particularly 1 -indolinyl), dihydrobenzodioxinyl, benzodioxolyl, 2,3-dihydrobenzofuranyl and dihydrobenzoxazinyl group, said heterocycloalkyi group being unsubstituted or substituted with 1 to 4 substituents independently selected from:

a fluorine atom; a (CrC6)-alkyl group (such as Me or Et); a -COOR7 group wherein R7 is a (CrC6)-alkyl group (such as a -CO-Me or -COO(tert-butyl) group); and an oxo group.

In another embodiment, in the compounds of formula (I), A represents an oxygen atom, one or two of B, D, E and G represent a nitrogen atom while the others of B, D, E and G represent carbon atoms, n = 0 and X represents -S-.

In this embodiment of the invention, G and B advantageously represent carbon atoms while one or both of E and D represent nitrogen atoms.

The invention therefore includes the compounds of formula (1-5) below, wherein E, D, R1 , R2, R3, R4, R5 and R6 are as defined in formula (I) above and wherein one or two of E and D represent nitrogen atoms:

In the compounds of formula (I-5), R1 and R2 advantageously represent hydrogen atoms.

In an embodiment of the compounds of formula (I-5), R4 and R5 represent hydrogen atoms and R3 represents a hydroxyl group.

In another embodiment, in formula (1-5) R6 is selected from:

■ a phenyl group, which is unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms or -OH groups; a halogen atom; an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms, (Ci-C6)-alkoxy or heterocycloalkyl groups; a cyano group; a sulphur group substituted with 5 fluorine atoms or with a (CrC6)-alkyl group substituted with two or more (such as 2 or 3) fluorine atoms; a sulfonyl-(CrC6)-alkyl group wherein said (CrC6)-alkyl group is unsubstituted or substituted with two or more (such as 2 or 3) fluorine atoms; a silane group substituted with three (CrC6)-alkyl groups; an amine group unsubstituted or substituted with one or more (such as 1 or 2) (d-C6)-alkyl groups; an amide group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl or (CrC6)-alkoxy groups; a heterocycloalkyl group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur; a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur and being unsubstituted or substituted with an oxo group; a -S02NH2 group; a -COOH group; a -O-cycloalkyl group; a -O-heterocycloalkyl group; and a -OCD3 group; and

■ a heteroaryl group comprising 3 to 9 carbon atoms and comprising between 1 to 3 heteroatoms independently selected from oxygen, nitrogen and sulphur, said heteroaryl group being unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms; a halogen atom; an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms; a cyano group; a sulphur group substituted with 5 fluorine atoms or with a (CrC6)-alkyl group substituted with two or more (such as 2 or 3) fluorine atoms; a sulfonyl-(CrC6)-alkyl group wherein said (C C6)-alkyl group is unsubstituted or substituted with two or more (such as 2 or 3) fluorine atoms; a silane group substituted with three (CrC6)-alkyl groups; an amine group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl groups; an amide group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl or (CrC6)-alkoxy groups; a heterocycloalkyl group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur; a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur and being unsubstituted or substituted with an oxo group; a -COO-(CrC6)-alkyl group; and an oxo group.

In another embodiment, in formula (I-5) R6 is selected from:

■ a phenyl group substituted with 1 or 2 substituents independently selected from: a (CrC6)-alkyl group (such as methyl); a halogen atom (such as fluorine); and a (C C6)-alkoxy group unsubstituted or substituted with one or more fluorine atoms (such as an -OCF3 group); and

- a pyridinyl group (more particularly pyridine-3-yl) substituted with 1 or 2 substituents independently selected from a halogen atom (such as fluorine) and a (Ci-C6)-alkoxy group (such as an -OEt group).

In another embodiment, in the compounds of formula (I), A represents an oxygen atom, B, D, E and G represent carbon atoms, n = 0 and X represents -0-.

The invention therefore includes the compounds of formula (I-6) below, wherein R1 , R2, R3, R4, R5 and R6 are as defined in formula (I) above:

In the compounds of formula (1-6), R1 and R2 advantageously represent hydrogen atoms.

In an embodiment of the compounds of formula (I-6), R4 and R5 advantageously represent hydrogen atoms and R3 a hydroxyl group.

In another embodiment, in formula (I-6) R6 represents a phenyl group which is unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms or -OH groups; a halogen atom; an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms, (Ci-C6)-alkoxy or heterocycloalkyl groups; a cyano group; a sulphur group substituted with 5 fluorine atoms or with a (CrC6)-alkyl group substituted with two or more (such as 2 or 3) fluorine atoms; a sulfonyl-(CrC6)-alkyl group wherein said (CrC6)-alkyl grou is unsubstituted or substituted with two or more (such as 2 or 3) fluorine atoms; a silane group substituted with three (CrC6)-alkyl groups; an amine group unsubstituted or substituted with one or more (such as 1 or 2) (d-C6)-alkyl groups; an amide group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl or (CrC6)-alkoxy groups; a heterocycloalkyl group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur; a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur and being unsubstituted or substituted with an oxo group; a -S02NH2 group; a -COOH group; a -O-cycloalkyl group; a -O-heterocycloalkyl group; and a -OCD3 group.

In another embodiment, in formula (I-6) R6 represents a phenyl group substituted by 1 or 2 substituents selected from a hydroxyl group and a halogen atom (such as fluorine or chlorine).

In another embodiment, in the compounds of formula (I), A represents a nitrogen atom (A = -NH-), B, D, E and G represent carbon atoms and X represents -CH2-.

The invention therefore includes the compounds of formula (1-7) below, wherein n, R1 , R2, R3, R4, R5 and R6 are as defined in formula (I) above:

In the compounds of formula (I-7), R1 and R2 advantageously represent hydrogen atoms.

In an embodiment of the compounds of formula (I-7), R4 advantageously represents a hydrogen atom.

In another embodiment, in formula (1-7) one of R3 or R5 represents a hydroxyl group, while the other of R3 or R5 represents a hydrogen atom.

In another embodiment, in formula (1-7) R6 is selected from:

■ a phenyl group, which is unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms or -OH groups; a halogen atom; an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms, (Ci-C6)-alkoxy or heterocycloalkyl groups; a cyano group; a sulphur group substituted with 5 fluorine atoms or with a (CrC6)-alkyl group substituted with two or more (such as 2 or 3) fluorine atoms; a sulfonyl-(CrC6)-alkyl group wherein said (CrC6)-alkyl group is unsubstituted or substituted with two or more (such as 2 or 3) fluorine atoms; a silane group substituted with three (CrC6)-alkyl groups; an amine group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl groups; an amide group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl or (CrC6)-alkoxy groups; a heterocycloalkyl group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur; a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur and being unsubstituted or substituted with an oxo group; a -S02NH2 group; a -COOH group; a -O-cycloalkyl group; a -O-heterocycloalkyl group; and a -OCD3 group; and

■ a heteroaryl group comprising 3 to 9 carbon atoms and comprising between 1 to 3 heteroatoms independently selected from oxygen, nitrogen and sulphur, said heteroaryl group being unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms; a halogen atom; an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms; a cyano group; a sulphur group substituted with 5 fluorine atoms or with a (CrC6)-alkyl group substituted with two or more (such as 2 or 3) fluorine atoms; a sulfonyl-(CrC6)-alkyl group wherein said (C C6)-alkyl group is unsubstituted or substituted with two or more (such as 2 or 3) fluorine atoms; a silane group substituted with three (CrC6)-alkyl groups; an amine group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl groups; an amide group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl or (CrC6)-alkoxy groups; a heterocycloalkyl group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur; a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur and being unsubstituted or substituted with an oxo group; a -COO-(CrC6)-alkyl group; and an oxo group.

In another embodiment, in formula (I-7) R6 is selected from:

■ a phenyl group substituted by 1 or 2 substituents selected from a halogen atom (such as fluorine or chlorine) and a -OCF3, -SCF3 or (d-C6)-alkyl group (such as tert-butyl); and

■ a pyridinyl group (more particularly pyridine-3-yl) substituted by 1 or 2 substituents selected from a halogen atom (such as fluorine) and a (CrC6)-alkoxy group (such as -OEt).

In another embodiment, in the compounds of formula (I), A represents an oxygen atom, B, D, E and G represent carbon atoms, n = 1 and X represents -0-.

The invention therefore includes the compounds of formula (I-8) below, wherein R1 , R2, R3, R4, R5 and R6 are as defined in formula (I) above:

In the compounds of formula (1-8), R1 and R2 advantageously represent hydrogen atoms.

In an embodiment of the compounds of formula (I-8), R3 represents an -OH group.

In another embodiment, in formula (I-8) R4 represents a hydrogen, fluorine or chlorine atom or a methyl group.

In another embodiment, in formula (I-8) R5 represents a hydrogen, fluorine or chlorine atom or a methyl group.

In another embodiment, in formula (1-8) R6 is selected from:

■ a phenyl group, which is unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms or -OH groups; a halogen atom; an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms, (Ci-C6)-alkoxy or heterocycloalkyl groups; a cyano group; a sulphur group substituted with 5 fluorine atoms or with a (CrC6)-alkyl group substituted with two or more (such as 2 or 3) fluorine atoms; a sulfonyl-(CrC6)-alkyl group wherein said (CrC6)-alkyl group is unsubstituted or substituted with two or more (such as 2 or 3) fluorine atoms; a silane group substituted with three (CrC6)-alkyl groups; an amine group unsubstituted or substituted with one or more (such as 1 or 2) (d-C6)-alkyl groups; an amide group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl or (CrC6)-alkoxy groups; a heterocycloalkyl group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur; a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur and being unsubstituted or substituted with an oxo group; a -S02NH2 group; a -COOH group; a -O-cycloalkyl group; a -O-heterocycloalkyl group; and a -OCD3 group;

■ a heteroaryl group comprising 3 to 9 carbon atoms and comprising between 1 to 3 heteroatoms independently selected from oxygen, nitrogen and sulphur, said heteroaryl group being unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms; a halogen atom; an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms; a cyano group; a sulphur group substituted with 5 fluorine atoms or with a (CrC6)-alkyl group substituted with two or more (such as 2 or 3) fluorine atoms; a sulfonyl-(CrC6)-alkyl group wherein said (C C6)-alkyl group is unsubstituted or substituted with two or more (such as 2 or 3) fluorine atoms; a silane group substituted with three (CrC6)-alkyl groups; an amine group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl; an amide group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl or (d-C6)-alkoxy groups; a heterocycloalkyi group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur; a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur and being unsubstituted or substituted with an oxo group; a -COO-(CrC6)-alkyl group; and an oxo group; and

- a heterocycloalkyi group comprising 4 to 9 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur, said heterocycloalkyi group being saturated or partially saturated and being unsubstituted or substituted with 1 to 4 substituents independently selected from:

a fluorine atom; an -OH group; a (CrC6)-alkyl group; a -COOR7 group wherein R7 is a (CrC6)-alkyl group; and an oxo group.

In another embodiment, in formula (I-8) R6 is selected from:

■ a phenyl group substituted with 1 or 2 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms (such as methyl and -CF3); a halogen atom (such as chlorine or fluorine); an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with a (CrC6)-alkoxy or a heterocycloalkyi (such as pyrrolidinyl) group (such as -OMe, -OEt, O-iPr, -0-(CH2)2- OCH3 and -0-(CH2)2-pyrrolidin-1 -yl); a -COOH group; and a -O-cycloalkyl group (such as a -O-cyclopropyl group);

- a heteroaryl group selected from an indole, benzofuran and pyridinyl group

(more particularly 3-pyridinyl), said heteroaryl group being unsubstituted or substituted with a (CrC6)-alkoxy group (such as -OEt); and

■ an indolinyl (more particularly 1 -indolinyl) or 2,3-dihydrobenzofuranyl group.

In another embodiment, in the compounds of formula (I), A represents an oxygen atom, B, E and G represent carbon atoms, D represents a carbon atom or a nitrogen atom, n = 1 and X represents -S-.

The invention therefore includes the compounds of formula (I-9) below, wherein D, R1 , R2, R3, R4, R5 and R6 are as defined in formula (I) above:

In the compounds of formula (1-9), R1 and R2 advantageously represent hydrogen atoms.

In an embodiment of the compounds of formula (I-9), D represents a carbon atom. In another embodiment, in formula (I-9) R3 represents a hydrogen atom or an -OH or -COOH group.

In another embodiment, in formula (1-9) R4 represents a hydrogen atom.

In another embodiment, in formula (1-9) R5 represents a hydrogen atom or an -OH group.

In another embodiment, in formula (1-9) R6 is selected from:

■ a phenyl group, which is unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms or -OH groups; a halogen atom; an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms, (Ci-C6)-alkoxy or heterocycloalkyl groups; a cyano group; a sulphur group substituted with 5 fluorine atoms or with a (CrC6)-alkyl group substituted with two or more (such as 2 or 3) fluorine atoms; a sulfonyl-(CrC6)-alkyl group wherein said (CrC6)-alkyl group is unsubstituted or substituted with two or more (such as 2 or 3) fluorine atoms; a silane group substituted with three (CrC6)-alkyl groups; an amine group unsubstituted or

substituted with one or more (such as 1 or 2) (d-C6)-alkyl groups; an amide group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl or (CrC6)-alkoxy groups; a heterocycloalkyi group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur; a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur and being unsubstituted or substituted with an oxo group; a -S02NH2 group; a -COOH group; a -O-cycloalkyl group; a -O-heterocycloalkyl group; and a -OCD3 group;

■ a heteroaryl group comprising 3 to 9 carbon atoms and comprising between 1 to 3 heteroatoms independently selected from oxygen, nitrogen and sulphur, said heteroaryl group being unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms; a halogen atom; an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms; a cyano group; a sulphur group substituted with 5 fluorine atoms or with a (CrC6)-alkyl group substituted with two or more (such as 2 or 3) fluorine atoms; a sulfonyl-(CrC6)-alkyl group wherein said (C C6)-alkyl group is unsubstituted or substituted with two or more (such as 2 or 3) fluorine atoms; a silane group substituted with three (CrC6)-alkyl groups; an amine group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl; an amide group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl or (d-C6)-alkoxy groups; a heterocycloalkyi group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur; a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur and being unsubstituted or substituted with an oxo group; a -COO-(CrC6)-alkyl group; and an oxo group; and

■ a heterocycloalkyi group comprising 4 to 9 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur, said heterocycloalkyi group being saturated or partially saturated and being unsubstituted or substituted with 1 to 4 substituents independently selected from:

a fluorine atom; an -OH group; a (CrC6)-alkyl group; a -COOR7 group wherein R7 is a (CrC6)-alkyl group; and an oxo group.

In another embodiment, in formula (I-9) R6 is selected from:

- a phenyl group substituted with 1 , 2 or 3 substituents independently selected from:

a (CrC6)-alkyl group (such as methyl or tert-butyl); a halogen atom (such as fluorine or chlorine); an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms (such as the groups -OMe, -OEt, -OCH2F, - OCHF2, -OCF3); a sulphur group substituted with a (CrC6)-alkyl group substituted with two or more (such as 2 or 3) fluorine atoms (such as a -SCF3 group); a sulfonyl-(CrC6)- alkyl group (such as a -S02Me group); an amine group unsubstituted or substituted with one or more (such as 1 or 2) (d-C6)-alkyl groups (such as the groups -NHEt and -NEt2); an amide group unsubstituted or substituted with one or more (such as 1 or 2) (Ci-C6)- alkyl or (CrC6)-alkoxy groups (such as a group -CO-NH-OMe); and a group -OCD3;

- a heteroaryl group selected from an indole, benzofuran, pyridinyl (such as

3-pyridinyl) and isoxazole group, said heteroaryl group being substituted with 1 or 2 substituents independently selected from: a (CrC6)-alkyl group (such as methyl); a halogen atom (such as fluorine); a (CrC6)-alkoxy group (such as -OEt); and an amine group; and

- a heterocycloalkyl group selected from an indolinyl (more particularly 1- indolinyl), dihydroazaindolinyl, benzodioxolyl (more particularly benzo[1 ,3]dioxolyl) and 2,3-dihydrobenzofuranyl group, said heterocycloalkyl group being unsubstituted or substituted with 1 or 2 substituents independently selected from a fluorine atom and a (C C6)-alkyl group (such as methyl).

In another embodiment, in the compounds of formula (I), A represents an oxygen atom, B, D, E and G represent carbon atoms, n = 1 and X represents -SO-.

The invention therefore includes the compounds of formula (1-10) below, wherein R1 ,

R2, R3, R4, R5 and R6 are as defined in formula (I) above:

In the compounds of formula (1-10), R1 and R2 advantageously represent hydrogen

In an embodiment of the compounds of formula (1-10), R3 represents an -OH group.

In another embodiment, in formula (1-10) R4 and R5 represent hydrogen atoms.

In another embodiment, in formula (1-10) R6 represents a phenyl group, which is unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms or -OH groups; a halogen atom; an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms, (Ci-C6)-alkoxy or heterocycloalkyl groups; a cyano group; a sulphur group substituted with 5 fluorine atoms or with a (CrC6)-alkyl group substituted with two or more (such as 2 or 3) fluorine atoms; a sulfonyl-(CrC6)-alkyl group wherein said (CrC6)-alkyl group is unsubstituted or substituted with two or more (such as 2 or 3) fluorine atoms; a silane group substituted with three (CrC6)-alkyl groups; an amine group unsubstituted or substituted with one or more (such as 1 or 2) (d-C6)-alkyl groups; an amide group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl or (CrC6)-alkoxy groups; a heterocycloalkyl group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur; a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur and being unsubstituted or substituted with an oxo group; a -S02NH2 group; a -COOH group; a -O-cycloalkyl group; a -O-heterocycloalkyl group; and a -OCD3 group.

In another embodiment, in formula (1-10) R6 represents a phenyl group substituted with a (CrC6)-alkoxy group unsubstituted or substituted with 1 , 2 or 3 fluorine atoms (such as a group -OCF3).

In another embodiment, in the compounds of formula (I), A represents an oxygen atom, B, D, E and G represent carbon atoms, n = 1 and X represents -S02-.

The invention therefore includes the compounds of formula (1-1 1 ) below, wherein R1 , R2, R3, R4, R5 and R6 are as defined in formula (I) above:

In the compounds of formula (1-1 1 ), R1 and R2 advantageously represent hydrogen atoms.

In an embodiment of the compounds of formula (1-1 1 ), R3 represents an -OH group.

In another embodiment, in formula (1-1 1 ) R4 and R5 represent hydrogen atoms.

In another embodiment, in formula (1-1 1 ) R6 represents a phenyl group, which is unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms or -OH groups; a halogen atom; an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms, (Ci-C6)-alkoxy or heterocycloalkyl groups; a cyano group; a sulphur group substituted with 5 fluorine atoms or with a (CrC6)-alkyl group substituted with two or more (such as 2 or 3) fluorine atoms; a sulfonyl-(CrC6)-alkyl group wherein said (CrC6)-alkyl group is unsubstituted or substituted with two or more (such as 2 or 3) fluorine atoms; a silane group substituted with three (CrC6)-alkyl groups; an amine group unsubstituted or substituted with one or more (such as 1 or 2) (d-C6)-alkyl groups; an amide group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl or (CrC6)-alkoxy groups; a heterocycloalkyl group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur; a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur and being unsubstituted or substituted with an oxo group; a -S02NH2 group; a -COOH group; a -O-cycloalkyl group; a -O-heterocycloalkyl group; and a -OCD3 group.

In another embodiment, in formula (1-1 1 ) R6 represents a phenyl group substituted with 1 or 2 substituents independently selected from: a (CrC6)-alkyl group (such as methyl); a halogen atom (such a chlorine or fluorine); and an -OH group.

In another embodiment, in the compounds of formula (I), A represents an oxygen atom, n = 1 , X represents -CH2-, and one or two of B, D, E and G represent nitrogen atoms.

The invention therefore includes the compounds of formula (1-12) below, wherein B, D,

E, G, R1 , R2, R3, R4, R5 an (I) above:

(1-12)

In the compounds of formula (1-12), R1 and R2 advantageously represent hydrogen atoms.

In an embodiment of the compounds of formula (1-12), D represents a nitrogen atom and B, E and G represent carbon atoms.

In another embodiment of the compounds of formula (1-12), D and E represent nitrogen atoms and B and G represent carbon atoms.

In another embodiment of the compounds of formula (1-12), B and E represent nitrogen atoms and D and G represent carbon atoms.

In another embodiment of the compounds of formula (1-12), B and G represent nitrogen atoms and D and E represent carbon atoms.

In another embodiment, in formula (1-12) R3 represents an -OH or -COOH group. In another embodiment, in formula (1-12) R4 represents a hydrogen or fluorine atom.

In another embodiment, in formula (1-12) R5 represents a hydrogen atom.

In another embodiment, in formula (1-12) R6 is selected from:

■ a phenyl group, which is unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms or -OH groups; a halogen atom; an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms, (Ci-C6)-alkoxy or heterocycloalkyi groups; a cyano group; a sulphur group substituted with 5

fluorine atoms or with a (CrC6)-alkyl group substituted with two or more (such as 2 or 3) fluorine atoms; a sulfonyl-(CrC6)-alkyl group wherein said (CrC6)-alkyl group is unsubstituted or substituted with two or more (such as 2 or 3) fluorine atoms; a silane group substituted with three (CrC6)-alkyl groups; an amine group unsubstituted or substituted with one or more (such as 1 or 2) (d-C6)-alkyl groups; an amide group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl or (CrC6)-alkoxy groups; a heterocycloalkyl group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur; a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur and being unsubstituted or substituted with an oxo group; a -S02NH2 group; a -COOH group; a -O-cycloalkyl group; a -O-heterocycloalkyl group; and a -OCD3 group;

■ a heteroaryl group comprising 3 to 9 carbon atoms and comprising between 1 to 3 heteroatoms independently selected from oxygen, nitrogen and sulphur, said heteroaryl group being unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms; a halogen atom; an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms; a cyano group; a sulphur group substituted with 5 fluorine atoms or with a (CrC6)-alkyl group substituted with two or more (such as 2 or 3) fluorine atoms; a sulfonyl-(CrC6)-alkyl group wherein said (C C6)-alkyl group is unsubstituted or substituted with two or more (such as 2 or 3) fluorine atoms; a silane group substituted with three (CrC6)-alkyl groups; an amine group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl; an amide group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl or (d-C6)-alkoxy groups; a heterocycloalkyl group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur; a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur and being unsubstituted or substituted with an oxo group; a -COO-(CrC6)-alkyl group; and an oxo group; and

■ a heterocycloalkyl group comprising 4 to 9 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur, said heterocycloalkyl group being saturated or partially saturated and being unsubstituted or substituted with 1 to 4 substituents independently selected from:

a fluorine atom; an -OH group; a (CrC6)-alkyl group; a -COOR7 group wherein R7 is a (CrC6)-alkyl group; and an oxo group.

In another embodiment, in formula (1-12) R6 is selected from:

■ a phenyl group substituted with 1 , 2 or 3 substituents independently selected from: a (CrC6)-alkyl group (such as methyl); a halogen atom (such as chlorine or fluorine); and a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms (such as the groups -OEt, -OCF3 or -OCHF2);

■ a pyridinyl (such as 3-pyridinyl) group substituted with 1 or 2 substituents independently selected from a halogen atom (such as fluorine) and a (CrC6)-alkoxy group (such as -OEt); and

■ an indolinyl group (more particularly an 1 -indolinyl group) substituted with 1 or 2 (CrC6)-alkyl groups (such a methyl).

Among the compounds of formula (I) which are part of the instant invention, mention may be made in particular of the following compounds, described in table 1 hereafter:

- 8-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-7-(3-fluoro-4-pyridyl)-5,6- dihydronaphthalen-2-ol (example 1 in table 1 );

8-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-7-(4-hydroxyphenyl)-5,6- dihydronaphthalen-2-ol (example 2);

- 7-(3,6-dihydro-2H-pyran-4-yl)-8-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-5,6-dihydronaphthalen-2-ol (example 3);

7-(2-chloro-4-fluoro-phenyl)-8-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 5,6-dihydronaphthalen-2-ol (example 4);

- 8-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-7-(1 H-indol-5-yl)-5,6- dihydronaphthalen-2-ol (example 5);

- 7-(2-fluoro-4-hydroxy-phenyl)-8-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-5,6-dihydronaphthalen-2-ol (example 6);

- 7-[2-chloro-4-(trifluoromethoxy)phenyl]-8-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-5,6-dihydronaphthalen-2-ol (example 7);

- 8-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-7-[4- (trifluoromethoxy)phenyl]-5,6-dihydronaphthalen-2-ol (example 8);

- 8-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-7-[4- (trifluoromethylsulfanyl)phenyl]-5,6-dihydronaphthalen-2-ol (example 9);

- 8-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-7-[2-fluoro-4- (trifluoromethoxy)phenyl]-5,6-dihydronaphthalen-2-ol (example 10);

- 7-(4-tert-butylphenyl)-8-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-5,6- dihydronaphthalen-2-ol (example 1 1 );

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-6-[4- (trifluoromethoxy)phenyl]-7,8-dihydronaphthalen-2-ol (example 12);

6-(2-chloro-4-fluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 7,8-dihydronaphthalen-2-ol (example 13);

- 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-7,8- dihydronaphthalen-2-ol (example 14);

5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-6-(4-hydroxyphenyl)-7,8- dihydronaphthalen-2-ol (example 15);

- 3-(2-fluoro-4-methyl-phenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2H-thiochromen-7-ol (example 16);

- 3-(4-chloro-3-methyl-phenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2H-thiochromen-7-ol (example 17);

- 3-(4-chloro-2-fluoro-phenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2H-thiochromen-7-ol (example 18);

- 4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-3-(1 H-indol-5-yl)-2H- thiochromen-7-ol (example 19);

- 4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-3-indolin-5-yl-2H- thiochromen-7-ol (example 20);

- 3-(2,4-dichlorophenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-2H- thiochromen-7-ol (example 21 );

- 3-(2-chloro-4-fluoro-phenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2H-thiochromen-7-ol (example 22);

- 3-(3-fluoro-4-methoxy-phenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2H-thiochromen-7-ol (example 23);

- 3-(2-fluoro-4-methoxy-phenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2H-thiochromen-7-ol (example 24);

- 3-(2-fluoro-4-methyl-phenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2H-thiochromene-7-carboxylic acid (example 25);

3-(4-ethoxy-2-fluoro-phenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2H-thiochromen-7-ol (example 26);

- 3-(6-ethoxy-2-fluoro-3-pyridyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2H-thiochromen-7-ol (example 27);

- 3-(2,3-dihydro-1 ,4-benzodioxin-6-yl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2H-thiochromen-7-ol (example 28);

- 3-(2,2-dimethylindolin-5-yl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2H-thiochromen-7-ol (example 29);

- 3-[4-(difluoromethoxy)-3-fluoro-phenyl]-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2H-thiochromen-7-ol (example 30);

- 3-(2,2-difluoro-1 ,3-benzodioxol-5-yl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2H-thiochromen-7-ol (example 31 );

- 3-(2,2-dimethyl-3H-benzofuran-5-yl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2H-thiochromen-7-ol (example 32);

- 3-[2-fluoro-4-(1 -hydroxy-1 -methyl-ethyl)phenyl]-4-[4-[(3S)-1 -(3- fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-2H-thiochromen-7-ol (example 33);

- 4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-3-[2-fluoro-4- (trideuteriomethoxy)phenyl]-2H-thiochromen-7-ol (example 34);

- 3-[4-(difluoromethoxy)-2-fluoro-phenyl]-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2H-thiochromen-7-ol (example 35);

3-(2-chloro-4-ethoxy-phenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl] 2H-thiochromen-7-ol (example 36);

- 4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-3-[2-fluoro-4- (trifluoromethoxy)phenyl]-2H-thiochromen-7-ol (example 37);

- 6-[4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-7-hydroxy-2H- thiochromen-3-yl]-4H-1 ,4-benzoxazin-3-one (example 38);

- 3-(4-ethoxy-2-methyl-phenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2H-thiochromen-7-ol (example 39);

- 3-(4-ethoxy-2,5-difluoro-phenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2H-thiochromen-7-ol (example 40);

- 3-(4-ethoxy-2,3-difluoro-phenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2H-thiochromen-7-ol (example 41 );

- 4-[4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-7-hydroxy-2H- thiochromen-3-yl]benzenesulfonamide (example 42);

3- (4-chloro-2-ethoxy-phenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl] 2H-thiochromen-7-ol (example 43);

4- [4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-3-[4-(oxetan-3-yloxy)phenyl]- 2H-thiochromen-7-ol (example 44);

- 3-(2-fluoro-6-methoxy-3-pyridyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2H-thiochromen-7-ol (example 45);

- 6-fluoro-5-[4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-7-hydroxy-2H- thiochromen-3-yl]pyridin-2-ol (example 46);

- 4-ethyl-6-[4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-7-hydroxy-2H- thiochromen-3-yl]-1 ,4-benzoxazin-3-one (example 47);

- [3-(2-fluoro-4-methyl-phenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl] 2H-thiochromen-7-yl] dihydrogen phosphate (example 48);

- 3-(2,6-difluoro-3-pyridyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-2H- thiochromen-7-ol (example 49);

- 3-(2,6-dichloro-3-pyridyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-2H- thiochromen-7-ol (example 50);

- 5-[4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-7-hydroxy-2H- thiochromen-3-yl]indolin-2-one (example 51 );

- 3-(4-tert-butylphenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-2H- thiochromen-7-ol (example 52);

- 3-(3-chloro-2-ethoxy-4-pyridyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2H-thiochromen-7-ol (example 53);

- 4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-3-[4- (trifluoromethoxy)phenyl]-2H-thiochromen-7-ol (example 54);

- 3-(6-chloro-2-fluoro-3-pyridyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2H-thiochromen-7-ol (example 55);

- 3-(2-chloro-6-methyl-3-pyridyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2H-thiochromen-7-ol (example 56);

- 3-(2-fluoro-4-methyl-phenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 1 -oxo-2H-thiochromen-7-ol (example 57);

- 3-(2-chloro-4-methyl-phenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl] 2H-thiochromen-7-ol (example 58);

- tert-butyl 6-[4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-7-hydroxy-2H thiochromen-3-yl]-2,3-dihydro-1 ,4-benzoxazine-4-carboxylate (example 59);

3-[4-(fluoromethoxy)phenyl]-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2H-thiochromen-7-ol (example 60);

- 3-[4-(fluoromethyl)phenyl]-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2H-thiochromen-7-ol (example 61 );

- 3-[4-(difluoromethyl)-2-fluoro-phenyl]-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2H-thiochromen-7-ol (example 62);

- 3-(3-chloro-4-ethoxy-2-fluoro-phenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2H-thiochromen-7-ol (example 63);

- 3-(2,3-difluoro-4-methyl-phenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2H-thiochromen-7-ol (example 64);

- tert-butyl N-[6-fluoro-5-[4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-7 hydroxy-2H-thiochromen-3-yl]-2-pyridyl]carbamate (example 65);

- 4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-3-[4- (trifluoromethylsulfanyl)phenyl]-2H-thiochromen-7-ol (example 66);

- 4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-3-(6-quinolyl)-2H- thiochromen-7-ol (example 67);

- 3-(2,4-dimethylthiazol-5-yl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2H-thiochromen-7-ol (example 68);

- 3-(2-ethoxy-3-fluoro-4-pyridyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2H-thiochromen-7-ol (example 69);

- 3-(2-fluoro-4-methyl-phenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl] 1 -oxo-2H-thiochromen-7-ol (example 70);

- 3-(2-fluoro-4-methyl-phenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl] 1 -oxo-2H-thiochromen-7-ol (example 71 );

- 3-(6-amino-2-fluoro-3-pyridyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2H-thiochromen-7-ol (example 72);

- 3-(3,3-dimethylindolin-5-yl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2H-thiochromen-7-ol (example 73);

- 3-[4-(diethylamino)-2-fluoro-phenyl]-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2H-thiochromen-7-ol (example 74);

- 3-(6-tert-butyl-2-fluoro-3-pyridyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2H-thiochromen-7-ol (example 75);

- 3-(6-ethoxy-2-fluoro-3-pyridyl)-4-[2-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxypyrimidin-5-yl]-2H-thiochromen-7-ol (example 76);

- 3-(2-fluoro-4-methyl-phenyl)-4-[2-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxypyrimidin-5-yl]-2H-thiochromen-7-ol (example 77);

- 3-(2-fluoro-4-methyl-phenyl)-4-[6-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxy-3- pyridyl]-2H-thiochromen-7-ol (example 78);

- 3-(6-ethoxy-2-fluoro-3-pyridyl)-4-[6-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxy-3- pyridyl]-2H-thiochromen-7-ol (example 79);

- 4-[6-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxy-3-pyridyl]-3-[4- (trifluoromethoxy)phenyl]-2H-thiochromen-7-ol (example 80);

- 3-(2,4-dichlorophenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-2H- chromen-7-ol (example 81 );

- 3-(2-chloro-4-fluoro-phenyl)-4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2H-chromen-7-ol (example 82);

- 4-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-3-(4-hydroxyphenyl)-2H- chromen-7-ol (example 83);

- 7-(2-chloro-4-fluoro-phenyl)-8-[4-[[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]amino]phenyl]-5,6-dihydronaphthalen-2-ol (example 84);

6-(2,4-dichlorophenyl)-5-[4-[[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]amino]phenyl]- 8,9-dihydro-7H-benzo[7]annulen-2-ol (example 85);

- 6-(6-ethoxy-2-fluoro-3-pyridyl)-5-[4-[[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]amino]phenyl]-8,9-dihydro-7H-benzo[7]annulen-2-ol (example 86);

- 5-[4-[[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]amino]phenyl]-6-[4- (trifluoromethoxy)phenyl]-8,9-dihydro-7H-benzo[7]annulen-2-ol (example 87);

- 5-[4-[[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]amino]phenyl]-6-[2-fluoro-4- (trifluoromethoxy)phenyl]-8,9-dihydro-7H-benzo[7]annulen-2-ol (example 88); 6-(4-tert-butylphenyl)-5-[4-[[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]amino]phenyl]- 8,9-dihydro-7H-benzo[7]annulen-2-ol (example 89);

- 5-[4-[[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]amino]phenyl]-6-[4- (trifluoromethylsulfanyl)phenyl]-8,9-dihydro-7H-benzo[7]annulen-2-ol (example 90);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(3-hydroxyphenyl)-2,3- dihydro-1 -benzoxepin-8-ol (example 91 );

4-(2-chloro-4-fluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzoxepin-8-ol (example 92);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(1 H-indol-5-yl)-2,3-dihydro- 1 -benzoxepin-8-ol (example 93);

- 4-(2-fluoro-4-hydroxy-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzoxepin-8-ol (example 94);

4-(2-chloro-3-fluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzoxepin-8-ol (example 95);

4-(2-fluoro-4-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzoxepin-8-ol (example 96);

4-(4-chloro-3-fluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzoxepin-8-ol (example 97);

4-(4-chloro-2-fluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzoxepin-8-ol (example 98);

4-(4-chloro-3-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzoxepin-8-ol (example 99);

4-(4-fluoro-2-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzoxepin-8-ol (example 100);

4-(3-chloro-2-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzoxepin-8-ol (example 101 );

- 4-(2,4-dichlorophenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-2,3- dihydro-1 -benzoxepin-8-ol (example 102);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(1 H-indol-6-yl)-2,3-dihydro- 1 -benzoxepin-8-ol (example 103);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-indolin-5-yl-2,3-dihydro-1 - benzoxepin-8-ol (example 104);

- 4-(3-chloro-2-methyl-phenyl)-9-fluoro-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzoxepin-8-ol (example 105);

- 9-fluoro-4-(2-fluoro-4-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzoxepin-8-ol (example 106);

- 9-fluoro-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-indolin-5-yl-2,3- dihydro-1 -benzoxepin-8-ol (example 107);

- 9-chloro-4-(2-fluoro-4-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzoxepin-8-ol (example 108);

- 9-chloro-4-(3-chloro-2-methyl-phenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzoxepin-8-ol (example 109);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(1 H-indol-4-yl)-2,3-dihydro- 1 -benzoxepin-8-ol (example 1 10);

4-(2-fluoro-4-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 9-methyl-2,3-dihydro-1 -benzoxepin-8-ol (example 1 1 1 );

4-(3-chloro-2-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 9-methyl-2,3-dihydro-1 -benzoxepin-8-ol (example 1 12);

- 9-fluoro-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(1 H-indol-5-yl)-2,3- dihydro-1 -benzoxepin-8-ol (example 1 13);

- 9-chloro-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(1 H-indol-5-yl)- 2,3-dihydro-1 -benzoxepin-8-ol (example 1 14);

- 9-chloro-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-indolin-5-yl-2,3- dihydro-1 -benzoxepin-8-ol (example 1 15);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-indolin-6-yl-2,3-dihydro-1 - benzoxepin-8-ol (example 1 16);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-indolin-4-yl-2,3-dihydro-1 - benzoxepin-8-ol (example 1 17);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-indolin-5-yl-9-methyl-2,3- dihydro-1 -benzoxepin-8-ol (example 1 18);

- 4-(4-ethoxy-2-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzoxepin-8-ol (example 1 19);

- 4-(benzofuran-5-yl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-2,3- dihydro-1 -benzoxepin-8-ol (example 120);

- 4-(2-fluoro-4-methoxy-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzoxepin-8-ol (example 121 );

- 4-(2,3-dimethylphenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-2,3- dihydro-1 -benzoxepin-8-ol (example 122);

- 9-chloro-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(1 H-indol-6-yl)- 2,3-dihydro-1 -benzoxepin-8-ol (example 123);

- 9-chloro-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(1 H-indol-4-yl)- 2,3-dihydro-1 -benzoxepin-8-ol (example 124);

- 9-chloro-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-indolin-6-yl-2,3- dihydro-1 -benzoxepin-8-ol (example 125);

4-(3-fluoro-2-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzoxepin-8-ol (example 126);

- 4-(6-ethoxy-3-pyridyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-2,3- dihydro-1 -benzoxepin-8-ol (example 127);

- 9-chloro-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-indolin-4-yl-2,3- dihydro-1 -benzoxepin-8-ol (example 128);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(1 H-indol-6-yl)-9-methyl- 2,3-dihydro-1 -benzoxepin-8-ol (example 129);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(1 H-indol-4-yl)-9-methyl- 2,3-dihydro-1 -benzoxepin-8-ol (example 130);

- 9-fluoro-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(1 H-indol-6-yl)-2,3 dihydro-1 -benzoxepin-8-ol (example 131 );

- 9-fluoro-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-indolin-6-yl-2,3- dihydro-1 -benzoxepin-8-ol (example 132);

- 9-fluoro-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(1 H-indol-4-yl)-2,3 dihydro-1 -benzoxepin-8-ol (example 133);

- 9-fluoro-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-indolin-4-yl-2,3- dihydro-1 -benzoxepin-8-ol (example 134);

4- (3-chloro-2-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl] 7-methyl-2,3-dihydro-1 -benzoxepin-8-ol (example 135);

5- [4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(3-hydroxyphenyl)-7- methyl-2,3-dihydro-1 -benzoxepin-8-ol (example 136);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-indolin-5-yl-7-methyl-2,3- dihydro-1 -benzoxepin-8-ol (example 137);

- 7-fluoro-4-(2-fluoro-4-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzoxepin-8-ol (example 138);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(1 H-indol-5-yl)-7-methyl- 2,3-dihydro-1 -benzoxepin-8-ol (example 139);

4-(2-fluoro-4-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 7-methyl-2,3-dihydro-1 -benzoxepin-8-ol (example 140);

4-(3-fluoro-4-isopropoxy-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzoxepin-8-ol (example 141 );

- 7-fluoro-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-indolin-5-yl-2,3- dihydro-1 -benzoxepin-8-ol (example 142);

7-chloro-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-indolin-5-yl-2,3- dihydro-1 -benzoxepin-8-ol (example 143);

- 7-chloro-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(1 H-indol-5-yl)- 2,3-dihydro-1 -benzoxepin-8-ol (example 144);

- 7-chloro-4-(2-fluoro-4-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzoxepin-8-ol (example 145);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-[4-(2- methoxyethoxy)phenyl]-2,3-dihydro-1 -benzoxepin-8-ol (example 146);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-[4-(2-pyrrolidin-1 - ylethoxy)phenyl]-2,3-dihydro-1 -benzoxepin-8-ol (example 147);

- 3-[5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8-hydroxy-2,3-dihydro-1 - benzoxepin-4-yl]-2-methoxy-benzoic acid (example 148);

4- [4-(cyclopropoxy)phenyl]-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzoxepin-8-ol (example 149);

5- [4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-[4-isopropoxy-2- (trifluoromethyl)phenyl]-2,3-dihydro-1 -benzoxepin-8-ol hydrochloride (example 150);

- 4-(2,3-dihydrobenzofuran-5-yl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzoxepin-8-ol (example 151 );

4-(4-ethoxy-2-fluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzoxepin-8-ol (example 152);

4-(2-chloro-4-ethoxy-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzoxepin-8-ol (example 153);

- 4-(2-chloro-4-methoxy-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzoxepin-8-ol (example 154);

- 4-(4-ethoxy-2-methyl-phenyl)-7-fluoro-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzoxepin-8-ol (example 155);

4-(benzofuran-5-yl)-7-fluoro-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzoxepin-8-ol (example 156);

5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(4-methoxy-2-methyl- phenyl)-2,3-dihydro-1 -benzoxepin-8-ol (example 157);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(3-hydroxyphenyl)-2,3- dihydro-1 -benzothiepin-8-ol (example 158);

4-(2-chloro-4-fluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzothiepin-8-ol (example 159);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(1 H-indol-5-yl)-2,3-dihydro 1 -benzothiepin-8-ol (example 160);

4-(4-chloro-3-fluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzothiepin-8-ol (example 161 );

4-(4-chloro-3-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl] 2,3-dihydro-1 -benzothiepin-8-ol (example 162);

4-(3-chloro-2-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl] 2,3-dihydro-1 -benzothiepin-8-ol (example 163);

4-(2-fluoro-4-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzothiepin-8-ol (example 164);

4-(4-fluoro-2-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzothiepin-8-ol (example 165);

- 4-(2,4-dichlorophenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-2,3- dihydro-1 -benzothiepin-8-ol (example 166);

4-(4-chloro-2-fluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzothiepin-8-ol (example 167);

4-(2-chloro-3-fluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzothiepin-8-ol (example 168);

- 4-(2-fluoro-4-hydroxy-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 169);

4-(2-chloro-3-fluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzothiepin-7-ol (example 170);

4-(2-fluoro-4-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzothiepin-7-ol (example 171 );

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(1 H-indol-6-yl)-2,3-dihydro 1 -benzothiepin-8-ol (example 172);

4-(3-chloro-2-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl] 2,3-dihydro-1 -benzothiepin-7-ol (example 173);

4-(3-chloro-4-fluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzothiepin-7-ol (example 174);

4-(2-chloro-4-fluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzothiepin-7-ol (example 175);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-indolin-5-yl-2,3-dihydro-1 - benzothiepin-8-ol (example 176);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(4-hydroxyphenyl)-2,3- dihydro-1 -benzothiepin-7-ol (example 177);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(1 H-indol-4-yl)-2,3-dihydro- 1 -benzothiepin-8-ol (example 178);

4-(4-chloro-3-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzothiepin-7-ol (example 179);

4-(4-fluoro-2-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzothiepin-7-ol (example 180);

4-(4-chloro-2-fluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzothiepin-7-ol (example 181 );

- 4-(2,4-dichlorophenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-2,3- dihydro-1 -benzothiepin-7-ol (example 182);

- 4-(2,3-dihydro-1 H-pyrrolo[2,3-b]pyridin-5-yl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin- 3- yl]oxyphenyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 183);

- 4-(benzofuran-5-yl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-2,3- dihydro-1 -benzothiepin-8-ol (example 184);

4- (4-ethoxy-3-fluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzothiepin-8-ol (example 185);

- 4-(4-ethoxy-2-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 186);

- 4-(6-ethoxy-2-fluoro-3-pyridyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 187);

- 4-[3-(difluoromethoxy)-4-fluoro-phenyl]-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 188);

- 4-(2-fluoro-4-methoxy-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 189);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-[3-fluoro-4- (trifluoromethoxy)phenyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 190);

- 4-[4-(difluoromethoxy)-3-fluoro-phenyl]-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 191 );

- 4-(2-fluoro-6-methyl-3-pyridyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 192);

- 4-(2,2-difluoro-1 ,3-benzodioxol-5-yl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 193);

5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(4-methylsulfonylphenyl)- 2,3-dihydro-1 -benzothiepin-8-ol (example 194);

4-(3-ethoxy-4-fluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzothiepin-8-ol (example 195);

4-(4-ethoxy-2-fluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzothiepin-8-ol (example 196);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(2-methyl-2,3- dihydrobenzofuran-5-yl)-2,3-dihydro-1 -benzothiepin-8-ol (example 197);

- 4-(2,2-dimethylindolin-5-yl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzothiepin-8-ol (example 198);

- 2-fluoro-5-[5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8-hydroxy-2,3- dihydro-1 -benzothiepin-4-yl]-N-methoxy-benzamide (example 199);

- 4-[4-(ethylamino)-2-fluoro-phenyl]-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 200);

- 4-(2,2-dimethyl-3H-benzofuran-5-yl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 201 );

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-[(2R)-2-methyl-2,3- dihydrobenzofuran-5-yl]-2,3-dihydro-1 -benzothiepin-8-ol (example 202);

- 4-(2,4-dichlorophenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-2,3- dihydro-1 -benzothiepine-8-carboxylic acid (example 203);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-[(2S)-2-methyl-2,3- dihydrobenzofuran-5-yl]-2,3-dihydro-1 -benzothiepin-8-ol (example 204);

- 4-(2,4-dichlorophenyl)-5-[6-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxy-3-pyridyl]-2,3- dihydro-1 -benzothiepin-8-ol (example 205);

- 4-(2-chloro-4-methyl-phenyl)-5-[6-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxy-3- pyridyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 206);

4-[4-(difluoromethoxy)-3-fluoro-phenyl]-5-[6-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxy-3-pyridyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 207);

- 4-(6-ethoxy-2-fluoro-3-pyridyl)-5-[6-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxy-3- pyridyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 208);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-[2-fluoro-4- (trideuteriomethoxy)phenyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 209);

4-(2-fluoro-4-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzothiepine-8-carboxylic acid (example 210);

4-(4-chloro-3-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzothiepine-8-carboxylic acid (example 21 1 );

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-[2-fluoro-4- (trifluoromethoxy)phenyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 212);

- 4-[4-(difluoromethoxy)-2-fluoro-phenyl]-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 213);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-[4- (trifluoromethoxy)phenyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 214);

- 4-(2,6-difluoro-3-pyridyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-2,3- dihydro-1 -benzothiepin-8-ol (example 215);

- 4-(4-tert-butylphenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-2,3- dihydro-1 -benzothiepin-8-ol (example 216);

- 4-(4-ethoxy-2,3-difluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 217);

4-[4-(fluoromethoxy)phenyl]-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzothiepin-8-ol (example 218);

4-(3,5-dimethylisoxazol-4-yl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 2,3-dihydro-1 -benzothiepin-8-ol (example 219);

- 4-(4-ethoxy-2,5-difluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 220);

- 4-(3-chloro-4-ethoxy-2-fluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 221 );

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-[4- (trifluoromethylsulfanyl)phenyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 222);

- 4-(6-amino-2-fluoro-3-pyridyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 223);

- 4-[4-(diethylamino)-2-fluoro-phenyl]-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]-2,3-dihydro-1 -benzothiepin-8-ol (example 224);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-1 -oxo-4-[4- (trifluoromethoxy)phenyl]-2,3-dihydro-1A4-benzothiepin-8-ol (example 225);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-1 -oxo-4-[4- (trifluoromethoxy)phenyl]-2,3-dihydro-1A4-benzothiepin-8-ol (example 226);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-1 -oxo-4-[4- (trifluoromethoxy)phenyl]-2,3-dihydro-1A4-benzothiepin-8-ol (example 227);

- 5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-4-(3-hydroxyphenyl)-1 ,1 - dioxo-2,3-dihydro-1 A6-benzothiepin-8-ol (example 228);

4-(2-chloro-4-fluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 1 ,1 -dioxo-2,3-dihydro-1 A6-benzothiepin-8-ol (example 229);

4-(2-fluoro-4-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 1 ,1 -dioxo-2,3-dihydro-1 A6-benzothiepin-8-ol (example 230);

- 4-(2,4-dichlorophenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-1 ,1 - dioxo-2,3-dihydro-1 A6-benzothiepin-8-ol (example 231 );

4-(2-chloro-3-fluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 1 ,1 -dioxo-2,3-dihydro-1 A6-benzothiepin-8-ol (example 232);

4-(4-chloro-2-fluoro-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 1 ,1 -dioxo-2,3-dihydro-1 A6-benzothiepin-8-ol (example 233);

4-(4-fluoro-2-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]- 1 ,1 -dioxo-2,3-dihydro-1 A6-benzothiepin-8-ol (example 234);

4-(3-chloro-2-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl] 1 ,1 -dioxo-2,3-dihydro-1 A6-benzothiepin-8-ol (example 235);

4-(4-chloro-3-methyl-phenyl)-5-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl] 1 ,1 -dioxo-2,3-dihydro-1 A6-benzothiepin-8-ol (example 236);

- 6-(2-fluoro-4-methyl-phenyl)-5-[6-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxy-3- pyridyl]-8,9-dihydro-7H-benzo[7]annulen-2-ol (example 237);

6-(2,4-dichlorophenyl)-5-[2-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxypyrimidin-5- yl]-8,9-dihydro-7H-benzo[7]annulen-2-ol (example 238);

- 6-(2,4-dichlorophenyl)-5-[6-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxy-3-pyridyl]-8,9 dihydro-7H-benzo[7]annulen-2-ol (example 239);

6-(6-ethoxy-2-fluoro-3-pyridyl)-5-[6-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxy-3- pyridyl]-8,9-dihydro-7H-benzo[7]annulen-2-ol (example 240);

6-[4-(difluoromethoxy)-3-fluoro-phenyl]-5-[6-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxy-3-pyridyl]-8,9-dihydro-7H-benzo[7]annulen-2-ol (example 241 );

- 6-(2,2-dimethylindolin-5-yl)-5-[6-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxy-3- pyridyl]-8,9-dihydro-7H-benzo[7]annulen-2-ol (example 242);

6-(4-chloro-3-fluoro-phenyl)-5-[5-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxypyrazin- 2-yl]-8,9-dihydro-7H-benzo[7]annulen-2-ol (example 243);

- 6-(2-fluoro-4-methyl-phenyl)-5-[2-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxypyrimidin-5-yl]-8,9-dihydro-7H-benzo[7]annulen-2-ol (example 244);

- 6-(2,4-dichlorophenyl)-1 -fluoro-5-[6-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxy-3- pyridyl]-8,9-dihydro-7H-benzo[7]annulen-2-ol (example 245);

- 6-(4-ethoxy-2,3-difluoro-phenyl)-5-[2-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxypyrimidin-5-yl]-8,9-dihydro-7H-benzo[7]annulen-2-ol (example 246);

- 6-(2,4-dichlorophenyl)-5-[6-[(3S)-1 -(3-fluoropropyl)pyrTolidin-3-yl]oxy-3-pyridyl]-8,9- dihydro-7H-benzo[7]annulene-2-carboxylic acid (example 247);

6-[4-(difluoromethoxy)-3-fluoro-phenyl]-5-[6-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxy-3-pyridyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid (example 248);

- 6-[4-(difluoromethoxy)-3-fluoro-phenyl]-1 -fluoro-5-[6-[(3S)-1 -(3- fluoropropyl)pyrrolidin-3-yl]oxy-3-pyridyl]-8,9-dihydro-7H-benzo[7]annulen-2-ol (example 249);

- 6-(4-chloro-3-methyl-phenyl)-1 -fluoro-5-[6-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxy-3-pyridyl]-8,9-dihydro-7H-benzo[7]annulen-2-ol (example 250);

- 6-(6-ethoxy-2-fluoro-3-pyridyl)-5-[2-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxypyrimidin-5-yl]-8,9-dihydro-7H-benzo[7]annulen-2-ol (example 251 );

6-(6-ethoxy-2-fluoro-3-pyridyl)-1 -fluoro-5-[6-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxy-3-pyridyl]-8,9-dihydro-7H-benzo[7]annulen-2-ol (example 252);

- 5-[6-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxy-3-pyridyl]-6-[4- (trifluoromethoxy)phenyl]-8,9-dihydro-7H-benzo[7]annulen-2-ol (example 253); 6-(4-chloro-3-fluoro-phenyl)-5-[5-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxypyrimidin-2-yl]-8,9-dihydro-7H-benzo[7]annulen-2-ol (example 254);

- 5-[(E)-2-(2-chloro-4-fluoro-phenyl)-1 -[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3- yl]oxyphenyl]but-1 -enyl]-1 H-indazole (example 255);

- 1 -[2,6-difluoro-4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxy-phenyl]-2-(2-fluoro-2- methyl-propyl)-3-methyl-1 ,3,4,9-tetrahydropyrido[3,4-b]indole (example 256);

- 1 -[2,6-difluoro-4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxy-phenyl]-2-(2-fluoro-2- methyl-propyl)-3-methyl-1 ,3,4,9-tetrahydropyrido[3,4-b]indole (example 257); and

- 2-[4-[(3S)-1 -(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-3-(4-hydroxyphenyl)-2,3- dihydro-1 ,4-benzoxathiin-6-ol (example 259).

The compounds of the invention can be prepared by the following processes, being understood that solvents, temperatures and other reaction conditions presented below may vary as deemed appropriate to the skilled person in the art.

The general methods described below for the preparation of the compounds of the invention are optionally modified by the use of appropriate reagents and conditions for the introduction of the various moieties found in the formula (I), (Γ) and (l-A) as described above. Besides, when the reaction schemes below illustrate the synthesis of compounds wherein the "A" moiety is linked to the pyrrolidinyl group in the configuration (S), similar reaction schemes may be used with corresponding reagents in the configuration (R) so as

to obtain different enantiomers in the whole scope of formula (Γ) according to the invention.

The following abbreviations and empirical formulae are used:

AcOH acetic acid

EtOAc ethyl acetate

AICIs aluminium trichloride

Boc tert-butyloxycarbonyl

P(Ph)2-(CH2)3-P(Ph)2 1 ,3-bis(diphenylphosphino)propane

Ph3P triphenylphosphine

Ph3P=0 triphenylphosphine oxide

Cs2C03 cesium carbonate

CO carbon monoxyde

DCM dichloromethane

DMF /V,/V-dimethylformamide

DMSO dimethyl sulfoxide

Et ethyl

EtOH ethanol

Et20 diethyl ether

Hal halogen atom

HCI hydrogen chloride

HPLC high-performance liquid chromatography

iPr isopropyl

K2C03 potassium carbonate

LCMS liquid chromatography/mass spectrometry

□ HMDS Lithium HexaMethylDiSilazide

Lutidine 2,6-dimethyl-pyridine

Me methyl

MeCN acetonitrile

MeOH methanol

MgS04 magnesium sulfate

NaOH sodium hydroxyde

NaCI sodium chloride

NaHCOs sodium bicarbonate

Pd(OAc)2 palladium acetate

PdCI2(PPh3)2 palladium chloride bis triphenylphosphine

Pd(dppf)CI2 1 ,1 'bis(diphenylphosphino)ferrocene]

dichloropalladium(ll)

Tf20 triflic anhydride

THF tetrahydrofuran

°C degrees Celsius

RT room temperature min (mn) minute(s)

ml_ millilitre(s)

mmol millimole(s) μηιοΙ micromole(s) μΜ micromolar nM nanomolar

ppm parts per million sex strong cation exchange

CHEME 1 : Preparation of compounds of the formula (I) with A = O: general process

Intermediate (la) Intermediate (lb) Intermediate (lc)

Intermediate (Ig) Compound (I)

According to SCHEME 1 , in which A = O, B = D = E = G = CH and X, n, R1 , R2, R3, R4, R5 and R6 are defined as described above, a substituted bicyclic ketone intermediate (la) is converted in STEP 1 into the corresponding enol triflate intermediate (lb) by treatment for example with triflic anhydride (Tf20) in solution in dichloromethane (DCM) in the presence of a base, for example pyridine, at room temperature (RT). Intermediate (lb) is subjected in STEP 2 to a Suzuki coupling with 4-hydroxyphenyl-boronic acid using for example [1 ,1 '-bis(diphenylphosphino) ferrocene]dichloropalladium(ll) (Pd(dppf)CI2), complex with DCM, as catalyst, in a mixture of dioxane and water and in the presence of a base, for example cesium carbonate (Cs2C03), at RT or by heating up to reflux. The intermediate (lc) obtained is brominated in STEP 3 using for example pyridinium tribromide in DCM or tetrahydrofurane (THF) at RT. This phenol derivative intermediate (Id) is then subjected in STEP 4 to a Mitsunobu reaction with tetramethyldiazenedicarboxamide and triphenylphosphine (Ph3P) in THF at RT to obtain N-Boc protected pyrrolidine intermediate (le) which is sequentially deprotected (STEP 5) using a 4M solution of hydrochloric acid in dioxane and alkylated (STEP 6) with the corresponding 1 -halogeno-3-fluoropropane, for example 1 -iodo-3-fluoropropane in Λ/,/V-dimethylformamide at 70°C in the presence of a base such as potassium carbonate (K2C03) to produce intermediate (Ig). Finally, this intermediate is engaged in a Suzuki reaction (STEP 7) with a suitable boronic reagent R6B(OR')2, wherein -B(OR')2 is a boronic acid or a pinacolate ester and R6 is as above defined, using for example Pd(dppf)CI2, complex with DCM, as catalyst, in a mixture of dioxane and water and in the presence of a base, for example Cs2C03, at RT or by heating up to reflux to obtain compound (I).

In the above-described reactions, it can be necessary to protect reactive functional groups, for example hydroxy, amino, thio or carboxy groups, where these groups are desired in the final product, to avoid their unwanted participation in the reactions. Conventional protecting groups can be used in accordance with standard practice, for example, see T.W. Greene and P. G. M. Wuts in "Protective Groups in Organic Chemistry", John Wiley and Sons, 2006.

When R3 or R5 represents an -OH group, this -OH group is protected, for example as a pivaloyi ester or a methyl ether. Deprotection can be performed just after STEP 6 or after STEP 7 by treating, with an aqueous solution of sodium hydroxide 2N (NaOH), a solution of the pivaloyi ester in methanol (MeOH) at RT, followed by acidification with an aqueous solution of hydrogen chloride 2N (HCI), or just after STEP 5, by treating a solution of the methyl ether in DCM by boron trifluoride at RT.

When R3 represents a -COOH group, this -COOH group is protected, for example as a methyl ester. Deprotection is performed just after STEP 7 by treating a solution of the methyl ester in MeOH with an aqueous solution of NaOH 2N, at RT, followed by acidification with an aqueous solution of HCI 2N.

In another embodiment of the invention, it can be advantageous for the preparation of intermediate (Ig) from SCHEME 1 to use a variation of SCHEME 1 , called SCHEME 1 a depicted below.

SCHEME 1 a: Pre aration of intermediate (Ig) from SCHEME 1 with A = O: variation

Intermediate (Ig)

According to SCHEME 1 a, in which A = O, B = D = E = G = CH and X, n, R1 , R2,

R3, R4 and R5 are defined as described above, an enol triflate intermediate (lb) (obtained as described in SCHEME 1 ) is subjected in STEP 1 to a Suzuki coupling with reagent (1 ) ((S)-1 -(3-fluoropropyl)-3-(4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2yl)-phenoxy)pyrrolidine) using for example (Pd(dppf)CI2), complex with DCM, as catalyst, in a mixture of dioxane and water and in the presence of a base, for example Cs2C03, at RT or by heating up to reflux. The preparation of reagent (1 ) is described hereunder in SCHEME 2.

The intermediate (Ih) obtained is brominated in STEP 2 using for example pyridinium tribromide in DCM or THF at RT to produce bromo derivative intermediate (Ig).

CHEME 2: Preparation of reagent (1 ) of SCHEME 1 a

Compound (d)

Reagent (1)

According to the above SCHEME 2, commercially available compound (a) (4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)phenol) is condensed in STEP 1 in THF at RT on compound (b), (R)-1 -N-Boc-3-hydroxypyrrolidine, using Ph3P and Ν,Ν,Ν',Ν'-tetramethylazodicarboxamide as coupling agent in THF as solvent.

Compound (c) thus obtained is N-deprotected in STEP 2 in MeOH at RT using an acidic agent, for example a solution of HCI 4N in dioxane.

Alkylation of the pyrrolidine nitrogen is then performed in STEP 3 by reacting compound (d) with the corresponding 1 -halogeno-3-fluoropropane, for example 1 -iodo-3-fluoropropane in acetonitrile (MeCN) in presence of K2C03 at about 40°C.

When A = NH in the compounds of formula (I) according to the invention, then the compounds of formula (I) can be prepared according to SCHEME 3 below.

general process

According to SCHEME 3, in which A = NH, B = D = E = G = CH and X, n, R1 , R2, R3, R4, R5 and R6 are defined as described above, a bromo derivative intermediate (Id) as defined in SCHEME 1 is subjected in STEP 1 to a Suzuki coupling with a suitable boronic reagent R6B(OR')2, wherein -B(OR')2 is a boronic acid or a pinacolate ester and R6 is as above defined, using for example Pd(dppf)CI2, complex with DCM, as catalyst, in a mixture of dioxane and water as solvent and in the presence of a base, for example Cs2C03, at RT or by heating up to reflux to obtain phenol intermediate (li) which is transformed into a triflate (Ij) in STEP 2 by treatment by Tf20 in DCM in the presence of pyridine. This triflate (Ij) is engaged in a Buchwald coupling (STEP 3) with 3-(S)-amino-pyrrolidine 1 -N-Boc protected in dioxane at 140°C using for example xantphos / Palladium acetate as catalytic system to produce intermediate (Ik). Finally, the Boc protecting group is removed in STEP 4 by a 1 M solution of anhydrous hydrochloric acid in DCM and the resulting NH pyrrolidine (II) is alkylated in STEP 5 with the corresponding disubstituted 1 -halogeno-3-fluoropropane, for example 1 -iodo-3-fluoropropane in DMF at 70°C in the presence of K2C03 as base to produce compound (I) as defined above.

CLAIMS

Compounds of the formula (l-A):

wherein:

- R1 and R2 represent independently a hydrogen atom or a deuterium atom;

- A represents an oxygen or nitrogen atom; and

- SERM-F represents a selective estrogen receptor modulator fragment comprising an aryl or heteroaryl group linked to the adjacent "A" group;

or a pharmaceutically acceptable salt thereof.

2. The compounds of formula (l-A) according to claim 1 , with the proviso that the compounds of formula (l-B) below are excluded:

(l-B)

wherein, in formula (l-B):

R1 and R2 represent independently a hydrogen atom or a deuterium atom;

R3 represents a hydrogen atom, a -COOH group, a -OH group or a -OPO(OH)2 group;

- R4 represents a hydrogen atom or a fluorine atom;

R5 represents a hydrogen atom or a -OH group;

wherein:

■ at least one of R3 or R5 is different from a hydrogen atom;

■ when R3 represents a -COOH group, a -OH group or a -OPO(OH)2 group, then R5 represents a hydrogen atom;

■ when R5 represents a -OH group, then R3 and R4 represent hydrogen atoms;

R6 is selected from:

■ a phenyl group or a heteroaryl group comprising 3 to 9 carbon atoms and comprising from 1 to 3 heteroatoms independently selected from oxygen, nitrogen and sulphur, said phenyl and heteroaryl groups being unsubstituted or substituted with 1 to 3 substituents independently selected from: a (CrC6)-alkyl group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms; a halogen atom; a -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more (such as 1 , 2 or 3) fluorine atoms; a cyano group; a sulphur group substituted with 5 fluorine atoms or (d-C6)-alkyl groups substituted with two or more (such as 2 or 3) fluorine atoms; a sulfonyl-(Ci- C6)-alkyl group wherein said (CrC6)-alkyl group are unsubstitued or substituted with two or more (such as 2 or 3) fluorine atoms; a silane group substituted with 3 (CrC6)-alkyl groups; an amine group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl groups; an amide group unsubstituted or substituted with one or more (such as 1 or 2) (CrC6)-alkyl groups; a heterocycloalkyl group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen or sulphur; or a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur and being unsubstituted or substituted with an oxo group; and

■ a cycloalkyl group or a heterocycloalkyl group comprising 4 to 9 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen or sulphur, said cycloalkyl or heterocycloalkyl groups being saturated or partially saturated and being unsubstituted or substituted with 1 to 4 substituents independently selected from:

a fluorine atom; a -OH group; a (CrC6)-alkyl group; a -COOR7 group wherein R7 is a (CrC6)-alkyl group; or an oxo group;

or a pharmaceutically acceptable salt thereof.

3. The compounds of formula (l-A) according to claim 1 or 2, characterized in that SERM-F is selected from the following structures (al), (bll), (clll) and (dIV), provided that when A represents a nitrogen atom then SERM-F represents the structure (al):

wherein:

B, D, E and G represent independently =CH- or nitrogen atoms;

n is an integer selected from 0 and 1 ;

- X represents -CH2-, -0-, -S-, -SO- or -S02-;

when n = 1 and X = CH2, then at least one of A, B, D, E or G is a nitrogen atom; - R3 represents a hydrogen atom or an -OH, -COOH or -OPO(OH)2 group;

R4 represents a hydrogen, fluorine or chlorine atom or a methyl group;

R5 represents a hydrogen, fluorine or chlorine atom, or a methyl or -OH group; wherein R3 and R5 do not simultaneously represent -OH groups or hydrogen atoms;

- R6 is selected from:

■ a phenyl group, which is unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more fluorine atoms or -OH groups; a halogen atom; an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more fluorine atoms, (CrC6)-alkoxy or heterocycloalkyi groups; a cyano group; a sulphur group substituted with 5 fluorine atoms or with a (CrC6)-alkyl group substituted with two or more fluorine atoms; a sulfonyl-(CrC6)-alkyl group wherein said (CrC6)-alkyl group is unsubstituted or substituted with two or more fluorine atoms; a silane group substituted with three (CrC6)-alkyl groups; an amine group unsubstituted or substituted with one or more (CrC6)-alkyl groups; an amide group unsubstituted or

substituted with one or more (CrC6)-alkyl or (d-C6)-alkoxy groups; a heterocycloalkyi group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur; a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur and being unsubstituted or substituted with an oxo group; a -SO2NH2 group; a -COOH group; a -O-cycloalkyl group; a -O-heterocycloalkyl group; and a -OCD3 group;

■ a heteroaryl group comprising 3 to 9 carbon atoms and comprising between 1 to 3 heteroatoms independently selected from oxygen, nitrogen and sulphur, said heteroaryl group being unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more fluorine atoms; a halogen atom; an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more fluorine atoms; a cyano group; a sulphur group substituted with 5 fluorine atoms or with a (CrC6)-alkyl group substituted with two or more fluorine atoms; a sulfonyl-(Ci-C6)-alkyl group wherein said (CrC6)-alkyl group is unsubstituted or substituted with two or more fluorine atoms; a silane group substituted with three (CrC6)-alkyl groups; an amine group unsubstituted or substituted with one or more (CrC6)-alkyl groups; an amide group unsubstituted or substituted with one or more (CrC6)-alkyl or (CrC6)-alkoxy groups; a heterocycloalkyi group saturated or partially saturated, comprising 3 to 5 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur; a heteroaryl group comprising 2 to 4 carbon atoms and comprising 1 to 3 heteroatoms selected from oxygen, nitrogen and sulphur and being unsubstituted or substituted with an oxo group; a -COO-(CrC6)-alkyl group; and an oxo group;

- a cycloalkyl group comprising 4 to 9 carbon atoms, which is saturated or partially saturated, and which is unsubstituted or substituted with 1 to 4 substituents independently selected from:

a fluorine atom; an -OH group; a (CrC6)-alkyl group; a -COOR7 group wherein R7 is a (CrC6)-alkyl group; and an oxo group; and

- a heterocycloalkyi group comprising 4 to 9 carbon atoms and comprising 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulphur, said heterocycloalkyi group being saturated or partially saturated and being unsubstituted or substituted with 1 to 4 substituents independently selected from:

a fluorine atom; an -OH group; a (CrC6)-alkyl group; a -COOR7 group wherein R7 is a (CrC6)-alkyl group; and an oxo group;

or a pharmaceutically acceptable salt thereof.

4. The compounds according to any of claims 1 to 3, characterized in that they respond to formula (I), wherein R1 , R2, R3, R4, R5, R6, A, B, D, E, G, X and n are as defined in any of claims 1 to 3:

or a pharmaceutically acceptable salt thereof.

5. The compounds according to any of claims 1 to 4, characterized in that R6 is selected from:

- a phenyl group, which is unsubstituted or substituted with 1 , 2 or 3 substituents independently selected from:

a (CrC6)-alkyl group unsubstituted or substituted with one or more fluorine atoms or -OH groups; a halogen atom; an -OH group; a (CrC6)-alkoxy group unsubstituted or substituted with one or more fluorine atoms, (CrC6)-alkoxy or heterocycloalkyi groups; a sulphur group substituted with a (CrC6)-alkyl group substituted with two or more fluorine atoms; a sulfonyl-(CrC6)-alkyl group; an amine group unsubstituted or substituted with one or more (CrC6)-alkyl groups; an amide group substituted with an (d-C6)-alkoxy groups; a -S02NH2 group; a -COOH group; a -O-cycloalkyl group; a -O-heterocycloalkyl group; and a -OCD3 group;

- a heteroaryl group selected from an indole, pyridinyl, benzofuran, isoxazole, quinolyl and thiazolyl group, said heteroaryl group being unsubstituted or substituted with 1 to 3 substituents independently selected from:

a (CrC6)-alkyl group; a halogen atom; an -OH group; a (CrC6)-alkoxy group; an amine group; an amide group substituted with a (CrC6)-alkoxy group; and

- a heterocycloalkyi group selected from an indolinyl, dihydroazaindolinyl, dihydrobenzodioxinyl, benzodioxolyl, 2,3-dihydrobenzofuranyl, dihydrobenzoxazinyl and 5,6-dihydro-2H-pyranyl group, said heterocycloalkyi group being being unsubstituted or substituted with 1 to 4 substituents independently selected from:

a fluorine atom; a (CrC6)-alkyl group; a -COOR7 group wherein R7 is a (CrC6)-alkyl group; and an oxo group;

or a pharmaceutically acceptable salt thereof.

6. The compounds according to any of claims 1 to 5, characterized in that they respond to formula (I-2), wherein X, n, R1 , R2, R3, R4, R5, R6, B, D, E and G are as defined in claim 3 or 4:

or a pharmaceutically acceptable salt thereof.

7. The compounds according to any of claims 1 to 5, characterized in that they respond to formula (I-3), wherein R1 , R2, R3, R4, R5 and R6 are as defined in claim 3 or 4:

or a pharmaceutically acceptable salt thereof.

8. The compounds according to any of claims 1 to 5, characterized in that they respond to formula (I-4), wherein R1 , R2, R3, R4, R5 and R6 are as defined in claim 3 or 4:

or a pharmaceutically acceptable salt thereof.

9. The compounds according to any of claims 1 to 5, characterized in that they respond to formula (I-5), wherein E, D, R1 , R2, R3, R4, R5 and R6 are as defined in claim 3 or 4 and wherein one or two of E and D represent nitrogen atoms:

or a pharmaceutically acceptable salt thereof.

10. The compounds according to any of claims 1 to 5, characterized in that they respond to formula (I-6), wherein R1 , R2, R3, R4, R5 and R6 are as defined in claim 3 or 4:

or a pharmaceutically acceptable salt thereof.

11. The compounds according to any of claims 1 to 5, characterized in that they respond to formula (I-7), wherein n, R1 , R2, R3, R4, R5 and R6 are as defined in claim 3

or a pharmaceutically acceptable salt thereof.

12. The compounds according to any of claims 1 to 5, characterized in that they respond to formula (I-8), wherein R1 , R2, R3, R4, R5 and R6 are as defined in claim 3 or

or a pharmaceutically acceptable salt thereof.

13. The compounds according to any of claims 1 to 5, characterized in that they respond to formula (I-9), wherein D, R1 , R2, R3, R4, R5 and R6 are as defined in claim 3 or 4:

or a pharmaceutically acceptable salt thereof.

14. The compounds according to any of claims 1 to 5, characterized in that they respond to formula (1-10), wherein R1 , R2, R3, R4, R5 and R6 are as defined in claim 3 or

or a pharmaceutically acceptable salt thereof.

15. The compounds according to any of claims 1 to 5, characterized in that they respond to formula (1-1 1 ), wherein R1 , R2, R3, R4, R5 and R6 are as defined in claim 3 or 4:

or a pharmaceutically acceptable salt thereof.

16. The compounds according to any of claims 1 to 5, characterized in that they respond to formula (1-12), wherein B, D, E, G, R1 , R2, R3, R4, R5 and R6 are as defined in claim 3 or 4:

or a pharmaceutically acceptable salt thereof.

17. A medicament, characterized in that it comprises a compound according to any of claims 1 to 16, or a pharmaceutically acceptable salt thereof.

18 A pharmaceutical composition, characterized in that it comprises a compound according to any of claims 1 to 16, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

19. A compound according to any of claims 1 to 16 for use as an inhibitor and degrader of estrogen receptors.

20. A compound according to any of claims 1 to 16 for use in the treatment of ovulatory dysfunction, cancer, endometriosis, osteoporosis, benign prostatic hypertrophy or inflammation.

21. A compound according to claim 20 for use in the treatment of an estrogen receptor dependent cancer.

22. A compound according to claim 20 or 21 , for use in the treatment of breast, ovarian, endometrial, prostate, uterine, cervical or lung cancer, or a metastasis thereof.

23. A compound according to any of claims 20 to 22, for use in the treatment of a cancer which is resistant to anti-hormonal treatment.