Granted Patent B2

US 12,545,640 · App. 17/765,169 · Granted Feb 10, 2026

Inventors: Sabine Boisnard (Paris, FR); Youssef El-Ahmad (Paris, FR); Eykmar Fett (Paris, FR); Frank Halley (Paris, FR); Eric Nicolai (Paris, FR); Michel Tabart (Paris, FR); Corinne Terrier (Paris, FR); Bertrand Vivet (Paris, FR)

Assignee: Sanofi

C07D207/12A61K9/2013A61K9/2018A61K9/2054A61K9/2059C07D207/38C07D401/12C07D403/12C07D405/12C07D413/12C07D413/14C07D417/12C07D419/12C07F5/025

Abstract

Claims (268)

1 . A compound of the formula (I)

wherein:

Ar represents a phenyl or a 6-membered heteroaryl group, said phenyl or 6-membered heteroaryl group being optionally substituted with one to three groups selected from halogen atoms, a —OH group, a (C 1 -C 3 )alkyl group, a (C 1 -C 3 )alkoxy group, a (C 1 -C 3 )perfluoroalkoxy group and an oxooxazolidinyl group,

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

R3 represents

(1) a —COR4 group,

(2) a —BOR5OR6 group,

(3) a —X—Z group,

(4) a (C 1 -C 6 )alkyl group or a (C 1 -C 6 )alkenyl group, substituted by 1 to 8 groups selected from a fluorine atom, a —OH group and a —COOH group,

(5) a —X—S(O) n (R7) p (R8) q group,

(6) a —NH 2 group or a —CN group,

(7) a —O—R11 group,

(8) a —NH—COR9 group,

(9) a —C(═NH)NHOH group,

(10) a —NH—C(NH)—R9′ group, or

(11) a —NHCOCOOR12 group or a —NHCOCONR12′R12″ group,

R4 represents a (C 1 -C 6 )alkyl group, a —NRR′ group, a —NHNH 2 group, a —NHNHCONH 2 group, a —NHNHCS-1H-imidazolyl group or a —NHSO 2 CH 3 group, wherein R and R′ independently represent a hydrogen atom, a OH group, a (C 1 -C 6 )alkoxy group or a (C 1 -C 6 )alkyl group,

R5 and R6 independently represent a hydrogen atom, a (C 1 -C 6 )alkyl group, or form together with the boron atom to which they are attached a 4 or 5-membered ring, said ring being optionally substituted by 1 to 4 (C 1 -C 4 )alkyl groups,

R7 and R8 independently represent a (C 1 -C 6 )alkyl group optionally partially or fully substituted by fluorine atoms, a —NH 2 group or a ═NH group,

R9 represents a hydrogen atom, a (C 1 -C 6 )alkoxy group, a (C 1 -C 6 )alkyl group or a (C 3 -C 6 )cycloalkyl group, wherein each (C 1 -C 6 )alkoxy group, (C 1 -C 6 )alkyl group or (C 3 -C 6 )cycloalkyl group is optionally substituted by one to three fluorine atom(s), a —OH group or a (C 1 -C 4 )alkyl group,

R9′ represents a (C 1 -C 6 )alkyl group or a (C 3 -C 6 )cycloalkyl group,

R11 represents a (C 1 -C 6 )alkyl group, optionally substituted by one to six fluorine atoms,

R12 represents a (C 1 -C 6 )alkyl group,

R12′ and R12″ independently represent a hydrogen group or a (C 1 -C 6 )alkyl group,

X represents a bond, a —NH— group, a —CONH— group or a —CO— group,

Z represents

(i) a 4 or 5-membered cycloalkyl,

(ii) a 4 or 5-membered heterocycloalkyl group comprising 1 to 4 heteroatoms selected from oxygen, nitrogen and sulfur,

(iii) a 4 or 5-membered heteroaryl group comprising 1 to 4 heteroatoms selected from oxygen, nitrogen and sulfur,

said cycloalkyl, heteroaryl or heterocycloalkyl group being optionally substituted by 1 to 3 groups selected from a —OH group, an oxo group, a ═NR12′R12″ group and a thiooxo group, or

(iv) a phenyl group optionally substituted by a hydroxy group, by a COOR12′ group, by a —CONH 2 group, by a —NO 2 group, by a —NH 2 group or by a (C 1 -C 6 )alkyl group itself optionally substituted by a hydroxy group,

n is an integer selected from 1 and 2, and

p and q together equal an integer selected from 1 and 2, with each of p and q being an integer selected from 0, 1, and 2,

wherein when n is 1, then p and q together equal 2 and when n is 2, then p and q together equal 1,

and wherein when n is 1 and p and q together equal 2, then R7 and R8 on the sulfur atom may form with the sulfur atom to which they are attached a 5-membered ring, optionally substituted by 1 to 3 groups selected from a (C 1 -C 6 )alkyl group and an oxo group,

or a pharmaceutically acceptable salt thereof.

2 . The compound of formula (I) according to claim 1 , wherein Ar represents a phenyl or a pyridinyl group, said phenyl or pyridinyl group being optionally substituted with one or two groups selected from chlorine, fluorine, hydroxy, methyl, trifluoromethoxy, 2-oxooxazolidine-3-yl and ethoxy,

or a pharmaceutically acceptable salt thereof.

3 . The compound of formula (I) according to claim 1 , wherein R3 represents a —COR4 group, wherein

R4 represents a (C 1 -C 6 )alkyl group, a —NRR′ group, a —NHNH 2 group, a —NHNHCONH 2 group, a —NHNHCS-1H-imidazolyl group or a —NHSO 2 CH 3 group, and

R and R′ independently represent a hydrogen atom, a —OH group, a (C 1 -C 6 )alkoxy group or a (C 1 -C 6 )alkyl group,

or a pharmaceutically acceptable salt thereof.

4 . The compound of formula (I) according to claim 1 , wherein R3 represents a —BOR5OR6 group, and

R5 and R6 independently represent a hydrogen atom, a (C 1 -C 6 )alkyl group, or form together with the boron atom to which they are attached a 5-membered ring, said ring being optionally substituted by 1 to 4 methyl groups,

or a pharmaceutically acceptable salt thereof.

5 . The compound of formula (I) according to claim 1 , wherein R3 represents a —X—Z group,

X represents a bond, a —NH— group, a —CONH— group or a —CO— group, and

Z represents

(i) a 4 or 5-membered cycloalkyl,

(ii) a 4 or 5-membered heterocycloalkyl group comprising 1 to 4 heteroatoms selected from oxygen, nitrogen and sulfur,

(iii) a 4 or 5-membered heteroaryl group comprising 1 to 4 heteroatoms selected from oxygen, nitrogen and sulfur,

said cycloalkyl, heteroaryl or heterocycloalkyl group being optionally substituted by 1 to 3 groups selected from a —OH group, an oxo group, a ═NR12′R12″ group and a thiooxo group, or

(iv) a phenyl group optionally substituted by a hydroxy group, by a COOR12′ group, by a —CONH 2 group, by a —NO 2 group, by a —NH 2 group or by a (C 1 -C 6 )alkyl group, itself optionally substituted by a hydroxy group,

with R12′ and R12″ independently selected from a hydrogen group and a (C 1 -C 6 )alkyl group,

or a pharmaceutically acceptable salt thereof.

6 . The compound of formula (I) according to claim 1 , wherein R3 represents

(i) a 4 or 5-membered cycloalkyl,

(ii) a 4 or 5-membered heterocycloalkyl group comprising 1 to 4 heteroatoms selected from oxygen, nitrogen and sulfur,

(iii) a 4 or 5-membered heteroaryl group comprising 1 to 4 heteroatoms selected from oxygen, nitrogen and sulfur,

said cycloalkyl, heteroaryl or heterocycloalkyl group being optionally substituted by 1 to 3 groups selected from a —OH group, an oxo group, a ═NR12′R12″ group and a thiooxo group, or

(iv) a phenyl group optionally substituted by a hydroxy group, by a COOR12′ group, by a —CONH 2 group, by a —NO 2 group, by a —NH 2 group or by a (C 1 -C 6 )alkyl group, itself optionally substituted by a hydroxy group,

with R12′ and R12″ independently selected from a hydrogen group and a (C 1 -C 6 )alkyl group,

or a pharmaceutically acceptable salt thereof.

7 . The compound of formula (I) according to claim 1 , wherein R3 represents

(i) a 4 or 5-membered cycloalkyl,

(ii) a 4 or 5-membered heterocycloalkyl group comprising 1 to 4 heteroatoms selected from oxygen, nitrogen and sulfur, or

(iii) a 4 or 5-membered heteroaryl group comprising 1 to 4 heteroatoms selected from oxygen, nitrogen and sulfur,

said cycloalkyl, heteroaryl or heterocycloalkyl group being optionally substituted by 1 to 3 groups selected from a —OH group and an oxo group,

or a pharmaceutically acceptable salt thereof.

8 . The compound of formula (I) according to claim 1 , wherein R3 represents a (C 1 -C 6 )alkyl group or a (C 1 -C 6 )alkenyl group, substituted by 1 to 4 groups selected from a fluorine atom, a —OH group and a —COOH group,

or a pharmaceutically acceptable salt thereof.

9 . The compound of formula (I) according to claim 1 , wherein R3 represents a —CONHSO 2 (CH 3 ) group, a —SO 2 NH 2 group, a —SO(CH 3 )NH group, a —SO 2 CH 3 group, a —NHSO 2 (CH 3 ) group or a —NHSO 2 (CF 3 ) group,

or a pharmaceutically acceptable salt thereof.

10 . The compound of formula (I) according to claim 1 , wherein R3 represents a —NH 2 group or a —CN group,

or a pharmaceutically acceptable salt thereof.

11 . The compound of formula (I) according to claim 1 , wherein R3 represents a —O—R11 group, wherein

R11 represents a (C 1 -C 6 )alkyl group optionally substituted by one to six fluorine atoms,

or a pharmaceutically acceptable salt thereof.

12 . The compound of formula (I) according to claim 1 , wherein R3 represents a —NH—COR9 group, wherein

R9 represents a (C 1 -C 6 )alkoxy group, a (C 1 -C 6 )alkyl group or a (C 3 -C 6 )cycloalkyl group, wherein each (C 1 -C 6 )alkyl group or (C 3 -C 6 )cycloalkyl group is optionally substituted by one to three fluorine atom(s), a —OH group or (C 1 -C 4 )alkyl group,

or a pharmaceutically acceptable salt thereof.

13 . The compound of formula (I) according to claim 1 , wherein R3 represents a —NH—C(NH)—R9′ group, wherein

R9′ represents a (C 1 -C 6 )alkyl group or a (C 3 -C 6 )cycloalkyl group,

or a pharmaceutically acceptable salt thereof.

14 . The compound of formula (I) according to claim 1 , wherein R3 represents a —NHCOCOOR12 group or a —NHCOCONR12′R12″ group, wherein

R12 represents a (C 1 -C 6 )alkyl group, and

R12′ and R12″ independently represent a hydrogen group or a (C 1 -C 6 )alkyl group,

or a pharmaceutically acceptable salt thereof.

15 . A pharmaceutical composition comprising a compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

16 . A method of inhibiting or degrading an estrogen receptor, the method comprising contacting a compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof, with an estrogen receptor.

17 . A method of treating ovulatory dysfunction, endometriosis, osteoporosis, benign prostatic hypertrophy or inflammation, the method comprising administering a compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof, to a patient in need thereof.

18 . A method of treating cancer, wherein the cancer is selected from breast, ovarian, endometrial, prostate, uterine, cervical, and lung cancer, or a metastasis thereof, and wherein the method comprising administering a compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof, to a patient in need thereof.

19 . The compound according to claim 1 , wherein Ar represents a phenyl or a 6-membered heteroaryl group, said phenyl or 6-membered heteroaryl group being optionally substituted with one to three groups selected from halogen atoms, a —OH group, a (C 1 -C 3 )alkyl group, a (C 1 -C 3 )alkoxy group, trifluoromethoxy and 2-oxooxazolidine-3-yl.

20 . The compound of formula (I) according to claim 5 , wherein R3 represents a —X—Z group,

Z is selected from

(i) a cyclobutenyl and a cyclopentenyl,

(ii) an azetidinyl, an oxetanyl, a dihydropyrazolyl, a dihydroisoxazolyl, and a dihydropyrrolyl,

(iii) a triazolyl,

wherein the groups in (i), (ii), and (iii) are optionally substituted by 1 to 3 groups selected from a —OH group, an oxo group, a ═NR12′R12″ group and a thiooxo group, and

(iv) a phenyl group optionally substituted by a hydroxy group, by a COOR12′ group, by a —CONH 2 group, by a —NO 2 group, by a —NH 2 group or by a (C 1 -C 6 )alkyl group, itself optionally substituted by a hydroxy group,

with R12′ and R12″ independently selected from a hydrogen group and a (C 1 -C 6 )alkyl group,

or a pharmaceutically acceptable salt thereof.

21 . The compound of formula (I) according to claim 5 , wherein R3 represents a —X—Z group,

Z is selected from

(i) a cyclobutenyl and a cyclopentenyl,

(ii) a 1,5-dihydro-2H-pyrrolyl, an oxazolidinyl, an imidazolidinyl, and a dioxazolyl,

(iii) a 1,2,4-triazolyl, an isoxazolyl, a thiazolyl, and an oxadiazolyl,

wherein the groups in (i), (ii), and (iii) are optionally substituted by 1 to 3 groups selected from a —OH group, an oxo group, a ═NR12′R12″ group and a thiooxo group, and

(iv) a phenyl group optionally substituted by a hydroxy group, by a COOR12′ group, by a —CONH 2 group, by a —NO 2 group, by a —NH 2 group or by a (C 1 -C 6 )alkyl group, itself optionally substituted by a hydroxy group,

with R12′ and R12″ independently selected from a hydrogen group and a (C 1 -C 6 )alkyl group,

or a pharmaceutically acceptable salt thereof.

22 . The compound of formula (I) according to claim 5 , wherein R3 represents a —X—Z group,

Z is selected from

(i) a cyclobutenyl and a cyclopentenyl,

(ii) a 1,2,4-dioxazolyl and an oxathiazolyl,

(iii) a 1,3,5-oxadiazolyl, a 1,3,4-oxadiazolyl, a 1,2,4-oxadiazolyl, a 1,2,5-oxadiazolyl, and a thiadiazolyl,

wherein the groups in (i), (ii), and (iii) are optionally substituted by 1 to 3 groups selected from a —OH group, an oxo group, a ═NR12′R12″ group and a thiooxo group, and

(iv) a phenyl group optionally substituted by a hydroxy group, by a COOR12′ group, by a —CONH 2 group, by a —NO 2 group, by a —NH 2 group or by a (C 1 -C 6 )alkyl group, itself optionally substituted by a hydroxy group,

with R12′ and R12″ independently selected from a hydrogen group and a (C 1 -C 6 )alkyl group,

or a pharmaceutically acceptable salt thereof.

23 . The compound of formula (I) according to claim 5 , wherein R3 represents a —X—Z group,

Z is selected from

(i) a cyclobutenyl and a cyclopentenyl,

(ii) a 1,3,4-oxathiazolyl, an oxathiadiazolyl and a pyrrolidinyl,

(iii) a 1,3,5-thiadiazolyl, a 1,2,4-thiadiazolyl, a 1,2,5-thiadiazolyl, a 1,3,4-thiadiazolyl, a tetrazolyl and a pyrazolyl,

wherein the groups in (i), (ii), and (iii) are optionally substituted by 1 to 3 groups selected from a —OH group, an oxo group, a ═NR12′R12″ group and a thiooxo group, and

(iv) a phenyl group optionally substituted by a hydroxy group, by a COOR12′ group, by a —CONH 2 group, by a —NO 2 group, by a —NH 2 group or by a (C 1 -C 6 )alkyl group, itself optionally substituted by a hydroxy group,

with R12′ and R12″ independently selected from a hydrogen group and a (C 1 -C 6 )alkyl group,

or a pharmaceutically acceptable salt thereof.

24 . The compound of formula (I) according to claim 6 , wherein R3 is selected from

(i) a cyclopentenyl,

(ii) a dihydropyrazolyl, a dihydroisoxazolyl, and a dihydropyrrolyl,

(iii) a triazolyl,

wherein the groups in (i), (ii), and (iii) are optionally substituted by 1 to 3 groups selected from a —OH group, an oxo group, a ═NR12′R12″ group and a thiooxo group, and

(iv) a phenyl group optionally substituted by a hydroxy group, by a COOR12′ group, by a —CONH 2 group, by a —NO 2 group, by a —NH 2 group or by a (C 1 -C 6 )alkyl group, itself optionally substituted by a hydroxy group,

with R12′ and R12″ independently being a hydrogen group or a (C 1 -C 6 )alkyl group,

or a pharmaceutically acceptable salt thereof.

25 . The compound of formula (I) according to claim 6 , wherein R3 is selected from

(i) a cyclopentenyl,

(ii) 1,5-dihydro-2H-pyrrolyl, an oxazolidinyl, an imidazolidinyl, and a dioxazolyl,

(iii) a 1,2,4-triazolyl, an isoxazolyl, a thiazolyl, and an oxadiazolyl,

wherein the groups in (i), (ii), and (iii) are optionally substituted by 1 to 3 groups selected from a —OH group, an oxo group, a ═NR12′R12″ group and a thiooxo group, and

(iv) a phenyl group optionally substituted by a hydroxy group, by a COOR12′ group, by a —CONH 2 group, by a —NO 2 group, by a —NH 2 group or by a (C 1 -C 6 )alkyl group, itself optionally substituted by a hydroxy group,

with R12′ and R12″ independently being a hydrogen group or a (C 1 -C 6 )alkyl group,

or a pharmaceutically acceptable salt thereof.

26 . The compound of formula (I) according to claim 6 , wherein R3 is selected from

(i) a cyclopentenyl,

(ii) a 1,2,4-dioxazolyl and an oxathiazolyl,

(iii) a 1,3,5-oxadiazolyl, a 1,3,4-oxadiazolyl, a 1,2,4-oxadiazolyl, a 1,2,5-oxadiazolyl, and a thiadiazolyl,

wherein the groups in (i), (ii), and (iii) are optionally substituted by 1 to 3 groups selected from a —OH group, an oxo group, a ═NR12′R12″ group and a thiooxo group, and

(iv) a phenyl group optionally substituted by a hydroxy group, by a COOR12′ group, by a —CONH 2 group, by a —NO 2 group, by a —NH 2 group or by a (C 1 -C 6 )alkyl group, itself optionally substituted by a hydroxy group,

with R12′ and R12″ independently being a hydrogen group or a (C 1 -C 6 )alkyl group,

or a pharmaceutically acceptable salt thereof.

27 . The compound of formula (I) according to claim 6 , wherein R3 is selected from

(i) a cyclopentenyl,

(ii) a 1,3,4-oxathiazolyl, an oxathiadiazolyl and a pyrrolidinyl,

(iii) a 1,3,5-thiadiazolyl, a 1,2,4-thiadiazolyl, a 1,2,5-thiadiazolyl, a 1,3,4-thiadiazolyl, a tetrazolyl, and a pyrazolyl,

wherein the groups in (i), (ii), and (iii) are optionally substituted by 1 to 3 groups selected from a —OH group, an oxo group, a ═NR12′R12″ group and a thiooxo group, and

(iv) a phenyl group optionally substituted by a hydroxy group, by a COOR12′ group, by a —CONH 2 group, by a —NO 2 group, by a —NH 2 group or by a (C 1 -C 6 )alkyl group, itself optionally substituted by a hydroxy group,

with R12′ and R12″ independently being a hydrogen group or a (C 1 -C 6 )alkyl group,

or a pharmaceutically acceptable salt thereof.

28 . The compound of formula (I) according to claim 7 , wherein R3 is selected from

(i) a cyclobutenyl,

(ii) an azetidinyl and an oxetanyl, or

(iii) a tetrazolyl,

said cyclobutenyl, azetidinyl, oxetanyl, or tetrazolyl is optionally substituted by 1 to 3 groups selected from a —OH group and an oxo group,

or a pharmaceutically acceptable salt thereof.

29 . The compound of formula (I) according to claim 11 , wherein R11 represents a (C 1 -C 6 )alkyl group optionally substituted by one to three fluorine atoms,

or a pharmaceutically acceptable salt thereof.

30 . A compound of formula (I) according to claim 1 , selected from:

(S)-3-(4-(8-(2,4-dichlorophenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydro-5H-benzo[7]annulen-9-yl)phenoxy)-1-(3-fluoropropyl)pyrrolidine (1)

(S)-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)boronic acid (2)

(S)-8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulene-3-carboxamide (3)

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

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

(S)-8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulene-3-carbohydrazide (6)

(S)-2-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-1,3,4-oxadiazole (7)

(S)-3-(4-(8-(2,4-dichlorophenyl)-3-(difluoromethyl)-6,7-dihydro-5H-benzo[7]annulen-9-yl)phenoxy)-1-(3-fluoropropyl)pyrrolidine (8)

(S)-2-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-1,3,4-thiadiazole (9)

1-(8-(2,4-dichlorophenyl)-9-(4-(((S)-1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-2,2,2-trifluoroethan-1-ol (10)

(S)-5-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-1,2-dihydro-3H-pyrazol-3-one (12)

(S)-3-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)isoxazol-5(4H)-one (13)

(S)-2-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulene-3-carbonyl)hydrazine-1-carboxamide (14)

(S)-8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-(methylsulfonyl)-6,7-dihydro-5H-benzo[7]annulene-3-carboxamide (15)

(S)-5-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-2H-tetrazole (16)

(S)-8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-N-(2H-tetrazol-5-yl)-6,7-dihydro-5H-benzo[7]annulene-3-carboxamide (17)

(S)-8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-N-hydroxy-6,7-dihydro-5H-benzo[7]annulene-3-carboxamide (18)

(S)-8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-N-methoxy-6,7-dihydro-5H-benzo[7]annulene-3-carboxamide (19)

(S,E)-3-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)acrylic acid (20)

(S)-4-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-1H-pyrazole (21)

(S)-8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulene-3-carbonitrile (22)

(S)-4-(9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-8-(4-(trifluoromethoxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-1H-pyrazole (23)

(S)-3-(4-(3-(difluoromethoxy)-8-(4-(trifluoromethoxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-9-yl)phenoxy)-1-(3-fluoropropyl)pyrrolidine (24)

Methyl (S)-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)carbamate (25)

(S)-8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-N-hydroxy-6,7-dihydro-5H-benzo[7]annulene-3-carboximidamide (26)

(S)-3-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-1,2,4-oxadiazol-5(4H)-one (27)

(S)-8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-amine (28)

4-(8-(2,4-dichlorophenyl)-9-(4-(((S)-1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-3H-1,2,3,5-oxathiadiazole 2-oxide hydrochloride (29)

(S)—N-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl) pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)methane sulfonamide (30)

(S)-5-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl) pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-1,3,4-oxadiazol-2(3H)-one (31)

Tert-butyl (S)-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl) pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)carbamate (32)

(S)-5-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-1,3,4-oxathiazol-2-one (33)

(S)-3-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-1,2,4-oxadiazole-5(4H)-thione (34)

(S)—N-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-1,1,1-trifluoromethanesulfonamide (35)

(S)-3-((8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)amino)-4-hydroxycyclobut-3-ene-1,2-dione (36)

(S)-3-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-1,2,4-thiadiazol-5(4H)-one (37)

(S)-1-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-3-methoxy-1,5-dihydro-2H-pyrrol-2-one (38)

(S)-1-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)ethan-1-one (39)

(S)-3-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)oxazolidin-2-one (40)

(S)-3-(8-(2-chloro-4-(2-oxooxazolidin-3-yl)phenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)oxazolidin-2-one (41)

(S)-4-(3-amino-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-8-yl)-3-chlorophenol (42)

5-(8-(2,4-dichlorophenyl)-9-(4-(((S)-1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)imidazolidine-2,4-dione (43)

(S)-8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-N-methoxy-N-methyl-6,7-dihydro-5H-benzo[7]annulene-3-carboxamide (44)

(S)-5-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-1,3,4-oxadiazole-2(3H)-thione (45)

(S)—N-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)acetimidamide (46)

(S)—N-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-2,2,2-trifluoroacetamide (47)

(S)—N-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl) acetamide (48)

1-(8-(2,4-dichlorophenyl)-9-(4-(((S)-1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)ethan-1-ol (49)

(S)-2-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)propan-2-ol (50)

(S)-3-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-1H-pyrazole (51)

(S)-4-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)phenol (52)

(S)-3-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)phenol (53)

(S)-2-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)phenol (54)

(S)-3-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)benzoic acid (55)

methyl (S)-4-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)benzoate (56)

methyl (S)-3-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)benzoate (57)

(S)-1-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)pyrrolidin-2-one (58)

(S)-8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-N′-(1H-imidazole-1-carbonothioyl)-6,7-dihydro-5H-benzo[7]annulene-3-carbohydrazide (59)

(S)—N-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)cyclopropanecarboxamide (60)

(S)-4-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)thiazol-2-amine (61)

(S)—N-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)pivalamide (62)

(S)-8-(2-chloro-4-methylphenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulene-3-carboxamide (63)

(S)-8-(2-chloro-4-methylphenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulene-3-carbonitrile 2,2,2-trifluoroacetate (64)

1-(8-(2-chloro-3-fluorophenyl)-9-(4-(((S)-1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-2,2,2-trifluoroethan-1-ol (65)

(S)—N-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-1-fluorocyclopropane-1-carboxamide (66)

(S)—N-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-1-methylcyclopropane-1-carboxamide (67)

(S)-3-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-2-hydroxycyclopent-2-en-1-one (68)

(S,Z)-4-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-N,3-dimethylthiazol-2(3H)-imine hydrochloride (69)

(S)-5-(8-(2-chloro-4-methylphenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-2H-tetrazole 2,2,2-trifluoroacetate (70)

tert-butyl (S)-(9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-8-phenyl-6,7-dihydro-5H-benzo[7]annulen-3-yl)carbamate (71)

(S)-4-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)benzoic acid (72)

(S)-3-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-1H-pyrazol-5-amine (73)

(S)-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)(3-hydroxyazetidin-1-yl)methanone (74)

(S)-8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-N-(oxetan-3-yl)-6,7-dihydro-5H-benzo[7]annulene-3-carboxamide (75)

ethyl (S)-2-((8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)amino)-2-oxoacetate (76)

(S)—N1-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)oxalamide (77)

(S)-8-(2-chloro-4-methylphenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-amine (78)

(S)-8-(6-ethoxy-2-fluoropyridin-3-yl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulene-3-carboxamide (79)

(S)-8-(6-ethoxy-2-fluoropyridin-3-yl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulene-3-carbonitrile 2,2,2-trifluoroacetate (80)

(S)-4-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)benzamide (81)

(S)-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)methanol (82)

methyl (S)-2-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)benzoate (83)

(S)—N-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-1-hydroxycyclopropane-1-carboxamide formate (84)

(S)-1-(8-(2,4-dichlorophenyl)-9-(4-(((S)-1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-4-hydroxypyrrolidin-2-one (85)

(S)-2-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)benzoic acid (86)

N-(8-(2,4-dichlorophenyl)-9-(4-(((S)-1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)-2,2-difluorocyclopropane-1-carboxamide (87)

(S)-3-((8-(2-chloro-4-methylphenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)amino)-4-hydroxycyclobut-3-ene-1,2-dione (88)

(S)-8-(2-chloro-3-fluorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-amine (89)

(S)—N-(8-(2-chloro-3-fluorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)methanesulfonamide (90)

(S)-1-(3-fluoropropyl)-3-(4-(8-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydro-5H-benzo[7]annulen-9-yl)phenoxy)pyrrolidine (91)

(S)-(9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-8-phenyl-6,7-dihydro-5H-benzo[7]annulen-3-yl)boronic acid (92)

(S)-2-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)acetic acid (93)

(S)-2-(3-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)phenyl)propan-2-ol (94)

(S)-2-(4-(8-(2,4-dichlorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)phenyl)propan-2-ol (95)

(S)-3-(4-(8-(2-chloro-3-fluorophenyl)-3-(3-nitrophenyl)-6,7-dihydro-5H-benzo[7]annulen-9-yl)phenoxy)-1-(3-fluoropropyl)pyrrolidine (96)

(S)-3-(8-(2-chloro-3-fluorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)aniline (97)

(S)-2-(4-(8-(2-chloro-3-fluorophenyl)-9-(4-((1-(3-fluoropropyl)pyrrolidin-3-yl)oxy)phenyl)-6,7-dihydro-5H-benzo[7]annulen-3-yl)phenyl)propan-2-ol (98)

or a pharmaceutically acceptable salt thereof.

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References Cited (151)