IP Library Granted Patent US 8,653,072
Granted Patent B2
US 8,653,072 · App. 13/739,124 · Granted Feb 18, 2014

Estrogen receptor ligands

Inventors: Patrik Rhonnstad (Kungsor, SE); Elisabet Kallin (Tullinge, SE); Theresa Apelqvist (Grodinge, SE); Mattias Wennerstal (Hagersten, SE); Aiping Cheng (Huddinge, SE)
Assignee: Karo Bio AB
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Quick Facts
Patent No.
US 8,653,072
App. No.
13/739,124
Granted
Feb 18, 2014
Kind
B2
Abstract

The invention provides a compound of formula (I) or a pharmaceutically acceptable ester, amide, carbamate, solvate or salt thereof, including a salt of such an ester, amide or carbamate, and a solvate of such an ester, amide, carbamate or salt. The invention also provides also provides the use of such compounds in the treatment or prophylaxis of a condition associated with a disease or disorder associated with estrogen receptor activity, wherein R 1 , R 2 , R 3 , R 5 and R 6 are as defined in the specification.

Claims (308)

1. A method for the treatment of a disease or disorder associated with estrogen receptor activity in a mammal, wherein said disease or disorder associated with estrogen receptor activity is selected from hot flashes, cardiovascular disease, impairment of cognitive functioning, age-related mild cognitive impairment, cerebral degenerative disorders, restenosis, obesity, anxiety, depression, hearing disorders, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, stroke, IBD, IBS, hypertension, lung cancer, colon cancer, breast cancer, prostate cancer and cholangiocarcinoma, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable ester, amide, carbamate, solvate or salt thereof, including a salt of such an ester, amide or carbamate, and a solvate of such an ester, amide, carbamate or salt,

wherein R 1 is selected from the group consisting of halogen, cyano, nitro, OR A , N(R B ) 2 , —C(O)C 1-4 alkyl, —SO 2 C 1-4 alkyl, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, haloC 1-6 alkyl, dihaloC 1-6 alkyl, trihaloC 1-6 alkyl, haloC 2-6 alkenyl, dihaloC 2-6 alkenyl, trihaloC 2-6 alkenyl, cyanoC 1-6 alkyl, C 1-4 alkoxyC 1-6 alkyl, C 3-8 cycloalkyl, C 3-8 cycloalkylC 1-6 alkyl, phenyl, benzyl, and 5-10 membered heterocyclyl, wherein said phenyl, benzyl or heterocyclyl group can be either unsubstituted or substituted with from 1 to 3 substituents, each substituent being selected from the group consisting of OR A , halogen, cyano, nitro, —C(O)C 1-4 alkyl, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, haloC 1-6 alkyl, dihaloC 1-6 alkyl and trihaloC 1-6 alkyl;

R 2 is selected from the group consisting of halogen, cyano, nitro, OR A , N(R B ) 2 , N(OH) 2 , —C(O)C 1-4 alkyl optionally substituted with from 1 to 3 halogens, —SO 2 C 1-4 alkyl, —C(O)NH—OH, —C(NH 2 )═N—OH, —C(CO 2 H)═N—OH, —C(NH 2 )═NH, —C(NHC 1-4 alkyl)=NH, —C(O—C 1-4 alkyl)=NH, —C(NH 2 )═N—NH 2 , —NH—C(NH 2 )═NH, —NH—C(O)NH 2 , —N═C(—NH—CH 2 CH 2 —NH—), —S—CN, —S—C(NH 2 )═NH, —S—C(NH 2 )═N—OH, —CO 2 H, —CH 2 —CO 2 H, —CH(OH)CO 2 H, —C(O)CO 2 H, SO 3 H, CH 2 SO 3 H, C 1-6 alkyl, haloC 1-6 alkyl, dihaloC 1-6 alkyl, trihaloC 1-6 alkyl, cyanoC 1-6 alkyl, C 1-4 alkoxyC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkylC 1-6 alkyl, phenyl, benzyl and 5-10 membered heterocyclyl wherein said phenyl, benzyl or heterocyclyl group can be either unsubstituted or substituted with from 1 to 3 substituents each substituent being selected from the group consisting of OR A , halogen, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, haloC 1-6 alkyl, dihaloC 1-6 alkyl and trihaloC 1-6 alkyl; provided that if one of R 1 and R 2 represents halogen, the other must represent a group other than halogen;

each of R 3 , R 4 , R 5 and R 6 is independently selected from the group consisting of hydrogen, OR A , halogen, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, haloC 1-6 alkyl, dihaloC 1-6 alkyl and trihaloC 1-6 alkyl;

each R A is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkylC 1-6 alkyl, C 6-10 aryl and C 6-10 arylC 1-6 alkyl, each optionally substituted by from 1 to 3 halogen atoms; and

each R B is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkylC 1-6 alkyl, C 6-10 aryl and C 6-10 arylC 1-6 alkyl, each optionally substituted by from 1 to 3 halogen atoms;

with the proviso that the compound of formula (I) is not

4-[3-(4,5-Dihydro-1H-imidazol-2-yl)-2-(3,5-dimethyl-isoxazol-4-yl)-indol-1-yl]-phenol;

1-(4-Hydroxy-phenyl)-2-(4-methyl-imidazol-1-yl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-(1H-pyrazol-3-yl)-1H-indole-3-carbonitrile;

1-(3-Chloro-4-hydroxy-phenyl)-2-(1-methyl-1H-pyrazol-4-yl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-prop-1-ynyl-1H-indole-3-carboxylic acid amide; or

1-(4-Hydroxy-phenyl)-2-thiazol-2-yl-1H-indole-3-carboxylic acid.

2. A method as claimed in claim 1 , in which each R A is independently selected from the group consisting of hydrogen, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, phenyl and benzyl.

3. A method as claimed in claim 2 , in which each R A independently represents hydrogen or C 1-4 alkyl.

4. A method as claimed in claim 1 , in which each R B is independently selected from the group consisting of hydrogen and C 1-4 alkyl.

5. A method as claimed in claim 1 , in which R 1 is selected from the group consisting of OR A , N(R B ) 2 , —C(O)C 1-4 alkyl, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, haloC 1-4 alkyl, dihaloC 1-4 alkyl, trihaloC 1-4 alkyl, haloC 2-4 alkenyl, dihaloC 2-4 alkenyl, trihaloC 2-4 alkenyl, phenyl, and 5-6 membered heterocyclyl, wherein said phenyl or heterocyclyl group can either be unsubstituted or substituted by 1 to 3 substituents selected from the group consisting of OR A , halogen, cyano, —C(O)C 1-4 alkyl, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, haloC 1-4 alkyl, dihaloC 1-4 alkyl and trihaloC 1-4 alkyl.

6. A method as claimed in claim 5 , in which R 1 is selected from the group consisting of OR A , N(R B ) 2 , —C(O)C 1-4 alkyl, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, phenyl, and 5-6 membered heterocyclyl, wherein said phenyl or heterocyclyl group can either be unsubstituted or substituted by 1 to 3 substituents selected from halogen, cyano, C 1-4 alkyl, —C(O)C 1-4 alkyl, and OR A in which R A represent hydrogen or C 1-4 alkyl.

7. A method as claimed in claim 1 , in which R 2 is selected from the group consisting of halogen, OR A , N(R B ) 2 , —C(O)C 1-4 alkyl optionally substituted with from 1 to 3 halogens, —C(NH 2 )═N—OH, —CO 2 H, —CH 2 —CO 2 H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, haloC 1-4 alkyl, dihaloC 1-4 alkyl, trihaloC 1-4 alkyl, haloC 2-4 alkenyl, dihaloC 2-4 alkenyl, trihaloC 2-4 alkenyl, phenyl, and 5-6 membered heterocyclyl, wherein said phenyl or heterocyclyl group can either be unsubstituted or substituted by 1 to 3 substituents selected from the group consisting of OR A , halogen, cyano, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, haloC 1-4 alkyl, dihaloC 1-4 alkyl and trihaloC 1-4 alkyl.

8. A method as claimed in claim 7 , in which R 2 is selected from the group consisting of —C(O)C 1-4 alkyl, —C(NH 2 )—N—OH, —CO 2 H, —CH 2 —CO 2 H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, and 5-6 membered heterocyclyl wherein said heterocyclyl group can either be unsubstituted or substituted by 1 to 3 substituents selected from halogen, cyano, C 1-4 alkyl, and OR A .

9. A method as claimed in claim 1 , in which each of R 3 , R 4 , R 5 and R 6 is independently selected from the group consisting of hydrogen, OR A , halogen, cyano, C 1-4 alkyl, haloC 1-4 alkyl, dihaloC 1-4 alkyl, and trihaloC 1-4 alkyl.

10. A method as claimed in claim 9 , in which each of R 3 , R 4 , R 5 and R 6 is independently selected from the group consisting of hydrogen, OH, halogen, cyano, methyl, or trifluoromethyl.

11. A method as claimed in claim 1 , in which R 1 is selected from the group consisting of OR A , N(R B ) 2 , —C(O)C 1-4 alkyl, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, haloC 1-4 alkyl, dihaloC 1-4 alkyl, trihaloC 1-4 alkyl, haloC 2-4 alkenyl, dihaloC 2-4 alkenyl, trihaloC 2-4 alkenyl, phenyl, and 5-6 membered heterocyclyl, wherein said phenyl or heterocyclyl group may be either unsubstituted or substituted as above by 1 to 3 substituents selected from the group consisting of OR A , halogen, cyano, —C(O)C 1-4 alkyl, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, haloC 1-4 alkyl, dihaloC 1-4 alkyl and trihaloC 1-4 alkyl;

R 2 is selected from the group consisting of halogen, OR A , N(R B ) 2 , —C(O)C 1-4 alkyl optionally substituted with from 1 to 3 halogens, —C(NH 2 )═N—OH, —CO 2 H, —CH 2 —CO 2 H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, haloC 1-4 alkyl, dihaloC 1-4 alkyl, trihaloC 1-4 alkyl, haloC 1-4 alkenyl, dihaloC 1-4 alkenyl, trihaloC 1-4 alkenyl, phenyl, and 5-6 membered heterocyclyl, wherein said phenyl or heterocyclyl group can either be unsubstituted or substituted by 1 to 3 substituents selected from the group consisting of OR A , halogen, cyano, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, haloC 1-4 alkyl, dihaloC 1-4 alkyl and trihaloC 1-4 alkyl;

each of R 3 , R 4 , R 5 and R 6 is independently selected from the group consisting of hydrogen, OR A , halogen, cyano, C 1-4 alkyl, haloC 1-4 alkyl, dihaloC 1-4 alkyl, and trihaloC 1-4 alkyl;

each R A is independently selected from the group consisting of hydrogen, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, phenyl and benzyl; and

each R B is independently selected from the group consisting of hydrogen and C 1-4 alkyl.

12. A method as claimed in claim 11 , in which R 1 is selected from the group consisting of OR A , N(R B ) 2 , —C(O)C 1-4 alkyl, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, phenyl, and 5-6 membered heterocyclyl, wherein said phenyl or heterocyclyl group can either be unsubstituted or substituted by 1 to 3 substituents selected from halogen, cyano, C 1-4 alkyl, —C(O)C 1-4 alkyl, and OR A ;

each R A independently represents hydrogen or C 1-4 alkyl; and

each R B is independently selected from the group consisting of hydrogen and C 1-4 alkyl.

13. A method as claimed in claim 11 , in which R 2 is selected from the group consisting of —C(O)C 1-4 alkyl optionally substituted with from 1 to 3 halogens, —C(NH 2 )═N—OH, —CO 2 H, —CH 2 —CO 2 H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, and 5-6 membered heterocyclyl wherein said heterocyclyl group can be either unsubstituted or substituted by 1 to 3 substituents selected from the group consisting of halogen, cyano, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, haloC 1-4 alkyl, dihaloC 1-4 alkyl and trihaloC 1-4 alkyl, and OR A , in which R A represents hydrogen or C 1-4 alkyl.

14. A method as claimed in claim 11 , in which R 2 is selected from the group consisting of —C(O)CH 3 , —C(NH 2 )═N—OH, —CO 2 H, —CH 2 —CO 2 H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, and 5-6 membered heterocyclyl wherein said heterocyclyl group can be either unsubstituted or substituted 1 to 3 substituents selected from halogen, cyano, C 1-4 alkyl, and OR A in which R A represents hydrogen or C 1-4 alkyl.

15. A method as claimed in claim 11 , in which each of R 3 , R 4 , R 5 and R 6 is independently selected from the group consisting of hydrogen, OH, halogen, cyano, methyl, or trifluoromethyl.

16. A method as claimed in claim 1 , in which R 1 is a 5-6 membered heterocyclyl group, wherein said heterocyclyl group is substituted with from 1 to 3 substituents selected from halogen, cyano and C 1-4 alkyl; R 2 is selected from the group consisting of —C(O)CH 3 , —C(NH 2 )═N—OH, —CO 2 H, and —CH 2 —CO 2 H; and each of R 3 , R 4 , R 5 and R 6 is independently selected from the group consisting of hydrogen and halogen.

17. A method as claimed in claim 16 , in which R 1 is a 5-membered heterocyclyl group, wherein said heterocyclyl group is substituted with two substituents independently selected from methyl and ethyl; R 2 is —C(NH 2 )═N—OH; and each of R 3 , R 4 , R 5 and R 6 is independently selected from the group consisting of hydrogen and halogen.

18. A method as claimed in claim 1 , in which the compound of formula (I) is any one of the following compounds:

2-Bromo-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-thiophen-3-yl-1H-indole-3-carbonitrile;

2-(3-Cyano-furan-2-yl)-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-pyrrol-1-yl-1H-indole-3-carbonitrile;

2-Dimethylamino-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-isopropyl-1H-indole-3-carbonitrile;

2-Acetyl-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

2-(3,5-Dimethyl-isoxazol-4-yl)-1-(4-hydroxy-phenyl)-1H-indole-3-carboxylic acid;

1-[1-(4-Hydroxy-phenyl)-2-phenyl-1H-indol-3-yl]-ethanone;

1-(4-Hydroxy-phenyl)-2-phenyl-1H-indole-3-carboxylic acid, amide;

(Z)-2-(3,5-dimethylisoxazol-4-yl)-N′-hydroxy-1-(4-hydroxyphenyl)-1H-indole-3-carboximidamide;

[2-(3,5-Dimethyl-isoxazol-4-yl)-1-(4-hydroxy-phenyl)-1H-indol-3-yl]-carbamic acid tert-butyl ester;

4-[3-Amino-2-(3,5-dimethyl-isoxazol-4-yl)-indol-1-yl]-phenol;

(Z)-2-(3,5-dimethylisoxazol-4-yl)-7-fluoro-N′-hydroxy-1-(4-hydroxyphenyl)-1H-indole-3-carboximidamide;

(Z)-2-(5-chlorothiophen-2-yl)-N′-hydroxy-1-(4-hydroxyphenyl)-1H-indole-3-carboximidamide;

1-(2,3-Difluoro-4-hydroxy-phenyl)-2-(3,5-dimethyl-isoxazol-4-yl)-1H-indole-3-carbonitrile;

2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1H-indole-3-carbohydrazonamide;

4-(2-(3,5-dimethylisoxazol-4-yl)-3-(1,2,4-oxadiazol-3-yl)-1H-indol-1-yl)phenol;

2-(3,5-Dimethyl-isoxazol-4-yl)-1-(4-hydroxy-phenyl)-1H-indole-3-carboxylic acid, methyl ester;

2-(3,5-Dimethyl-isoxazol-4-yl)-1-(4-hydroxy-phenyl)-1H-indole-3-carboxylic acid, hydroxyamide;

4-[2-(3,5-Dimethyl-isoxazol-4-yl)-3-methanesulfonyl-indol-1-yl]-phenol;

1-[2-(3,5-Dimethyl-isoxazol-4-yl)-1-(4-hydroxy-phenyl)-1H-indol-3-yl]-2,2,2-trifluoro-ethanone;

4-(3-bromo-2-(3,5-dimethylisoxazol-4-yl)-1H-indol-1-yl)phenol;

2-Bromo-5-fluoro-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

(Z)-2-(4-fluorophenoxy)-N′-hydroxy-1-(4-hydroxyphenyl)-1H-indole-3-carboximidamide;

4-(2-(3,5-dimethylisoxazol-4-yl)-3-nitro-1H-indol-1-yl)phenol;

4-(3-(dihydroxyamino)-2-(3,5-dimethylisoxazol-4-yl)-1H-indol-1-yl)phenol;

N-(2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1H-indol-3-yl)acetamide

N-(2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1H-indol-3-yl)methanesulfonamide;

1-(2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1H-indol-3-yl)urea;

4-(2-(3,5-dimethylisoxazol-4-yl)-3-thiocyanato-1H-indol-1-yl)phenol;

(E)-2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1H-indol-3-yl N′-hydroxycarbamimidothioate;

4-(3-benzyl-2-phenyl-1H-indol-1-yl)phenol;

2-(2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1H-indol-3-yl)-2-oxoacetamide;

(Z)-2-(2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1H-indol-3-yl)-2-(hydroxyimino)acetamide;

2-(2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1H-indol-3-yl)-2-hydroxyacetamide;

2-(2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1H-indol-3-yl)acetamide;

2-((Z)-But-1-enyl)-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-(2-methyl-prop-1-enyl)-1H-indole-3-carbonitrile;

1-(2,3-Difluoro-4-hydroxy-phenyl)-2-(2-methyl-allyl)-1H-indole-3-carbonitrile;

(Z)-2-(5-ethyl-3-methylisoxazol-4-yl)-N′-hydroxy-1-(4-hydroxyphenyl)-1H-indole-3-carboximidamide;

4-(2-(3,5-dimethylisoxazol-4-yl)-3-phenyl-1H-indol-1-yl)phenol;

4-(3-chloro-2-(3,5-dimethylisoxazol-4-yl)-1H-indol-1-yl)phenol;

2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1H-indole-3-sulfonamide;

2-(3,5-dimethylisoxazol-4-yl)-1-(2-fluoro-4-hydroxyphenyl)-1H-indole-3-carboximidamide;

1-(4-Hydroxy-phenyl)-2-phenyl-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-methyl-1H-indole-3-carbonitrile;

2-(3-Cyano-thiophen-2-yl)-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-((E)-propenyl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-thiophen-2-yl-1H-indole-3-carbonitrile;

2-(3,5-Dimethyl-isoxazol-4-yl)-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-pyridin-4-yl-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-(1-methyl-1H-pyrrol-2-yl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-(3-methyl-thiophen-2-yl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-isopropylamino-1H-indole-3-carbonitrile;

2-Ethylamino-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

2-Butylamino-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-piperidin-1-yl-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-pyrrolidin-1-yl-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-morpholin-4-yl-1H-indole-3-carbonitrile;

2-Diethylamino-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

2-Ethynyl-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-vinyl-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-1H-indole-2,3-dicarbonitrile;

1-(4-Hydroxy-phenyl)-2-prop-1-ynyl-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-pyridin-2-yl-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-(2-methyl-allyl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-((Z)-propenyl)-1H-indole-3-carbonitrile;

2-(Butyl-methyl-amino)-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-((Z)-1-methyl-propenyl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-imidazol-1-yl-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-[1,2,4]triazol-1-yl-1H-indole-3-carbonitrile;

2-(3,5-Dimethyl-pyrazol-1-yl)-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-pyrazol-1-yl-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-(5-methyl-imidazol-1-yl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-(5-methyl-pyrazol-1-yl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-(3-methyl-pyrazol-1-yl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-thiazol-2-yl-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-(2-methoxy-thiazol-4-yl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-thiazol-4-yl-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-(3-methyl-but-2-enyl)-1H-indole-3-carbonitrile;

2-((E)-But-1-enyl)-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-(5-methyl-thiophen-2-yl)-1H-indole-3-carbonitrile;

2-(5-Acetyl-thiophen-2-yl)-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-(1-methyl-1H-pyrazol-4-yl)-1H-indole-3-carbonitrile;

2-(5-Chloro-thiophen-2-yl)-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-(4-methyl-thiophen-3-yl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-(4-methyl-thiophen-2-yl)-1H-indole-3-carbonitrile;

2-(4-Cyano-thiophen-3-yl)-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-(2-methyl-2H-pyrazol-3-yl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-indole-3-carbonitrile;

2-(2-Acetyl-pyrrol-1-yl)-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

2-(2-Ethyl-pyrrol-1-yl)-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

2-(2-Cyano-pyrrol-1-yl)-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(4-Hydroxy-phenyl)-2-(2-methyl-pyrrol-1-yl)-1H-indole-3-carbonitrile;

1-(3-Chloro-5-fluoro-4-hydroxy-phenyl)-2-phenyl-1H-indole-3-carbonitrile;

1-(3-Chloro-5-fluoro-4-hydroxy-phenyl)-2-(3-cyano-thiophen-2-yl)-1H-indole-3-carbonitrile;

1-(3-Chloro-5-fluoro-4-hydroxy-phenyl)-2-(3-cyano-furan-2-yl)-1H-indole-3-carbonitrile;

2-Bromo-1-(3-chloro-5-fluoro-4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

2-Bromo-1-(2-fluoro-4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(2-Fluoro-4-hydroxy-phenyl)-2-phenyl-1H-indole-3-carbonitrile;

2-Bromo-1-(3-fluoro-4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

2-Bromo-1-(2,3-difluoro-4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

2-Bromo-1-(2,5-difluoro-4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

2-Bromo-1-(3-chloro-4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

2-Bromo-1-(3,5-difluoro-4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(3-Fluoro-4-hydroxy-phenyl)-2-phenyl-1H-indole-3-carbonitrile;

1-(3,5-Difluoro-4-hydroxy-phenyl)-2-phenyl-1H-indole-3-carbonitrile;

1-(3-Chloro-4-hydroxy-phenyl)-2-phenyl-1H-indole-3-carbonitrile;

1-(2,3-Difluoro-4-hydroxy-phenyl)-2-phenyl-1H-indole-3-carbonitrile;

1-(2,5-Difluoro-4-hydroxy-phenyl)-2-phenyl-1H-indole-3-carbonitrile;

1-(3,5-Difluoro-4-hydroxy-phenyl)-2-thiophen-3-yl-1H-indole-3-carbonitrile;

1-(3,5-Difluoro-4-hydroxy-phenyl)-2-thiophen-2-yl-1H-indole-3-carbonitrile;

1-(3,5-Difluoro-4-hydroxy-phenyl)-2-(3,5-dimethyl-isoxazol-4-yl)-1H-indole-3-carbonitrile;

1-(3,5-Difluoro-4-hydroxy-phenyl)-2-(1-methyl-1H-pyrrol-2-yl)-1H-indole-3-carbonitrile;

1-(3,5-Difluoro-4-hydroxy-phenyl)-2-(3-methyl-thiophen-2-yl)-1H-indole-3-carbonitrile;

1-(3,5-Difluoro-4-hydroxy-phenyl)-2-(1-methyl-1H-pyrazol-4-yl)-1H-indole-3-carbonitrile;

1-(3,5-Difluoro-4-hydroxy-phenyl)-2-pyridin-4-yl-1H-indole-3-carbonitrile;

1-(3-Chloro-4-hydroxy-phenyl)-2-thiophen-3-yl-1H-indole-3-carbonitrile;

1-(3-Chloro-4-hydroxy-phenyl)-2-thiophen-2-yl-1H-indole-3-carbonitrile;

1-(3-Chloro-4-hydroxy-phenyl)-2-(3,5-dimethyl-isoxazol-4-yl)-1H-indole-3-carbonitrile;

1-(3-Chloro-4-hydroxy-phenyl)-2-(1-methyl-1H-pyrrol-2-yl)-1H-indole-3-carbonitrile;

1-(3-Chloro-4-hydroxy-phenyl)-2-(3-methyl-thiophen-2-yl)-1H-indole-3-carbonitrile;

1-(3-Chloro-4-hydroxy-phenyl)-2-pyridin-4-yl-1H-indole-3-carbonitrile;

1-(3-Fluoro-4-hydroxy-phenyl)-2-thiophen-3-yl-1H-indole-3-carbonitrile;

1-(3-Fluoro-4-hydroxy-phenyl)-2-thiophen-2-yl-1H-indole-3-carbonitrile;

2-(3,5-Dimethyl-isoxazol-4-yl)-1-(3-fluoro-4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(3-Fluoro-4-hydroxy-phenyl)-2-(1-methyl-1H-pyrrol-2-yl)-1H-indole-3-carbonitrile;

1-(3-Fluoro-4-hydroxy-phenyl)-2-(3-methyl-thiophen-2-yl)-1H-indole-3-carbonitrile;

1-(3-Fluoro-4-hydroxy-phenyl)-2-(1-methyl-1H-pyrazol-4-yl)-1H-indole-3-carbonitrile;

1-(3-Fluoro-4-hydroxy-phenyl)-2-pyridin-4-yl-1H-indole-3-carbonitrile;

2-Dimethylamino-1-(2-fluoro-4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

2-(3,5-Dimethyl-isoxazol-4-yl)-1-(2-fluoro-4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(3-Fluoro-4-hydroxy-phenyl)-2-((E)-propenyl)-1H-indole-3-carbonitrile;

1-(3-Fluoro-4-hydroxy-phenyl)-2-((Z)-propenyl)-1H-indole-3-carbonitrile;

1-(2,3-Difluoro-4-hydroxy-phenyl)-2-((Z)-propenyl)-1H-indole-3-carbonitrile;

1-(2,3-Difluoro-4-hydroxy-phenyl)-2-vinyl-1H-indole-3-carbonitrile;

1-(2,3-Difluoro-4-hydroxy-phenyl)-2-thiophen-3-yl-1H-indole-3-carbonitrile;

1-(2,3-Difluoro-4-hydroxy-phenyl)-2-thiophen-2-yl-1H-indole-3-carbonitrile;

1-(2,3-Difluoro-4-hydroxy-phenyl)-2-(3-methyl-thiophen-2-yl)-1H-indole-3-carbonitrile;

1-(2,3-Difluoro-4-hydroxy-phenyl)-2-(1-methyl-1H-pyrrol-2-yl)-1H-indole-3-carbonitrile;

2-(2-Acetyl-pyrrol-1-yl)-1-(3-fluoro-4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(3-Fluoro-4-hydroxy-phenyl)-2-pyrrol-1-yl-1H-indole-3-carbonitrile;

1-(2,3-Difluoro-4-hydroxy-phenyl)-2-pyrrol-1-yl-1H-indole-3-carbonitrile;

1-(2,3-Difluoro-4-hydroxy-phenyl)-2-prop-1-ynyl-1H-indole-3-carbonitrile;

1-(3-Fluoro-4-hydroxy-phenyl)-2-(2-methyl-prop-1-enyl)-1H-indole-3-carbonitrile;

1-(2,3-Difluoro-4-hydroxy-phenyl)-2-(2-methyl-prop-1-enyl)-1H-indole-3-carbonitrile;

2-(2-Acetyl-pyrrol-1-yl)-1-(2,3-difluoro-4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(3-Fluoro-4-hydroxy-phenyl)-2-pyrazol-1-yl-1H-indole-3-carbonitrile;

1-(2,3-Difluoro-4-hydroxy-phenyl)-2-pyrazol-1-yl-1H-indole-3-carbonitrile;

2-(2,5-Dimethyl-pyrrol-1-yl)-1-(3-fluoro-4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

2-(2-Ethyl-pyrrol-1-yl)-1-(3-fluoro-4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

2-(2-Cyano-pyrrol-1-yl)-1-(3-fluoro-4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(3-Fluoro-4-hydroxy-phenyl)-2-(2-methyl-pyrrol-1-yl)-1H-indole-3-carbonitrile;

1-(2,3-Difluoro-4-hydroxy-phenyl)-2-(2-ethyl-pyrrol-1-yl)-1H-indole-3-carbonitrile;

2-(2-Cyano-pyrrol-1-yl)-1-(2,3-difluoro-4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

1-(2,3-Difluoro-4-hydroxy-phenyl)-2-(2-methyl-pyrrol-1-yl)-1H-indole-3-carbonitrile;

1-(2-Fluoro-4-hydroxy-phenyl)-2-pyrrol-1-yl-1H-indole-3-carbonitrile;

1-(2,3-difluoro-4-hydroxyphenyl)-2-(3-methylbut-2-enyl)-1H-indole-3-carbonitrile;

[1-(4-Hydroxy-phenyl)-2-phenyl-1H-indol-3-yl]-acetonitrile;

[1-(4-Hydroxy-phenyl)-2-phenyl-1H-indol-3-yl]-acetic acid;

2-[1-(4-Hydroxy-phenyl)-2-phenyl-1H-indol-3-yl]-acetamide;

4-(3-Isopropenyl-2-phenyl-indol-1-yl)-phenol;

4-[3-(2-Methyl-2H-pyrazol-3-yl)-2-phenyl-indol-1-yl]-phenol;

4-(2-Phenyl-3-thiazol-4-yl-indol-1-yl)-phenol;

4-(2-Phenyl-3-prop-1-ynyl-indol-1-yl)-phenol;

1-(4-Hydroxy-phenyl)-2-((E)-propenyl)-1H-indole-3-carboxylic acid, amide;

1-(4-Hydroxy-phenyl)-2-(2-methyl-prop-1-enyl)-1H-indole-3-carboxylic acid, amide;

1-(4-Hydroxy-phenyl)-2-((Z)-1-methyl-propenyl)-1H-indole-3-carboxylic acid, amide;

4-(2-Phenyl-3-pyrazol-1-yl-indol-1-yl)-phenol;

4-(3-Imidazol-1-yl-2-phenyl-indol-1-yl)-phenol;

4-[3-(5-Methyl-pyrazol-1-yl)-2-phenyl-indol-1-yl]-phenol;

2-Bromo-1-(4-hydroxy-phenyl)-1H-indole-3-carboxylic acid, amide;

1-(4-Hydroxy-phenyl)-2-((Z)-3,3,3-trifluoro-propenyl)-1H-indole-3-carbonitrile;

(Z)-2-bromo-N′-hydroxy-1-(4-hydroxyphenyl)-1H-indole-3-carboximidamide;

(Z)—N′-hydroxy-1-(4-hydroxyphenyl)-2-(1H-pyrrol-1-yl)-1H-indole-3-carboximidamide;

2-(3,5-Dimethyl-isoxazol-4-yl)-1-(4-hydroxy-phenyl)-1H-indole-3-carboxylic acid, amide;

(Z)—N′-hydroxy-1-(4-hydroxyphenyl)-2-(2-methylprop-1-enyl)-1H-indole-3-carboximidamide;

1-(4-Hydroxy-phenyl)-2-phenyl-1H-indole-3-carboxylic acid; hydroxyamide;

(Z)—N′-hydroxy-1-(4-hydroxyphenyl)-2-phenyl-1H-indole-3-carboximidamide;

1-(4-Hydroxy-phenyl)-2-pyrrol-1-yl-1H-indole-3-carboxylic acid, amide;

[1-(4-Hydroxy-phenyl)-2-pyrrol-1-yl-1H-indol-3-yl]-carbamic acid tert-butyl ester;

2-(3,5-Dimethyl-isoxazol-4-yl)-1-(4-hydroxy-phenyl)-N-methyl-1H-indole-3-carboxamidine;

Methyl 2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1H-indole-3-carbimidate;

N-((2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1H-indol-3-yl)(imino)methyl)acetamide;

2-(5-ethyl-3-methylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1H-indole-3-carboxamide;

(Z)-2-(2-ethyl-1H-pyrrol-1-yl)-N′-hydroxy-1-(4-hydroxyphenyl)-1H-indole-3-carboximidamide;

(Z)—N′-hydroxy-1-(4-hydroxyphenyl)-2-(2-methyl-1H-pyrrol-1-yl)-1H-indole-3-carboximidamide;

1-(4-hydroxyphenyl)-2-(2-methyl-1H-pyrrol-1-yl)-1H-indole-3-carboxamide;

4-(3-chloro-2-(3,5-dimethylisoxazol-4-yl)-1H-indol-1-yl)phenol;

(Z)-2-((Z)-but-2-en-2-yl)-N′-hydroxy-1-(4-hydroxyphenyl)-1H-indole-3-carboximidamide;

(Z)—N′-hydroxy-1-(4-hydroxyphenyl)-2-(5-methyl-1H-pyrazol-1-yl)-1H-indole-3-carboximidamide;

(Z)—N′-hydroxy-1-(4-hydroxyphenyl)-2-(4-methylthiophen-3-yl)-1H-indole-3-carboximidamide;

(Z)-2-(2,5-dimethyl-1H-pyrrol-1-yl)-N′-hydroxy-1-(4-hydroxyphenyl)-1H-indole-3-carboximidamide;

(Z)—N′-hydroxy-1-(4-hydroxyphenyl)-2-phenoxy-1H-indole-3-carboximidamide;

1-(4-Hydroxy-phenyl)-2-phenyl-1H-indole-3-carboxylic acid;

2-(3,5-Dimethyl-isoxazol-4-yl)-1-(3-fluoro-4-hydroxy-phenyl)-1H-indole-3-carboxylic acid;

2-(3,5-Dimethyl-isoxazol-4-yl)-1-(2-fluoro-4-hydroxy-phenyl)-1H-indole-3-carboxylic acid;

1-(2,3-Difluoro-4-hydroxy-phenyl)-2-(3,5-dimethyl-isoxazol-4-yl)-1H-indole-3-carboxylic acid;

1-(4-Hydroxy-phenyl)-2-((Z)-propenyl)-1H-indole-3-carboxylic acid;

1-(4-Hydroxy-phenyl)-2-((E)-propenyl)-1H-indole-3-carboxylic acid;

1-(4-Hydroxy-phenyl)-2-(2-methyl-prop-1-enyl)-1H-indole-3-carboxylic acid;

1-(4-Hydroxy-phenyl)-2-(2-methyl-allyl)-1H-indole-3-carboxylic acid;

1-(4-Hydroxy-phenyl)-2-((Z)-1-methyl-propenyl)-1H-indole-3-carboxylicacid;

1-(3-Fluoro-4-hydroxy-phenyl)-2-thiophen-3-yl-1H-indole-3-carboxylic acid;

1-(3-Fluoro-4-hydroxy-phenyl)-2-thiophen-2-yl-1H-indole-3-carboxylic acid;

1-(3-Fluoro-4-hydroxy-phenyl)-2-(1-methyl-1H-pyrrol-2-yl)-1H-indole-3-carboxylic acid;

1-(3-Fluoro-4-hydroxy-phenyl)-2-(3-methyl-thiophen-2-yl)-1H-indole-3-carboxylic acid;

2-Bromo-1-(4-hydroxy-phenyl)-1H-indole-3-carboxylic acid;

1-(4-Hydroxy-phenyl)-2-pyrrol-1-yl-1H-indole-3-carboxylic acid;

2,7-Dibromo-1-(2,5-difluoro-4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

2-Bromo-4-fluoro-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

4-Fluoro-1-(4-hydroxy-phenyl)-2-pyrrol-1-yl-1H-indole-3-carbonitrile;

4-Fluoro-1-(4-hydroxy-phenyl)-2-phenyl-1H-indole-3-carbonitrile;

2-(3,5-Dimethyl-isoxazol-4-yl)-4-fluoro-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

4-Fluoro-1-(4-hydroxy-phenyl)-2-(2-methyl-prop-1-enyl)-1H-indole-3-carbonitrile;

5-Fluoro-1-(4-hydroxy-phenyl)-2-phenyl-1H-indole-3-carbonitrile;

2-(3,5-Dimethyl-isoxazol-4-yl)-5-fluoro-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

5-Fluoro-1-(4-hydroxy-phenyl)-2-pyrrol-1-yl-1H-indole-3-carbonitrile;

5-Fluoro-1-(4-hydroxy-phenyl)-2-(2-methyl-prop-1-enyl)-1H-indole-3-carbonitrile;

(Z)-2-(3,5-dimethylisoxazol-4-yl)-5-fluoro-N′-hydroxy-1-(4-hydroxyphenyl)-1H-indole-3-carboximidamide;

(Z)-2-(3,5-dimethylisoxazol-4-yl)-4-fluoro-N′-hydroxy-1-(4-hydroxyphenyl)-1H-indole-3-carboximidamide;

(Z)-5-fluoro-N′-hydroxy-1-(4-hydroxyphenyl)-2-(2-methylprop-1-enyl)-1H-indole-3-carboximidamide;

4-Chloro-2-(3,5-dimethyl-isoxazol-4-yl)-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

2-(3,5-dimethylisoxazol-4-yl)-4,5-difluoro-1-(4-hydroxyphenyl)-1H-indole-3-carbonitrile;

2-(4-cyano-1-methyl-1H-pyrazol-5-yl)-4-fluoro-1-(4-hydroxyphenyl)-1H-indole-3-carbonitrile;

2-(3,5-dimethylisoxazol-4-yl)-5-fluoro-1-(4-hydroxyphenyl)-1H-indole-3-carboximidamide;

2-(3,5-dimethylisoxazol-4-yl)-5-fluoro-1-(4-hydroxyphenyl)-1H-indole-3-carboxamide;

2-Bromo-7-fluoro-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

2-(3,5-Dimethyl-isoxazol-4-yl)-7-fluoro-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

2-(3,5-Dimethyl-isoxazol-4-yl)-4,7-difluoro-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile;

(Z)-2-(3,5-dimethylisoxazol-4-yl)-4,7-difluoro-N′-hydroxy-1-(4-hydroxyphenyl)-1H-indole-3-carboximidamide;

1-(2,5-Difluoro-4-hydroxy-phenyl)-2-(3,5-dimethyl-isoxazol-4-yl)-1H-indole-3-carbonitrile;

1-(3-bromo-4-hydroxyphenyl)-2-(2-methylprop-1-enyl)-1H-indole-3-carboxamide;

(Z)-2-(3,5-dimethylisoxazol-4-yl)-1-(2-fluoro-4-hydroxyphenyl)-N′-hydroxy-1H-indole-3-carboximidamide;

(Z)-1-(2,5-difluoro-4-hydroxyphenyl)-2-(3,5-dimethylisoxazol-4-yl)-N′-hydroxy-1H-indole-3-carboximidamide;

(Z)-1-(3,5-difluoro-4-hydroxyphenyl)-2-(3,5-dimethylisoxazol-4-yl)-N′-hydroxy-1H-indole-3-carboximidamide;

(Z)-2-(3,5-dimethylisoxazol-4-yl)-1-(3-fluoro-4-hydroxyphenyl)-N′-hydroxy-1H-indole-3-carboximidamide;

(Z)-1-(3-chloro-4-hydroxyphenyl)-2-(3,5-dimethylisoxazol-4-yl)-N′-hydroxy-1H-indole-3-carboximidamide;

2-(3,5-dimethylisoxazol-4-yl)-1-(2-fluoro-4-hydroxyphenyl)-1H-indole-3-carboxamide;

(Z)-1-(2,3-difluoro-4-hydroxyphenyl)-2-(3,5-dimethylisoxazol-4-yl)-N′-hydroxy-1H-indole-3-carboximidamide;

1-(2,3-difluoro-4-hydroxyphenyl)-2-(3,5-dimethylisoxazol-4-yl)-1H-indole-3-carboxamide;

1-(2-fluoro-4-hydroxyphenyl)-2-(3-methylthiophen-2-yl)-1H-indole-3-carbonitrile;

2-(3,5-dimethyl-1H-pyrazol-4-yl)-1-(2-fluoro-4-hydroxyphenyl)-1H-indole-3-carbonitrile;

1-(2-fluoro-4-hydroxyphenyl)-2-(1-methyl-1H-pyrazol-5-yl)-1H-indole-3-carbonitrile;

1-(2-fluoro-4-hydroxyphenyl)-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-indole-3-carbonitrile;

1-(2-fluoro-4-hydroxyphenyl)-2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)-1H-indole-3-carbonitrile;

(Z)-1-(2-fluoro-4-hydroxyphenyl)-N′-hydroxy-2-(3-methylthiophen-2-yl)-1H-indole-3-carboximidamide;

(Z)-1-(2-fluoro-4-hydroxyphenyl)-N′-hydroxy-2-(1-methyl-1H-pyrazol-5-yl)-1H-indole-3-carboximidamide;

(Z)-1-(2-fluoro-4-hydroxyphenyl)-N′-hydroxy-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-indole-3-carboximidamide;

(Z)-4-fluoro-1-(2-fluoro-4-hydroxyphenyl)-N′-hydroxy-2-(1-methyl-1H-pyrazol-5-yl)-1H-indole-3-carboximidamide;

(Z)-4-fluoro-1-(2-fluoro-4-hydroxyphenyl)-N′-hydroxy-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-indole-3-carboximidamide;

(Z)-2-(3,5-dimethyl-1H-pyrazol-4-yl)-4-fluoro-1-(2-fluoro-4-hydroxyphenyl)-N′-hydroxy-1H-indole-3-carboximidamide;

(Z)-4-fluoro-1-(2-fluoro-4-hydroxyphenyl)-N′-hydroxy-2-(3-methylthiophen-2-yl)-1H-indole-3-carboximidamide;

(Z)-2-(3,5-dimethylisoxazol-4-yl)-4-fluoro-1-(2-fluoro-4-hydroxyphenyl)-N′-hydroxy-1H-indole-3-carboximidamide;

(Z)-1-(2-fluoro-4-hydroxyphenyl)-N′-hydroxy-2-(3-methylthiophen-2-yl)-1H-indole-3-carboximidamide;

(Z)-1-(2-fluoro-4-hydroxyphenyl)-N′-hydroxy-2-(1-methyl-1H-pyrazol-5-yl)-1H-indole-3-carboximidamide;

(Z)-1-(2-fluoro-4-hydroxyphenyl)-N′-hydroxy-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-indole-3-carboximidamide;

(Z)-2-(3,5-dimethyl-1H-pyrazol-4-yl)-1-(2-fluoro-4-hydroxyphenyl)-N′-hydroxy-1H-indole-3-carboximidamide;

methyl 2-(3,5-dimethylisoxazol-4-yl)-1-(2-fluoro-4-hydroxyphenyl)-1H-indole-3-carbimidate;

2-(3,5-dimethylisoxazol-4-yl)-1-(3-fluoro-4-hydroxyphenyl)-1H-indole-3-carboxamide;

1-(2,5-difluoro-4-hydroxyphenyl)-2-(3,5-dimethylisoxazol-4-yl)-1H-indole-3-carboximidamide;

2-(3,5-dimethylisoxazol-4-yl)-1-(3-fluoro-4-hydroxyphenyl)-1H-indole-3-carboximidamide;

(Z)-1-(3-fluoro-4-hydroxyphenyl)-N′-hydroxy-2-(1H-pyrrol-1-yl)-1H-indole-3-carboximidamide;

1-(3-fluoro-4-hydroxyphenyl)-2-(1H-pyrrol-1-yl)-1H-indole-3-carboxamide;

(Z)-1-(2,3-difluoro-4-hydroxyphenyl)-N′-hydroxy-2-(1H-pyrrol-1-yl)-1H-indole-3-carboximidamide;

1-(2,3-difluoro-4-hydroxyphenyl)-2-(1H-pyrrol-1-yl)-1H-indole-3-carboxamide;

(Z)-2-(2,5-dimethyl-1H-pyrrol-1-yl)-1-(3-fluoro-4-hydroxyphenyl)-N′-hydroxy-1H-indole-3-carboximidamide;

(Z)-1-(3-fluoro-4-hydroxyphenyl)-N′-hydroxy-2-(2-methyl-1H-pyrrol-1-yl)-1H-indole-3-carboximidamide;

1-(3,5-difluoro-4-hydroxyphenyl)-2-(3,5-dimethylisoxazol-4-yl)-1H-indole-3-carboxamide; and

(Z)-2-(3,5-dimethylisoxazol-4-yl)-6-fluoro-N′-hydroxy-1-(4-hydroxyphenyl)-1H-indole-3-carboximidamide.

19. A method for the treatment of a disease or disorder associated with estrogen receptor activity in a mammal, wherein said disease or disorder associated with estrogen receptor activity is selected from hot flashes, cardiovascular disease, impairment of cognitive functioning, age-related mild cognitive impairment, cerebral degenerative disorders, restenosis, obesity, anxiety, depression, hearing disorders, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, stroke, IBD, IBS, hypertension, lung cancer, colon cancer, breast cancer, prostate cancer and cholangiocarcinoma, which comprises administering to the mammal a therapeutically effective amount of a pharmaceutical composition which comprises a compound of formula (I) as defined in claim 1 , or a pharmaceutically acceptable ester, amide, carbamate, solvate or salt thereof, including a salt of such an ester, amide or carbamate, and a solvate of such an ester, amide, carbamate or salt, together with a pharmaceutically acceptable carrier.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 11, 2019
From: ARDENIA INVESTMENTS, LTD.
To: OASMIA PHARMACEUTICAL AB
Reel/Frame 050338/0853 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 12, 2017
From: KARO PHARMA AB
To: OASMIA PHARMACEUTICAL AB
Reel/Frame 043844/0275 →
CHANGE OF NAME Recorded Jun 27, 2017
From: KARO BIO AB
To: KARO PHARMA AB
Reel/Frame 043008/0358 →
Priority Claims (2)
GB 0806944.5 · Apr 16, 2008 · national
GB 0823367.8 · Dec 22, 2008 · national
Continuity (2)
Division 12736438
Related Publication 20130131061A1 · May 23, 2013