DK2276732T3 - Hidtil ukendte østrogenreceptorligander - Google Patents

Hidtil ukendte østrogenreceptorligander Download PDF

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Publication number
DK2276732T3
DK2276732T3 DK09731606.1T DK09731606T DK2276732T3 DK 2276732 T3 DK2276732 T3 DK 2276732T3 DK 09731606 T DK09731606 T DK 09731606T DK 2276732 T3 DK2276732 T3 DK 2276732T3
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Prior art keywords
indole
phenyl
hydroxy
carbonitrile
alkyl
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DK09731606.1T
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English (en)
Inventor
Patrik Rhönnstad
Elisabet Kallin
Theresa Apelqvist
Aiping Cheng
L Mattias Wennerstã
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Karobio Ab
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Priority claimed from GB0806944A external-priority patent/GB0806944D0/en
Priority claimed from GB0823367A external-priority patent/GB0823367D0/en
Application filed by Karobio Ab filed Critical Karobio Ab
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Publication of DK2276732T3 publication Critical patent/DK2276732T3/da

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    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
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Claims (17)

1. Forbindelse med formlen (I) eller en farmaceutisk acceptabel ester, amid, carbamat, solvat eller salt deraf, herunder et salt af en sådan ester, amid eller carbamat, og et solvat af en sådan ester, amid, carbamat eller salt,
(i) hvor R1 er valgt fra gruppen bestående af halogen, cyano, nitro, ORA, N(RB)2, -C(0)Ci_4alkyl, -S02Ci.4alkyl, Ci_6alkyl, C2.6alkenyl, C2.6alkynyl, haloCi_6alkyl, dihalo-Ci.6alkyl, trihaloCi.6alkyl, haloC2.6alkenyl, dihaloC2.6alkenyl, trihaloC2.6alkenyl, cyano-Ci_6alkyl, Ci.4alkoxyCi.6 alkyl, C3-8cycloalkyl, C3-8cycloalkylCi.6 alkyl, phenyl, benzyl og 5-1 O-leddet heterocyclyl, hvor phenyl-, benzyl- eller heterocyclylgruppen enten kan være usubstitueret eller substitueret med fra 1 til 3 substituenter, idet hver substituent er valgt fra gruppen bestående af ORA, halogen, cyano, nitro, -C(0)Ci_4alkyl, Ci_6alkyl, C2.6alkenyl, C2.6alkynyl, haloCi_6alkyl, dihaloCi_6alkyl og tri h a 10C1 _6a I kyl; R2 er valgt fra gruppen bestående af halogen, cyano, nitro, ORA, N(RB)2, N(OH)2, -C(0)Ci_4alkyl, som eventuelt er substitueret med fra 1 til 3 halogener, -S02C-|.4alkyl, -C(0)NH-0H, -C(NH2)=N-OH, -C(C02H)=N-0H, -C(NH2)=NH, -C(NH Ci_4alkyl)=NH, -C(0-Ci.4alkyl)=NH, -C(NH2)=N-NH2, -NH-C(NH2)=NH, -NH-C(0)NH2, -N=C(-NH-CH2CH2-NH-), -S-CN, -S-C(NH2)=NH, -S-C(NH2)=N-OH, -co2h, -ch2-co2h, -CH(0H)C02H, -C(0)C02H, SOsH, CH2S03H, Ci_6alkyl, haloCi.6alkyl, dihaloCi.6alkyl, trihaloCi.6alkyl, cyanoCi_6alkyl, Ci.4alkoxyCi.6 alkyl, C2.6alkenyl, C2.6alkynyl, C3.8cyclo-alkyl, C3.8cycloalkylCi.6alkyl, phenyl, benzyl og 5-1 O-leddet heterocyclyl, hvorphenyl-, benzyl- eller heterocyclylgruppen enten kan være usubstitueret eller substitueret med fra 1 til 3 substituenter, idet hver substituent er valgt fra gruppen bestående af ORA, halogen, cyano, nitro, Ci_6alkyl, C2.6alkenyl, C2.6alkynyl, haloCi_6alkyl, dihaloCi_6alkyl og trihaloCi_6alkyl; med det forbehold, at hvis én af R1 og R2 betegner halogen, skal den anden betegne en anden gruppe end halogen; hver af R3, R4, R5 og R6 er uafhængigt valgt fra gruppen bestående af hydrogen, ORA, halogen, cyano, nitro, C^alkyl, C2-6alkenyl, C2-6alkynyl, haloCi.6alkyl, dihaloC^alkyl og trihaloCi.6alkyl; hver Ra er uafhængigt valgt fra gruppen bestående af hydrogen, Ci_6alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C3-8cycloalkylCi.6alkyl, C6-ioaryl og C6-ioarylCi.6alkyl, hver eventuelt substitueret med fra 1 til 3 halogenatomer; og hver Rb er uafhængigt valgt fra gruppen bestående af hydrogen, Ci^alkyl, C2-6alkenyl, C2-6alkynyl, C3.8cycloalkyl, C3.8cycloalkylCi.6alkyl, C6-ioaryl og C6-ioarylCi-6alkyl, hver eventuelt substitueret med fra 1 til 3 halogenatomer; med det forbehold, at forbindelsen med formlen (I) ikke er 4-[3-(4,5-Dihydro-1 H-imida-zol-2-yl)-2-(3,5-dimethyl-isoxazol-4-yl)-indol-1-yl]-phenol; 1-(4-Hydroxy-phenyl)-2-(4-methyl-imidazol-1 -yl)-1 H-indol-3-carbonitril; 1 -(4-Hydroxy-phenyl )-2-(1 H-pyrazol-3-yl)-1 H-indol-3-carbonitril; 1-(3-Chlor-4-hydroxy-phenyl)-2-(1-methyl-1 H-pyrazol-4-yl)-1 H-indol-3-carbonitril; 1-(4-Hydroxy-phenyl)-2-prop-1-ynyl-1H-indol-3-carboxylsyreamid; eller 1 -(4-Hydroxy-phenyl )-2-thiazol-2-yl-1 H-indol-3-carboxylsyre.
2. Forbindelse ifølge krav 1, hvor hver RA uafhængigt er valgt fra gruppen bestående af hydrogen, Ci_4alkyl, C2-4alkenyl, C2-4alkynyl, C3.6cycloalkyl, phenyl og benzyl, fortrinsvis hydrogen og Ci.4alkyl.
3. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor hver RB uafhængigt er valgt fra gruppen bestående af hydrogen og Ci.4alkyl.
4. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor R1 er valgt fra gruppen bestående af ORA, N(RB)2, -C(0)Ci.4alkyl, Ci.6alkyl, C2-6alkenyl, C2-6alkynyl, haloCi^alkyl, dihaloCi.4alkyl, tri h a 10C1 _4a I kyl, haloC2-4alkenyl, dihaloC2-4alkenyl, trihalo-C2-4alkenyl, phenyl og 5-6-leddet heterocyclyl, hvor phenyl- eller heterocyclylgruppen enten kan være usubstitueret eller substitueret med 1 til 3 substituenter, der er valgt fra gruppen bestående af ORA, halogen, cyano, -C(0)Ci-4alkyl, Ci-4alkyl, C2-4alkenyl, C2-4alkynyl, haloCi_4alkyl, dihaloCi_4alkyl og trihaloCi_4alkyl, fortrinsvis ORA, N(RB)2, -C(0)Ci_4alkyl, Ci_4alkyl, C2-4alkenyl, C2-4alkynyl, phenyl og 5-6-leddet heterocyclyl, hvor phenyl- eller heterocyclylgruppen enten kan være usubstitueret eller substitueret med 1 til 3 substituenter, der er valgt blandt halogen, cyano, C^alkyl, -C(0)Ci^alkyl og ORA, hvor Ra betegner hydrogen eller Ci^alkyl.
5. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor R2 er valgt fra gruppen bestående af halogen, ORA, N(RB)2, -C(0)Ci^alkyl, som eventuelt er substitueret med fra 1 til 3 halogener, -C(NH2)=N-OH, -C02H, -CH2-C02H, Ci.6alkyl, C2.6alke-nyl, C2.6alkynyl, haloCi^alkyl, dihaloCi^alkyl, trihaloCi^alkyl, haloC^alkenyl, dihalo-C2-4alkenyl, trihaloC^alkenyl, phenyl og 5-6-leddet heterocyclyl, hvor phenyl- eller he-terocyclylgruppen enten kan være usubstitueret eller substitueret med 1 til 3 substituenter, der er valgt fra gruppen bestående af ORA, halogen, cyano, -C(0)Ci^alkyl, Ci^alkyl, C^alkenyl, C^alkynyl, haloCi^alkyl, dihaloCi^alkyl og trihaloC^alkyl, fortrinsvis -C(0)C^alkyl, -C(NH2)=N-OH, -C02H, -CH2-C02H, C^alkyl, C^alkenyl, C2_4alkynyl og 5-6-leddet heterocyclyl, hvor heterocyclylgruppen enten kan være usubstitueret eller substitueret med 1 til 3 substituenter, der er valgt blandt halogen, cyano, Ci^alkyl, -C(0)Ci^alkyl og ORA.
6. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor hver af R3, R4, R5 og R6 uafhængigt er valgt fra gruppen bestående af hydrogen, ORA, halogen, cyano, Ci^alkyl, haloCi.4alkyl, dihaloCi^alkyl og trihaloCi^alkyl, fortrinsvis hydrogen, OH, halogen, cyano, methyl og trifluormethyl.
7. Forbindelse ifølge krav 1, hvor R1 er valgt fra gruppen bestående af ORA, N(RB)2, -C(0)Ci-4alkyl, Ci^alkyl, C2.6alkenyl, C2.6alkynyl, haloC^alkyl, dihaloC^alkyl, trihalo-Ci.4alkyl, haloC2.4alkenyl, dihaloC2.4alkenyl, trihaloC^alkenyl, phenyl og 5-6-leddet heterocyclyl, hvor phenyl- eller heterocyclylgruppen enten kan være usubstitueret eller substitueret som ovenfor med 1 til 3 substituenter, der er valgt fra gruppen bestående af ORa, halogen, cyano, -C(0)Ci.4alkyl, Ci.4alkyl, C2.4alkenyl, C^alkynyl, haloCi^alkyl, dihaloCi.4alkyl og trihaloCi_4alkyl; R2 er valgt fra gruppen bestående af halogen, ORA, N(RB)2, -C(0)Ci^alkyl, som eventuelt er substitueret med fra 1 til 3 halogener, -C(NH2)=N-OH, -C02H, -CH2-C02H, Ci-6alkyl, C2.6alkenyl, C2-6alkynyl, haloCi.4alkyl, dihaloCi.4alkyl, trihaloCi^alkyl, halo-Ci_4alkenyl, dihaloCi_4alkenyl, trihaloCi.4alkenyl, phenyl og 5-6-leddet heterocyclyl, hvor phenyl- eller heterocyclylgruppen enten kan være usubstitueret eller substitueret med 1 til 3 substituenter, der er valgt fra gruppen bestående af ORA, halogen, cyano, -C(0)Ci.4alkyl, Ci.4alkyl, C2.4alkenyl, C2.4alkynyl, haloCi_4alkyl, dihaloCi.4alkyl og tri-haloCi_4alkyl; hver af R3, R4, R5 og R6 uafhængigt er valgt fra gruppen bestående af hydrogen, ORA, halogen, cyano, Ci.4alkyl, haloCi_4alkyl, dihaloCi_4alkyl og trihaloCi.4alkyl; hver Ra uafhængigt er valgt fra gruppen bestående af hydrogen, Ci.4alkyl, C2.4alkenyl, C2.4alkynyl, C3-6cycloalkyl, phenyl og benzyl; og hver Rb uafhængigt er valgt fra gruppen bestående af hydrogen og Ci_4alkyl.
8. Forbindelse ifølge krav 7, hvor R1 er valgt fra gruppen bestående af ORA, N(RB)2, -C(0)Ci_4alkyl, Ci_4alkyl, C2.4alkenyl, C2.4alkynyl, phenyl og 5-6-leddet heterocyclyl, hvor phenyl- eller heterocyclylgruppen enten kan være usubstitueret eller substitueret med 1 til 3 substituenter, der er valgt blandt halogen, cyano, Ci^alkyl, -C(0)Ci^alkyl og ORA; hver Ra uafhængigt betegner hydrogen eller Ci^alkyl; og hver Rb uafhængigt er valgt fra gruppen bestående af hydrogen og Ci^alkyl.
9. Forbindelse ifølge krav 7 eller krav 8, hvor R2 er valgt fra gruppen bestående af -C^OJC^alkyl, som eventuelt er substitueret med fra 1 til 3 halogener, -C(NH2)=N-OH, -C02H, -CH2-C02H, Ci^alkyl, C^alkenyl, C^alkynyl og 5-6-leddet heterocyclyl, hvor heterocyclylgruppen enten kan være usubstitueret eller substitueret med 1 til 3 substituenter, der er valgt fra gruppen bestående af halogen, cyano, -C(0)Ci^alkyl, Ci^alkyl, C^alkenyl, C^alkynyl, haloC^alkyl, dihaloC^alkyl og trihaloCi^alkyl og ORA, hvor RA betegner hydrogen eller Ci^alkyl, R2 er fortrinsvis valgt fra gruppen bestående af -C(0)CH3, -C(NH2)=N-OH, -C02H, -CH2-C02H, C^alkyl, C^alkenyl, C^alkynyl og 5-6-leddet heterocyclyl, hvor heterocyclylgruppen enten kan være usubstitueret eller substitueret med 1 til 3 substituenter, der er valgt blandt halogen, cyano, C^alkyl, -C(0)C1^alkyl og ORA, hvor RA betegner hydrogen eller C^alkyl.
10. Forbindelse ifølge et hvilket som helst af kravene 7 til 9, hvor hver af R3, R4, R5 og R6 uafhængigt er valgt fra gruppen bestående af hydrogen, OH, halogen, cyano, methyl eller trifluormethyl.
11. Forbindelse ifølge krav 1, hvor R1 er en 5-6-leddet heterocyclylgruppe, hvor hetero-cyclylgruppen er substitueret med fra 1 til 3 substituenter, der er valgt blandt halogen, cyano og Ci_4alkyl; R2 er valgt fra gruppen bestående af-C(0)CH3, -C(NH2)=N-OH, -C02H og -CH2-C02H; og hver af R3, R4, R5 og R6 uafhængigt er valgt fra gruppen bestående af hydrogen og halogen.
12. Forbindelse ifølge krav 11, hvor R1 er en 5-leddet heterocyclylgruppe, hvor hetero-cyclylgruppen er substitueret med to substituenter, der uafhængigt er valgt blandt methyl og ethyl; R2 er -C(NH2)=N-OH; og hver af R3, R4, R5 og R6 uafhængigt er valgt fra gruppen bestående af hydrogen og halogen.
13. Forbindelse ifølge krav 1, som er en hvilken som helst af følgende forbindelser:
2-Brom-1 -(4-hydroxy-phenyl)-1 H-indol-3-carbonitril; 1 -(4-Hydroxy-phenyl)-2-thiophen-3-yl-1 H-indol-3-carbonitril; 2-(3-Cyano-furan-2-yl)-1-(4-hydroxy-phenyl)-1H-indol-3-carbonitril; 1 -(4-Hydroxy-phenyl)-2-pyrrol-1 -yl-1 H-indol-3-carbonitril;
2-Dimethylamino-1 -(4-hydroxy-phenyl)-1 H-indol-3-carbonitril; 1 -(4-Hydroxy-phenyl)-2-isopropyl-1 H-indol-3-carbonitril;
2-Acetyl-1 -(4-hydroxy-phenyl)-1 H-indol-3-carbonitril; 2-(3,5-Dimethyl-isoxazol-4-yl)-1-(4-hydroxy-phenyl)-1 H-indol-3-carboxylsyre; 1-[1-(4-Hydroxy-phenyl)-2-phenyl-1H-indol-3-yl]-ethanon; 1-(4-Hydroxy-phenyl)-2-phenyl-1 H-indol-3-carboxylsyre, amid; (Z)-2-(3,5-dimethylisoxazol-4-yl)-N'-hydroxy-1-(4-hydroxyphenyl)-1 H-indol-3-carboximidamid; [2-(3,5-Dimethyl-isoxazol-4-yl)-1-(4-hydroxy-phenyl)-1 H-indol-3-yl]-carbamin-syre-tert-butylester; 4-[3-Am i n 0-2-(3,5-d i m ethyl-i soxazol-4-y I )-indol-1-yl]-phenol; (Z)-2-(3,5-dimethylisoxazol-4-yl)-7-fluor-N'-hydroxy-1-(4-hydroxyphenyl)-1H- indol-3-carboximidamid; (Z)-2-(5-chlorthiophen-2-yl)-N'-hydroxy-1-(4-hydroxyphenyl)-1H-indol-3- carboximidamid; 1- (2,3-Difluor-4-hydroxy-phenyl)-2-(3,5-dimethyl-isoxazol-4-yl )-1 H-indol-3-carbonitril; 2- (3,5-dimethylisoxazol-4-yl )-1 -(4-hydroxyphenyl)-1H-indol-3-carbohydrazon-amid; 4-(2-(3,5-dimethylisoxazol-4-yl )-3-(1,2,4-oxadiazol-3-yl)-1 H-indol-1 -yl)phenol; 2-(3,5-Dimethyl-isoxazol-4-yl)-1-(4-hydroxy-phenyl)-1H-indol-3-carboxylsyre, methylester; 2-(3,5-Dimethyl-isoxazol-4-yl)-1-(4-hydroxy-phenyl )-1 H-indol-3-carboxylsyre, hydroxyamid; 4-[2-(3,5-Dimethyl-isoxazol-4-yl)-3-methansulfonyl-indol-1-yl]-phenol; 1 -[2-(3,5-Dimethyl-isoxazol-4-yl)-1 -(4-hydroxy-phenyl)-1 H-indol-3-yl]-2,2,2-trifluor-ethanon; 4-(3-brom-2-(3,5-dimethylisoxazol-4-yl)-1 H-indol-1 -yl)phenol;
2-Brom-5-fluor-1-(4-hydroxy-phenyl)-1 H-indol-3 -carbonitril; (Z)-2-(4-fluorphenoxy)-N'-hydroxy-1-(4-hydroxyphenyl)-1H-indol-3- carboximidamid; 4-(2-(3,5-dimethylisoxazol-4-yl)-3-nitro-1 H-indol-1-yl)phenol; 4-(3-(dihydroxyamino)-2-(3,5-dimethylisoxazol-4-yl)-1 H-indol-1-yl)phenol; N-(2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1 H-indol-3-yl)acetamid; N-(2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1 H-indol-3-yl)methan-sulfonamid; 1 -(2-(3,5-dimethylisoxazol-4-yl)-1 -(4-hydroxyphenyl)-1 H-indol-3-yl)urea; 4-(2-(3,5-dimethylisoxazol-4-yl)-3-thiocyanato-1 H-indol-1-yl)phenol; (E)-2-(3,5-dimethylisoxazol-4-yl)-1 -(4-hydroxyphenyl)-1 H-indol-3-yl N'-hydroxycarbamimidothioat; 4-(3-benzyl-2-phenyl-1 H-indol-1 -yl)phenol; 2-(2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1 H-indol-3-yl)-2-oxo-acetamid; (Z)-2-(2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1 H-indol-3-yl)-2-(hydroxyimino)acetamid; 2-(2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1 H-indol-3-yl)-2-hydroxy-acetamid; 2-(2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1 H-indol-3-yl)acetamid; 2- ((Z)-But-1 -enyl)-1 -(4-hydroxy-phenyl)-1 H-indol-3-carbonitril; 1 -(4-Hydroxy-phenyl)-2-(2-methyl-prop-1 -enyl)-1 H-indol-3-carbonitril; 1-(2,3-Difluor-4-hydroxy-phenyl)-2-(2-methyl-allyl)-1 H-indol-3-carbonitril; (Z)-2-(5-ethyl-3-methylisoxazol-4-yl)-N'-hydroxy-1-(4-hydroxyphenyl)-1 H-indol- 3- carboximidamid; 4- (2-(3,5-dimethylisoxazol-4-yl)-3-phenyl-1 H-indol-1-yl)phenol; 4-(3-chlor-2-(3,5-dimethylisoxazol-4-yl)-1 H-indol-1-yl)phenol; 2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl )-1 H-indol-3-sulfonamid; 2-(3,5-dimethylisoxazol-4-yl)-1-(2-fluor-4-hydroxyphenyl)-1 H-indol-3-carboximidamid; 1 -(4-Hydroxy-phenyl)-2-phenyl-1 H-indol-3-carbonitril; 1 -(4-Hydroxy-phenyl)-2-methyl-1 H-indol-3-carbonitril; 2-(3-Cyano-thiophen-2-yl)-1-(4-hydroxy-phenyl)-1H-indol-3-carbonitril; 1 -(4-Hydroxy-phenyl)-2-((E)-propenyl)-1 H-indol-3-carbonitril; 1- (4-Hydroxy-phenyl)-2-thiophen-2-yl-1H-indol-3-carbonitril; 2- (3,5-Dimethyl-isoxazol-4-yl)-1-(4-hydroxy-phenyl)-1H-indol-3-carbonitril; 1 -(4-Hydroxy-phenyl)-2-pyridin-4-yl-1 H-indol-3-carbonitril; 1 -(4-Hydroxy-phenyl )-2-(1 -methyl-1 H-pyrrol-2-yl)-1 H-indol-3-carbonitril; 1- (4-Hydroxy-phenyl)-2-(3-methyl-thiophen-2-yl)-1H-indol-3-carbonitril; 1 -(4-Hydroxy-phenyl)-2-isopropylamino-1 H-indol-3-carbonitril;
2- Ethylamino-1 -(4-hydroxy-phenyl)-1 H-indol-3-carbonitril;
2-Butylamino-1 -(4-hydroxy-phenyl)-1 H-indol-3-carbonitril; 1 -(4-Hydroxy-phenyl)-2-piperidin-1 -yl-1 H-indol-3-carbonitril; 1 -(4-Hydroxy-phenyl)-2-pyrrolidin-1 -yl-1 H-indol-3-carbonitril; 1 -(4-Hydroxy-phenyl)-2-morpholin-4-yl-1 H-indol-3-carbonitril; 2-Diethylamino-1 -(4-hydroxy-phenyl)-1 H-indol-3-carbonitril;
2-Ethynyl-1 -(4-hydroxy-phenyl)-1 H-indol-3-carbonitril; 1 -(4-Hydroxy-phenyl)-2-vinyl-1 H-indol-3-carbonitril; 1-(4-Hydroxy-phenyl )-1 H-indol-2,3-dicarbon itril; 1-(4-Hydroxy-phenyl)-2-prop-1-ynyl-1H-indol-3-carbonitril; 1-(4-Hydroxy-phenyl)-2-pyridin-2-yl-1H-indol-3-carbonitril; 1-(4-Hydroxy-phenyl)-2-(2-methyl-allyl)-1H-indol-3-carbonitril; 1- (4-Hydroxy-phenyl)-2-((Z)-propenyl)-1H-indol-3-carbonitril; 2- (Butyl-methyl-amino)-1-(4-hydroxy-phenyl)-1H-indol-3-carbonitril; 1-(4-Hydroxy-phenyl)-2-((Z)-1-methyl-propenyl)-1H-indol-3-carbonitril; 1-(4-Hydroxy-phenyl)-2-imidazol-1-yl-1H-indol-3-carbonitril; 1- (4-Hydroxy-phenyl)-2-[1,2,4]triazol-1-yl-1H-indol-3-carbonitril; 2- (3,5-Dimethyl-pyrazol-1-yl)-1-(4-hydroxy-phenyl)-1H-indol-3-carbonitril; 1 -(4-Hydroxy-phenyl)-2-pyrazol-1 -yl-1 H-indol-3-carbonitril; 1-(4-Hydroxy-phenyl)-2-(5-methyl-imidazol-1-yl)-1H-indol-3-carbonitril; 1-(4-Hydroxy-phenyl)-2-(5-methyl-pyrazol-1-yl)-1H-indol-3-carbon itril; 1-(4-Hydroxy-phenyl)-2-(3-methyl-pyrazol-1-yl)-1H-indol-3-carbon itril; 1 -(4-Hydroxy-phenyl)-2-thiazol-2-yl-1 H-indol-3-carbon itril; 1-(4-Hydroxy-phenyl)-2-(2-methoxy-thiazol-4-yl)-1H-indol-3-carbon itril; 1 -(4-Hydroxy-phenyl)-2-thiazol-4-yl-1 H-indol-3-carbon itril; 1- (4-Hydroxy-phenyl)-2-(3-methyl-but-2-enyl)-1H-indol-3-carbonitril; 2- ((E)-But-1-enyl)-1-(4-hydroxy-phenyl)-1H-indol-3-carbonitril; 1-(4-Hydroxy-phenyl)-2-(5-methyl-thiophen-2-yl)-1H-indol-3-carbon itril; 2-(5-Acetyl-thiophen-2-yl)-1-(4-hydroxy-phenyl)-1H-indol-3-carbonitril; 1 -(4-Hydroxy-phenyl)-2-(1 -methyl-1 H-pyrazol-4-yl)-1 H-indol-3-carbonitril; 2-(5-Chlor-thiophen-2-yl)-1-(4-hydroxy-phenyl)-1H-indol-3-carbonitril; 1-(4-Hydroxy-phenyl)-2-(4-methyl-thiophen-3-yl)-1H-indol-3-carbonitril; 1- (4-Hydroxy-phenyl)-2-(4-methyl-thiophen-2-yl)-1 H-indol-3-carbonitril; 2- (4-Cyano-thiophen-3-yl)-1-(4-hydroxy-phenyl)-1H-indol-3-carbonitril; 1-(4-Hydroxy-phenyl)-2-(2-methyl-2H-pyrazol-3-yl)-1H-indol-3-carbonitril; 1- (4-Hydroxy-phenyl )-2-(1,3,5-trimethyl-1 H-pyrazol-4-yl)-1 H-indol-3-carbonitril; 2- (2-Acetyl-pyrrol-1 -yl)-1 -(4-hydroxy-phenyl)-1 H-indol-3-carbonitril; 2-(2-Ethyl-pyrrol-1-yl)-1-(4-hydroxy-phenyl)-1H-indol-3-carbonitril; 2-(2-Cyano-pyrrol-1-yl)-1-(4-hydroxy-phenyl)-1H-indol-3-carbonitril; 1 -(4-Hydroxy-phenyl)-2-(2-methyl-pyrrol-1 -yl)-1 H-indol-3-carbonitril; 1-(3-Chlor-5-fluor-4-hydroxy-phenyl)-2-phenyl-1H-indol-3-carbonitril; 1-(3-Chlor-5-fluor-4-hydroxy-phenyl)-2-(3-cyano-thiophen-2-yl)-1H-indol-3- carbonitril; 1- (3-Chlor-5-fluor-4-hydroxy-phenyl)-2-(3-cyano-furan-2-yl)-1H-indol-3-carbonitril;
2- Brom-1-(3-chlor-5-fluor-4-hydroxy-phenyl)-1H-indol-3-carbonitril;
2-Brom-1 -(2-fluor-4-hydroxy-phenyl)-1 H-indol-3-carbonitril; 1 -(2-Fluor-4-hydroxy-phenyl)-2-phenyl-1 H-indol-3-carbonitril;
2-Brom-1 -(3-fluor-4-hydroxy-phenyl)-1 H-indol-3-carbonitril;
2-Brom-1-(2,3-d ifluor-4-hydroxy-phenyl)-1 H-indol-3-carbonitril;
2-Brom-1-(2,5-difluor-4-hydroxy-phenyl)-1 H-indol-3-carbonitril;
2-Brom-1 -(3-chlor-4-hydroxy-phenyl)-1 H-indol-3-carbonitril;
2-Brom-1-(3,5-difluor-4-hydroxy-phenyl)-1 H-indol-3-carbonitril; 1 -(3-Fluor-4-hydroxy-phenyl)-2-phenyl-1 H-indol-3-carbonitril; 1-(3,5-Difluor-4-hydroxy-phenyl)-2-phenyl-1 H-indol-3-carbonitril; 1 -(3-Chlor-4-hydroxy-phenyl)-2-phenyl-1 H-indol-3-carbonitril; 1-(2,3-Difluor-4-hydroxy-phenyl)-2-phenyl-1 H-indol-3-carbonitril; 1-(2,5-Difluor-4-hydroxy-phenyl)-2-phenyl-1 H-indol-3-carbonitril; 1-(3,5-Difluor-4-hydroxy-phenyl)-2-thiophen-3-yl-1H-indol-3-carbonitril; 1-(3,5-Difluor-4-hydroxy-phenyl)-2-thiophen-2-yl-1H-indol-3-carbonitril; 1-(3,5-Difluor-4-hydroxy-phenyl)-2-(3,5-dimethyl-isoxazol-4-yl)-1 H-indol-3-carbonitril; 1 -(3,5-Difluor-4-hydroxy-phenyl)-2-(1 -methyl-1 H-pyrrol-2-yl)-1 H-indol-3-carbonitril; 1-(3,5-Difluor-4-hydroxy-phenyl)-2-(3-methyl-thiophen-2-yl)-1 H-indol-3-carbonitril; 1 -(3,5-Difluor-4-hydroxy-phenyl)-2-(1 -methyl-1 H-pyrazol-4-yl)-1 H-indol-3-carbonitril; 1-(3,5-Difluor-4-hydroxy-phenyl)-2-pyridin-4-yl-1 H-indol-3-carbonitril; 1-(3-Chlor-4-hydroxy-phenyl)-2-thiophen-3-yl-1 H-indol-3-carbonitril; 1-(3-Chlor-4-hydroxy-phenyl)-2-thiophen-2-yl-1 H-indol-3-carbonitril; 1-(3-Chlor-4-hydroxy-phenyl)-2-(3,5-dimethyl-isoxazol-4-yl)-1H-indol-3-carbo- nitril; 1-(3-Chlor-4-hydroxy-phenyl)-2-(1-methyl-1H-pyrrol-2-yl)-1H-indol-3-carbonitril; 1-(3-Chlor-4-hydroxy-phenyl)-2-(3-methyl-thiophen-2-yl)-1H-indol-3-carbonitril; 1-(3-Chlor-4-hydroxy-phenyl)-2-pyridin-4-yl-1H-indol-3-carbonitril; 1-(3-Fluor-4-hydroxy-phenyl)-2-thiophen-3-yl-1H-indol-3-carbonitril; 1- (3-Fluor-4-hydroxy-phenyl)-2-thiophen-2-yl-1H-indol-3-carbonitril; 2- (3,5-Dimethyl-isoxazol-4-yl)-1-(3-fluor-4-hydroxy-phenyl)-1 H-indol-3-carbo-nitril; 1 -(3-Fluor-4-hydroxy-phenyl)-2-(1 -methyl-1 H-pyrrol-2-yl)-1 H-indol-3-carbonitril; 1-(3-Fluor-4-hydroxy-phenyl)-2-(3-methyl-thiophen-2-yl)-1 H-indol-3-carbonitril; 1 -(3-Fluor-4-hydroxy-phenyl)-2-(1 -methyl-1 H-pyrazol-4-yl)-1 H-indol-3-carbo-nitril; 1- (3-Fluor-4-hydroxy-phenyl)-2-pyridin-4-yl-1H-indol-3-carbonitril;
2- Dimethylamino-1-(2-fluor-4-hydroxy-phenyl)-1H-indol-3-carbonitril; 2-(3,5-Dimethyl-isoxazol-4-yl)-1-(2-fluor-4-hydroxy-phenyl)-1H-indol-3-carbo- nitril; 1-(3-Fluor-4-hydroxy-phenyl)-2-((E)-propenyl)-1H-indol-3-carbonitril; 1-(3-Fluor-4-hydroxy-phenyl)-2-((Z)-propenyl)-1H-indol-3-carbonitril; 1-(2,3-Difluor-4-hydroxy-phenyl)-2-((Z)-propenyl)-1H-indol-3-carbonitril; 1-(2,3-Difluor-4-hydroxy-phenyl)-2-vinyl-1 H-indol-3-carbonitril; 1-(2,3-Difluor-4-hydroxy-phenyl)-2-thiophen-3-yl-1H-indol-3-carbonitril; 1-(2,3-Difluor-4-hydroxy-phenyl)-2-thiophen-2-yl-1 H-indol-3-carbonitril; 1- (2,3-Difluor-4-hydroxy-phenyl)-2-(3-methyl-thiophen-2-yl)-1H-indol-3-carbo-nitril; 1 -(2,3-Difluor-4-hydroxy-phenyl)-2-(1 -methyl-1 H-pyrrol-2-yl)-1 H-indol-3-carbo-nitril; 2- (2-Acetyl-pyrrol-1 -yl)-1 -(3-fluor-4-hydroxy-phenyl)-1 H-indol-3-carbonitril; 1 -(3-Fluor-4-hydroxy-phenyl)-2-pyrrol-1 -yl-1 H-indol-3-carbonitril; 1 -(2,3-Difluor-4-hydroxy-phenyl)-2-pyrrol-1 -yl-1 H-indol-3-carbonitril; 1- (2,3-Difluor-4-hydroxy-phenyl)-2-prop-1-ynyl-1H-indol-3-carbonitril; 1 -(3-Fluor-4-hydroxy-phenyl)-2-(2-methyl-prop-1 -enyl)-1 H-indol-3-carbonitril; 1 -(2,3-Difluor-4-hydroxy-phenyl)-2-(2-methyl-prop-1 -enyl)-1 H-indol-3-carbonitril; 2- (2-Acetyl-pyrrol-1 -yl)-1 -(2,3-difluor-4-hydroxy-phenyl)-1 H-indol-3-carbonitril; 1 -(3-Fluor-4-hydroxy-phenyl)-2-pyrazol-1 -yl-1 H-indol-3-carbonitril; 1 -(2,3-Difluor-4-hydroxy-phenyl)-2-pyrazol-1 -yl-1 H-indol-3-carbonitril; 2-(2,5-Dimethyl-pyrrol-1 -yl)-1 -(3-fluor-4-hydroxy-phenyl)-1 H-indol-3-carbonitril; 2-(2-Ethyl-pyrrol-1-yl)-1-(3-fluor-4-hydroxy-phenyl)-1H-indol-3-carbonitril; 2-(2-Cyano-pyrrol-1 -yl)-1 -(3-fluor-4-hydroxy-phenyl)-1 H-indol-3-carbonitril; 1 -(3-Fluor-4-hydroxy-phenyl)-2-(2-methyl-pyrrol-1 -yl)-1 H-indol-3-carbonitril; 1- (2,3-Difluor-4-hydroxy-phenyl)-2-(2-ethyl-pyrrol-1-yl)-1H-indol-3-carbonitril; 2- (2-Cyano-pyrrol-1-yl)-1-(2,3-difluor-4-hydroxy-phenyl)-1H-indol-3-carbonitril; 1 -(2,3-Difluor-4-hydroxy-phenyl)-2-(2-methyl-pyrrol-1 -yl)-1 H-indol-3-carbonitril; 1 -(2-Fluor-4-hydroxy-phenyl)-2-pyrrol-1 -yl-1 H-indol-3-carbonitril; 1- (2,3-difluor-4-hydroxyphenyl)-2-(3-methylbut-2-enyl)-1 H-indol-3-carbonitril; [1 -(4-Hydroxy-phenyl)-2-phenyl-1 H-indol-3-yl]-acetonitril; [1 -(4-Hydroxy-phenyl)-2-phenyl-1 H-indol-3-yl]-eddikesyre; 2- [1 -(4-Hydroxy-phenyl)-2-phenyl-1 H-indol-3-yl]-acetamid; 4-(3-lsopropenyl-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)-1 H-indol-3-carboxylsyre, amid; 1-(4-Hydroxy-phenyl)-2-(2-methyl-prop-1-enyl)-1 H-indol-3-carboxylsyre, amid; 1- (4-Hydroxy-phenyl)-2-((Z)-1-methyl-propenyl)-1H-indol-3-carboxylsyre, amid; 4-(2-Phenyl-3-pyrazol-1-yl-indol-1-yl)-phenol; 4-(3-lmidazol-1 -yl-2-phenyl-indol-1 -yl)-phenol; 4-[3-(5-Methyl-pyrazol-1 -yl)-2-phenyl-indol-1 -yl]-phenol;
2- Brom-1-(4-hydroxy-phenyl)-1 H-indol-3-carboxylsyre, amid; 1-(4-Hydroxy-phenyl)-2-((Z)-3,3,3-trifluor-propenyl)-1 H-indol-3-carbonitril; (Z)-2-brom-N'-hydroxy-1-(4-hydroxyphenyl)-1 H-indol-3-carboximidamid; (Z)-N'-hydroxy-1-(4-hydroxyphenyl)-2-(1H-pyrrol-1-yl)-1 H-indol-3-carboximid-amid; 2-(3,5-Dimethyl-isoxazol-4-yl)-1-(4-hydroxy-phenyl)-1H-indol-3-carboxylsyre, amid; (Z)-N'-hydroxy-l -(4-hydroxyphenyl)-2-(2-methylprop-1 -enyl)-1 H-indol-3-carboximidamid; 1-(4-Hydroxy-phenyl)-2-phenyl-H-indol-3 -carboxylsyre; hydroxyamid; (Z)-N'-hydroxy-1-(4-hydroxyphenyl)-2-phenyl-1H-indol-3-carboximidamid; 1- (4-Hydroxy-phenyl)-2-pyrrol-1-yl-1 H-indol-3-carboxylsyre, amid; [1 -(4-Hydroxy-phenyl)-2-pyrrol-1 -yl-1 H-indol-3-yl]-carbaminsyre-tert-butylester; 2- (3,5-Dimethyl-isoxazol-4-yl)-1-(4-hydroxy-phenyl)-N-methyl-1 H-indol-3-carboxamidin; Methyl 2-(3,5-dimethylisoxazol-4-yl)-1 -(4-hydroxyphenyl)-1 H-indol-3-carbimidat; N-((2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1H-indol-3-yl)(imino)- methyl)acetamid; 2-(5-ethyl-3-methylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1H-indol-3-carboxamid; (Z)-2-(2-ethyl-1 H-pyrrol-1 -yl)-N'-hydroxy-1 -(4-hydroxyphenyl)-1 H-indol-3-carboximidamid; (Z)-N'-hydroxy-l -(4-hydroxyphenyl)-2-(2-methyl-1 H-pyrrol-1 -yl)-1 H-indol-3-carboximidamid; 1 -(4-hydroxyphenyl)-2-(2-methyl-1 H-pyrrol-1 -yl)-1 H-indol-3-carboxamid; 4-(3-chlor-2-(3,5-dimethylisoxazol-4-yl)-1 H-indol-1-yl)phenol; (Z)-2-((Z)-but-2-en-2-yl)-N'-hydroxy-1-(4-hydroxyphenyl)-1 H-indol-3-carboximidamid; (Z)-N'-hydroxy-l -(4-hydroxyphenyl)-2-(5-methyl-1 H-pyrazol-1 -yl)-1 H-indol-3-carboximidamid; (Z)-N'-hydroxy-1-(4-hydroxyphenyl)-2-(4-methylthiophen-3-yl)-1 H-indol-3-carboximidamid; (Z)-2-(2,5-dimethyl-1 H-pyrrol-1 -yl)-N'-hydroxy-1 -(4-hydroxyphenyl)-1 H-indol-3-carboximidamid; (Z)-N'-hydroxy-1-(4-hydroxyphenyl)-2-phenoxy-1H-indol-3-carboximidamid; 1- (4-Hydroxy-phenyl)-2-phenyl-1H-indol-3-carboxylsyre; 2- (3,5-Dimethyl-isoxazol-4-yl)-1-(3-fluor-4-hydroxy-phenyl)-1H-indol-3-carboxyl-syre; 2-(3,5-Dimethyl-isoxazol-4-yl)-1-(2-fluor-4-hydroxy-phenyl)-1H-indol-3- carboxylsyre; 1-(2,3-Difluor-4-hydroxy-phenyl)-2-(3,5-dimethyl-isoxazol-4-yl)-1H-indol-3- carboxylsyre; 1-(4-Hydroxy-phenyl)-2-((Z)-propenyl)-1H-indol-3-carboxylsyre; 1-(4-Hydroxy-phenyl)-2-((E)-propenyl)-1 H-indol-3-carboxylsyre; 1 -(4-Hydroxy-phenyl)-2-(2-methyl-prop-1 -enyl)-1 H-indol-3-carboxylsyre; 1-(4-Hydroxy-phenyl)-2-(2-methyl-allyl)-1 H-indol-3-carboxylsyre; 1 -(4-Hydroxy-phenyl)-2-((Z)-1 -methyl-propenyl)-1 H-indol-3-carboxylsyre; 1-(3-Fluor-4-hydroxy-phenyl)-2-thiophen-3-yl-1 H-indol-3-carboxylsyre; 1-(3-Fluor-4-hydroxy-phenyl)-2-thiophen-2-yl-1 H-indol-3-carboxylsyre; 1 -(3-Fluor-4-hydroxy-phenyl)-2-(1 -methyl-1 H-pyrrol-2-yl)-1 H-indol-3-carboxyl-syre; 1-(3-Fluor-4-hydroxy-phenyl)-2-(3-methyl-thiophen-2-yl)-1 H-indol-3-carboxyl-syre;
2-Brom-1 -(4-hydroxy-phenyl)-1 H-indol-3-carboxylsyre; 1 -(4-Hydroxy-phenyl)-2-pyrrol-1 -yl-1 H-indol-3-carboxylsyre; 2,7-Dibrom-1-(2,5-difluor-4-hydroxy-phenyl)-1 H-indol-3-carbonitril;
2-Brom-4-fluor-1 -(4-hydroxy-phenyl)-1 H-indol-3-carbonitril;
4-Fluor-1 -(4-hydroxy-phenyl)-2-pyrrol-1 -yl-1 H-indol-3-carbonitril;
4-Fluor-1 -(4-hydroxy-phenyl)-2-phenyl-1 H-indol-3-carbonitril; 2-(3,5-Dimethyl-isoxazol-4-yl)-4-fluor-1-(4-hydroxy-phenyl)-1 H-indol-3-carbonitril;
4- Fluor-1 -(4-hydroxy-phenyl)-2-(2-methyl-prop-1 -enyl)-1 H-indol-3-carbonitril;
5- Fluor-1 -(4-hydroxy-phenyl)-2-phenyl-1 H-indol-3-carbonitril; 2-(3,5-Dimethyl-isoxazol-4-yl)-5-fluor-1-(4-hydroxy-phenyl)-1 H-indol-3-carbo-nitril;
5-Fluor-1 -(4-hydroxy-phenyl)-2-pyrrol-1 -yl-1 H-indol-3-carbonitril;
5-Fluor-1 -(4-hydroxy-phenyl)-2-(2-methyl-prop-1 -enyl)-1 H-indol-3-carbonitril; (Z)-2-(3,5-dimethylisoxazol-4-yl)-5-fluor-N'-hydroxy-1-(4-hydroxyphenyl)-1 H-indol-3-carboximidamid; (Z)-2-(3,5-dimethylisoxazol-4-yl)-4-fluor-N'-hydroxy-1-(4-hydroxyphenyl)-1 H-indol-3-carboximidamid; (Z)-5-fluor-N'-hydroxy-1 -(4-hydroxyphenyl)-2-(2-methylprop-1 -enyl)-1 H-indol-3-carboximidamid;
4-Chlor-2-(3,5-dimethyl-isoxazol-4-yl)-1-(4-hydroxy-phenyl)-1 H-indol-3-carbo-nitril; 2-(3,5-dimethylisoxazol-4-yl)-4,5-difluor-1-(4-hydroxyphenyl)-1 H-indol-3-carbo-nitril; 2-(4-cyano-1 -methyl-1 H-pyrazol-5-yl)-4-fluor-1 -(4-hydroxyphenyl)-1 H-indol-3-carbonitril; 2-(3,5-dimethylisoxazol-4-yl)-5-fluor-1-(4-hydroxyphenyl)-1 H-indol-3-carboximidamid; 2-(3,5-dimethylisoxazol-4-yl)-5-fluor-1-(4-hydroxyphenyl)-1 H-indol-3-carboxamid;
2-Brom-7-fluor-1 -(4-hydroxy-phenyl)-1 H-indol-3-carbonitril; 2-(3,5-Dimethyl-isoxazol-4-yl)-7-fluor-1-(4-hydroxy-phenyl)-1 H-indol-3-carbo-nitril; 2-(3,5-Dimethyl-isoxazol-4-yl)-4,7-difluor-1-(4-hydroxy-phenyl)-1 H-indol-3-carbonitril; (Z)-2-(3,5-dimethylisoxazol-4-yl)-4,7-difluor-N'-hydroxy-1-(4-hydroxyphenyl)-1 H-indol-3-carboximidamid; 1-(2,5-Difluor-4-hydroxy-phenyl)-2-(3,5-dimethyl-isoxazol-4-yl)-1 H-indol-3-carbonitril; 1-(3-brom-4-hydroxyphenyl)-2-(2-methylprop-1-enyl)-1 H-indol-3-carboxamid; (Z)-2-(3,5-dimethylisoxazol-4-yl)-1-(2-fluor-4-hydroxyphenyl)-N'-hydroxy-1 H-indol-3-carboximidamid; (Z)-1-(2,5-difluor-4-hydroxyphenyl)-2-(3,5-dimethylisoxazol-4-yl)-N'-hydroxy-1 H-indol-3-carboximidamid; (Z)-1-(3,5-difluor-4-hydroxyphenyl)-2-(3,5-dimethylisoxazol-4-yl)-N'-hydroxy-1 H-indol-3-carboximidamid; (Z)-2-(3,5-dimethylisoxazol-4-yl)-1-(3-fluor-4-hydroxyphenyl)-N'-hydroxy-1 H-indol-3-carboximidamid; (Z)-1-(3-chlor-4-hydroxyphenyl)-2-(3,5-dimethylisoxazol-4-yl)-N'-hydroxy-1H- indol-3-carboximidamid; 2-(3,5-dimethylisoxazol-4-yl)-1 -(2-fluor-4-hydroxyphenyl)-1 H-indol-3-carboxamid; (Z)-1-(2,3-difluor-4-hydroxyphenyl)-2-(3,5-dimethylisoxazol-4-yl)-N'-hydroxy-1 H-indol-3-carboximidamid; 1-(2,3-difluor-4-hydroxyphenyl)-2-(3,5-dimethylisoxazol-4-yl)-1 H-indol-3-carboxamid; 1- (2-fluor-4-hydroxyphenyl)-2-(3-methylthiophen-2-yl)-1 H-indol-3-carbonitril; 2- (3,5-dimethyl-1 H-pyrazol-4-yl)-1 -(2-fluor-4-hydroxyphenyl)-1 H-indol-3-carbo-nitril; 1 -(2-fluor-4-hydroxyphenyl)-2-(1 -methyl-1 H-pyrazol-5-yl)-1 H-indol-3-carbonitril; 1 -(2-fluor-4-hydroxyphenyl)-2-(1,3,5-trimethyl-1 H-pyrazol-4-yl)-1 H-indol-3- carbonitril; 1 -(2-fluor-4-hydroxyphenyl)-2-(3-(trifluormethyl)-1 H-pyrazol-4-yl)-1 H-indol-3-carbonitril; (Z)-1-(2-fluor-4-hydroxyphenyl)-N'-hydroxy-2-(3-methylthiophen-2-yl)-1H-indol- 3- carboximidamid; (Z)-1 -(2-fluor-4-hydroxyphenyl)-N'-hydroxy-2-(1 -methyl-1 H-pyrazol-5-yl)-1 H-indol-3-carboximidamid; (Z)-1 -(2-fluor-4-hydroxyphenyl)-N'-hydroxy-2-(1,3,5-trimethyl-1 H-pyrazol-4-yl)-1 H-indol-3-carboximidamid; (Z)-4-fluor-1 -(2-fluor-4-hydroxyphenyl)-N'-hydroxy-2-(1 -methyl-1 H-pyrazol-5-yl)-1 H-indol-3-carboximidamid; (Z)-4-fluor-1 -(2-fluor-4-hydroxyphenyl)-N'-hydroxy-2-(1,3,5-trimethyl-1 H-pyrazol- 4- yl)-1H-indol-3-carboximidamid; (Z)-2-(3,5-dimethyl-1 H-pyrazol-4-yl)-4-fluor-1-(2-fluor-4-hydroxyphenyl)-N'-hydroxy-1 H-indol-3-carboximidamid; (Z)-4-fluor-1-(2-fluor-4-hydroxyphenyl)-N'-hydroxy-2-(3-methylthiophen-2-yl)-1 H-indol-3-carboximidamid; (Z)-2-(3,5-dimethylisoxazol-4-yl)-4-fluor-1-(2-fluor-4-hydroxyphenyl)-N'-hydroxy-1 H-indol-3-carboximidamid; (Z)-1-(2-fluor-4-hydroxyphenyl)-N'-hydroxy-2-(3-methylthiophen-2-yl)-1 H-indol- 3-carboximidamid; (Z)-1 -(2-fluor-4-hydroxyphenyl)-N'-hydroxy-2-(1 -methyl-1 H-pyrazol-5-yl)-1 H-indol-3-carboximidamid; (Z)-1 -(2-fluor-4-hydroxyphenyl)-N'-hydroxy-2-(1,3,5-trimethyl-1 H-pyrazol-4-yl)-1 H-indol-3-carboximidamid; (Z)-2-(3,5-dimethyl-1 H-pyrazol-4-yl)-1 -(2-fluor-4-hydroxyphenyl)-N'-hydroxy-1 H-indol-3-carboximidamid; methyl 2-(3,5-dimethylisoxazol-4-yl)-1 -(2-fluor-4-hydroxyphenyl)-1 H-indol-3-carbimidat; 2-(3,5-dimethylisoxazol-4-yl)-1-(3-fluor-4-hydroxyphenyl)-1 H-indol-3-carboxamid; 1- (2,5-difluor-4-hydroxyphenyl)-2-(3,5-dimethylisoxazol-4-yl)-1 H-indol-3-carboximidamid; 2- (3,5-dimethylisoxazol-4-yl)-1-(3-fluor-4-hydroxyphenyl)-1 H-indol-3-carboximidamid; (Z)-1 -(3-fluor-4-hydroxyphenyl)-N'-hydroxy-2-(1 H-pyrrol-1 -yl)-1 H-indol-3-carboximidamid; 1 -(3-fluor-4-hydroxyphenyl)-2-(1 H-pyrrol-1 -yl)-1 H-indol-3-carboxamid; (Z)-1-(2,3-d ifluor-4-hydroxyphenyl)-N'-hydroxy-2-(1 H-pyrrol-1-yl )-1 H-indol-3- carboximidamid; 1-(2,3-difluor-4-hydroxyphenyl)-2-(1H-pyrrol-1-yl)-1H-indol-3-carboxamid; (Z)-2-(2,5-dimethyl-1 H-pyrrol-1 -yl)-1 -(3-fluor-4-hydroxyphenyl)-N'-hydroxy-1 H-indol-3-carboximidamid; (Z)-1-(3-fluor-4-hydroxyphenyl)-N'-hydroxy-2-(2-methyl-1 H-pyrrol-1 -yl)-1 H-indol- 3- carboximidamid; 1- (3,5-difluor-4-hydroxyphenyl)-2-(3,5-dimethylisoxazol-4-yl)-1H-indol-3-carboxamid; og (Z)-2-(3,5-dimethylisoxazol-4-yl)-6-fluor-N'-hydroxy-1-(4-hydroxyphenyl)-1H- indol-3-carboximidamid; eller en farmaceutisk acceptabel ester, amid, carbamat, solvat eller salt deraf, herunder et salt af en sådan ester, amid eller carbamat, og et solvat af en sådan ester, amid, carbamat eller salt deraf.
14. Forbindelse ifølge krav 1, som er en hvilken som helst af følgende forbindelser: (Z)-2-(3,5-dimethylisoxazol-4-yl)-N'-hydroxy-1-(4-hydroxyphenyl)-1H-indol-3- carboximidamid; 2- (lsobut-1 -enyl)-1 -(4-hydroxyphenyl)-1 H-indol-3-carbonitril; 4- (2-(3,5-dimethylisoxazol-4-yl)-3-phenyl-1H-indol-1-yl)phenol; 1 -(4-Hydroxy-phenyl)-2-((Z)-propenyl)-1 H-indol-3-carbonitril; 4-(3-lsopropenyl-2-phenyl-indol-1-yl)-phenol; (Z)-N'-hydroxy-l -(4-hydroxyphenyl)-2-(2-methyl-1 H-pyrrol-1 -yl)-1 H-indol-3-carboximidamid; (Z)-2-((Z)-but-2-en-2-yl)-N'-hydroxy-1-(4-hydroxyphenyl)-1 H-indol-3-carboximidamid; (Z)-2-(2,5-dimethyl-1 H-pyrrol-1 -yl)-N'-hydroxy-1 -(4-hydroxyphenyl)-1 H-indol-3-carboximidamid;
5-Fluor-1 -(4-hydroxy-phenyl)-2-(2-methyl-prop-1 -enyl)-1 H-indol-3-carbonitril; (Z)-2-(3,5-dimethylisoxazol-4-yl)-5-fluor-N'-hydroxy-1-(4-hydroxyphenyl)-1H- indol-3-carboximidamid; (Z)-5-fluor-N'-hydroxy-1 -(4-hydroxyphenyl)-2-(2-methylprop-1 -enyl)-1 H-indol-3-carboximidamid; (Z)-2-(3,5-dimethylisoxazol-4-yl)-1-(2-fluor-4-hydroxyphenyl)-N'-hydroxy-1H- indol-3-carboximidamid; eller en farmaceutisk acceptabel ester, amid, carbamat, solvat eller salt deraf, herunder et salt af en sådan ester, amid eller carbamat, og et solvat af en sådan ester, amid, carbamat eller salt deraf.
15. Farmaceutisk præparat, som omfatter en forbindelse ifølge et hvilket som helst af kravene 1 til 14 sammen med en farmaceutisk acceptabel bærer og eventuelt i kombination med ét eller flere yderligere terapeutiske midler.
16. Forbindelse ifølge et hvilket som helst af kravene 1 til 14 til anvendelse som lægemiddel.
17. Forbindelse ifølge krav 16 til anvendelse til behandling eller profylakse af en tilstand, som er valgt blandt knogletab, knoglefrakturer, osteoporose, bruskdegenerering, endometriose, uterin fibroid sygdom, hedeture, forøgede niveauer af LDL-cholesterol, kardiovaskulær sygdom, svækkelse af kognitive funktioner, aldersrelateret mild kognitiv svækkelse, cerebrale degenerative lidelser, restenose, gynækomasti, vaskulærglat muskelcelle-proliferation, obesitet, inkontinens, angst, depression, perimenopausal depression, fødselsdepression, præmenstruelt syndrom, manisk depression, demens, obsessiv kompulsiv adfærd, opmærksomhedsforstyrrelse, hyperaktivitetslidelse ved opmærksomhedsforstyrrelse, søvnlidelser, irritabilitet, impulsivitet, vredeshåndtering, hørelidelser, multipel sklerose, Parkinsons sygdom, Alzheimers sygdom, Huntingtons sygdom, amyotrofisk lateral sklerose, rygmarvsskade, slagtilfælde, autoimmun sygdom, inflammation, IBD, IBS, seksuel dysfunktion, hypertension, retinal degeneration, lungecancer, coloncancer, brystcancer, uteruscancer, prostatacancer og cholangiocar-cinom.
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Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK2486010T3 (da) 2009-10-07 2019-09-23 Karo Pharma Ab Østrogenreceptorligander
IN2012DN02556A (da) 2009-10-07 2015-08-28 Karobio Ab
AU2011210765A1 (en) 2010-01-28 2012-09-13 President And Fellows Of Harvard College Compositions and methods for enhancing proteasome activity
EP2536717B1 (en) * 2010-02-17 2014-06-04 Janssen Pharmaceutica, N.V. Aminothiazolones as estrogen related receptor-alpha modulators
US20130059850A1 (en) * 2010-05-06 2013-03-07 Merck Sharp & Dohme Corp. Aza-indole derivatives useful as modulators of faah
GB201105979D0 (en) * 2011-04-07 2011-05-18 Karobio Ab Novel estrogen receptor ligands
EP3552664A1 (en) 2011-05-12 2019-10-16 Proteostasis Therapeutics, Inc. Proteostasis regulators
GB201113538D0 (en) * 2011-08-04 2011-09-21 Karobio Ab Novel estrogen receptor ligands
EP2567959B1 (en) 2011-09-12 2014-04-16 Sanofi 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors
US9849135B2 (en) 2013-01-25 2017-12-26 President And Fellows Of Harvard College USP14 inhibitors for treating or preventing viral infections
WO2015073528A1 (en) 2013-11-12 2015-05-21 Proteostasis Therapeutics, Inc. Proteasome activity enhancing compounds
AU2014352830B2 (en) * 2013-11-21 2018-12-13 Concordia University, Inc. Substituted (4'-hydroxyphenyl)cycloalkane compounds and uses thereof as selective agonists of the estrogen receptor beta isoform
EP3076964A1 (en) 2013-12-05 2016-10-12 Karo Pharma AB Estrogen receptor beta agonists for use in treating mesothelioma
WO2016036721A1 (en) 2014-09-02 2016-03-10 The Regents Of The University Of California Estrogen receptor ligand treatment for neurodegenerative diseases
GB201417456D0 (en) * 2014-10-02 2014-11-19 Karobio Ab Treatment of cancer
WO2016097036A1 (en) * 2014-12-17 2016-06-23 Karo Bio Ab Estrogen receptor ligand for use in treating melanoma
EP3241830A1 (de) 2016-05-04 2017-11-08 Bayer CropScience Aktiengesellschaft Kondensierte bicyclische heterocyclen-derivate als schädlingsbekämpfungsmittel
AU2017314083B2 (en) 2016-08-15 2020-12-10 Bayer Aktiengesellschaft Condensed bicyclic heterocycle derivatives as pest control agents
US11624095B2 (en) 2017-09-27 2023-04-11 Case Western Reserve University Method of quantifying HIV reservoirs by induced transcription based sequencing
JP2021514949A (ja) 2018-02-21 2021-06-17 バイエル・アクチエンゲゼルシヤフト 有害生物防除剤としての縮合二環式ヘテロ環誘導体
US11034669B2 (en) 2018-11-30 2021-06-15 Nuvation Bio Inc. Pyrrole and pyrazole compounds and methods of use thereof
JP2023520400A (ja) * 2020-04-03 2023-05-17 バーテックス ファーマシューティカルズ インコーポレイテッド アルファ－１－アンチトリプシン欠損症（ａａｔｄ）を治療するためのアルファ－１－アンチトリプシンモジュレーターとしてのインドール誘導体
WO2021203007A1 (en) * 2020-04-03 2021-10-07 Vertex Pharmaceuticals Incorporated Substituted 5-hydroxyindole compounds as modulators of alpha-1 antitrypsin

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3799943A (en) * 1971-06-23 1974-03-26 Sterling Drug Inc 1,2-diphenylindoles
US3878225A (en) * 1973-03-01 1975-04-15 Hoechst Co American Condensed pyrroles bearing an N-phenyl substituent
US4056624A (en) * 1976-05-14 1977-11-01 American Hoechst Corporation Method of treating dermal inflammation
DE4426625A1 (de) 1994-07-27 1996-03-14 Schering Ag 2-Phenylindole, Verfahren zu deren Herstellung, diese enthaltende pharmazeutische Präparate sowie deren Verwendung zur Herstellung von Arzneimitteln
PT802183E (pt) 1996-04-19 2002-03-28 American Home Prod Agentes estrogenicos
CZ299334B6 (cs) 1998-05-15 2008-06-25 Wyeth Farmaceutický prostredek
ES2209462T3 (es) 1998-06-30 2004-06-16 Eli Lilly And Company Agonistas de 5-ht1f.
AU3859400A (en) 1999-03-04 2000-09-21 American Home Products Corporation N-substituted benzoyl indoles as estrogenic agents
DE60003025T2 (de) 1999-04-02 2004-03-18 Bristol-Myers Squibb Pharma Co. Arylsulfonyle als faktor xa inhibitoren
US20030220377A1 (en) * 2002-05-08 2003-11-27 Richard Chesworth Indole compounds and their use as estrogen agonists/antagonists
DK1569901T3 (da) * 2002-12-10 2009-02-16 Wyeth Corp Aryl-, aryloxy- og alkoxysubstituerede 1H-indol-3-yl-glyoxylsyrederivater som inhibitorer af plasminogenaktivatorinhibitor-1 (PAI-1)
US7250440B2 (en) 2003-08-12 2007-07-31 Wyeth (Hydroxyphenyl)-1H-indole-3-carbaldehyde oxime derivatives as estrogenic agents
CN1867329A (zh) * 2003-08-12 2006-11-22 惠氏公司 作为***药剂的(4－羟基苯基)－1h－吲哚－3－甲醛肟衍生物
US7772271B2 (en) 2004-07-14 2010-08-10 Ptc Therapeutics, Inc. Methods for treating hepatitis C
US7781478B2 (en) * 2004-07-14 2010-08-24 Ptc Therapeutics, Inc. Methods for treating hepatitis C
US7868037B2 (en) * 2004-07-14 2011-01-11 Ptc Therapeutics, Inc. Methods for treating hepatitis C
BRPI0511834A (pt) 2004-07-14 2008-01-08 Ptc Therapeutics Inc métodos por tratar hepatite c
AR056690A1 (es) 2005-10-14 2007-10-17 Athersys Inc Derivados de indol como inhibidores de indol como inhibidores del receptor 3 de histamina para el tartamiento de trastornos del sueno y cognitivos obesidad y otros trastornos de snc
JP2010505898A (ja) 2006-10-13 2010-02-25 カロ バイオ アクチェブラーグ エストロゲン受容体リガンドとして有用な２−フェニルインデン誘導体
JP5107589B2 (ja) * 2007-02-13 2012-12-26 旭化成株式会社 インドール誘導体
JP2009105642A (ja) 2007-10-23 2009-05-14 Canon Inc データ再生装置及びそのデータ通信方法、データ再生システム、並びにプログラム
US8126781B2 (en) * 2009-02-06 2012-02-28 Cross Loop, Inc. Real-time collaborative selection of service providers

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