IP Library › Granted Patent US 8,921,378
Granted Patent B2
US 8,921,378 · App. 14/112,727 · Granted Dec 30, 2014

Androgen receptor modulating carboxamides

Inventors: Olli Törmäkangas (Turku, FI); Gerd Wohlfahrt (Helsinki, FI); Harri Salo (Turku, FI); Rathna Durga Ramasubramanian (Turku, FI); Pranab Kumar Patra (Noida, IN); Arputharaj Ebenezer Martin (Noida, IN); Terhi Heikkinen (Lieto, FI); Anniina Vesalainen (Paimio, FI); Anu Moilanen (Turku, FI); Arja Karjalainen (Espoo, FI)
Assignee: Orion Corporation
C07D487/04C07D231/14C07D403/04C07D471/04C07D403/14C07D401/14C07D403/12C07D401/04C07D413/14C07D413/12C07D513/04
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Quick Facts
Patent No.
US 8,921,378
App. No.
14/112,727
Granted
Dec 30, 2014
Kind
B2
Abstract

Compounds of formula (I) or (II) wherein R x , R z , R 9 , R 10 , R 14 , R 14 ′, R 15 , R 15 ′, A and B are as defined in the claims and pharmaceutically acceptable salts and esters thereof, are disclosed. The compounds possess utility as tissue-selective androgen receptor modulators (SARM) and are useful as medicaments in the treatment of prostate cancer and other AR dependent conditions and diseases where AR antagonism is desired.

Claims (149)

1. A compound of formula (I) or (II)

wherein ring A is any one of the following groups or tautomers thereof

wherein

R X is halogen or CF 3 ;

R X is hydrogen or halogen;

R 1 is hydroxy C 3-7 alkyl, imidazolyl or —R A OC(O)—R B ;

R A is C 1-7 alkyl;

R B is C 1-7 alkyl, hydroxy C 1-7 alkyl or carboxy C 1-7 alkyl;

R 2 is C 1-7 alkyl, C 2-7 alkenyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl C 1-7 alkyl, methylpyrazolyl or pyrimidinyl;

R 3 is halogen or pyridinyl;

R 4 is pyridinyl;

R 5 is C 1-7 alkyl, C 2-7 alkenyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl C 1-7 alkyl, cyano, hydroxy C 1-7 alkyl, oxo C 1-7 alkyl, halogen or methylpyrazolyl;

R 6 is C 1-7 alkyl, C 2-7 alkenyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl C 1-7 alkyl, hydroxy, hydroxy C 1-7 alkyl, cyano C 1-7 alkyl or C 1-7 alkoxycarbamoyl C 1-7 alkyl;

R 7 is hydroxy C 4 alkyl;

R 8 is halogen, C 2-7 alkyl, C 2-7 alkenyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl C 1-7 alkyl, cyano, carboxy, oxo C 1-7 alkyl, halo C 1-7 alkyl, hydroxy C 1-7 alkyl, tetrahydro-2H-thiopyran or —C(O)—NHR 20 ;

R 9 is hydrogen, hydroxy, halogen, nitro, amino, cyano, oxo, C 1-7 alkyl, C 2-7 alkenyl, C 3-7 cycloalkyl, C 1-7 alkoxy, halo C 1-7 alkyl, hydroxy C 1-7 alkyl, cyano C 1-7 alkyl, amino C 1-7 alkyl, oxo C 1-7 alkyl, C 1-7 alkoxy C 1-7 alkyl, C 1-7 alkylamino, hydroxy C 1-7 alkylamino, C 1-7 alkoxy C 1-7 alkylamino, C 1-7 alkylamino C 1-7 alkyl, hydroxy C 1-7 alkylamino C 1-7 alkyl, hydroxyimino C 1-7 alkyl, C 1-7 alkoxycarbamoyl C 1-7 alkyl, —C(O)R 11 , —OC(O)R 17 , —NH—C(O)R 18 —NH—SO 2 —R 19 or an optionally substituted 5-12 membered carbocyclic or heterocyclic ring, each group linked to B-ring via a bond or via a C 1-7 alkylene linker;

R 10 is hydrogen, halogen, C 1-7 alkyl, C 2-7 alkenyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl C 1-7 alkyl, oxo, hydroxy C 1-7 alkyl, oxo C 1-7 alkyl or an optionally substituted 5 or 6 membered carbocyclic or heterocyclic ring;

R 11 is hydrogen, hydroxy, C 1-7 alkyl, hydroxy C 1-7 alkyl, C 2-7 alkenyl, C 3-7 cycloalkyl, halo C 1-7 alkyl, C 1-7 alkoxy, NR 12 R 13 , or an optionally substituted 5-12 membered carbocyclic or heterocyclic ring;

R 12 is hydrogen, C 1-7 alkyl, C 2-7 alkenyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl C 1-7 alkyl, C 1-7 alkoxy, hydroxy C 1-7 alkyl, amino C 1-7 alkyl or C 1-7 alkyl amino C 1-7 alkyl;

R 13 is hydrogen or C 1-7 alkyl;

R 14 and R 15 are, independently, hydrogen or C 1-7 alkyl;

R 14 ′ and R 15 ′ are, independently, hydrogen or C 1-7 alkyl, or R 14 ′ and R 15 ′ together form a bond;

R 17 is C 1-7 alkyl, C 2-7 alkenyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl C 1-7 alkyl, C 1-7 alkoxy, amino C 1-7 alkyl, C 1-7 alkylamino or C 1-7 alkylamino C 1-7 alkyl;

R 18 is C 1-7 alkyl, C 2-7 alkenyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl C 1-7 alkyl, amino C 1-7 alkyl, C 1-7 alkylamino or C 1-7 alkylamino C 1-7 alkyl;

R 19 is C 1-7 alkyl, C 2-7 alkenyl, C 3-7 cycloalkyl or C 3-7 cycloalkyl C 1-7 alkyl;

R 20 is hydrogen, C 1-7 alkyl, C 2-7 alkenyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl C 1-7 alkyl or C 1-7 alkoxy;

R 21 is cyano C 1-7 alkyl or, in case R x is CF 3 , R 21 can also be hydroxy C 1-7 alkyl;

R 22 is hydroxy C 1-7 alkyl;

R 23 is C 1-7 alkyl or hydroxy C 1-7 alkyl;

R 24 is hydroxy, halogen or C 1 —, alkoxy;

ring B is chosen from any one of the following groups and tautomers thereof

or pharmaceutically acceptable salts thereof;

with the proviso that the compound of formula (II) is not any of the following compounds:

(S)-3-acetyl-N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H-pyrazole-5-carboxamide;

(S)—N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-(pyridin-4-yl)-1H-pyrazole-3-carboxamide;

(S)—N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-(2-fluoroethyl)-2-methyl-1H-imidazole-4-carboxamide;

(S)—N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-3-(1H-imidazol-4-yl)-1,2,4-oxadiazole-5-carboxamide;

(S)-5-acetyl-N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)isoxazole-3-carboxamide;

N—((S)-1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1-hydroxyethyl)isoxazole-3-carboxamide;

(S)-5-acetyl-N-(2-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propyl)isoxazole-3-carboxamide;

(S)—N-(2-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propyl)-2-methyl-1H-imidazole-4-carboxamide;

N—((S)-1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-3-(1-hydroxyethyl)-1H-pyrazole-5-carboxamide;

(R)—N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-methyl-1H-imidazole-4-carboxamide;

(S)—N-{1-[3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl]propan-2-yl}-2-methyl-1H-imidazole-4-carboxamide;

(S)—N-{1-[3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1-methyl-1H-imidazole-4-carboxamide;

(S)—N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-3H-imidazo[4,5-b]pyridine-5-carboxamide;

(S)—N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide;

(S)—N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-(pyridin-3-yl)-1H-pyrazole-3-carboxamide;

(S)—N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-methyl-1-(3-oxobutyl)-1H-imidazole-4-carboxamide;

(S)—N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-(3-hydroxy-3-methylbutyl)-2-methyl-1H-imidazole-4-carboxamide;

(S)—N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)imidazo[1,2-a]pyridine-2-carboxamide;

(S)—N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-(pyridin-3-yl)-1H-imidazole-4-carboxamide;

(S)—N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(2-hydroxypropan-2-yl)oxazole-4-carboxamide;

(S)—N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)imidazo[1,2-a]pyrimidine-2-carboxamide;

(S)—N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-3-fluoroimidazo[1,2-a]pyridine-2-carboxamide;

(S)—N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-4,5,6,7-tetrahydro-2H-indazole-3-carboxamide;

(S)—N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide;

(S)—N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2,4,6,7-tetrahydropyrano[4,3-c]pyrazole-3-carboxamide;

(S)—N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-(6-methylpyridin-2-yl)-1H-imidazole-4-carboxamide;

(S)—N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-6,7-dihydro-4H-pyrano[3,4-d]isoxazole-3-carboxamide; or

(S)—N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(2-hydroxypropan-2-yl)isoxazole-3-carboxamide.

2. The compound according to claim 1 , wherein the compound is of formula (I), wherein R x is halogen; R 14 is C 1-7 alkyl; and ring A is chosen from groups (1), (2), (3), (5), (6), (7) and (8).

3. The compound according to claim 2 , wherein R x is chloro, R 14 is methyl, and ring A is any of groups (1), (2), (5), (6) or (7), R 1 is hydroxy C 3-7 alkyl, imidazolyl or carboxy C 1-7 alkyl carbonyloxy C 1-7 alkyl; R 2 is C 1-7 alkyl, C 2-7 alkenyl or methylpyrazolyl; R 5 is C 1-7 alkyl, C 3-7 cycloalkyl, hydroxy C 1-7 alkyl or methylpyrazolyl; R 6 is C 1-7 alkyl, cyano C 1-7 alkyl or hydroxy C 1-7 alkyl; and R 8 is C 1-7 alkyl, halogen, oxo C 1-7 alkyl or hydroxy C 1-7 alkyl.

4. The compound according to claim 1 , wherein the compound is of formula (II) wherein R 14 is C 1-7 alkyl; R 14 ′, R 15 and R 15 ′ is hydrogen; ring B is chosen from groups (1′), (2′), (3′), (4′), (8′), (16′), (17′), (21′), (23′), (24′), (25′), (26′), (29′), (39′), (40′), (42′) and (43′); R 9 is hydrogen, halogen, cyano, oxo, C 1-7 alkyl, C 2-7 alkenyl, C 3-7 cycloalkyl, halo C 1-7 alkyl, cyano C 1-7 alkyl, hydroxy C 1-7 alkyl, oxo C 1-7 alkyl, —NH—SO 2 —R 19 or an optionally substituted 5-12 membered heterocyclic ring, wherein each R 9 group is linked to B-ring via a bond or via a C 1-7 alkylene linker; R 10 is hydrogen, C 1-7 alkyl or C 3-7 cycloalkyl; and R 19 is C 1-7 alkyl.

5. The compound according to claim 4 , wherein the 5-12 membered heterocyclic ring is pyrazole, pyridine, isoxazole or imidazole ring, wherein the 5-12 membered heterocyclic ring is attached to B-ring via a bond or via C 1-7 alkylene linker.

6. The compound according to claim 5 , wherein the 5-12 membered heterocyclic ring contains comprises 1-3 substituents chosen from C 1-7 alkyl, C 3-7 cycloalkyl, halogen and hydroxy C 1-7 alkyl.

7. The compound according to claim 4 , wherein R z is hydrogen or fluoro, R 14 is methyl; R 14 ′, R 15 and R 15 ′ is hydrogen; ring B is any of groups (1′), (2′), (4′), (17′), (21′) or (25′); R 9 is hydrogen, halogen, cyano, oxo, C 1-7 alkyl, C 2-7 alkenyl, C 3-7 cycloalkyl, halo C 1-7 alkyl, hydroxy C 1-3 alkyl, cyano C 1-7 alkyl, pyrazolyl, N-methylpyrazolyl, pyridinyl, isoxazolyl, imidazolyl or imidazolyl methyl; and R 10 is hydrogen, C 1-7 alkyl or C 3-7 cycloalkyl.

8. The compound according to claim 1 , wherein the compound is

(S)—N-(1-(3-(3-Chloro-4-cyano-2,5-difluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-methyl-1H-imidazole-5-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-2,5-difluorophenyl)-1H-pyrazol-1-yl)-propan-2-yl)-2-(2-hydroxypropan-2-yl)oxazole-5-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-6-cyanoimidazo[1,2-a]pyridine-2-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-7-oxo-5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidine-2-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-3-isopropyl-1,2,4-oxadiazole-5-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5,7-dimethylimidazo[1,2-c]pyrimidine-2-carboxamide;

(S)-5-((1H-Imidazol-1-yl)methyl)-N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)isoxazole-3-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-oxo-5,6-dihydroimidazo[1,2-c]pyrimidine-2-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1,6-dihydropyrrolo[2,3-c]pyrazole-5-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)imidazo[2,1-b]thiazole-6-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-6-nitroimidazo[1,2-a]pyridine-2-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)-propan-2-yl)-1-isopropyl-2-methyl-1H-imidazole-4-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(2-hydroxypropan-2-yl)-1H-pyrazole-3-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)-propan-2-yl)-1-(2,2-difluoroethyl)-2-methyl-1H-imidazole-4-carboxamide;

N—((S)-1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)-propan-2-yl)-1-((R)-2-hydroxypropyl)-2-methyl-1H-imidazole-4-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1′-methyl-1′1H-1,4′-bipyrazole-3-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H,2′H-3,3′-bipyrazole-5-carboxamide;

N—((S)-1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)-propan-2-yl)-1-((S)-2-hydroxypropyl)-2-methyl-1H-imidazole-4-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-3,3′-bipyridine-6-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)-propan-2-yl)-6-(3,3-dimethylureido)imidazo[1,2-a]pyridine-2-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)-propan-2-yl)-6-(methylsulfonamido)imidazo[1,2-a]pyridine-2-carboxamide;

N—((S)-1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1-hydroxy-2-methylpropyl)isoxazole-3-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1,5-dimethyl-1H-pyrazol-3-yl)-1,2,4-oxadiazole-3-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(isoxazol-3-yl)-1,2,4-oxadiazole-3-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)-propan-2-yl)-3-(1H-imidazol-4-yl)-1H-pyrazole-5-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(chloropropan-2-yl)oxazole-4-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)-propan-2-yl)-2-(2-propen-2-yl)oxazole-4-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-N-5-cyclopropylisoxazole-3,5-dicarboxamide;

(S)-2-Bromo-N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H-imidazole-4-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-(2-methylprop-1-enyl)-1H-pyrazole-3-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-cyclopropyl-1H-pyrazole-3-carboxamide;

N—((S)-1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(1-hydroxyethyl)-1H-imidazole-4-carboxamide;

(S)-2-acetyl-N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H-imidazole-4-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(2-hydroxypropan-2-yl)-1H-imidazole-4-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)-propan-2-yl)-2-cyclopropyl-1-methyl-1H-imidazole-4-carboxamide;

(S)—N 4 -(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H-imidazole-2,4-dicarboxamide:

4-(1-(3-((S)-1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl-carbamoyl)-1H-pyrazol-5-yl)ethoxy)-4-oxobutanoic acid;

(S)-5-Chloro-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)-propan-2-yl)-pyrazine-2-carboxamide;

N—((S)-1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-((S)-2-hydroxypropyl)-2-methyl-1H-imidazole-4-carboxamide;

(S)-1-Butyl-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-methyl-1H-imidazole-4-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(2-hydroxypropan-2-yl)-1H-pyrazole-3-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1′-methyl-1′1H-1,4′-bipyrazole-3-carboxamide;

N—((S)-1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-((R)-2-hydroxypropyl)-2-methyl-1H-imidazole-4-carboxamide;

(S)-2-Bromo-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)-propan-2-yl)-1H-imidazole-4-carboxamide;

N—((S)-1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1-hydroxy-2-methylpropyl)isoxazole-3-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-(2-cyanoethyl)-2-methyl-1H-imidazole-4-carboxamide;

N—((S)-1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-(1-cyanoethyl)-2-methyl-1H-imidazole-4-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-(2-methylprop-1-enyl)-1H-pyrazole-3-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-3-(1H-imidazol-4-yl)-1H-pyrazole-5-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-cyclopropyl-1H-pyrazole-3-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-(6-(dimethylamino)pyridin-3-yl)-1H-pyrazole-3-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-2-carboxamide);

N—((S)-1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(1-hydroxyethyl)-1H-imidazole-4-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-isopropyl-1H-imidazole-4-carboxamide;

(S)-2-Butyl-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-methyl-1H-imidazole-4-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(2-hydroxypropan-2-yl)-1-methyl-1H-imidazole-4-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1-methyl-2-(1-methyl-1H-pyrazol-4-yl)-1H-imidazole-4-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-cyclopropyl-1-methyl-1H-imidazole-4-carboxamide;

(S)—N 4 -(1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H-imidazole-2,4-dicarboxamide;

(S)—N-(1-(3-(4-Cyano-3-(trifluoromethyl)phenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(2-hydroxypropan-2-yl)oxazole-4-carboxamide or a pharmaceutically acceptable salt thereof.

9. The compound according to claim 1 , wherein the compound is

(S)—N-(2-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propyl)-2-(2-hydroxypropan-2-yl)oxazole-4-carboxamide;

(R)—N-(2-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propyl)-2-(2-hydroxypropan-2-yl)oxazole-4-carboxamide;

(R)—N-(2-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propyl)-2-(2-hydroxypropan-2-yl)-1H-imidazole-4-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(2,2,2-trifluoroethyl)-1H-imidazole-4-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(trifluoromethyl)-1H-imidazole-4-carboxamide;

N—((S)-1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-3-((S)-1-hydroxyethyl)-1,2,4-oxadiazole-5-carboxamide;

N—((S)-1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-3-((R)-1-hydroxyethyl)-1,2,4-oxadiazole-5-carboxamide;

(S)—N-(2-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propyl)-3-(2-hydroxypropan-2-yl)-1,2,4-oxadiazole-5-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-3-(2-hydroxypropan-2-yl)-1,2,4-oxadiazole-5-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-cyclopropyl-1H-imidazole-4-carboxamide;

(S)—N 4 -(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-N 2 ,N 2 -dimethyl-1H-imidazole-2,4-dicarboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(2-ethoxypropan-2-yl)-1H-imidazole-4-carboxamide;

N—((S)-1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(1-ethoxyethyl)-1H-imidazole-4-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(2-ethoxypropan-2-yl)oxazole-4-carboxamide;

(S)—N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(2-hydroxy-2-methyl propyl)-1H-pyrazole-3-carboxamide;

or a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

11. A method for the treatment of an androgen receptor dependent cancer, comprising administering to a subject in need thereof a therapeutically effective amount of a compound according to claim 1 .

12. The method according to claim 11 , wherein the androgen receptor dependent cancer is prostate cancer.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 23, 2013
From: TÖRMÄKANGAS, OLLI; WOHLFAHRT, GERD; SALO, HARRI; RAMASUBRAMANIAN, RATHNA DURGA; PATRA, PRANAB KUMAR; MARTIN, ARPUTHARAJ EBENEZER; HEIKKINEN, TERHI; VESALAINEN, ANNIINA; MOILANEN, ANU; KARJALAINEN, ARJA
To: ORION CORPORATION
Reel/Frame 031838/0818 →
Priority Claims (1)
IN 570/KOL/2011 · Apr 21, 2011 · national
Continuity (1)
Related Publication 20140094474A1 · Apr 3, 2014