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US 8,263,635 B2Granted
Inhibitors of CYP 17
AssigneeNovartis AG
InventorsMark G. Bock, Christoph Gaul, Venkateshwar Rao Gummadi, Saumitra Sengupta
Life of this patent
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Abstract
The present invention provides compounds of Formula (I) and (II), or a pharmaceutically acceptable salts thereof, where R53, R54, p, q, and n are as defined herein. The compounds of the present invention have been found to be useful as 17α-hydroxylase/C17,20-lyase inhibitors.
Claims16
A compound of Formula (Ib)
- wherein
- R50, R51 and R52 are each independently H, halo, -OH, -CN, (C1-C4)alkyl, halo-substituted(C1-C4)alkyl, hydroxy-substituted (C1-C4)alkyl, -(CH2)r -O(C1-C4)alkyl, -(CH2)r —CH(O(C1-C4)alkyl)2, -NH2, -NH(C1-C4)alkyl, -N((C1-C4)alkyl)2, -NHC(O)-(C1-C4)alkyl, —C(O)NH2, -C(O)-NH(C1-C4)alkyl, -C(O)-N((C1-C4)alkyl)2, or -C(O)-O(C1-C4)alkyl;
- wherein
- n is 1;
- R53 is
- (i) phenyl optionally substituted with 1 to 3 substituents selected from halo, -CN, -OH, (C1-C6)alkyl, halo-substituted (C1-C6)alkyl, (C1-C6)alkoxy, -NH2, -NH(C1-C4)alkyl, -N((C1-C4)alkyl)2, -NHC(O)-(C1-C4)alkyl, -C(O)NH2, -C(O)-NH(C1-C4)alkyl, -C(O)-N((C1-C4)alkyl)2, or a 5- to 6-membered heterocycle,
- (ii) biphenyl optionally substituted with 1 to 3 substituents selected from (C1-C4)alkyl or halo,
- (iii) phenyl fused to an additional phenyl, a 5- to 6-membered heteroaryl, a 5- to 6-membered partially or fully saturated cycloalkyl, or a 5- to 6-membered partially or fully saturated heterocycle, where said fused phenyl is optionally substituted with 1 to 4 substituents each independently selected from halo, -CN, (C1-C6)alkyl, (C1-C6)alkoxy, hydroxy-substituted (C1-C4)alkyl, halo-substituted (C1-C4)alkyl, cyclopropyl, oxo, -NH2, -NH(C1-C4)alkyl, -N((C1-C4)alkyl)2, -NHC(O)-(C1-C4)alkyl, or ═N-OH,
- (iv) 5- to 6-membered heteroaryl optionally substituted with 1 to 3 substituents selected from halo, -CN, -OH, (C1-C6)alkyl, halo-substituted (C1-C6)alkyl, (C1-C6)alkoxy, -NH2, -NH(C1-C4)alkyl, -N((C1-C4)alkyl)2, -NHC(O)-(C1-C4)alkyl, -C(O)NH2, -C(O)-NH(C1-C4)alkyl, -C(O)-N((C1-C4)alkyl)2, or a 5- to 6-membered heterocycle,
- (v) 5- to 6-membered heteroaryl fused to another 5- to 6-membered heteroaryl, phenyl, 5- to 6-membered partially or fully saturated cycloalkyl, or a 5- to 6-membered partially or fully saturated heterocycle, where said fused heteroaryl is optionally substituted with 1 to 4 substituents each independently selected from halo, -CN, (C1-C6)alkyl, (C1-C6)alkoxy, hydroxy-substituted (C1-C4)alkyl, halo-substituted (C1-C4)alkyl, cyclopropyl, oxo, -NH2, -NH(C1-C4)alkyl, -N((C1-C4)alkyl)2, -NHC(O)-(C1-C4)alkyl, or ═N-OH;
- R54 is (C1-C4)alkyl, halo-substituted (C1-C4)alkyl, or -CH2OH, or two R54 taken together with the carbon atom(s) to which they are attached form a 3- to 6-membered fully or partially saturated carbocyclic;
- p is 0, 1, 2, or 3;
- with the proviso that when R50, R51, and R52 are H and R53 is phenyl, R53 is not unsubstituted or substituted with halogen or CF3,
- or a pharmaceutically acceptable salt thereof.
11 more elements
A compound of Formula (Ib)
- wherein:
- n is 1;
- R53 is
- (i) phenyl optionally substituted with 1 to 3 substituents selected from halo, -CN, -OH, (C1-C6)alkyl, halo-substituted (C1-C6)alkyl, (C1-C6)alkoxy, -NH2, -NH(C1-C4)alkyl, -N((C1-C4)alkyl)2, -NHC(O)-(C1-C4)alkyl, -C(O)NH2, -C(O)-NH(C1-C4)alkyl, -C(O)-N((C1-C4)alkyl)2, or a 5- to 6-membered heterocycle,
- (ii) biphenyl optionally substituted with 1 to 3 substituents selected from (C1-C4)alkyl or halo,
- (iii) phenyl fused to an additional phenyl, a 5- to 6-membered heteroaryl, a 5- to 6-membered partially or fully saturated cycloalkyl, or a 5- to 6-membered partially or fully saturated heterocycle, where said fused phenyl is optionally substituted with 1 to 4 substituents each independently selected from halo, -CN, (C1-C6)alkyl, (C1-C6)alkoxy, hydroxy-substituted (C1-C4)alkyl, halo-substituted (C1-C4)alkyl, cyclopropyl, oxo, -NH2, -NH(C1-C4)alkyl, -N((C1-C4)alkyl)2, -NHC(O)-(C1-C4)alkyl, or ═N-OH,
- (iv) 5- to 6-membered heteroaryl optionally substituted with 1 to 3 substituents selected from halo, -CN, -OH, (C1-C6)alkyl, halo-substituted (C1-C6)alkyl, (C1-C6)alkoxy, -NH2, -NH(C1-C4)alkyl, -N((C1-C4)alkyl)2, -NHC(O)-(C1-C4)alkyl, -C(O)NH2, -C(O)-NH(C1-C4)alkyl, -C(O)-N((C1-C4)alkyl)2, or a 5- to 6-membered heterocycle,
- (v) 5- to 6-membered heteroaryl fused to another 5- to 6-membered heteroaryl, phenyl, 5- to 6-membered partially or fully saturated cycloalkyl, or a 5- to 6-membered partially or fully saturated heterocycle, where said fused heteroaryl is optionally substituted with 1 to 4 substituents each independently selected from halo, -CN, (C1-C6)alkyl, (C1-C6)alkoxy, hydroxy-substituted (C1-C4)alkyl, halo-substituted (C1-C4)alkyl, cyclopropyl, oxo, -NH2, -NH(C1-C4)alkyl, -N((C1-C4)alkyl)2, -NHC(O)-(C1-C4)alkyl, or ═N-OH;
- R54 is (C1-C4)alkyl, halo-substituted (C1-C4)alkyl, or -CH2OH, or two R54 taken together with the carbon atom(s) to which they are attached form a 3- to 6-membered fully or partially saturated carbocyclic ring;
- p is 0, 1, 2, or 3;
- R50, R51 and R52 are each independently H, halo, -OH, -CN, (C1-C4)alkyl, halo-substituted (C1-C4)alkyl, hydroxy-substituted (C1-C4)alkyl, -(CH2)r-O(C1-C4)alkyl, -(CH2)r—CH(O(C1-C4)alkyl)2, -NH2, -NH(C1-C4)alkyl, -N((C1-C4)alkyl)2, -NHC(O)-(C1-C4)alkyl, -C(O)NH2, -C(O)-NH(C1-C4)alkyl, -C(O)-N((C1-C4)alkyl)2, or -C(O)-O(C1-C4)alkyl;
- r is 0, 1 or 2;
- with the proviso that when R50, R51, and R52 are H and R53 is phenyl, R53 is not unsubstituted or substituted with halogen or CF3;
- or a pharmaceutically acceptable salt thereof.
11 more elements
A compound selected from the group consisting of
- 1-Benzothiazol-6-yl-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(2-Chloro-pyridin-4-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(4-Chloro-thieno[3,2-c]pyridin-2-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(1H-Indazol-6-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(3-Methyl-1H-indazol-6-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- and
- 1-Benzothiazol-6-yl-4-methyl-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- Or a pharmaceutically acceptable salt thereof.
5 more elements
A compound selected from the group consisting of
- 1-Naphthalen-2-yl-3-pyridin-3-yl-imidazolidin-2-one;
- 1-Benzo [b]thiophen-5-yl-3-pyridin-3-yl-imidazolidin-2-one;
- 1-(4-Methyl-pyridin-3-yl)-3-naphthalen-2-yl-imidazolidin-2-one;
- 1-(4-Methyl-pyridin-3-yl)-3-(5-methyl-thiophen-2-yl)-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-Benzo[b]thiophen-2-yl-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-Benzo[b]thiophen-5-yl-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(1H-Indazol-5-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(3-Methyl-benzofuran-5-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(5-Chloro-thiophen-2-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(3,4-Difluoro-phenyl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(3-Chloro-4-fluoro-phenyl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(2,3-Dihydro-benzofuran-5-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(4-Chloro-3-fluoro-phenyl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(4-Methyl-pyridin-3-yl)-3-m-tolyl-imidazolidin-2-one;
- 1-(3-Methoxy-phenyl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(2-Chloro-pyridin-4-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(4-Fluoro-3-methyl-phenyl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(2,2-Difluoro-benzo[1,3]dioxol-5-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(4-Methyl-pyridin-3-yl)-3-phenyl-imidazolidin-2-one;
- 1-(4-Methyl-pyridin-3-yl)-3-(3-trifluoromethyl-phenyl)-imidazolidin-2-one;
- 1-(2-Methoxy-pyridin-4-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(5-Difluoromethyl-thiophen-3-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(3-Chloro-phenyl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(4-Fluoro-3-trifluoromethyl-phenyl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(3-Difluoromethyl-4-fluoro-phenyl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(4-Methyl-pyridin-3-yl)-3-(5-methyl-thiophen-3-yl)-imidazolidin-2-one;
- 1-(4-Chloro-thieno[3,2-c]pyridin-2-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(4-Chloro-thieno[3,2-c]pyridin-3-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(4-Methyl-pyridin-3-yl)-3-(2-methyl-pyridin-4-yl)-imidazolidin-2-one;
- 1-(3-Methyl-benzo[d]isoxazol-5-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(3-Methyl-1H-indazol-6-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 2-Fluoro-5-[3-(4-methyl-pyridin-3-yl)-2-oxo-imidazolidin-1-yl]-benzonitrile;
- 3-[3-(4-Methyl-pyridin-3-yl)-2-oxo-imidazolidin-1-yl]-benzonitrile;
- 2-Chloro-4-[3-(4-methyl-pyridin-3-yl)-2-oxo-imidazolidin-1-yl]-benzonitrile;
- 1-(1-Methyl-1H-indazol-5-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(3-Amino-1H-indazol-5-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(4-Methyl-pyridin-3-yl)-3-thieno[3,2-c]pyridin-2-yl-imidazolidin-2-one;
- 1-(1H-Indazol-6-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(3-Amino-1H-indazol-6-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-(4-methoxy-pyridin-3-yl)-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-(4-difluoromethyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-(4-hydroxymethyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-(4-trifluoromethyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-Indan-5-yl-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(1H-Benzotriazol-5-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(3-Chloro-imidazo[1,2-a]pyridin-7-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(4-Methyl-pyridin-3-yl)-3-(2-trifluoromethyl-pyridin-4-yl)-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-(4-dimethoxymethyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-(5-chloro-4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(4-Methylpyridin-3-yl)-3-(5-(trifluoromethyl)thiophen-2-yl)imidazolidin-2-one;
- 1-(4-Methylpyridin-3-yl)-3-(4-methylthieno[3,2-c]pyridin-2-yl)imidazolidin-2-one;
- 1-(Benzo[d]thiazol-6-yl)-3-(4-(1-hydroxyethyl)pyridin-3-yl)imidazolidin-2-one;
- 1-(Benzo[d]thiazol-6-yl)-3-(4-ethylpyridin-3-yl)imidazolidin-2-one;
- 1-(4-Methylpyridin-3-yl)-3-(3-(trifluoromethyl)-1H-indazol-6-yl)imidazolidin-2-one;
- 1-Benzothiazol-6-yl-4-methyl-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-pyridin-3-yl-4-trifluoromethyl-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-4-methyl-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 3-Benzothiazol-6-yl-1-pyridin-3-yl-4-trifluoromethyl-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-(4-methyl-pyridin-3-yl)-4-trifluoromethyl-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-4,5-dimethyl-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-(4-pyrrolidin-1-ylmethyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-(4-morpholin-4-ylmethyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-(4-cyclopropylaminomethyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-(6-fluoro-4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-[4-(2-morpholin-4-yl-ethoxy)-pyridin-3-yl]-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-[4-(1-methyl-pyrrolidin-2-ylmethoxy)-pyridin-3-yl]-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-{4-[(5-methyl-1H-pyrazol-3-ylamino)-methyl]-pyridin-3-yl}-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-[4-(1-methyl-piperidin-4-ylmethoxy)-pyridin-3-yl]-imidazolidin-2-one;
- 3-(3-Benzothiazol-6-yl-2-oxo-imidazolidin-1-yl)-isonicotinamide;
- 1-Benzothiazol-6-yl-3-(4-methyl-5-trifluoromethyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-Isothiazol-4-yl-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(4-Methyl-pyridin-3-yl)-3-(5-trifluoromethyl-thiophen-2-yl)-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-[4-(1-hydroxy-1-methyl-ethyl)-pyridin-3-yl]-imidazolidin-2-one;
- 1-(4-Methyl-pyridin-3-yl)-3-(4-methyl-thieno[3,2-c]pyridin-2-yl)-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-[4-(1-hydroxy-ethyl)-pyridin-3-yl]-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-(4-ethyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(4-Methyl-pyridin-3-yl)-3-(3-trifluoromethyl-1H-indazol-6-yl)-imidazolidin-2-one;
- 1-(3-Cyclopropyl-1H-indazol-6-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-(4-Methyl-pyridin-3-yl)-3-quinolin-7-yl-imidazolidin-2-one;
- 3-Benzothiazol-6-yl-4,4-dimethyl-1-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-4,4-dimethyl-3-pyridin-3-yl-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-4,4-dimethyl-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 3-Benzothiazol-6-yl-4-methyl-1-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-4-methyl-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-4,5-dimethyl-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-(4-pyrrolidin-1-ylmethyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-(4-morpholin-4-ylmethyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-(4-cyclopropylaminomethyl-pyridin-3-yl)-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-3-{4-[(5-methyl-1H-pyrazol-3-ylamino)-methyl]-pyridin-3-yl}-imidazolidin-2-one;
- 1-Benzothiazol-6-yl-4,4-dimethyl-3-pyridin-3-yl-imidazolidin-2-one;
- and
- 3-Benzothiazol-6-yl-4-methyl-1-(4-methyl-pyridin-3-yl)-imidazolidin-2-one;
- or a pharmaceutically acceptable salt thereof.
92 more elements
A compound which is 1-(2-Chloro-pyridin-4-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one having the structure:
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.