US 2014/0228386 A1Published application

17a-HYDROXYLASE/C17,20-LYASE INHIBITORS

AssigneeNovartis AG

InventorsMark Gary 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), or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, R5 and R6 are as defined herein. The compounds of the present invention have been found to be useful as 17α-hydroxylase/C17,20-lyase inhibitors.

Claims24

Dependent claims

A compound of Formula (I)

wherein
R1 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, (C3-C5)cycloalkyl, or a 5- to 6-membered heterocycle,
(ii) 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, (C3-C5)cycloalkyl, oxo, —NH2, —NH(C1-C4)alkyl, —N((C1-C4)alkyl)2, —NHC(O)—(C1-C4)alkyl, or ═N—OH,
(iii) 5- to 6-membered heteroaryl optionally substituted with 1 to 3 substituents each independently 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, (C3-C5)cycloalkyl, or a 5- to 6-membered heterocycle, or
(iv) 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, (C3-C5)cycloalkyl, oxo, —NH2, —NH(C1-C4)alkyl, —N((C1-C4)alkyl)2, —NHC(O)—(C1-C4)alkyl, or ═N—OH;
R2 and R5 are each independently CH3 or H;
R3 and R4 are each independently CH3 or H, or taken together with the carbon atoms to which they are attached form a cyclopropyl;
and
R6 is (C3-C5)cycloalkyl, where the cycloalkyl is optionally substituted with hydroxy;
or a pharmaceutically acceptable salt thereof.

8 more elements

A compound selected from the group consisting of

1-(2-Chloropyridin-4-yl)-3-(4-cyclopropylpyridin-3-yl)imidazolidin-2-one;
1-(4-Cyclopropylpyridin-3-yl)-3-(2-(trifluoromethyl)pyridin-4-yl)imidazolidin-2-one;
1-(4-Cyclopropylpyridin-3-yl)-3-(naphthalen-2-yl)imidazolidin-2-one;
1-(Benzo[b]thiophen-5-yl)-3-(4-cyclopropylpyridin-3-yl)imidazolidin-2-one;
1-(4-Cyclopropylpyridin-3-yl)-3-(3-(trifluoromethyl)phenyl)imidazolidin-2-one;
1-(Benzo[b]thiophen-2-yl)-3-(4-cyclopropylpyridin-3-yl)imidazolidin-2-one;
1-(6-Chloro-2-methylpyrimidin-4-yl)-3-(4-cyclopropylpyridin-3-yl)imidazolidin-2-one;
1-(4-Cyclopropylpyridin-3-yl)-3-(4-(trifluoromethyl)pyridin-2-yl)imidazolidin-2-one;
1-(4-Cyclopropylpyridin-3-yl)-3-(2-methoxypyridin-4-yl)imidazolidin-2-one;
1-(6-Chloropyrimidin-4-yl)-3-(4-cyclopropylpyridin-3-yl)imidazolidin-2-one;
1-(4-Cyclopropylpyridin-3-yl)-3-(4-(trifluoromethyl)pyrimidin-2-yl)imidazolidin-2-one;
1-(4-Cyclopropylpyridin-3-yl)-3-(2-(trifluoromethyl)pyrimidin-4-yl)imidazolidin-2-one;
1-(4-Cyclopropylpyridin-3-yl)-3-(3-(trifluoromethyl)benzo[b]thiophen-5-yl)imidazolidin-2-one;
1-(4-Cyclopropylpyridin-3-yl)-3-(2-fluorobenzo[b]thiophen-5-yl)imidazolidin-2-one;
1-(4-Cyclopropylpyridin-3-yl)-3-(3-methylbenzo[b]thiophen-5-yl)imidazolidin-2-one;
1-(Benzo[b]thiophen-6-yl)-3-(4-cyclopropylpyridin-3-yl)imidazolidin-2-one;
1-(4-Cyclopropylpyridin-3-yl)-3-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)imidazolidin-2-one;
1-(4-Cyclopropylpyridin-3-yl)-3-(3-methylbenzo[b]thiophen-6-yl)imidazolidin-2-one;
1-(4-Cyclopropylpyridin-3-yl)-3-(3-methylbenzofuran-5-yl)imidazolidin-2-one;
1-(2-Chlorobenzo[b]thiophen-5-yl)-3-(4-cyclopropylpyridin-3-yl)imidazolidin-2-one;
1-(4-Cyclopropylpyridin-3-yl)-3-(2,3-dihydro-1H-inden-5-yl)imidazolidin-2-one;
1-(4-Cyclopropylpyridin-3-yl)-3-(5-fluorobenzo[b]thiophen-2-yl)imidazolidin-2-one;
1-(4-Cyclopropylpyridin-3-yl)-3-(3-(trifluoromethyl)benzo[b]thiophen-6-yl)imidazolidin-2-one;
1-(4-Cyclopropyl-pyridin-3-yl)-3-(2-fluoro-3-methyl-benzo[b]thiophen-5-yl)imidazolidin-2-one;
1-(4-Cyclopropyl-pyridin-3-yl)-3-(2-fluoro-benzo[b]thiophene-6-yl)imidazolidin-2-one;
1-(4-Cyclopropyl-pyridin-3-yl)-3-(4-fluoro-benzo[b]thiophen-6-yl)imidazolidin-2-one;
1-(4-Cyclopropyl-pyridin-3-yl)-3-(5-fluoro-benzo[b]thiophen-6-yl)imidazolidin-2-one;
1-(4-Cyclopropylpyridin-3-yl)-3-(6-fluorobenzo[b]thiophen-5-yl)imidazolidin-2-one;
1-(4-Cyclopropylpyridin-3-yl)-3-(5-fluoro-3-methylbenzo[b]thiophen-6-yl)imidazolidin-2-one;
1-(2-Chloro-pyridin-4-yl)-3-[4-(1-hydroxy-cyclobutyl)pyridin-3-yl]-imidazolidin-2-one;
1-(2-Chloropyridin-4-yl)-3-(4-cyclopentyl-pyridin-3-yl)imidazolidin-2-one;
1-(2-Chloropyridin-4-yl)-3-[4-(1-hydroxycyclopentyl)-pyridin-3-yl]imidazolidin-2-one;
1-[4-(1-Hydroxy-cyclopropyl)-pyridin-3-yl]-3-(3-trifluoromethylphenyl)imidazolidin-2-one;
1-(4-cyclopropylpyridin-3-yl)-3-(6-cyclopropylpyrimidin-4-yl)imidazolidin-2-one;
1-(4-cyclopropylpyridin-3-yl)-3-(2-cyclopropylpyridin-4-yl)imidazolidin-2-one;
1-(4-cyclopropylpyridin-3-yl)-3-(5-fluoro-4-methylpyridin-2-yl)imidazolidin-2-one;
1-(4-cyclopropylpyridin-3-yl)-3-(2-cyclopropylpyrimidin-4-yl)imidazolidin-2-one;
1-(6-chloro-2-(trifluoromethyl)pyrimidin-4-yl)-3-(4-cyclopropylpyridin-3-yl)imidazolidin-2-one;
1-(4-cyclopropylpyridin-3-yl)-3-(2,6-dichloropyridin-4-yl)imidazolidin-2-one;
1-(2-chloro-6-cyclopropylpyridin-4-yl)-3-(4-cyclopropylpyridin-3-yl)imidazolidin-2-one;
1-(2-cyclopropyl-6-(trifluoromethyl)pyridin-4-yl)-3-(4-cyclopropylpyridin-3-yl)imidazolidin-2-one;
and
1-(2,6-bis(trifluoromethyl)pyridin-4-yl)-3-(4-cyclopropylpyridin-3-yl)imidazolidin-2-one;
or a pharmaceutically acceptable salt thereof.

41 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/113,718Filed 27 Apr 2012
Priority: IN 1256/DEL/201128 Apr 2011
Published: 14 Aug 2014
Term ends: Not estimatedThe source records don’t support an estimate.

Classification14 codes

A61K 31/506
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: not condensed and containing further heterocyclic rings
A61K 31/4439
Containing further heterocyclic ring systems: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/444
Containing further heterocyclic ring systems: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
A61K 45/06
Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00: mixtures of active ingredients without…

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Abstract

A compound of Formula (I)

wherein
R1 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, (C3-C5)cycloalkyl, or a 5- to 6-membered heterocycle,
(ii) 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, (C3-C5)cycloalkyl, oxo, —NH2, —NH(C1-C4)alkyl, —N((C1-C4)alkyl)2, —NHC(O)—(C1-C4)alkyl, or ═N—OH,
(iii) 5- to 6-membered heteroaryl optionally substituted with 1 to 3 substituents each independently 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, (C3-C5)cycloalkyl, or a 5- to 6-membered heterocycle, or
(iv) 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, (C3-C5)cycloalkyl, oxo, —NH2, —NH(C1-C4)alkyl, —N((C1-C4)alkyl)2, —NHC(O)—(C1-C4)alkyl, or ═N—OH;
R2 and R5 are each independently CH3 or H;
R3 and R4 are each independently CH3 or H, or taken together with the carbon atoms to which they are attached form a cyclopropyl;
and
R6 is (C3-C5)cycloalkyl, where the cycloalkyl is optionally substituted with hydroxy;
or a pharmaceutically acceptable salt thereof.

8 more elements

Facts

Application

14/113,718Filed 27 Apr 2012

Priority

IN 1256/DEL/201128 Apr 2011

Published

14 Aug 2014

Term ends

Not estimatedThe source records don’t support an estimate.

Classification14 codes

A61K 31/506
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: not condensed and containing further heterocyclic rings
A61K 31/4439
Containing further heterocyclic ring systems: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/444
Containing further heterocyclic ring systems: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
A61K 45/06
Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00: mixtures of active ingredients without…