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US 8,476,268 B2Granted
Pyrrolidine-1,2-dicarboxamide derivatives
AssigneeNovartis AG
InventorsRobin Alec Fairhurst, Vito Guagnano, Patricia Imbach-Weese, Giorgio Caravatti, Pascal Furet
Life of this patent
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Abstract
The present invention relates to a compound of formula (I) or a salt thereof, wherein the substituents are as defined in the description, to compositions and use of the compounds in the treatment of diseases ameloriated by inhibition of phosphatidylinositol 3-kinase.
Claims5
A compound of formula (IA)
- or a salt thereof, wherein
- R1 represents one of the following substituents:
- (1) substituted, C1-C7-alkyl, wherein said substituents are independently selected from one to nine of the following moieties:
- deuterium and fluoro, or one to two of the following moieties:
- C3-C5-cycloalkyl;
- (2) optionally substituted C3-C5-cycloalkyl wherein said substituents are independently selected from one to four of the following moieties:
- deuterium, methyl, fluoro, cyano and aminocarbonyl;
- (3) optionally substituted phenyl wherein said substituents are independently selected from one to two of the following moieties:
- deuterium, halo, cyano, C1-C7-alkyl, C1-C7-alkylamino, di(C1-C7-alkyl)amino, C1-C7-alkylaminocarbonyl, di(C1-C7-alkyl)aminocarbonyl and C1-C7-alkoxy;
- (4) optionally mono- or di-substituted amine;
- wherein said substituents are independently selected from the following moieties:
- deuterium;
- C1-C7-alkyl which is unsubstituted or substituted by one or more substituents selected from deuterium, fluoro, chloro and hydroxy;
- phenylsulfonyl which is unsubstituted or substituted by one or more groups selected from C1-C7-alkyl, C1-C7-alkoxy and di(C1-C7-alkyl)amino-C1-C7-alkoxy);
- (5) substituted sulfonyl;
- wherein said substituent is selected from the following moieties:
- C1-C7-alkyl which is unsubstituted or substituted by one or more substituents selected from deuterium and fluoro;
- and pyrrolidino which is unsubstituted or substituted by one or more substituents selected from deuterium, hydroxy and oxo;
- (6) fluoro and chloro;
- and
- R3 is selected from:
- hydrogen;
- fluoro;
- chloro;
- and optionally substituted methyl;
- wherein said substituents are independently selected from one to three of the following moieties:
- deuterium, fluoro, chloro and dimethylamino.
24 more elements
A compound, in free form or in pharmaceutically acceptable salt form, selected from,
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-{[5-(2-cyclopropyl-pyridin-4-yl)-4-methyl-thiazol-2-yl]-amide};
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({5-[2-(2-fluoro-phenyl)-pyridin-4-yl]-4-methyl-thiazol-2-yl}-amide);
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-{[5-(2-cyclobutyl-pyridin-4-yl)-4-methyl-thiazol-2-yl]-amide};
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(1-methyl-cyclopropyl)-pyridin-4-yl]-thiazol-2-yl}-amide);
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(1-methyl-cyclobutyl)-pyridin-4-yl]-thiazol-2-yl}-amide);
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-{[5-(2-cyclobutyl-pyridin-4-yl)-thiazol-2-yl]-amide};
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({5-[2-(1-methyl-cyclopropyl)-pyridin-4-yl]-thiazol-2-yl}-amide);
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({5-[2-(1-trifluoromethyl-cyclopropyl)-pyridin-4-yl]-thiazol-2-yl}-amide);
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide);
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({5-[2-(1-trifluoromethyl-cyclobutyl)-pyridin-4-yl]-thiazol-2-yl}-amide);
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(1-trifluoromethyl-cyclopropyl)-pyridin-4-yl]-thiazol-2-yl}-amide);
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(1-trifluoromethyl-cyclobutyl)-pyridin-4-yl]-thiazol-2-yl}-amide);
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({5-[2-(1-methyl-cyclobutyl)-pyridin-4-yl]-thiazol-2-yl}-amide);
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({5-[2-(1-cyano-cyclopropyl)-pyridin-4-yl]-4-methyl-thiazol-2-yl}-amide);
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({5-[2-(1-cyano-cyclobutyl)-pyridin-4-yl]-4-methyl-thiazol-2-yl}-amide);
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({5-[2-(1-carbamoyl-cyclobutyl)-pyridin-4-yl]-4-methyl-thiazol-2-yl}-amide);
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({5-[2-(2-dimethylamino-1,1-dimethyl-ethyl)-pyridin-4-yl]-4-methyl-thiazol-2-yl}-amide);
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-{[5-(2-diethylamino-pyridin-4-yl)-4-methyl-thiazol-2-yl]-amide};
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-{[5-(2-diethylamino-pyridin-4-yl)-thiazol-2-yl]-amide};
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-[(5-{2-[1-(4-methoxy-phenyl)-1-methyl-ethyl]-pyridin-4-yl}-4-methyl-thiazol-2-yl)-amide];
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-[(5-{2-[1-(4-methoxy-phenyl)-1-methyl-ethyl]-pyridin-4-yl}-thiazol-2-yl)-amide];
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-[(5-{2-[1-(4-methoxy-phenyl)-cyclopropyl]-pyridin-4-yl}-4-methyl-thiazol-2-yl)-amide];
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-[(5-{2-[1-(4-methoxy-phenyl)-cyclopropyl]-pyridin-4-yl}-thiazol-2-yl)-amide];
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-{[5-(2-{1-[4-(3-dimethylamino-propoxy)-phenyl]-1-methyl-ethyl]-pyridin-4-yl)-4-methyl-thiazol-2-yl}-amide} (Example 31);
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(1-d3-methyl-cyclobutyl)-pyridin-4-yl]-thiazol-2-yl}-amide);
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({5-[2-(1-d3-methyl-cyclobutyl)-pyridin-4-yl]-thiazol-2-yl}-amide);
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-d3-methyl-5-[2-(1-methyl-cyclopropyl)-pyridin-4-yl]-thiazol-2-yl}-amide);
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-d3-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide);
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-dimethylaminomethyl-5-[2-(1-d3-methyl-cyclobutyl)-pyridin-4-yl]-thiazol-2-yl}-amide);
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-chloro-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide);
- and
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-fluoromethyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide);
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({5-[2-(2-fluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-4-methyl-thiazol-2-yl}-amide);
- and
- (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({5-[2-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-pyridin-4-yl]-4-methyl-thiazol-2-yl}-amide.
32 more elements
Dependencies are inferred from the claim text.