2-Carboxamide Cycloamino Urea Derivatives in Combination with HSP90 Inhibitors for the Treatment of Proliferative Diseases

A pharmaceutical combination comprising:

• (a) a compound of formula (I),
• wherein
• A represents a heteroaryl selected from the group consisting of:
• R1 represents one of the following substituents:
• (1) unsubstituted or substituted, preferably substituted C1-C7-alkyl, wherein said substituents are independently selected from one or more, preferably one to nine of the following moieties:
• deuterium, 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 or more, preferably one to four of the following moieties:
• deuterium, C1-C4-alkyl (preferably methyl), fluoro, cyano, aminocarbonyl;
• (3) optionally substituted phenyl wherein said substituents are independently selected from one or more, preferably 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, 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 the group of deuterium, fluoro, chloro, hydroxy), phenylsulfonyl (which is unsubstituted or substituted by one or more, preferably one, C1-C7-alkyl, C1-C7-alkoxy, 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 the group of deuterium, fluoro), pyrrolidino, (which is unsubstituted or substituted by one or more substituents selected from the group of deuterium, hydroxy, oxo;
• particularly one oxo);
• (6) fluoro, chloro;
• R2 represents hydrogen;
• R3 represents (1) hydrogen, (2) fluoro, chloro, (3) optionally substituted methyl, wherein said substituents are independently selected from one or more, preferably one to three of the following moieties:
• deuterium, fluoro, chloro, dimethylamino;
• with the exception of (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({5-[2-(tert-butyl)-pyrimidin-4-yl]-4-methyl-thiazol-2-yl}-amide),
• or a pharmaceutically acceptable salt thereof;
• and
• (b) at least one Hsp90 inhibitor or a pharmaceutically acceptable salt thereof.