5-Substituted-1,2,4-thiadiazolyl derivatives, process of their preparation and pharmaceutical composition containing thereof

This invention concerns compounds of formula (I), the N-oxide forms, the pharmaceutically acceptable acid addition salts and stereochemically isomeric forms thereof, wherein X is CH or N; R1 is hydrogen, C1-6alkyl, C1-6alkyloxy, C1-6alkylthio, amino, mono- or di(C1-6alkyl)amino, Ar1, Ar1NH-, C3-6cycloalkyl, hydroxymethyl or benzyloxymethyl; R2 is hydrogen, C1-6alkyl, amino, aminocarbonyl, mono- or di(C1-6alkyl)amino, C1-6alkyloxycarbonyl, C1-6alkylcarbonylamino, hydroxy or C1-6alkyloxy; R3, R4 and R5 are each independently selected from hydrogen, halo, C1-6alkyl, C1-6alkyloxy, trifluoromethyl, nitro, amino, cyano, azido, C1-6alkyloxyC1-6alkyl, C1-6alkylthio, C1-6alkyloxycarbonyl or Het1; formula (1) is Ar2, Ar2CH2- or Het2; Ar1 and Ar2 optionally substituted phenyl; Het1 and Het2 are optionally substituted monocyclic heterocycles; having angiogenesis inhibiting activity; their preparation, compositions containing them and their use as a medicine. 5-Substituovaný 1,2,4-tiadiazolylový derivát vzorca (I), jeho N-oxidové formy, farmaceuticky prijateľné adičné soli s kyselinami a stereochemicky izomérne formy, kde R1 je vodík, C1-4alkyl, alebo di(C1-4alkyl)aminoskupina; R3, R4 a R5 sú každý nezávisle vybraný z vodíka, halogénu, C1-4alkylu, C1-4alkyloxyskupiny alebo trifluórmetylu; kruh s A je Ar2, Ar2CH2- alebo Het2, kde Ar2 je fenyl a Het2 je tiadiazolyl, pyridinyl, pyrimidinyl alebo pyrazinyl. Spôsob jeho prípravy a použitie ako inhibítor angiogenézy a na výrobu liečiva, farmaceutický prostriedok, medziprodukt a spôsob jeho prípravy.ŕ