ANNELATED AZAHETEROCYCLIC AMIDES CONTAINING A PYRIMIDINE FRAGMENT AND METHOD FOR THE PRODUCTION AND USE THEREOF

摘要

The invention relates to novel annelated azaheterocycles of general formula 1, containing a pyrimidine fragment in the form of free bases or pharmaceutically acceptable salts, to pharmaceutical compositions containing said compounds and to the use of said compounds for producing medicinal preparations and therapeutic cocktails for treating human and homothermal diseases caused by a class I phosphoinositol kinase (PI3Ks) activity (and mutant isoforms thereof), in particular oncological diseases, to the use of said compounds as "molecular pharmacological instruments" for studying (in vitro and in vivo) biochemical mechanisms of (PI3Ks) kinase action, in particular class I kinases (PI3Ks) and mutant isoforms thereof. In the formula 1, X is an oxygen atom,a sulphur atom or an optionally nitrogen-substituted group; Y is a nitrogen atom or an optionally carbon-substituted CH group; Z is an oxygen atom; R1 is a hydrogen atom or optionally substituted C1-C6 alkyl or Z is a nitrogen atom which, together with an carbon atom, to which it is bound, form, via Z and R1, an optionally substituted imidazoline cycle; R2 and R3, independently from each other, are optionally substituted alkyl, optionally substituted aryl or heterocycle, wherein Y is an optionally carbon-substituted CH group, X=O,S, or R2 is hydrogen, R3 is substituted aminoalkyl or optionally substituted azaheterocyclyl alkyl, wherein optionally substituted azaheterocyclyl alkyl or R2 is hydrogen, R3 is substituted aminoalkyl or optionally substituted azaheterocyclyl alkyl, R1 is substituted aminoalkyl, substituted hydroxy alkyl or optionally substituted azaheterocyclyl alkyl, Y is an optionally carbon-substituted CH group, X=O,S; R4 is hydrogen or lower alkyl.