Substituted thiazoles and oxazoles, drug containing such a compound, use of such a compound for the manufacture of a medicament, method of preparation of the drug and method of preparation of the compounds, and substituted thiazoles and oxazoles with intermediate use

摘要

Thiazoles and oxazoles of the formula IMAGE in which A denotes an n-alkylene group which is optionally mono- or disubstituted by methyl or ethyl groups, X denotes an oxygen or sulphur atom, R1 denotes a hydrogen or halogen atom, a trifluoromethyl, alkyl, phenyl or piperidino group or an amino group which is optionally substituted by one or two alkyl groups or an alkanoyl or benzoyl group, R2 denotes a hydrogen atom or an alkyl group, R3 denotes a hydrogen atom or an alkyl group which can be substituted in the 2- or 3-position by a hydroxyl group, or R3 together with R4 denotes an alkoxycarbonylmethylene group or an ethylene group, where the methylene group adjacent to the N or O atom can be replaced by a carbonyl group, R4 denotes a hydrogen atom, an alkyl group which is optionally substituted by a phenyl, carboxyl, alkoxycarbonyl or cyano group or, in the 2- or 3-position, by a hydroxyl group, or an alkenyl group and R5 denotes a hydroxyl, alkoxy, carboxyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl group, an alkoxy group having 1 to 6 carbon atoms which is substituted at the end by a carboxyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl group, an alkoxy group having 2 to 7 carbon atoms which is substituted at the end by a hydroxyl, alkoxy, phenylalkoxy, amino, alkylamino, dialkylamino, pyrrolidino, piperidino or hexamethyleneimino group, or an ethylene group which is optionally substituted by an alkyl group and which is substituted at the end by a carboxyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl group, their optical isomers, their diastereomers and their acid addition salts. The novel lactams of the formula I, their optical isomers and diastereomers are useful intermediates for the preparation of the morpholines of the formula I, in which R3 and R4 together represent an ethylene group. These morpholines and the other compounds of the above formula I (excepting the lactams), their optical isomers and their diastereomers and also their acid addition salts, in particular their physiologically tolerable acid addition salts with inorganic or organic acids, have valuable pharmacological properties, namely an effect on the metabolism, preferably a blood sugar-lowering and body fat-reducing effect, and also a lowering effect on the atherogenic beta -lipoproteins VLDL and LDL. The novel compounds of the above formula I can be prepared by methods which are known per se.