α-SUBSTITUTED DERIVATIVES OF CARBOXYLIC ACIDS Russian patent published in 2003 - IPC

FIELD: organic chemistry, medicine, pharmacy, biochemistry. SUBSTANCE: invention relates to α-substituted derivatives of carboxylic acid characterized by general formulas: (I) , (II) , (III) and (IV) or their pharmacologically acceptable (C₁-C₆)-esters, or their pharmacologically acceptable amides or their pharmacologically acceptable salts. In above given formulas (I) and (II) R₁ represents (C₁-C₆)-alkyl group; R₂ represents hydrogen atom; R₃ represents: (i) hydrogen atom; (ii) (C₁-C₆)-alkyl group; (iii) benzyl group optionally comprising one substituent α₁; in phenyl moiety; A represents group =CH-. In formula (I) B represents oxygen atom and in formula (II) B represents oxygen atom of sulfur atom; W₁ and W₂ each represents independently alkylene group; X represents hydrogen atom; Y represents oxygen atom or group S(O)p (wherein p = whole number from 0 to 2); Z₁ represents: (i) (C₁-C₆)-alkoxy-group; (ii) (C₁-C₆)-alkylthio-group; (iii) phenyloxy-group (optionally comprising 1-3 substituents α₁,) (iv) phenylthio-group optionally comprising 1-3 substituents α₁, (v) hydroxy-group, or (vi) glucopyraneuronosyl group; and indicated substituent α₁ represents halogen atom; Z₂ represents glucopyraneuronosyl group or phenyl group comprising one substituent α₂. Indicated substituent α₁ represents halogen atom; indicated substituent α₂ represents adamantyl group. In formula (III) B represents oxygen or sulfur atom; Y represents oxygen or sulfur atom; benzyl group in phenyl moiety comprises optionally 1-5 substituents α₁, that represents: (i) (C₁-C₆)-alkyl group; (ii) halogen atom; (iii) hydroxyl group; Z₃ represents: (i) (C₁-C₆)-alkyl group; (ii) phenyl group comprising optionally 1-5 substituents α₁, having above indicated values. Other symbols in formula (III) have values indicated above. In formula (IV) B represents oxygen atom; R₃ represents: (i) hydrogen atom; (ii) (C₁-C₆)-alkylsulfonyl group; R₄ represents: (i) hydrogen atom; (ii) phenyl group comprising optionally one substituent α₁, Z₄ represents: (i) (C₁-C₆)-alkoxy-group; (ii) phenoxy-group comprising optionally 1- 3 substituents α₁, wherein indicated substituent α₁ represents: (i) (C₁-C₆)-alkyl group; (ii) adamantyl group; (iii) benzoyl group, or (iv) amino-group comprising optionally one substituent β, wherein substituent β represents phenylaminocarbonyl group comprising 1-5 substituents γ, in aryl moiety wherein indicated substituent γ represents (C₁-C₆)-alkyl group or (C₁-C₆)-halogenalkyl group. Other symbols have values determined above. Compounds of formulas (I), (II), (III) and (IV) elicit hypoglycemic activity and can be used as component of medicinal agent taken among agents improving insulin-resistance, hypoglycemic agents, immunoregulating agents, inhibitors of aldose reductase, inhibitors of 5-lipoxygenase, suppressors (inhibitors) of lipid peroxidation process, activators of PPAR, antagonists of leukotrienes, promoters in formation of adipocytes and antagonists of calcium. Invention relates also to pharmaceutical composition with hypoglycemic activity, agents improving above indicated states and to methods for treatment of these states, in part, to methods for prophylaxis or treatment of such diseases as diabetes mellitus, insufficient tolerance to glucose, neurosis, cataract, diseases of coronary artery and gestational diabetes mellitus. EFFECT: valuable medicinal properties of compounds. 142 cl, 6 tbl, 41 ex