AROMATIC DERIVATIVES OF SULFANILAMIDES CARBONIC ANHYDRASE II (CA II) INHIBITORS, METHODS FOR PRODUCTION AND USE THEREOF

摘要

FIELD: chemistry.;SUBSTANCE: present invention relates to novel aromatic sulphonamide derivatives, general formula 1 and pharmaceutically acceptable salts thereof, which are selective inhibitors of carbonic anhydrase II (CA II). Substituted sulphonamides correspond to general formula 1; ,;where A is phenyl or thiophene; R₁ is C₁-C₅alkyl, C_-3C₆cycloalkyl, -C(O)R₃; provided that R₁ is not methyl, when A is phenyl, R₂ represents hydrogen; R₃ is a 5-6 member heterocyclyl with one or two heteroatoms, selected from nitrogen or oxygen atoms; R₂ is C₁-C₃alkyl, C₁-C₃alkoxy. Invention also relates to a method of producing compounds of general formula 1. Method involves two stages: a) sulphochlorination of corresponding oxazole derivative of general formula 5 (a-o) or 6 (a-j) with a mixture chlorosulphonic acid and thionyl chloride to produce intermediate sulphochlorides of formula 7 (a-o) or 8 (a-j), respectively, and b) with subsequent conversion of obtained sulphochlorides into primary sulphamides of formula 9 (b-o) or 10 (a-j) by reacting with ammonia according to following scheme; ,;where; ,;where R₁ is C₁-C₅alkyl, C₃-C₆cycloalkyl; NR'Rʺ is a morpholine or pyrrolidine.;EFFECT: compounds can be used for treating glaucoma, in particular, open-angle glaucoma, and other diseases caused by high intraocular pressure, age-related macular degeneration, diabetic macular edema, diabetic retinopathy, hypertensive retinopathy and retinal vasculopathy mediated by activity of carbonic anhydrase II.;11 cl, 2 dwg, 2 tbl, 57 ex