New aminopyrrole derivatives are alpha-2 adrenergic receptor modulators, useful for treating metabolic syndrome e.g. hypertension, high cholesterol, insulin resistance, glucose intolerance, atherosclerosis and coronary heart disease

摘要

Aminopyrrole derivatives (I) are new. Aminopyrrole derivatives of formula (I) and their salts are new. R12 : H, linear or branched 1-8C alkyl, 2-8C alkene, 1-8C acyl or 1-8C alkylsulfonyl; either R1-R5 : H, halo, linear or branched 1-8C alkyl, 2-8C alkene, linear or branched 1-8C alkoxy, 3-6C alkoxy, 5-6C bicycloalkyl, polyether chain, 1-5C perfluoroalkyl, 1-8C acyl, OH, SH, primary-, secondary- or tertiary-amine, CN, CO 2H or CO 2R1a; or R1R2, R2R3, R4R3, R4R5 : 4-6C ring; R1a : linear or branched 1-8C alkyl or 3-6C cycloalkyl; R6-R11 : H, linear or branched 1-8C alkyl, 2-8C alkene, 3-6C cycloalkyl or 1-5C perfluoroalkyl; n : 1 or 2; and R13 : H or CH 3. Provided that (I) excludes: R10, R11 is CH 3or H, and then R1 or R5 is cyclopropyl or H; R8, R9 is CH 3or H, and then R1 or R5 is cyclopropyl or H; R10, R11 is CH 3or H, and then R1 or R5 is Cl or H; and #R10, R11 is CH 3or H, then R1 or R5 is Cl or H and R3 is I. [Image] ACTIVITY : Analgesic; Antianginal; Hypotensive; Metabolic; Antidiabetic; Antiarteriosclerotic; Cardiant; Vasotropic; Nephrotropic; Anorectic. MECHANISM OF ACTION : Alpha-2 adrenergic receptor modulator. The alpha -2 adrenergic receptor modulating activity of (I) was tested using competition assay. The result showed that (3-chloro-2-methyl-phenyl)-(4-methyl-4,5-dihydro-3H-pyrrol-2-yl)-amine exhibited an inhibition constant (Ki) value of greater than 10 -> 5>mu m.