| 摘要 |
3-Aryl-5-alkyl-1,2,4-oxadiazole derivatives are provided to reduce eating by competing with MCH R1(melanin-concentrating hormone receptor subtype-1) associated with obesity, so that the compounds are useful for preventing or treating obesity. The 3-aryl-5-alkyl-1,2,4-oxadiazole derivatives represented by the formula(1) are useful as antagonist of MCH R1, wherein R1 is (C3-C5) branched alkyl, (C1-C3)dialkylamino(C1-C3)alkyl or (C1-C3) linear alkyl which is optionally substituted by pyridine, piperidine or (C5-C7) cycloalkyl; R2 is halogen-substituted phenyl, CF3-substituted phenyl, phenyl substituted by phenoxy which is optionally substituted by halogen or (benzo[1,3]dioxol-5-yl)phenyl; and X is -NHCO or -NHCONH-. A method for preparing the 3-aryl-5-alkyl-1,2,4-oxadiazole derivatives represented by the formula(1a) comprises the steps of: (1) reacting 4-aminobenzonitrile represented by the formula(2) with organic acid(R2COOH) in the presence of solvent and binding reagent to prepare amide compounds represented by the formula(3); (2) reacting the amide compounds represented by the formula(3) with hydroxylamine hydrochloride in the presence of solvent to prepare amidoxime represented by the formula(4); and (3) reacting the amidoxime represented by the formula(4) with another organic acid(R1COOH) in the presence of solvent and binding reagent to prepare 1,2,4-oxadiazole ring.
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