Abstract: Based on the SAR of TZDs, 3-methyl-1-phenyl-2-pyrazoline-5-one was selected as a substitute for TZD, 3-methyl-1-phenyl-4-{4-[(5-methyl-2-phenyloxazol-4-yl)methoxy]benzylene(benzyl)}-2-pyrazol-5-one compounds were designed and synthesized in order to find some more hypoglycemic active agents and further investigate the SAR of this class of compounds. The butanedione monoxime reacted with(substituted ) benzaldehyde via cyclization and chlorination to give 4-(chloromethyl)-5-methyl-2-phenyloxazole derivatives, which condensed with 4-hydroxybenzaldehyde or vanillin, and then followed by Knoevenagel reaction with 3-methyl-1-phenyl-2-pyrazol-5-one to give compounds Ⅰa—Ⅰh. Compounds Ⅰa—Ⅰh were hydrogenated with Pa-C to give Ⅱa—Ⅱh, and their hypoglycemic activity were evaluated with glucose oxidase kit and insulin load test on normal mouse. Sixteen new target compounds were synthesized. All the compounds were characterized by ¹H NMR, IR, MS and elemental analysis. The preliminary pharmacological test shows that the compounds have a good hypoglycemic activity and can enhance the action of insulin, especially Ib, Id and If.

Key words: Pyrazolone derivative, Synthesis, Hypoglycemic activity, Insulin sensitizers