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Studies on Hypolipidemic Agents. II. Synthesis and Pharmacological Properties of Alkylpyrazole Derivatives

1984; Pharmaceutical Society of Japan; Volume: 32; Issue: 4 Linguagem: Inglês

10.1248/cpb.32.1568

1347-5223

KUNIO SEKI, JUNICHI ISEGAWA, Minoru Fukuda, M. OHKI,

Retinoids in leukemia and cellular processes

A series of 5-alkylpyrazole derivatives was synthesized and evaluated for potent hypolipidemic activity in rats. Many pyrazole derivatives with an alkyl group at the 5 position of the pyrazole ring were found to possess high hypolipidemic activity. Homologation of the alkyl chain led to marked increase in activity, but introduction of other substituents at other sites on the pyrazole ring failed to enhance the activity. In addition, the replacement of the pyrazole ring with an isoxazole ring resulted in a marked decrease in activity. Among the compounds tested, 5-n-tridecylpyrazole-3-carboxylic acid (5k) exhibited the most favorable spectrum of activity and was as effective as clofibrate. This compound, 5k, showed fairly low toxicity in an acute test (LD50=10.0g/kg) and hence is now undergoing further pharmacological evaluation.