Chemistry and hypoglycemic activity of benzimidoylpyrazoles

A series of benzimidoylpyrazoles was synthesized and evaluated as hypoglycemic agents. Methyl 1-(N-cyclohexylbenzimidoyl)-5-methyl-3-pyrazolecarboxylate (13) and methyl 1-[N-(4-methoxyphenyl)benzimidoyl]-5-methyl-3-pyrazolecarboxylate (33) are two of the more interesting compounds. A comparison of these benzimidoylpyrazoles with classical standards (tolazamide, phenformin, and buformin) in several experimental models show that these compounds seem to combine in one molecule some of the biological activities of the beta-cytotrophic sulfonylureas and some of the activities of the biguanides. A synthetic scheme for the preparation of the benzimidolypyrazoles and a preliminary structure-activity relationship are presented.