Chemistry and hypoglycemic activity of N-[[(Dialkylamino)alkoxy]phenyl]benzamidines

A series of N-[[(dialkylamino)alkoxyl]phenyl]benzamidines was synthesized and evaluated for hypoglycemic activity in the glucose-primed rat. Structure-activity relationship indicated that N'-phenyl-N-[4-[2(diisopropylamino)-ethoxy]phenyl]benzamidine dihydrobromide (7), N'-(4-chlorophenyl)-N-[4-[2-(diisopropylamino)ethoxy]phenyl]-benzamidine dihydrochloride (31), and N'-phenyl-N-[4-[(diisopropylamino)propoxy]phenyl]benzamidine dihydrobromide (11) are some of the more interesting compounds. A comparison of these hypoglycemic agents with classical standards (tolazamide, phenformin, and buformin) in several experimental models showed that the benzamidines seem to combine in one molecule some of the biological activities of the beta-cytotrophic sulfonylureas and some of the activities of the biguanides.