Synthesis and hypoglycemic activity of pyridylalcohols

Abstract
The potent hypoglycemic activity of 3-(3-methyl-2-pyridyl)propan-1-ol (1) prompted synthesis and study of related structures. Some variables studied were the position of the methyl and alcohol side chains, the distance between the heterocyclic ring and the hydroxyl group, the effect of additional nuclear substitution and the effects of branching and substitution on the alcohol side chain. The compounds were tested in 48 h fasted rats at a dose of 150 mg/kg po (por os). The corresponding propionic acid, the acetate and methyl ether of 1 and the 5-methyl analogue of 1 had comparable hypoglycemic potency but compounds all caused a concomitant elevation of hepatic triglycerides and/or death in the test animals when observations were continued for 4-24 h.