Synthesis and hypoglycemic activity of pyridyl alcohols

The potent hypoglycemic activity of 3-(3-methyl-2-pyridyl)propan-1-ol (1) prompted us to synthesize and study related structures. Some of the 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, usually at a dose of 150 mg/kg po. 1, the corresponding propionic acid 12, the acetate and methyl ether of 1 (22 and 23), and the 5-methyl analogue of 1 (29) were of comparable hypoglycemic potency. However, these compounds all caused a concomitant elevation of hepatic triglycerides and/or death in the test animals when observations were continued for 4--24 h.