Abstract
The metabolite of loprinone (E-1020) in dogs, 5-(2-aminopyridin-5-yl)-1, 2-dihydro-6-methyl-2-oxo-3-pyridine-carbonitrile (9), was prepared via ozonolysis of imidazo[1, 2-α]pyridinylpyridines and evaluated for positive inotropic activity. Its potency was less than that of loprinone and milrinone. Among compounds related to loprinone which were synthesized using the versatile intermediates (10a, b) obtained during the preparation of 9, only 5-(2-aminoimidazo[1, 2-α]pyridin-6-yl)-1, 2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile (27) retained the activity of loprinone. The electron-withdrawing substituents at hte 2-position of imidazo[1, 2-α]pyridine reduced the activity of the parent compound.The ozonolysis of imidazo[1, 2-α]pyridine derivatives under neutral confitions afforded 2-acylaminopyridine derivatives in a 30-55% yield independent of the substituents at the 2-position of imidazo[1, 2-α]pyridine. It is possible to use imidazo[1, 2-α]pyridine as protected 2-aminopyridines, and 2, 3-unsubstituted imidazo[1, 2-α]pyridines are convenient for that purpose from the viewpoint of ease of preparation of the starting material.