Correlation of chick embryo teratogenicity with the nicotinic activity of a series of tetrahydropyrimidines.

Abstract

AbstractNicotine, anabasine, nornicotine, β‐nicotyrine, and 34 substituted 1,4,5,6‐tetrahydropyrimidines, 2‐imidazolines, and 4,5,6,7‐tetrahydro‐1, H‐l, 3‐diazepines were injected into the yolk sac of chick eggs on day 4 of incubation at a dose of 1 or 2.5 mg/egg. The embryopathic results were compared with toxicological and pharmacological data and chemical structure. Abnormalities were similar to those induced by nicotine and anabasine but only compounds with nicotinic activity, as measured on the chick spinalis muscle, were teratogenic. All but one of the teratogenic compounds were 2‐pyridylsubstituted, and in this series teratogenic and nicotinic potency decreased in the order 3′‐>4′‐>2′‐pyridyl. There was a highly significant negative correlation between spine length and nicotinic potency of the compounds.