Synthesis and evaluation of Azepino[2, 1-b]quinazolones as antitussive agents
Kunal Nepalia
Laboratory for Drug Design, I.S.F. College of Pharmacy, Moga, Punjab, India.
Abstract:
Getting lead from vasicine, 7,8,9,10-tetrahydroazepino[2,1-b]quinazoline(6H)-12-one,a synthetic analogue of the alkaloid was synthesised and found to be 6-10 times more potent than aminophylline as per our previous investigation. The structural features of 7,8,9,10-tetrahydroazepino[2,1-b]quinazolones which comprises of azepine ring having nitrogen at bridgehead fused with quinazolone ring sufficiently fulfills some of the necessary features for antitussive activity. Thus a series of azepino[2,1-b]quinazolones has been synthesized and evaluated for antitussive activity using citric acid induced cough model in Guinea pigs. The compounds KN-1 to KN-16 caused marked decrease in cough frequency and increase in cough latency. KN-3 [2,4- dibromo 7,8,9,10-tetrahydroazepino [2,1-b] quinazolin-12(6H)-one] showed marked antitussive effect as compared to codeine (10 mg/kg) followed by KN-1 (7,8,9,10-tetrahydroazepino [2,1-b]quinazolin-12(6H)-one). Various substitutions were made at Ring A and B, all substituents other than bromine were found to reduce the potential of the unsubstituted 7,8,9,10-tetrahydroazepino[2,1-b] quinazolin-12(6H)-one as antitussive. The overall weight of evidence may conclude that the azepinoquinazolone skeleton is quite active as far as antitussive activity is concerned with the dibromo derivative (KN-3) showing better activity than codeine. Our study can thus give new dimensions to molecules with azepinoquinazolone skeleton as their potential as bronchodilator has already been proved.
