Synthesis and In Vitro Antibacterial Evaluation of Novel Imidazo[2′, 1′:5, 1]‐1, 2, 4‐triazolo[4, 3‐c]‐quinazoline Derivatives of 5‐Thioxo‐1, 2, 4‐triazole, 4‐Oxothiazolidine, and their Open‐chain Counterparts

Abstract

Two novel series of imidazo[2′, 1′:5, 1]-1, 2, 4-triazolo[4, 3-c]quinazolines bearing 5-thioxo-1, 2, 4-triazoles, 6a—f, and 4-oxothiazolidines, 7a—f, were synthesized from corresponding thiosemicarbazide derivatives, 5a—f. The stepwise methodology applied to the preparation of compounds 5a—f was initiated with reaction of the parent 3-amino-1, 2, 4-triazolo[4, 3-c]quinazolines, 2, with ethyl 2-chloroacetoacetate resulting in annelation of the imidazole ring to give esters, 3a—c. However, hydrazinolysis of these ester derivatives gave the corresponding acid hydrazides, 4a—c, which on reaction with the appropriate alkyl isothiocyanate yielded compounds 5a—f. In turn, compounds 5, were cyclized with potassium hydroxide or with ethyl bromoacetate to give the corresponding thioxotriazoles 6 and oxothiazolidines 7, respectively. All synthesized compounds were screened for their in vitro antibacterial activity against various Gram-positive and Gram-negative bacteria. Some test compounds were found to possess potent antibacterial activities. Compound, 7f, exhibited much higher potency than the reference standard ciprofloxacin, against both types of bacteria, particularly, Gram-positive organisms.