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.
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.
Nasr
Magda N
MN
Department of Pharmaceutical Organic Chemistry, College of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
Gineinah
Magdy M
MM
El-Bendary
Eman R
ER
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D015169:Colony Count, Microbial; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011799:Quinazolines / Q000138:chemical synthesis / Q000494:pharmacology*; D052999:Quinazolinones; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology*
C482262:4-oxothiazolidine; C482261:5-thioxo-1,2,4-triazole; D000900:Anti-Bacterial Agents; D011799:Quinazolines; D052999:Quinazolinones; D013844:Thiazoles; D014230:Triazoles; C121779:triazolo(4,3-a)quinazolinone