Design, synthesis and antimycobacterial activity of some novel imidazo[1,2-c]pyrimidines.
Tuberculosis, due to its relentless nature, is now a major public health threat. The concomitant resurgence of TB with the MDR- or XDR-TB and HIV/AIDS pandemic has exposed the frailties of the current drug armatorium. Based on isosteric replacement and good 3D structural similarity between PA-824, a novel antimycobacterial agent undergoing clinical trials, and imidazo[1,2-c]pyrimidines, we have designed novel imidazo[1,2-c]pyrimidines. The designed molecules were synthesized by nucleophilic displacement of chloro group of various substituted 4-chloropyrimidines by ethanolamine followed by cyclisation of these 4-(2-hydroxyethyl)aminopyrimidines to imidazo[1,2-c]pyrimidines in good yield. All the compounds were screened for their antimycobacterial activity on Mycobacterium tuberculosis H37Rv strain by 1% proportion method. Some of the synthesized compounds exhibited potent antimycobacterial activity with MIC values in the range of 2-20 microg/mL.
Department of Pharmaceutical Chemistry, LM College of Pharmacy, Navrangpura, Ahmedabad 380 009, Gujarat, India. mahesh.chhabria@rediffmail.com
Mahesh T
MT
Chhabria
Mitesh H
MH
Jani
D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014376:Tuberculosis / Q000188:drug therapy*
D000995:Antitubercular Agents; D007093:Imidazoles; D011743:Pyrimidines; C029899:imidazole