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Synthesis and Antimycobacterial Activity of Azetidine‐, Quinazoline‐, and Triazolo‐thiadiazole‐containing Pyrazines
Author(s) -
Bonde Chandrakant G.,
Peepliwal Ashok,
Gaikwad Naresh J.
Publication year - 2010
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200900165
Subject(s) - antimycobacterial , lipophilicity , chemistry , quinazoline , mycobacterium tuberculosis , aryl , stereochemistry , minimum inhibitory concentration , combinatorial chemistry , in vitro , tuberculosis , organic chemistry , biochemistry , medicine , alkyl , pathology
The re‐emergence of tuberculosis (TB) as a global health problem over the past few decades, accompanied by the rise of drug‐resistant strains of Mycobacterium tuberculosis , emphasizes the need for the discovery of new therapeutic drugs against this disease. The emerging serious problem both in terms of TB control and clinical management prompted us to synthesize a novel series of N ‐[2‐(substituted aryl)‐3‐chloro‐4‐oxoazetidin‐1‐yl]‐2‐(pyrazin‐2‐yloxy)acetamide, 6‐(substituted aryl)‐3‐[(pyrazin‐2‐yloxy)methyl][1,2,4]triazolo[3,4‐ b ][1,3,4]thiadiazole, and N ‐[6‐({2‐[(pyrazin‐2‐yloxy)acetyl] hydrazino}sulfonyl)‐2‐methyl‐4‐oxo‐1,4‐dihydroquinazolin‐3(2 H )yl]‐substituted aryl sulfonamides. The compounds were synthesized using the appropriate synthetic route. All synthesized compounds were assayed in vitro for antimycobacterial activity against the H37 Rv strain of Mycobacterium tuberculosis . The minimum inhibitory concentration (MIC) was determined for the test compounds as well as for the reference standards. The compound which exhibited good antimycobacterial activity contains the substituents fluorine and methoxy. These electron‐withdrawing or ‐donating substituents amend the lipophilicity of the test compounds which, in turn, alter the permeability across the bacterial cell membrane. Compounds 28 , 37 , and 43 showed good antimycobacterial activity while compound 51 showed a promising antimycobacterial activity.