Synthesis and antimycobacterial activity of azetidine-, quinazoline-, and triazolo-thiadiazole-containing pyrazines.
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(2H)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.
Bonde
Chandrakant G
CG
School of Pharmacy and Technology Management (Shirpur Campus), NMiMS University, Dist-Dhule, Shirpur (M.S.), India. chandubonde@yahoo.co.in
Peepliwal
Ashok
A
Gaikwad
Naresh J
NJ
D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D001384:Azetidines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D002473:Cell Wall / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D010539:Permeability; D011719:Pyrazines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D011799:Quinazolines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D013844:Thiazoles / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*
D000995:Antitubercular Agents; D001384:Azetidines; D011719:Pyrazines; D011799:Quinazolines; D013830:Thiadiazoles; D013844:Thiazoles