Odingo, Joshua; O’Malley, Theresa; Kesicki, Edward A.; Alling, Torey; Bailey, Mai Ann; Early, Julie; Ollinger, Juliane; Dalai, Suryakanta; Kumar, Naresh; Singh, Ravindra Vikram; Hipskind, Philip A.; Cramer, Jeffrey W.; Ioerger, Thomas; Sacchettini, James; Vickers, Richard; Parish, Tanya published the artcile< Synthesis and evaluation of the 2,4-diaminoquinazoline series as anti-tubercular agents>, COA of Formula: C6H2Cl2N2S, the main research area is diaminoquinazoline preparation tuberculostatic Mycobacterium tuberculosis; 2,4-Diaminoquinazoline; Antibacterial activity; Dioxygenase; Mycobacterium tuberculosis; Tuberculosis.
The 2,4-diaminoquinazoline class of compounds has previously been identified as an effective inhibitor of Mycobacterium tuberculosis growth. The authors conducted an extensive evaluation of the series for its potential as a lead candidate for tuberculosis drug discovery. Three segments of the representative mol. N-(4-fluorobenzyl)-2-(piperidin-1-yl)quinazolin-4-amine were examined systematically to explore structure-activity relationships influencing potency. The authors determined that the benzylic amine at the 4-position, the piperidine at 2-position and the N-1 (but not N-3) are key activity determinants. The 3-deaza analog retained similar activity to the parent mol. Biol. activity was not dependent on iron or carbon source availability. The authors demonstrated through pharmacokinetic studies in rats that good in vivo compound exposure is achievable. A representative compound demonstrated bactericidal activity against both replicating and nonreplicating M. tuberculosis. The authors isolated and sequenced M. tuberculosis mutants resistant to this compound and observed mutations in Rv3161c, a gene predicted to encode a dioxygenase, suggesting that the compound may act as a prodrug.
Bioorganic & Medicinal Chemistry published new progress about Mycobacterium tuberculosis. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, COA of Formula: C6H2Cl2N2S.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia