212960-46-8Relevant academic research and scientific papers
Synthesis and biological activity of substituted 2,4-diaminopyrimidines that inhibit Bacillus anthracis
Nammalwar, Baskar,Bunce, Richard A.,Berlin, K. Darrell,Bourne, Christina R.,Bourne, Philip C.,Barrow, Esther W.,Barrow, William W.
, p. 387 - 396 (2012/10/08)
A series of substituted 2,4-diaminopyrimidines 1 has been prepared and evaluated for activity against Bacillus anthracis using previously reported (±)-3-{5-[(2,4-diamino-5-pyrimidinyl)methyl]-2,3-dimethoxyphenyl} -1-(1-propyl-2(1H)-phthalazinyl)-2-propen-1-one (1a), with a minimum inhibitory concentration (MIC) value of 1-3 μg/mL, as the standard. In the current work, the corresponding isobutenyl (1e) and phenyl (1h) derivatives displayed the most significant activity in terms of the lowest MICs with values of 0.5 μg/mL and 0.375-1.5 μg/mL, respectively. It is likely that the S isomers of 1 will bind the substrate-binding pocket of dihydrofolate reductase (DHFR) as in B. anthracis was found for (S)-1a. The final step in the convergent synthesis of target systems 1 from (±)-1-(1-substituted-2(1H)- phthalazinyl)-2-propen-1-ones 6 with 2,4-diamino-5-(5-iodo-3,4-dimethoxybenzyl) pyrimidine (13) was accomplished via a novel Heck coupling reaction under sealed-tube conditions.
