1348084-98-9Relevant academic research and scientific papers
Synthesis and antiplasmodial activity of novel 2,4-diaminopyrimidines
Martyn, Derek C.,Nijjar, Amarjit,Celatka, Cassandra A.,Mazitschek, Ralph,Cortese, Joseph F.,Tyndall, Erin,Liu, Hanlan,Fitzgerald, Maria M.,O'Shea, Thomas J.,Danthi, Sanjay,Clardy, Jon
experimental part, p. 228 - 231 (2010/04/02)
Two sets of diaminopyrimidines, totalling 45 compounds, were synthesized and assayed against Plasmodium falciparum. The SAR was relatively shallow, with only the presence of a 2-(pyrrolidin-1-yl)ethyl group at R2 significantly affecting activity. A subsequent series addressed high Log D values by introducing more polar side groups, with the most active compounds possessing diazepine and N-benzyl-4-aminopiperidyl groups at R1/R2. A final series attempted to address high in vitro microsomal clearance by replacing the C6-Me group with CF3, however antiplasmodial activity decreased without any improvement in clearance. The C6-CF3 group decreased hERG inhibition, probably as a result of decreased amine basicity at C2/C4.
