Scientific Publications

Synthesis and antiplasmodial activity of novel 2,4-diaminopyrimidines.

Publication TypeJournal Article
AuthorsMartyn, DC, Nijjar A., Celatka CA, Mazitschek R., Cortese JF, Tyndall E., Liu H., Fitzgerald MM, O'Shea TJ, Danthi S., and Clardy J.
AbstractTwo 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 R(2) significantly affecting activity. A subsequent series addressed high LogD values by introducing more polar side groups, with the most active compounds possessing diazepine and N-benzyl-4-aminopiperidyl groups at R(1)/R(2). A final series attempted to address high in vitro microsomal clearance by replacing the C6-Me group with CF(3), however antiplasmodial activity decreased without any improvement in clearance. The C6-CF(3) group decreased hERG inhibition, probably as a result of decreased amine basicity at C2/C4.
Year of Publication2010
JournalBioorganic & medicinal chemistry letters
Volume20
Issue1
Pages228-31
Date Published (YYYY/MM/DD)2010/01/01
ISSN Number0960-894X
DOI10.1016/j.bmcl.2009.10.133
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/19914064?dopt=Abstract