کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1372461 | 981870 | 2010 | 4 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Synthesis and antiplasmodial activity of novel 2,4-diaminopyrimidines Synthesis and antiplasmodial activity of novel 2,4-diaminopyrimidines](/preview/png/1372461.png)
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.
The synthesis, antiplasmodial activity and selected DMPK properties of novel 2,4-diaminopyrimidines is reported.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 20, Issue 1, 1 January 2010, Pages 228–231