کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1394399 | 1501157 | 2013 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Selective and potent adenosine A3 receptor antagonists by methoxyaryl substitution on the N-(2,6-diarylpyrimidin-4-yl)acetamide scaffold Selective and potent adenosine A3 receptor antagonists by methoxyaryl substitution on the N-(2,6-diarylpyrimidin-4-yl)acetamide scaffold](/preview/png/1394399.png)
The influence of diverse methoxyphenyl substitution patterns on the N-(2,6-diarylpyrimidin-4-yl)acetamide scaffold is herein explored in order to modulate the A3 adenosine receptor antagonistic profile. As a result, novel ligands exhibiting excellent potency (Ki on A3 AR < 20 nM) and selectivity profiles (above 100-fold within the adenosine receptors family) are reported. Moreover, our joint theoretical and experimental approach allows the identification of novel pharmacophoric elements conferring A3AR selectivity, first established by a robust computational model and thereafter characterizing the most salient features of the structure–activity and structure–selectivity relationships in this series.
Diverse methoxyphenyl substitutions on the N-(2,6-diarylpyrimidin-4-yl)acetamide scaffold have been explored through a collaborative computational and synthetic effort, characterizing and rationalizing their enhanced potency and selectivity on the human adenosine A3 receptor.Figure optionsDownload as PowerPoint slideHighlights
► Novel 2,6-diaryl-4-acetamidopyrimidines were obtained.
► Three compounds exhibit low nanomolar Ki values.
► Potent and selective A3 adenosine receptor antagonists were identified.
► A putative binding mode for the compounds prepared was proposed.
Journal: European Journal of Medicinal Chemistry - Volume 59, January 2013, Pages 235–242