کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1358057 | 981317 | 2014 | 11 صفحه PDF | دانلود رایگان |
Structure–activity relationships of 2-alkynyladenine derivatives were explored by varying substituents at the 9-, 8- and 2-positions of the purine moiety in order to optimize A2A adenosine receptor antagonist activity in vitro. A propargyl group at the 9-position was found to be important for A2A antagonist activity, and the introduction of a halogen, aryl, or heteroaryl at the 8-position further enhanced activity. A series of 8-substituted 2-alkynyl-N9-propargyladenine derivatives exhibited potent antagonist activity, with IC50 values in the low nM range. Compound 4a from this series was found to be orally active at a dose of 3 mg/kg in a mouse catalepsy model and a 6-hydroxydopamine-lesioned rat model of Parkinson’s disease.
A series of 8-substituted 2-alkynyl-N9-propargyladenine derivatives exhibited potent antagonist activity for A2A adenosine receptor, with IC50 values in the low nM range.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 22, Issue 12, 15 June 2014, Pages 3072–3082