کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10592640 | 981796 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
From virtual to clinical: The discovery of PGN-1531, a novel antagonist of the prostanoid EP4 receptor
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: From virtual to clinical: The discovery of PGN-1531, a novel antagonist of the prostanoid EP4 receptor From virtual to clinical: The discovery of PGN-1531, a novel antagonist of the prostanoid EP4 receptor](/preview/png/10592640.png)
چکیده انگلیسی
Following a hit-finding and lead optimization programme against the EP4 receptor (EP4R), five structurally diverse series of hit compounds were discovered using a combination of virtual screening methods. The most favoured hit, compound 6, was demonstrated to be a competitive antagonist of the EP4R. Compound 73 was identified following several rounds of optimization, which centred on improving both the primary EP4R affinity and selectivity against the related EP2R as well as the aqueous solubility. The work culminated in the identification of PGN-1531, the sodium salt of 73, which showed a marked improvement in solubility (>10Â mg/mL). PGN-1531 is a potent and selective antagonist at EP4Rs in vitro and in vivo, with the potential to alleviate the symptoms of migraine that result from cerebral vasodilatation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 24, Issue 9, 1 May 2014, Pages 2212-2221
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 24, Issue 9, 1 May 2014, Pages 2212-2221
نویسندگان
Jon Sutton, David E. Clark, Christopher Higgs, Marcel J. de Groot, Neil V. Harris, Andrea Taylor, Peter M. Lockey, Karen Maubach, Amanda Woodrooffe, Richard J. Davis, Robert A. Coleman, Kenneth L. Clark,