کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1370823 | 981830 | 2011 | 4 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Optimization of the physicochemical and pharmacokinetic attributes in a 6-azauracil series of P2X7 receptor antagonists leading to the discovery of the clinical candidate CE-224,535
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
High throughput screening (HTS) of our compound file provided an attractive lead compound with modest P2X7 receptor antagonist potency and high selectivity against a panel of receptors and channels, but also with high human plasma protein binding and a predicted short half-life in humans. Multi-parameter optimization was used to address the potency, physicochemical and pharmacokinetic properties which led to potent P2X7R antagonists with good disposition properties. Compound 33 (CE-224,535) was advanced to clinical studies for the treatment of rheumatoid arthritis.
Figure optionsDownload as PowerPoint slide
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 12, 15 June 2011, Pages 3708–3711
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 12, 15 June 2011, Pages 3708–3711
نویسندگان
Allen J. Duplantier, Mark A. Dombroski, Chakrapani Subramanyam, Aimee M. Beaulieu, Shang-Poa Chang, Christopher A. Gabel, Crystal Jordan, Amit S. Kalgutkar, Kenneth G. Kraus, Jeff M. Labasi, Christopher Mussari, David G. Perregaux, Rick Shepard,