کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1367338 981625 2006 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Development of 6-substituted indolylquinolinones as potent Chek1 kinase inhibitors
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Development of 6-substituted indolylquinolinones as potent Chek1 kinase inhibitors
چکیده انگلیسی

Through a comparison of X-ray co-crystallographic data for 1 and 2 in the Chek1 active site, it was hypothesized that the affinity of the indolylquinolinone series (2) for Chek1 kinase would be improved via C6 substitution into the hydrophobic region I (HI) pocket. An efficient route to 6-bromo-3-indolyl-quinolinone (9) was developed, and this series was rapidly optimized for potency by modification at C6. A general trend was observed among these low nanomolar Chek1 inhibitors that compounds with multiple basic amines, or elevated polar surface area (PSA) exhibited poor cell potency. Minimization of these parameters (basic amines, PSA) resulted in Chek1 inhibitors with improved cell potency, and preliminary pharmacokinetic data are presented for several of these compounds.

6-Substituted 3-(indol-2-yl)quinolinones are reported as potent Chek1 inhibitors.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 16, Issue 22, 15 November 2006, Pages 5907–5912
نویسندگان
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