کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1369559 | 981782 | 2014 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Highly potent and selective 3-N-methylquinazoline-4(3H)-one based inhibitors of B-RafV600E kinase
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Herein we describe the design of a novel series of ATP competitive B-Raf inhibitors via structure-based methods. These 3-N-methylquinazoline-4(3H)-one based inhibitors exhibit both excellent cellular potency and striking B-Raf selectivity. Optimization led to the identification of compound 16, a potent, selective and orally available agent with excellent pharmacokinetic properties and robust tumor growth inhibition in xenograft studies. Our work also demonstrates that by replacing an aryl amide with an aryl sulfonamide, a multikinase inhibitor such as AZ-628, can be converted to a selective B-Raf inhibitor, a finding that should have broad application in kinase drug discovery.
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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 24, Issue 8, 15 April 2014, Pages 1923–1927
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 24, Issue 8, 15 April 2014, Pages 1923–1927
نویسندگان
Steve Wenglowsky, Li Ren, Jonas Grina, Joshua D. Hansen, Ellen R. Laird, David Moreno, Victoria Dinkel, Susan L. Gloor, Gregg Hastings, Sumeet Rana, Kevin Rasor, Hillary L. Sturgis, Walter C. Voegtli, Guy Vigers, Brandon Willis, Simon Mathieu,