کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1371488 981846 2012 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors
چکیده انگلیسی

Variously substituted indolin-2-ones were synthesized and evaluated for activity against KDR, Flt-1, FGFR-1 and PDGFR. Extension at the 5-position of the oxindole ring with ethyl piperidine (compound 7i) proved to be the most beneficial for attaining both biochemical and cellular potencies. Further optimization of 7i to balance biochemical and cellular potencies with favorable ADME/ PK properties led to the identification of 8h, a compound with a clean CYP profile, acceptable pharmacokinetic and toxicity profiles, and robust efficacy in multiple xenograft tumor models.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 22, Issue 15, 1 August 2012, Pages 4979–4985
نویسندگان
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