کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1393993 1501124 2015 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cyclopentyl-pyrimidine based analogues as novel and potent IGF-1R inhibitor
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Cyclopentyl-pyrimidine based analogues as novel and potent IGF-1R inhibitor
چکیده انگلیسی


• Identified 2-amino-4-pyrazolecyclopentylpyrimidine scaffold as IGF-1R inhibitor.
• Compound 6f exhibit promising cell based activity across a panel of cell lines.
• Compound 6f may serve as a lead for developing newer anti-cancer agents.

A series of novel 2-amino-4-pyrazolecyclopentylpyrimidines have been prepared and evaluated as IGF-1R tyrosin kinase inhibitors. The in vitro activity was found to depend strongly on the substitution pattern in the 2- amino ring, 4-pyrazolo moieties and size of fused saturated ring with the central pyrimidine core. A stepwise optimization by combination of active fragments led to discovery of compound 6f and 6k, two structures with IGF-1R IC50 of 20 nM and 10 nM, respectively. 6f was further profiled for its anti cancer activity across various cell lines and pharmacokinetic studies in Sprague Dawley rats.

Design, synthesis, and biological evaluation of novel 2-amino-4-pyrazolecyclopentylpyrimidines as IGR-1R tyrosin kinase inhibitors.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 92, 6 March 2015, Pages 246–256
نویسندگان
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