کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5219741 1383366 2012 16 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Design and synthesis of 2(1H)-pyrazinones as inhibitors of protein kinases
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Design and synthesis of 2(1H)-pyrazinones as inhibitors of protein kinases
چکیده انگلیسی

Kinase enzymes play a key role in the development and progression of cancer. Inhibitors of deregulated kinases are effective small molecule anticancer drugs. The 2(1H)-pyrazinone heterocycle is a previously unexploited motif that can fulfil the structural requirements for ATP-competitive inhibition of kinases. Rapid solution-phase syntheses of novel 3,5- and 3,6-disubstituted-2(1H)-pyrazinones were developed through selective, sequential substitution of 2,5-dihalo-3-benzyloxypyrazine and 3,5-dihalo-2(1H)-pyrazinone intermediates. Palladium-catalysed cross-couplings and SNAr reactions were used to introduce substituents chosen on the basis of the calculated physicochemical properties of the target pyrazinones. Representative compounds demonstrated good solubility, kinase inhibitory activity and antiproliferative activity in human tumour cells, confirming the suitability of this chemical class as a kinase-focused library.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Tetrahedron - Volume 68, Issue 47, 25 November 2012, Pages 9713-9728
نویسندگان
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