کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1370547 | 981822 | 2015 | 4 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Ligand efficient tetrahydro-pyrazolopyridines as inhibitors of ERK2 kinase
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موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
A series of structure based drug design hypotheses and focused screening efforts drove improvements in the potency and lipophilic efficiency of tetrahydro-pyrazolopyridine based ERK2 inhibitors. Elaboration of a fragment chemical lead established a new lipophilic aryl–Tyr interaction resulting in a substantial potency improvement. Subsequent cleavage of the lipophilic moiety led to reconfiguration of the ligand bound binding cleft. The reconfiguration established a polar contact between a newly liberated N–H and a vicinal Asp, resulting in further improvements in lipophilic efficiency and in vitro clearance.
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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 25, Issue 17, 1 September 2015, Pages 3626–3629
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 25, Issue 17, 1 September 2015, Pages 3626–3629
نویسندگان
Jeffrey T. Bagdanoff, Rama Jain, Wooseok Han, Daniel Poon, Patrick S. Lee, Cornelia Bellamacina, Mika Lindvall,