کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10591725 | 981760 | 2013 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Discovery of 1-(1,3,5-triazin-2-yl)piperidine-4-carboxamides as inhibitors of soluble epoxide hydrolase
ترجمه فارسی عنوان
کشف 1- (1،3،5-تریازین-2 -یل) پیپریدین-4-کاربوکامید به عنوان مهارکننده هیدرولاز اپوکسی سدیم
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موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
چکیده انگلیسی
1-(1,3,5-Triazin-yl)piperidine-4-carboxamide inhibitors of soluble epoxide hydrolase were identified from high through-put screening using encoded library technology. The triazine heterocycle proved to be a critical functional group, essential for high potency and P450 selectivity. Phenyl group substitution was important for reducing clearance, and establishing good oral exposure. Based on this lead optimization work, 1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-{[[4-bromo-2-(trifluoromethoxy)]-phenyl]methyl}-4-piperidinecarboxamide (27) was identified as a useful tool compound for in vivo investigation. Robust effects on a serum biomarker, 9, 10-epoxyoctadec-12(Z)-enoic acid (the epoxide derived from linoleic acid) were observed, which provided evidence of robust in vivo target engagement and the suitability of 27 as a tool compound for study in various disease models.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 12, 15 June 2013, Pages 3584-3588
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 12, 15 June 2013, Pages 3584-3588
نویسندگان
Reema K. Thalji, Jeff J. McAtee, Svetlana Belyanskaya, Martin Brandt, Gregory D. Brown, Melissa H. Costell, Yun Ding, Jason W. Dodson, Steve H. Eisennagel, Rusty E. Fries, Jeffrey W. Gross, Mark R. Harpel, Dennis A. Holt, David I. Israel,