کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1375354 | 981937 | 2010 | 5 صفحه PDF | دانلود رایگان |
Inhibition of sEH is hypothesized to lead to an increase in epoxyeicosatrienoic acids resulting in the potentiation of their anti-inflammatory and vasodilatory effects. In an effort to explore sEH inhibition as an avenue for the development of vasodilatory and cardio- or renal-protective agents, a lead identified through high-throughput screening was optimized, guided by the determination of a solid state co-structure with sEH. Replacement of potential toxicophores was followed by optimization of cell-based potency and ADME properties to provide a new class of functionally potent sEH inhibitors with attractive in vitro metabolic profiles and high and sustained plasma exposures after oral administration in the rat.
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Journal: Bioorganic & Medicinal Chemistry Letters - Volume 20, Issue 2, 15 January 2010, Pages 571–575