Document Report Card
Basic Information
ID: ALA1153202
Journal: Bioorg Med Chem Lett
Title: Optimization of piperidyl-ureas as inhibitors of soluble epoxide hydrolase.
Authors: Eldrup AB, Soleymanzadeh F, Farrow NA, Kukulka A, De Lombaert S.
Abstract: 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.
CiteXplore: 19969453