Optimization of piperidyl-ureas as inhibitors of soluble epoxide hydrolase.

Article Details

Citation

Eldrup AB, Soleymanzadeh F, Farrow NA, Kukulka A, De Lombaert S

Optimization of piperidyl-ureas as inhibitors of soluble epoxide hydrolase.

Bioorg Med Chem Lett. 2010 Jan 15;20(2):571-5. doi: 10.1016/j.bmcl.2009.11.091. Epub 2009 Nov 22.

PubMed ID
19969453 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Bifunctional epoxide hydrolase 2P34913Details