Peptidyl-urea based inhibitors of soluble epoxide hydrolases
نویسندگان
چکیده
منابع مشابه
Peptidyl-urea based inhibitors of soluble epoxide hydrolases.
We prepared a series of amino acid derived cyclohexyl and adamantyl ureas and tested them as inhibitors of the human soluble epoxide hydrolase, and obtained very potent compounds (K(I)=15nM) that are >10-fold more soluble than previously described sEH inhibitors. While our lead compound 2 showed low apparent bioavailability in dogs and rats, this series of compounds revealed that sEH inhibitor ...
متن کاملPotent urea and carbamate inhibitors of soluble epoxide hydrolases.
The soluble epoxide hydrolase (sEH) plays a significant role in the biosynthesis of inflammation mediators as well as xenobiotic transformations. Herein, we report the discovery of substituted ureas and carbamates as potent inhibitors of sEH. Some of these selective, competitive tight-binding inhibitors with nanomolar K(i) values interacted stoichiometrically with the homogenous recombinant mur...
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N,N'-disubstituted urea-based soluble epoxide hydrolase (sEH) inhibitors are promising therapeutics for hypertension, inflammation, and pain in multiple animal models. The drug absorption and pharmacological efficacy of these inhibitors have been reported extensively. However, the drug metabolism of these inhibitors is not well described. Here we reported the metabolic profile and associated bi...
متن کاملOccurrence of urea-based soluble epoxide hydrolase inhibitors from the plants in the order Brassicales
Recently, dibenzylurea-based potent soluble epoxide hydrolase (sEH) inhibitors were identified in Pentadiplandra brazzeana, a plant in the order Brassicales. In an effort to generalize the concept, we hypothesized that plants that produce benzyl glucosinolates and corresponding isothiocyanates also produce these dibenzylurea derivatives. Our overall aim here was to examine the occurrence of ure...
متن کاملEnhancement of Soluble Expression and Biochemical Characterization of Two Epoxide Hydrolases from Bacillus
Background: Enantiopure epoxides are important intermediates in the synthesis of high-value chiral chemicals. Epoxide hydrolases have been exploited in biocatalysis for kinetic resolution of racemic epoxides to produce enantiopure epoxides and vicinal diols. It is necessary to obtain sufficient stable epoxide hydrolases with high enantioselectivity to meet the requirements of i...
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ژورنال
عنوان ژورنال: Bioorganic & Medicinal Chemistry Letters
سال: 2006
ISSN: 0960-894X
DOI: 10.1016/j.bmcl.2006.07.073