| Assay Method Information | |
| | Inhibitors of Soluble Epoxide Hydrolase (sEH) |
| Description: | Scores of sEH inhibitors are known, of a variety of chemical structures. Derivatives in which the urea, carbamate or amide pharmacophore are particularly useful as sEH inhibitors. As used herein, pharmacophore refers to the section of the structure of a ligand that binds to the sEH. Derivatives that are metabolically stable are of use, as they are expected to have greater activity in vivo. Selective and competitive inhibition of sEH in vitro by a variety of urea, carbamate, and amide derivatives is taught, for example, by Morisseau et al., Proc. Natl. Acad. Sci. U.S.A, 96:8849-8854 (1999).Derivatives of urea are transition state mimetics that form a group of sEH inhibitors. Within this group, N, N′-dodecyl-cyclohexyl urea (DCU), is an inhibitor, while N-cyclohexyl-N′-dodecylurea (CDU) is a particular embodiment. Some compounds, such as dicyclohexylcarbodiimide (a lipophilic diimide), can decompose to an active urea inhibitor such as DCU. Any particular urea derivative or other compound can be easily tested for its ability to inhibit sEH by standard assays, such as those discussed herein. The production and testing of urea and carbamate derivatives as sEH inhibitors is set forth in detail in, for example, Morisseau et al., Proc Natl Acad Sci (USA) 96:8849-8854 (1999).N-Adamantyl-N′-dodecyl urea ( ADU ) is both metabolically stable and has particularly high activity on sEH. Both the 1- and the 2-adamantyl ureas have been tested and have about the same high activity as an inhibitor of sEH. Adamantyl ureas of use include, e.g., 12-(3-Adamantan-1-yl-ureido)dodecanoic acid (AUDA), 12-(3-Adamantan-1-yl-ureido)dodecanoic acid butyl ester (AUDA-BE), and Adamantan-1-yl-3-{5-[2-(2-ethoxyethoxy)ethoxy]pentyl}urea (AEPU). |
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