Journal
BIOCHEMICAL PHARMACOLOGY
Volume 63, Issue 9, Pages 1599-1608Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0006-2952(02)00952-8
Keywords
epoxide hydrolase; blood pressure; immune response; urea inhibitors; structure-activity relationships; solubility
Categories
Funding
- NIEHS NIH HHS [1P30-ES05707, P42-ES04699, R01-ES02710] Funding Source: Medline
Ask authors/readers for more resources
The soluble epoxide hydrolase (sEH) is involved in the metabolism of arachidonic, linoleic, and other fatty acid epoxides, endogenous chemical mediators that play an important role in blood pressure regulation and inflammation. 1,3-Disubstituted ureas, carbamates, and amides are new potent and stable inhibitors of sEH. However, the poor solubility of the lead compounds limits their use. Inhibitor structure-activity relationships were investigated to better define the structural requirements for inhibition and to identify points in the molecular topography that could accept polar groups without diminishing inhibition potency. Results indicate that lipophilicity is an important factor controlling inhibitor potency. Polar groups could be incorporated into one of the alkyl groups without loss of activity if they were placed at a sufficient distance from the urea function. The resulting compounds had a 2-fold higher water solubility. These findings will facilitate the rational design and optimization of sEH inhibitors with better physical properties. (C) 2002 Published by Elsevier Science Inc.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available