PMID- 12007563
OWN - NLM
STAT- MEDLINE
DCOM- 20020710
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 63
IP  - 9
DP  - 2002 May 1
TI  - Structural refinement of inhibitors of urea-based soluble epoxide hydrolases.
PG  - 1599-608
AB  - 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.
FAU - Morisseau, Christophe
AU  - Morisseau C
AD  - Department of Entomology, University of California, Davis, CA 95616, USA.
FAU - Goodrow, Marvin H
AU  - Goodrow MH
FAU - Newman, John W
AU  - Newman JW
FAU - Wheelock, Craig E
AU  - Wheelock CE
FAU - Dowdy, Deanna L
AU  - Dowdy DL
FAU - Hammock, Bruce D
AU  - Hammock BD
LA  - eng
GR  - 1P30-ES05707/ES/NIEHS NIH HHS/United States
GR  - P42-ES04699/ES/NIEHS NIH HHS/United States
GR  - R01-ES02710/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Recombinant Proteins)
RN  - 8W8T17847W (Urea)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - Animals
MH  - Enzyme Inhibitors/chemistry/*pharmacology
MH  - Epoxide Hydrolases/*antagonists & inhibitors
MH  - Humans
MH  - Mice
MH  - Models, Chemical
MH  - Protein Conformation
MH  - Recombinant Proteins/chemistry
MH  - Solubility
MH  - Structure-Activity Relationship
MH  - Urea/chemistry/*pharmacology
EDAT- 2002/05/15 10:00
MHDA- 2002/07/12 10:01
CRDT- 2002/05/15 10:00
PHST- 2002/05/15 10:00 [pubmed]
PHST- 2002/07/12 10:01 [medline]
PHST- 2002/05/15 10:00 [entrez]
AID - S0006295202009528 [pii]
AID - 10.1016/s0006-2952(02)00952-8 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2002 May 1;63(9):1599-608. doi: 10.1016/s0006-2952(02)00952-8.