PMID- 19520575
OWN - NLM
STAT- MEDLINE
DCOM- 20091207
LR  - 20131121
IS  - 1464-3405 (Electronic)
IS  - 0960-894X (Linking)
VI  - 19
IP  - 15
DP  - 2009 Aug 1
TI  - Unsymmetrical non-adamantyl N,N'-diaryl urea and amide inhibitors of soluble 
      expoxide hydrolase.
PG  - 4259-63
LID - 10.1016/j.bmcl.2009.05.102 [doi]
AB  - Incorporation of an adamantyl group in prototypical soluble expoxide hydrolase 
      (sEH) inhibitors afforded improved enzyme potency. We explored replacement of the 
      adamantyl group in unsymmetrical ureas and amides with substituted aryl rings to 
      identify equipotent and metabolically stable sEH inhibitors. We found that aryl 
      rings, especially those substituted in the para position with a strongly electron 
      withdrawing substituent, afforded enzyme IC(50) values comparable to the 
      adamantyl compounds in an ether substituted, unsymmetrical N,N'-diaryl urea or 
      amide scaffold.
FAU - Anandan, Sampath-Kumar
AU  - Anandan SK
AD  - Arete Therapeutics, Inc., 3912 Trust Way, Hayward, CA 94545, USA. 
      skumar@aretetherapeutics.com
FAU - Webb, Heather K
AU  - Webb HK
FAU - Do, Zung N
AU  - Do ZN
FAU - Gless, Richard D
AU  - Gless RD
LA  - eng
PT  - Journal Article
DEP - 20090530
PL  - England
TA  - Bioorg Med Chem Lett
JT  - Bioorganic & medicinal chemistry letters
JID - 9107377
RN  - 0 (Amides)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Fluorescent Dyes)
RN  - 8W8T17847W (Urea)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - Amides/chemistry
MH  - Area Under Curve
MH  - Chemistry, Pharmaceutical/*methods
MH  - Drug Design
MH  - Electrons
MH  - Enzyme Inhibitors/chemistry/pharmacology
MH  - Epoxide Hydrolases/*antagonists & inhibitors/*chemistry
MH  - Fluorescent Dyes/pharmacology
MH  - Humans
MH  - Inhibitory Concentration 50
MH  - Models, Chemical
MH  - Molecular Structure
MH  - Solubility
MH  - Urea/*chemistry
EDAT- 2009/06/13 09:00
MHDA- 2009/12/16 06:00
CRDT- 2009/06/13 09:00
PHST- 2009/04/07 00:00 [received]
PHST- 2009/05/22 00:00 [accepted]
PHST- 2009/06/13 09:00 [entrez]
PHST- 2009/06/13 09:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
AID - S0960-894X(09)00792-6 [pii]
AID - 10.1016/j.bmcl.2009.05.102 [doi]
PST - ppublish
SO  - Bioorg Med Chem Lett. 2009 Aug 1;19(15):4259-63. doi: 10.1016/j.bmcl.2009.05.102. 
      Epub 2009 May 30.