PMID- 19653681
OWN - NLM
STAT- MEDLINE
DCOM- 20100701
LR  - 20211020
IS  - 1520-4804 (Electronic)
IS  - 0022-2623 (Print)
IS  - 0022-2623 (Linking)
VI  - 52
IP  - 16
DP  - 2009 Aug 27
TI  - 14,15-Epoxyeicosa-5,8,11-trienoic acid (14,15-EET) surrogates containing epoxide 
      bioisosteres: influence upon vascular relaxation and soluble epoxide hydrolase 
      inhibition.
PG  - 5069-75
LID - 10.1021/jm900634w [doi]
AB  - All-cis-14,15-epoxyeicosa-5,8,11-trienoic acid (14,15-EET) is a labile, 
      vasodilatory eicosanoid generated from arachidonic acid by cytochrome P450 
      epoxygenases. A series of robust, partially saturated analogues containing 
      epoxide bioisosteres were synthesized and evaluated for relaxation of 
      precontracted bovine coronary artery rings and for in vitro inhibition of soluble 
      epoxide hydrolase (sEH). Depending upon the bioisostere and its position along 
      the carbon chain, varying levels of vascular relaxation and/or sEH inhibition 
      were observed. For example, oxamide 16 and N-iPr-amide 20 were comparable (ED(50) 
      1.7 microM) to 14,15-EET as vasorelaxants but were approximately 10-35 times less 
      potent as sEH inhibitors (IC(50) 59 and 19 microM, respectively); unsubstituted 
      urea 12 showed useful activity in both assays (ED(50) 3.5 microM, IC(50) 16 nM). 
      These data reveal differential structural parameters for the two pharmacophores 
      that could assist the development of potent and specific in vivo drug candidates.
FAU - Falck, J R
AU  - Falck JR
AD  - Departments of Biochemistry and Pharmacology, University of Texas Southwestern 
      Medical Center, Dallas, TX 75390, USA. j.falck@utsouthwestern.edu
FAU - Kodela, Ravinder
AU  - Kodela R
FAU - Manne, Rajkumar
AU  - Manne R
FAU - Atcha, Krishnam Raju
AU  - Atcha KR
FAU - Puli, Narender
AU  - Puli N
FAU - Dubasi, Narsimhaswamy
AU  - Dubasi N
FAU - Manthati, Vijay L
AU  - Manthati VL
FAU - Capdevila, Jorge H
AU  - Capdevila JH
FAU - Yi, Xiu-Yu
AU  - Yi XY
FAU - Goldman, Daniel H
AU  - Goldman DH
FAU - Morisseau, Christophe
AU  - Morisseau C
FAU - Hammock, Bruce D
AU  - Hammock BD
FAU - Campbell, William B
AU  - Campbell WB
LA  - eng
GR  - R01 HL085727/HL/NHLBI NIH HHS/United States
GR  - P01 DK038226/DK/NIDDK NIH HHS/United States
GR  - R01 HL051055-14/HL/NHLBI NIH HHS/United States
GR  - ES04699/ES/NIEHS NIH HHS/United States
GR  - DK38226/DK/NIDDK NIH HHS/United States
GR  - R01 13833/PHS HHS/United States
GR  - P42 ES004699-23S2/ES/NIEHS NIH HHS/United States
GR  - R37 ES002710/ES/NIEHS NIH HHS/United States
GR  - R01 HL051055/HL/NHLBI NIH HHS/United States
GR  - R37 ES002710-27/ES/NIEHS NIH HHS/United States
GR  - P01 DK038226-220006/DK/NIDDK NIH HHS/United States
GR  - HL85727/HL/NHLBI NIH HHS/United States
GR  - R01 GM031278-25A1/GM/NIGMS NIH HHS/United States
GR  - GM32178/GM/NIGMS NIH HHS/United States
GR  - P42 ES004699/ES/NIEHS NIH HHS/United States
GR  - HL51055/HL/NHLBI NIH HHS/United States
GR  - R01 GM031278/GM/NIGMS NIH HHS/United States
GR  - R37 ES02710/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Med Chem
JT  - Journal of medicinal chemistry
JID - 9716531
RN  - 0 (Epoxy Compounds)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Vasodilator Agents)
RN  - 81276-03-1 (14,15-epoxy-5,8,11-eicosatrienoic acid)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - FC398RK06S (8,11,14-Eicosatrienoic Acid)
SB  - IM
MH  - 8,11,14-Eicosatrienoic Acid/*analogs & derivatives/chemical 
      synthesis/chemistry/pharmacology
MH  - Animals
MH  - Cattle
MH  - Coronary Vessels/drug effects/physiology
MH  - Epoxide Hydrolases/*antagonists & inhibitors
MH  - Epoxy Compounds/*chemical synthesis/chemistry/pharmacology
MH  - Humans
MH  - In Vitro Techniques
MH  - Isometric Contraction/drug effects
MH  - Recombinant Proteins/antagonists & inhibitors
MH  - Solubility
MH  - Stereoisomerism
MH  - Structure-Activity Relationship
MH  - Vasodilation/*drug effects
MH  - Vasodilator Agents/chemical synthesis/chemistry/pharmacology
PMC - PMC2888647
MID - NIHMS137043
EDAT- 2009/08/06 09:00
MHDA- 2010/07/02 06:00
PMCR- 2010/08/01
CRDT- 2009/08/06 09:00
PHST- 2009/08/06 09:00 [entrez]
PHST- 2009/08/06 09:00 [pubmed]
PHST- 2010/07/02 06:00 [medline]
PHST- 2010/08/01 00:00 [pmc-release]
AID - 10.1021/jm900634w [doi]
PST - ppublish
SO  - J Med Chem. 2009 Aug 27;52(16):5069-75. doi: 10.1021/jm900634w.