PMID- 25119815
OWN - NLM
STAT- MEDLINE
DCOM- 20160302
LR  - 20211021
IS  - 1520-4804 (Electronic)
IS  - 0022-2623 (Print)
IS  - 0022-2623 (Linking)
VI  - 57
IP  - 16
DP  - 2014 Aug 28
TI  - 14,15-Epoxyeicosa-5,8,11-trienoic Acid (14,15-EET) surrogates: carboxylate 
      modifications.
PG  - 6965-72
LID - 10.1021/jm500262m [doi]
AB  - The cytochrome P450 eicosanoid 14,15-epoxyeicosa-5,8,11-trienoic acid (14,15-EET) 
      is a powerful endogenous autacoid that has been ascribed an impressive array of 
      physiologic functions including regulation of blood pressure. Because 14,15-EET 
      is chemically and metabolically labile, structurally related surrogates 
      containing epoxide bioisosteres were introduced and have become useful in vitro 
      pharmacologic tools but are not suitable for in vivo applications. A new 
      generation of EET mimics incorporating modifications to the carboxylate were 
      prepared and evaluated for vasorelaxation and inhibition of soluble epoxide 
      hydrolase (sEH). Tetrazole 19 (ED50 0.18 muM) and oxadiazole-5-thione 25 (ED50 
      0.36 muM) were 12- and 6-fold more potent, respectively, than 14,15-EET as 
      vasorelaxants; on the other hand, their ability to block sEH differed 
      substantially, i.e., 11 vs >500 nM. These data will expedite the development of 
      potent and specific in vivo drug candidates.
FAU - Falck, John R
AU  - Falck JR
AD  - Departments of Biochemistry and Pharmacology, University of Texas Southwestern 
      Medical Center , 5323 Harry Hines Boulevard, Dallas, Texas 75390, United States.
FAU - Koduru, Sreenivasulu Reddy
AU  - Koduru SR
FAU - Mohapatra, Seetaram
AU  - Mohapatra S
FAU - Manne, Rajkumar
AU  - Manne R
FAU - Atcha, Krishnam Raju
AU  - Atcha KR
FAU - Atcha, Raju
AU  - Atcha R
FAU - Manthati, Vijaya L
AU  - Manthati VL
FAU - Capdevila, Jorge H
AU  - Capdevila JH
FAU - Christian, Sarah
AU  - Christian S
FAU - Imig, John D
AU  - Imig JD
FAU - Campbell, William B
AU  - Campbell WB
LA  - eng
GR  - R01 HL083297/HL/NHLBI NIH HHS/United States
GR  - P01 DK038226/DK/NIDDK NIH HHS/United States
GR  - GM32178/GM/NIGMS NIH HHS/United States
GR  - HL83297/HL/NHLBI NIH HHS/United States
GR  - DK38226/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140819
PL  - United States
TA  - J Med Chem
JT  - Journal of medicinal chemistry
JID - 9716531
RN  - 0 (Enzyme Inhibitors)
RN  - 0 
      (N1-butyl-N2-(12-(2-oxido-3H-1,2,3,5-oxathiadiazol-4-yl)dodec-5-en-1-yl)oxalamide)
RN  - 0 (Oxadiazoles)
RN  - 0 (Tetrazoles)
RN  - 0 (Vasodilator Agents)
RN  - 288-94-8 (1H-tetrazole)
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)
RN  - QU60N5OPLG (Oxamic Acid)
SB  - IM
EIN - J Med Chem. 2014 Nov 13;57(21):9218. Atcha, Krishnam Raju [added]
MH  - 8,11,14-Eicosatrienoic Acid/*analogs & derivatives/chemistry
MH  - Animals
MH  - Cattle
MH  - Chemistry Techniques, Synthetic
MH  - Coronary Vessels/drug effects
MH  - Enzyme Inhibitors/chemistry/pharmacology
MH  - Epoxide Hydrolases/antagonists & inhibitors
MH  - Humans
MH  - In Vitro Techniques
MH  - Molecular Mimicry
MH  - Oxadiazoles/chemistry/pharmacology
MH  - Oxamic Acid/analogs & derivatives/chemistry/pharmacology
MH  - Tetrazoles/chemistry/pharmacology
MH  - Vasodilation/drug effects
MH  - Vasodilator Agents/chemical synthesis/*chemistry/*pharmacology
PMC - PMC4148164
EDAT- 2014/08/15 06:00
MHDA- 2016/03/05 06:00
PMCR- 2015/08/13
CRDT- 2014/08/15 06:00
PHST- 2014/08/15 06:00 [entrez]
PHST- 2014/08/15 06:00 [pubmed]
PHST- 2016/03/05 06:00 [medline]
PHST- 2015/08/13 00:00 [pmc-release]
AID - 10.1021/jm500262m [doi]
PST - ppublish
SO  - J Med Chem. 2014 Aug 28;57(16):6965-72. doi: 10.1021/jm500262m. Epub 2014 Aug 19.