PMID- 31870649
OWN - NLM
STAT- MEDLINE
DCOM- 20210128
LR  - 20240327
IS  - 1464-3405 (Electronic)
IS  - 0960-894X (Print)
IS  - 0960-894X (Linking)
VI  - 30
IP  - 3
DP  - 2020 Feb 1
TI  - Imidazolidine-2,4,5- and pirimidine-2,4,6-triones - New primary pharmacophore for 
      soluble epoxide hydrolase inhibitors with enhanced water solubility.
PG  - 126908
LID - S0960-894X(19)30886-8 [pii]
LID - 10.1016/j.bmcl.2019.126908 [doi]
AB  - A series of inhibitors of the soluble epoxide hydrolase (sEH) containing 
      imidazolidine-2,4,5-trione or pirimidine-2,4,6-trione has been synthesized. 
      Inhibition potency of the described compounds ranges from 8.4 muM to 0.4 nM. The 
      tested compounds possess higher water solubility than their preceding ureas. 
      Molecular docking indicates new bond between the triones and the active site of 
      sEH that in part explain the observed potency of the new pharmacophores. While 
      less potent than the corresponding ureas, the modifications of urea group 
      reported herein yield compounds with higher water solubility, thus permitting 
      easier formulation.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Burmistrov, Vladimir
AU  - Burmistrov V
AD  - Department of Entomology and Nematology, and Comprehensive Cancer Center, 
      University of California, Davis, CA 95616, USA; Department of Chemistry, 
      Technology and Equipment of Chemical Industry, Volzhsky Polytechnic Institute 
      (Branch) Volgograd State Technical University, Volzhsky 404121, Russia.
FAU - Morisseau, Christophe
AU  - Morisseau C
AD  - Department of Entomology and Nematology, and Comprehensive Cancer Center, 
      University of California, Davis, CA 95616, USA.
FAU - D'yachenko, Vladimir
AU  - D'yachenko V
AD  - Department of Chemistry, Technology and Equipment of Chemical Industry, Volzhsky 
      Polytechnic Institute (Branch) Volgograd State Technical University, Volzhsky 
      404121, Russia.
FAU - Karlov, Dmitry
AU  - Karlov D
AD  - Skolkovo Institute of Science and Technology, Skolkovo Innovation Center, Moscow 
      143026, Russia; Department of Chemistry, Lomonosov Moscow State University, 
      Moscow 119991, Russia; Institute of Physiologically Active Compounds, Russian 
      Academy of Sciences, Chernogolovka, Moscow Region 142432, Russia.
FAU - Butov, Gennady M
AU  - Butov GM
AD  - Department of Chemistry, Technology and Equipment of Chemical Industry, Volzhsky 
      Polytechnic Institute (Branch) Volgograd State Technical University, Volzhsky 
      404121, Russia.
FAU - Hammock, Bruce D
AU  - Hammock BD
AD  - Department of Entomology and Nematology, and Comprehensive Cancer Center, 
      University of California, Davis, CA 95616, USA. Electronic address: 
      bdhammock@ucdavis.edu.
LA  - eng
GR  - P42 ES004699/ES/NIEHS NIH HHS/United States
GR  - R35 ES030443/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20191218
PL  - England
TA  - Bioorg Med Chem Lett
JT  - Bioorganic & medicinal chemistry letters
JID - 9107377
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Imidazolidines)
RN  - 0 (Pyrimidines)
RN  - 8W8T17847W (Urea)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - K8CXK5Q32L (pyrimidine)
RN  - PJY633525U (Adamantane)
SB  - IM
MH  - Adamantane/chemistry/metabolism
MH  - Binding Sites
MH  - Catalytic Domain
MH  - Enzyme Inhibitors/*chemistry/metabolism
MH  - Epoxide Hydrolases/*antagonists & inhibitors/metabolism
MH  - Humans
MH  - Imidazolidines/*chemistry/metabolism
MH  - Inhibitory Concentration 50
MH  - Molecular Docking Simulation
MH  - Pyrimidines/*chemistry/metabolism
MH  - Solubility
MH  - Structure-Activity Relationship
MH  - Urea/chemistry/metabolism
PMC - PMC6957307
MID - NIHMS1547870
OTO - NOTNLM
OT  - Adamantane
OT  - Epoxyeicosatrienoic acids
OT  - Imidazolidine-2,4,5-trione
OT  - Inhibitor
OT  - Pirimidine-2,4,6-trione
OT  - Soluble epoxide hydrolase
OT  - Urea
COIS- Declaration of interests The authors declare that they have no known competing 
      financial interests or personal relationships that could have appeared to 
      influence the work reported in this paper.
EDAT- 2019/12/25 06:00
MHDA- 2021/01/29 06:00
PMCR- 2020/12/17
CRDT- 2019/12/25 06:00
PHST- 2019/08/26 00:00 [received]
PHST- 2019/12/09 00:00 [revised]
PHST- 2019/12/10 00:00 [accepted]
PHST- 2019/12/25 06:00 [pubmed]
PHST- 2021/01/29 06:00 [medline]
PHST- 2019/12/25 06:00 [entrez]
PHST- 2020/12/17 00:00 [pmc-release]
AID - S0960-894X(19)30886-8 [pii]
AID - 10.1016/j.bmcl.2019.126908 [doi]
PST - ppublish
SO  - Bioorg Med Chem Lett. 2020 Feb 1;30(3):126908. doi: 10.1016/j.bmcl.2019.126908. 
      Epub 2019 Dec 18.