PMID- 32229350
OWN - NLM
STAT- MEDLINE
DCOM- 20210223
LR  - 20210223
IS  - 1090-2120 (Electronic)
IS  - 0045-2068 (Linking)
VI  - 99
DP  - 2020 Jun
TI  - Quinazoline-4(3H)-one derivatives as novel and potent inhibitors of soluble 
      epoxide hydrolase: Design, synthesis and biological evaluation.
PG  - 103736
LID - S0045-2068(19)31676-1 [pii]
LID - 10.1016/j.bioorg.2020.103736 [doi]
AB  - Inhibition of soluble epoxide hydrolase (sEH) is considered as a promising target 
      to reduce blood pressure, improve insulin sensitivity, and decrease inflammation. 
      In this study, a series of some novel quinazoline-4(3H)-one derivatives (3a-t) 
      with varying steric and electronic properties was designed, synthesized and 
      evaluated as sEH Inhibitors. Most of the synthesized compounds had similar 
      inhibitory activity to the commercial reference inhibitor, 
      12-(3-adamantan-1-ylureido)dodecanoic acid, and amongst them, 
      4-chloro-N-(4-(4-oxo-3,4-dihydroquinazoline-2-yl)phenyl)benzamide (3g) was 
      identified as the most active sEH inhibitor (IC(50) = 0.5 nM), about 2-fold more 
      potent compared to the reference inhibitor. The results of molecular modeling 
      followed by biological studies indicate that a quinazolinone ring serves as a 
      suitable scaffold to develop novel small molecule candidates to inhibit sEH and 
      the nature of substituent on the amide moiety has a moderate effect on the 
      activity.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Hejazi, Leila
AU  - Hejazi L
AD  - Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti 
      University of Medical Sciences, Tehran, Iran.
FAU - Rezaee, Elham
AU  - Rezaee E
AD  - Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti 
      University of Medical Sciences, Tehran, Iran.
FAU - Tabatabai, Sayyed Abbas
AU  - Tabatabai SA
AD  - Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti 
      University of Medical Sciences, Tehran, Iran. Electronic address: 
      sa_tabatabai@sbmu.ac.ir.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200320
PL  - United States
TA  - Bioorg Chem
JT  - Bioorganic chemistry
JID - 1303703
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Quinazolinones)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - EC 3.3.2.10 (EPHX2 protein, human)
SB  - IM
MH  - Dose-Response Relationship, Drug
MH  - *Drug Design
MH  - Enzyme Inhibitors/chemical synthesis/chemistry/*pharmacology
MH  - Epoxide Hydrolases/*antagonists & inhibitors/metabolism
MH  - Humans
MH  - Molecular Docking Simulation
MH  - Molecular Structure
MH  - Quinazolinones/chemical synthesis/chemistry/*pharmacology
MH  - Structure-Activity Relationship
OTO - NOTNLM
OT  - Biological study
OT  - Inhibitor
OT  - Molecular modeling
OT  - Quinazoline-4(3H)-one
OT  - Soluble epoxide hydrolase
COIS- Declaration of Competing Interest 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- 2020/04/02 06:00
MHDA- 2021/02/24 06:00
CRDT- 2020/04/02 06:00
PHST- 2019/10/05 00:00 [received]
PHST- 2020/02/03 00:00 [revised]
PHST- 2020/03/07 00:00 [accepted]
PHST- 2020/04/02 06:00 [pubmed]
PHST- 2021/02/24 06:00 [medline]
PHST- 2020/04/02 06:00 [entrez]
AID - S0045-2068(19)31676-1 [pii]
AID - 10.1016/j.bioorg.2020.103736 [doi]
PST - ppublish
SO  - Bioorg Chem. 2020 Jun;99:103736. doi: 10.1016/j.bioorg.2020.103736. Epub 2020 Mar 
      20.