PMID- 36687110
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230201
IS  - 2470-1343 (Electronic)
IS  - 2470-1343 (Linking)
VI  - 8
IP  - 2
DP  - 2023 Jan 17
TI  - Benzoxazolone-5-Urea Derivatives as Human Soluble Epoxide Hydrolase (sEH) 
      Inhibitors.
PG  - 2445-2454
LID - 10.1021/acsomega.2c06936 [doi]
AB  - Inhibition of soluble epoxide hydrolase (sEH) is indicated as a new therapeutic 
      modality against a variety of inflammatory diseases, including metabolic, renal, 
      and cardiovascular disorders. In our ongoing research on sEH inhibitors, we 
      synthesized novel benzoxazolone-5-urea analogues with highly potent sEH 
      inhibitory properties inspired by the crystallographic fragment scaffolds 
      incorporating a single H-bond donor/acceptor pair. The tractable SAR results 
      indicated that the aryl or benzyl fragments flanking the benzoxazolone-urea 
      scaffold conferred potent sEH inhibition, and compounds 31-39 inhibited the sEH 
      activity with IC(50) values in the range of 0.39-570 nM. Docking studies and 
      molecular dynamics simulations with the most potent analogue 33 provided valuable 
      insights into potential binding interactions of the inhibitor in the sEH binding 
      region. In conclusion, benzoxazolone-5-ureas furnished with benzyl groups on the 
      urea function can be regarded as novel lead structures, which allow the 
      development of advanced analogues with enhanced properties against sEH.
CI  - (c) 2023 The Authors. Published by American Chemical Society.
FAU - Gur Maz, Tugce
AU  - Gur Maz T
AUID- ORCID: 0000-0001-8916-2492
AD  - Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Tac 
      Sok. No:3 Yenimahalle, 06560 Ankara, Turkey.
FAU - Koc, Beyzanur
AU  - Koc B
AD  - Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Tac 
      Sok. No:3 Yenimahalle, 06560 Ankara, Turkey.
FAU - Jordan, Paul M
AU  - Jordan PM
AD  - Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, 
      Friedrich Schiller University Jena, Philosophenweg 14, D-7743 Jena, Germany.
FAU - Ibis, Kubra
AU  - Ibis K
AUID- ORCID: 0000-0002-6898-0258
AD  - Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Tac 
      Sok. No:3 Yenimahalle, 06560 Ankara, Turkey.
FAU - Caliskan, Burcu
AU  - Caliskan B
AUID- ORCID: 0000-0003-2391-5644
AD  - Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Tac 
      Sok. No:3 Yenimahalle, 06560 Ankara, Turkey.
FAU - Werz, Oliver
AU  - Werz O
AUID- ORCID: 0000-0002-5064-4379
AD  - Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, 
      Friedrich Schiller University Jena, Philosophenweg 14, D-7743 Jena, Germany.
FAU - Banoglu, Erden
AU  - Banoglu E
AUID- ORCID: 0000-0003-4737-1733
AD  - Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Tac 
      Sok. No:3 Yenimahalle, 06560 Ankara, Turkey.
LA  - eng
PT  - Journal Article
DEP - 20230104
PL  - United States
TA  - ACS Omega
JT  - ACS omega
JID - 101691658
PMC - PMC9850727
COIS- The authors declare no competing financial interest.
EDAT- 2023/01/24 06:00
MHDA- 2023/01/24 06:01
PMCR- 2023/01/04
CRDT- 2023/01/23 04:57
PHST- 2022/10/27 00:00 [received]
PHST- 2022/12/23 00:00 [accepted]
PHST- 2023/01/23 04:57 [entrez]
PHST- 2023/01/24 06:00 [pubmed]
PHST- 2023/01/24 06:01 [medline]
PHST- 2023/01/04 00:00 [pmc-release]
AID - 10.1021/acsomega.2c06936 [doi]
PST - epublish
SO  - ACS Omega. 2023 Jan 4;8(2):2445-2454. doi: 10.1021/acsomega.2c06936. eCollection 
      2023 Jan 17.