PMID- 35466565
OWN - NLM
STAT- MEDLINE
DCOM- 20220622
LR  - 20220727
IS  - 1860-7187 (Electronic)
IS  - 1860-7179 (Linking)
VI  - 17
IP  - 12
DP  - 2022 Jun 20
TI  - Discovery and Optimization of Piperazine Urea Derivatives as Soluble Epoxide 
      Hydrolase (sEH) Inhibitors.
PG  - e202200137
LID - 10.1002/cmdc.202200137 [doi]
AB  - Soluble epoxide hydrolase (sEH) is implicated as a potential therapeutic target 
      for inflammation-related pathologies in the context of cardiovascular, central 
      nervous system and metabolic diseases. In our search for novel sEH inhibitors, we 
      designed and synthesized novel analogs of the piperazine urea derivative 4, a 
      previously discovered dual microsomal prostaglandin E(2) synthase-1 
      (mPGES-1)/soluble epoxide hydrolase (sEH) inhibitor, to evaluate their potential 
      as sEH inhibitors. We identified two 1,3,4-oxadiazol-5-one and -thione congeners 
      (compounds 19 and 20), which demonstrated selective sEH inhibition with IC(50) 
      values in the two-digit nanomolar range (42 and 56 nM, respectively). These 
      results suggest that the installation of terminal 1,3,4-oxadiazol-5-one/thione 
      functions to the benzyl end can be regarded as a promising secondary 
      pharmacophore in addition to the urea group for sEH inhibition, and compound 19 
      can be regarded as novel lead structure for further optimization of improved sEH 
      inhibitors.
CI  - (c) 2022 Wiley-VCH GmbH.
FAU - Capan, Irfan
AU  - Capan I
AD  - Department of Material and Material Processing Technologies, Technical Sciences 
      Vocational College, Gazi University, 06374, Ankara, Turkey.
FAU - Jordan, Paul M
AU  - Jordan PM
AD  - Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, 
      Friedrich-Schiller-University Jena, Philosophenweg 14, 7743, Jena, Germany.
FAU - Olgac, Abdurrahman
AU  - Olgac A
AD  - Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Tac 
      Sok. No:3, 06560, Yenimahalle, Ankara, Turkey.
FAU - Caliskan, Burcu
AU  - Caliskan B
AD  - Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Tac 
      Sok. No:3, 06560, Yenimahalle, Ankara, Turkey.
FAU - Kretzer, Christian
AU  - Kretzer C
AD  - Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, 
      Friedrich-Schiller-University Jena, Philosophenweg 14, 7743, Jena, Germany.
FAU - Werz, Oliver
AU  - Werz O
AD  - Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, 
      Friedrich-Schiller-University Jena, Philosophenweg 14, 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, 06560, Yenimahalle, Ankara, Turkey.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220512
PL  - Germany
TA  - ChemMedChem
JT  - ChemMedChem
JID - 101259013
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Heterocyclic Compounds)
RN  - 0 (Piperazines)
RN  - 0 (Thiones)
RN  - 8W8T17847W (Urea)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - Enzyme Inhibitors/chemistry/pharmacology
MH  - *Epoxide Hydrolases/metabolism
MH  - *Heterocyclic Compounds
MH  - Piperazines/pharmacology
MH  - Structure-Activity Relationship
MH  - Thiones
MH  - Urea
OTO - NOTNLM
OT  - epoxide hydrolase
OT  - inhibitor
OT  - oxadiazole
OT  - piperazine
OT  - urea
EDAT- 2022/04/26 06:00
MHDA- 2022/06/23 06:00
CRDT- 2022/04/25 06:17
PHST- 2022/04/21 00:00 [revised]
PHST- 2022/03/15 00:00 [received]
PHST- 2022/04/26 06:00 [pubmed]
PHST- 2022/06/23 06:00 [medline]
PHST- 2022/04/25 06:17 [entrez]
AID - 10.1002/cmdc.202200137 [doi]
PST - ppublish
SO  - ChemMedChem. 2022 Jun 20;17(12):e202200137. doi: 10.1002/cmdc.202200137. Epub 
      2022 May 12.