PMID- 23726028
OWN - NLM
STAT- MEDLINE
DCOM- 20140113
LR  - 20211021
IS  - 1464-3405 (Electronic)
IS  - 0960-894X (Print)
IS  - 0960-894X (Linking)
VI  - 23
IP  - 13
DP  - 2013 Jul 1
TI  - Synthesis and biological evaluation of sorafenib- and regorafenib-like sEH 
      inhibitors.
PG  - 3732-7
LID - S0960-894X(13)00594-5 [pii]
LID - 10.1016/j.bmcl.2013.05.011 [doi]
AB  - To reduce the pro-angiogenic effects of sEH inhibition, a structure-activity 
      relationship (SAR) study was performed by incorporating structural features of 
      the anti-angiogenic multi-kinase inhibitor sorafenib into soluble epoxide 
      hydrolase (sEH) inhibitors. The structural modifications of this series of 
      molecules enabled the altering of selectivity towards the pro-angiogenic kinases 
      C-RAF and vascular endothelial growth factor receptor-2 (VEGFR-2), while 
      retaining their sEH inhibition. As a result, sEH inhibitors with greater potency 
      against C-RAF and VEGFR-2 were obtained. Compound 4 (t-CUPM) possesses inhibition 
      potency higher than sorafenib towards sEH but similar against C-RAF and VEGFR-2. 
      Compound 7 (t-CUCB) selectively inhibits sEH, while inhibiting HUVEC cell 
      proliferation, a potential anti-angiogenic property, without liver cancer cell 
      cytotoxicity. The data presented suggest a potential rational approach to control 
      the angiogenic responses stemming from sEH inhibition.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Hwang, Sung Hee
AU  - Hwang SH
AD  - Department of Entomology and UC Davis Comprehensive Cancer Center, University of 
      California, Davis, One Shields Avenue, Davis, CA 95616-8584, USA.
FAU - Wecksler, Aaron T
AU  - Wecksler AT
FAU - Zhang, Guodong
AU  - Zhang G
FAU - Morisseau, Christophe
AU  - Morisseau C
FAU - Nguyen, Long V
AU  - Nguyen LV
FAU - Fu, Samuel H
AU  - Fu SH
FAU - Hammock, Bruce D
AU  - Hammock BD
LA  - eng
GR  - ES02710/ES/NIEHS NIH HHS/United States
GR  - R01 HL059699/HL/NHLBI NIH HHS/United States
GR  - R01 ES002710/ES/NIEHS NIH HHS/United States
GR  - T32CA108459/CA/NCI NIH HHS/United States
GR  - P42 ES004699/ES/NIEHS NIH HHS/United States
GR  - P42 ES04699/ES/NIEHS NIH HHS/United States
GR  - U54 NS079202/NS/NINDS NIH HHS/United States
GR  - R37 ES002710/ES/NIEHS NIH HHS/United States
GR  - HL059699/HL/NHLBI NIH HHS/United States
GR  - T32 CA108459/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130515
PL  - England
TA  - Bioorg Med Chem Lett
JT  - Bioorganic & medicinal chemistry letters
JID - 9107377
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Pyridines)
RN  - 24T2A1DOYB (regorafenib)
RN  - 25X51I8RD4 (Niacinamide)
RN  - 9ZOQ3TZI87 (Sorafenib)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - Cell Proliferation/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/chemical synthesis/chemistry/*pharmacology
MH  - Epoxide Hydrolases/*antagonists & inhibitors/metabolism
MH  - Human Umbilical Vein Endothelial Cells/drug effects
MH  - Humans
MH  - Molecular Structure
MH  - Niacinamide/*analogs & derivatives/chemical synthesis/chemistry/pharmacology
MH  - Phenylurea Compounds/chemical synthesis/chemistry/*pharmacology
MH  - Pyridines/chemical synthesis/chemistry/*pharmacology
MH  - Solubility
MH  - Sorafenib
MH  - Structure-Activity Relationship
PMC - PMC3744640
MID - NIHMS487839
EDAT- 2013/06/04 06:00
MHDA- 2014/01/15 06:00
PMCR- 2014/07/01
CRDT- 2013/06/04 06:00
PHST- 2013/04/09 00:00 [received]
PHST- 2013/04/28 00:00 [revised]
PHST- 2013/05/06 00:00 [accepted]
PHST- 2013/06/04 06:00 [entrez]
PHST- 2013/06/04 06:00 [pubmed]
PHST- 2014/01/15 06:00 [medline]
PHST- 2014/07/01 00:00 [pmc-release]
AID - S0960-894X(13)00594-5 [pii]
AID - 10.1016/j.bmcl.2013.05.011 [doi]
PST - ppublish
SO  - Bioorg Med Chem Lett. 2013 Jul 1;23(13):3732-7. doi: 10.1016/j.bmcl.2013.05.011. 
      Epub 2013 May 15.