PMID- 26520661
OWN - NLM
STAT- MEDLINE
DCOM- 20161005
LR  - 20181113
IS  - 1464-3405 (Electronic)
IS  - 0960-894X (Print)
IS  - 0960-894X (Linking)
VI  - 25
IP  - 23
DP  - 2015 Dec 1
TI  - 1,3-Disubstituted and 1,3,3-trisubstituted adamantyl-ureas with isoxazole as 
      soluble epoxide hydrolase inhibitors.
PG  - 5514-9
LID - S0960-894X(15)30176-1 [pii]
LID - 10.1016/j.bmcl.2015.10.066 [doi]
AB  - Adamantyl ureas are good soluble epoxide hydrolase (sEH) inhibitors; however they 
      have limited solubility and rapid metabolism, thus limiting their usefulness in 
      some therapeutic indications. Herein, we test the hypothesis that nodal 
      substitution on the adamantane will help solubilize and stabilize the compounds. 
      A series of compounds containing adamantane derivatives and isoxazole functional 
      groups were developed. Overall, the presence of methyl on the nodal positions of 
      adamantane yields higher water solubility than previously reported urea-based sEH 
      inhibitors while maintaining high inhibition potency. However, it did not improve 
      microsomal stability.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Burmistrov, Vladimir
AU  - Burmistrov V
AD  - Department of Entomology and Nematology, and UC Davis Comprehensive Cancer 
      Center, University of California at Davis, One Shields Avenue, Davis, CA 95616, 
      USA; Department of Chemistry, Technology and Equipment of Chemical Industry, 
      Volzhsky Polytechnic Institute (Branch) Volgograd State Technical University, 
      Volzhsky, Russia.
FAU - Morisseau, Christophe
AU  - Morisseau C
AD  - Department of Entomology and Nematology, and UC Davis Comprehensive Cancer 
      Center, University of California at Davis, One Shields Avenue, Davis, CA 95616, 
      USA.
FAU - Danilov, Dmitry
AU  - Danilov D
AD  - Department of Chemistry, Technology and Equipment of Chemical Industry, Volzhsky 
      Polytechnic Institute (Branch) Volgograd State Technical University, Volzhsky, 
      Russia.
FAU - Harris, Todd R
AU  - Harris TR
AD  - Department of Entomology and Nematology, and UC Davis Comprehensive Cancer 
      Center, University of California at Davis, One Shields Avenue, Davis, CA 95616, 
      USA.
FAU - Dalinger, Igor
AU  - Dalinger I
AD  - N.D. Zelinsky Institute of Organic Chemistry (ZIOC) of Russian Academy of 
      Sciences, Moscow, Russia.
FAU - Vatsadze, Irina
AU  - Vatsadze I
AD  - N.D. Zelinsky Institute of Organic Chemistry (ZIOC) of Russian Academy of 
      Sciences, Moscow, Russia.
FAU - Shkineva, Tatiana
AU  - Shkineva T
AD  - N.D. Zelinsky Institute of Organic Chemistry (ZIOC) of Russian Academy of 
      Sciences, Moscow, 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, 
      Russia.
FAU - Hammock, Bruce D
AU  - Hammock BD
AD  - Department of Entomology and Nematology, and UC Davis Comprehensive Cancer 
      Center, University of California at Davis, One Shields Avenue, Davis, CA 95616, 
      USA. Electronic address: bdhammock@ucdavis.edu.
LA  - eng
GR  - P42 ES004699/ES/NIEHS NIH HHS/United States
GR  - R01 ES002710/ES/NIEHS NIH HHS/United States
PT  - Journal Article
DEP - 20151023
PL  - England
TA  - Bioorg Med Chem Lett
JT  - Bioorganic & medicinal chemistry letters
JID - 9107377
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Isoxazoles)
RN  - 8W8T17847W (Urea)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - PJY633525U (Adamantane)
SB  - IM
MH  - Adamantane/*chemistry/pharmacology
MH  - Drug Stability
MH  - Enzyme Inhibitors/chemistry/pharmacology
MH  - Epoxide Hydrolases/*antagonists & inhibitors
MH  - Humans
MH  - Inhibitory Concentration 50
MH  - Isoxazoles/*chemistry/pharmacology
MH  - Microsomes/chemistry/drug effects
MH  - Solubility
MH  - Structure-Activity Relationship
MH  - Urea/*chemistry/*pharmacology
PMC - PMC4654407
MID - NIHMS735522
OTO - NOTNLM
OT  - Adamantane
OT  - Inhibitor
OT  - Isocyanate
OT  - Isoxazole
OT  - Soluble epoxide hydrolase
OT  - Urea
EDAT- 2015/11/02 06:00
MHDA- 2016/10/07 06:00
PMCR- 2016/12/01
CRDT- 2015/11/02 06:00
PHST- 2015/08/01 00:00 [received]
PHST- 2015/10/19 00:00 [revised]
PHST- 2015/10/21 00:00 [accepted]
PHST- 2015/11/02 06:00 [entrez]
PHST- 2015/11/02 06:00 [pubmed]
PHST- 2016/10/07 06:00 [medline]
PHST- 2016/12/01 00:00 [pmc-release]
AID - S0960-894X(15)30176-1 [pii]
AID - 10.1016/j.bmcl.2015.10.066 [doi]
PST - ppublish
SO  - Bioorg Med Chem Lett. 2015 Dec 1;25(23):5514-9. doi: 10.1016/j.bmcl.2015.10.066. 
      Epub 2015 Oct 23.