From Wikipedia, the free encyclopedia
URB597
Names
Preferred IUPAC name
3′-Carbamoyl[1,1′-biphenyl]-3-yl cyclohexylcarbamate
Identifiers
ChEMBL
ChemSpider
ECHA InfoCard
100.164.994
MeSH
URB597
UNII
InChI=1S/C20H22N2O3/c21-19(23)16-8-4-6-14(12-16)15-7-5-11-18(13-15)25-20(24)22-17-9-2-1-3-10-17/h4-8,11-13,17H,1-3,9-10H2,(H2,21,23)(H,22,24)
Y Key: ROFVXGGUISEHAM-UHFFFAOYSA-N
Y InChI=1/C20H22N2O3/c21-19(23)16-8-4-6-14(12-16)15-7-5-11-18(13-15)25-20(24)22-17-9-2-1-3-10-17/h4-8,11-13,17H,1-3,9-10H2,(H2,21,23)(H,22,24)
Key: ROFVXGGUISEHAM-UHFFFAOYAO
O=C(NC1CCCCC1)OC2=CC=CC(C3=CC=CC(C(N)=O)=C3)=C2
Properties
C 20 H 22 N 2 O 3
Molar mass
338.407 g·mol−1
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
URB597 (KDS-4103 ) is a relatively selective and irreversible inhibitor of the enzyme
fatty acid amide hydrolase (FAAH).
[1]
[2] FAAH is the primary degradatory enzyme for the
endocannabinoid
anandamide and, as such, inhibition of FAAH leads to an accumulation of
anandamide in the
CNS and
periphery where it activates
cannabinoid receptors . URB597 has been found to elevate anandamide levels and have activity against
neuropathic pain in a
mouse model .
[3]
Preclinical studies have shown FAAH inhibitors to increase
BDNF levels in the
hippocampus and
prefrontal cortex ,
[4] highlighting their potential in
addiction treatment as "enviromimetics".
[5] Indeed, Chauvet et al. found that chronic URB597 administration in
rats "significantly reduces cocaine-seeking behaviour and cue- and stress-induced relapse".
[6]
URB597 was at one point being developed by
Kadmus Pharmaceuticals, Inc. for
clinical trials in
humans .
[7]
See also
References
^ Mor, Marco; Rivara, S; Lodola, A; Plazzi, PV; Tarzia, G; Duranti, A; Tontini, A; Piersanti, G; Kathuria, S; Piomelli, Daniele (2004).
"Cyclohexylcarbamic acid 3'- or 4'-substituted biphenyl-3-yl esters as fatty acid amide hydrolase inhibitors: synthesis, quantitative structure-activity relationships, and molecular modeling studies" (PDF) . J Med Chem . 47 (21): 4998–5008.
doi :
10.1021/jm031140x .
PMID
15456244 .
S2CID
43473180 .
^ Alexander, JP; Cravatt, BF (2005).
"Mechanism of Carbamate Inactivation of FAAH: Implications for the Design of Covalent Inhibitors and In Vivo Functional Probes for Enzymes" . Chem. Biol . 12 (11): 1179–87.
doi :
10.1016/j.chembiol.2005.08.011 .
PMC
1994809 .
PMID
16298297 .
^ Russo, R; Loverme, J; La Rana, G; Compton, TR; Parrott, J; Duranti, A; Tontini, A; Mor, M; Tarzia, G; Calignano, A.; Piomelli, D. (2007).
"The fatty-acid amide hydrolase inhibitor URB597 (cyclohexylcarbamicacid 3′-carbamoylbiphenyl-3-yl ester) reduces neuropathic pain after oral administration in mice" (PDF) . J Pharmacol Exp Ther . 322 (1): 236–42.
doi :
10.1124/jpet.107.119941 .
PMID
17412883 .
S2CID
40603248 .
^ Bambico, Francis R.; Duranti, Andrea; Nobrega, José N.; Gobbi, Gabriella (March 2016).
"The fatty acid amide hydrolase inhibitor URB597 modulates serotonin-dependent emotional behaviour, and serotonin1A and serotonin2A/C activity in the hippocampus" . European Neuropsychopharmacology . 26 (3): 578–590.
doi :
10.1016/j.euroneuro.2015.12.027 .
hdl :
11576/2631931 .
ISSN
1873-7862 .
PMID
26747370 .
S2CID
45109526 .
^ Solinas, Marcello; Chauvet, Claudia; Lafay-Chebassier, Claire; Jaafari, Nematollah; Thiriet, Nathalie (2021-02-01).
"Environmental enrichment-inspired pharmacological tools for the treatment of addiction" . Current Opinion in Pharmacology . 56 : 22–28.
doi :
10.1016/j.coph.2020.09.001 .
ISSN
1471-4892 .
PMID
32966941 .
S2CID
221888359 .
^ Chauvet, Claudia; Nicolas, Céline; Thiriet, Nathalie; Lardeux, MD; Virginie; Duranti, Andrea; Solinas, Marcello (2014-12-19).
"Chronic Stimulation of the Tone of Endogenous Anandamide Reduces Cue- and Stress-Induced Relapse in Rats" . International Journal of Neuropsychopharmacology . 18 (1): pyu025.
doi :
10.1093/ijnp/pyu025 .
ISSN
1461-1457 .
PMC
4368869 .
PMID
25522382 . {{
cite journal }}
: CS1 maint: multiple names: authors list (
link )
^
Kadmus Pharmaceuticals official website
Archived December 19, 2005, at the
Wayback Machine
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