546141-08-6

Basic information

• Product Name: URB597
• Synonyms: N-Cyclohexylcarbamic acid 3'-(aminocarbonyl)[1,1'-biphenyl]-3-yl ester;3'-CarbaMoyl-[1,1'-biphenyl]-3-yl cyclohexylcarbaMate;3-(3-carbaMoylphenyl)phenyl N-cyclohexylcarbaMate;CarbaMic acid,N-cyclohexyl-, 3'-(aMinocarbonyl)[1,1'-biphenyl]-3-yl ester;KDS 4103 N-Cyclohexylcarbamic acid 3'-(aminocarbonyl)[1,1'-biphenyl]-3-yl ester;N-Cyclohexylcarbamic acid 3'-(aminocarbonyl)[1,1'-biphenyl]-3-yl ester URB 597 KDS 4103;URB 597, >=98%;APD597(URB597)
• CAS NO: 546141-08-6
• Molecular Formula: C20H22N2O3
• Molecular Weight: 338.4
• EINECS: 1312995-182-4
• Product Categories: Research Chemical;Chemical for Research;HFC80014;Inhibitor;Inhibitors;Pharmaceutical intermediate;URB-597 ada@tuskwei.com sky;18031153937@189.cn
• Mol File: 546141-08-6.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 533.2 °C at 760 mmHg
• Flash Point: 276.3 °C
• Appearance: white/powder
• Density: 1.23
• Storage Temp.: 2-8°C
• Solubility: DMSO: ~14 mg/mL, soluble
• PKA: 11.74±0.20(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months.
• CAS DataBase Reference: URB597(CAS DataBase Reference)
• NIST Chemistry Reference: URB597(546141-08-6)
• EPA Substance Registry System: URB597(546141-08-6)

Safety Data

• Hazard Codes: N
• Statements: 50/53
• Safety Statements: 22-24/25-60-61
• RIDADR: UN 3077 9/PG 3
• WGK Germany: 3
• Hazardous Substances Data: 546141-08-6(Hazardous Substances Data)

Usage

Description

Different sources of media describe the Description of 546141-08-6 differently. You can refer to the following data:
1. URB597 is a potent, orally bioavailable FAAH inhibitor with IC50 of 4.6 nM, with no activity on other cannabinoid-related targets. Phase 1.
2. URB-597 (546141-08-6) is a potent and selective fatty acid amide hydrolase (FAAH) inhibitor, IC50 = 3-5 nM.1?Produces cannabinoid CB1 and CB2 receptor-mediated analgesia in inflammatory pain states without causing side effects associated with cannabinoid receptor activation.2?Attenuates the anxiolytic-like effect of acetaminophen in a mouse model.3?Exerts anti-inflammatory effects in rat hippocampus and ameliorates age-related deficits.4?Off target effects of URB-597: Reduces tyrosine hydroxylase expression.5 Improves cognitive?impairment caused by chronic cerebral hypoperfusion in a mouse model via inhibition of mTOR-dependent autophagy.6

In vitro

URB597 binds in the hydrophobic pocket and catalytic core of FAAH that connects the active site residues to the membrane surface of FAAH. URB597 inhibits FAAH activity in human liver microsomes with IC50 of 3 nM. URB597 reduces the expression of the LPS-induced enzymes cyclo-oxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS; NOS2) in primary rat microglial cell, with a concomitant reduction in the release of the inflammatory mediators prostaglandin E2 (PGE2) and (NO) nitric oxide. URB597 evokes Ca2+ entry in HEK293-F Cells transiently expressing human or rat TRPA1 gene. URB597 also activates Ca2+ entry in rat DRG neurons natively expressed TRPA1 channels.

In vivo

URB597 inhibits [3H]anandamide hydrolysis in rat brain membranes with a parallel increase in brain anandamide, OEA, and PEA content by inhibition of FAAH. URB597 enhances the hypothermia effect induced by ethanolamide by inhibiting FAAH.When delivered intraperitonealy (0.3 mg/kg) URB597 reduces allodynia and hyperalgesia through cannabinoid CB1 and CB2 receptor-mediated analgesia in rats with inflammatory pain.URB597 reduces the reduction in body weight gain and sucrose intake induced by the chronic mild stress in rats through inhibition of brain FAAH activity. URB597 could reverse most depressive-like symptoms induced by adolescent THC exposure in femal rats.

General Description

URB597 binds to active sites of fatty acid amide hydrolases and inhibits their activity. URB597 alters expression of tyrosine hydroxylase and interacts with abnormal-cannabidiol (Abn-CBD) and peroxisome proliferator-activated receptors (PPARs). URB597 elicits antinociception property via cannabinoid receptor by maintaining endocannabinoid anandamide (AEA) levels. URB597 reduces abnormal hyperactivity in neurons and could be for treatment of seizures and improving synaptic plasticity.

Biochem/physiol Actions

Potent, selective fatty acid amide hydrolase (FAAH) inhibitor.

References

1) Piomelli et al. (2006), Pharmacological profile of the selective FAAH inhibitor KDS-4103 (URB597); CNS Drugs Rev., 12 21 2) Jayamanne et al. (2006), Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models; Br. J. Pharmacol., 147 281 3) Zaitone et al. (2012), Inhibition of fatty acid amide hydrolase by URB597 attenuates the anxiolytic-like effect of acetaminophen in the mouse elevated plus-maze test; Behav. Pharmacol., 23 417 4) Murphy et al. (2012), The fatty acid amide hydrolase inhibitor URB597 exerts anti-inflammatory effects in hippocampus of aged rats and restores an age-related deficit in long-term potentiation; Neuroinflammation, 9 79 5) Bosier et al. (2013), The FAAH inhibitor URB597 efficiently reduces tyrosine hydroxylase expression through CB- and FAAH-independent mechanisms; Br. J. Pharmacol., 169 794 6) Wang et al. (2017), URB597 improves cognitive impairment induced by chronic cerebral hypoperfusion by inhibiting mTOR-dependent autophagy; Neuroscience, 344 293

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Relevant articles and documents

Characterization of the fatty acid amide hydrolase inhibitor cyclohexyl carbamic acid 3′-carbamoyl-biphenyl-3-yl ester (URB597): Effects on anandamide and oleoylethanolamide deactivation

Fatty acid amide hydrolase (FMH) is an intracellular serine enzyme that catalyzes the hydrolysis of bioactive fatty acid ethanolamides such as anandamide and oleoylethanolamide (OEA). Genetic deletion of the faah gene in mice elevates brain anandamide levels and amplifies the effects of this endogenous cannabinoid agonist. Here, we show that systemic administration of the selective FAAH inhibitor URB597 (cyclohexyl carbamic acid 3′-carbamoyl-biphenyl-3-yl ester; 0.3 mg/kg i.p.) increases anandamide levels in the brain of rats and wild-type mice but has no such effect in FAAH-null mutants. Moreover, URB597 enhances the hypothermic actions of anandamide (5 mg/kg i.p.) in wild-type mice but not in FAAH-null mice. In contrast, the FAAH inhibitor does not affect anandamide or OEA levels in the rat duodenum at doses that completely inhibit FAAH activity. In addition, URB597 does not alter the hypophagic response elicited by OEA (5 and 10 mg/kg i.p.), which is mediated by activation of peroxisome proliferator-activated receptor type-α. Finally, exogenously administered OEA (5 mg/kg i.p.) was eliminated at comparable rates in wild-type and FAAH-/- mice. Our results indicate that URB597 increases brain anandamide levels and magnifies anandamide responses by inhibiting intracellular FAAH activity. The results also suggest that an enzyme distinct from FAAH catalyzes OEA hydrolysis in the duodenum, where this lipid substance acts as a local satiety factor. Copyright

MODULATION OF ANXIETY THROUGH BLOCKADE OF ANANDAMIDE HYDROLYSIS

Fatty acid amide hydrolase inhibitors of the Formula (I) are provided, wherein X is NH, CH2, O, or S; Q is O or S; Z is O or N; R is an aromatic moiety selected from the group consisting of substituted or unsubstituted aryl; substituted or unsubstituted b