3-(3-carbamoylphenyl)phenyl N-cyclohexylcarbamate

• ChemBase ID: 69295
• Molecular Formular: C20H22N2O3
• Molecular Mass: 338.40028
• Monoisotopic Mass: 338.16304257
• SMILES: C(=O)(NC1CCCCC1)Oc1cc(ccc1)c1cc(ccc1)C(=O)N
• Canonical SMILES: O=C(Oc1cccc(c1)c1cccc(c1)C(=O)N)NC1CCCCC1
• InChI: 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)
• InChIKey: ROFVXGGUISEHAM-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 3-(3-carbamoylphenyl)phenyl N-cyclohexylcarbamate
• IUPAC Traditional name: 3-(3-carbamoylphenyl)phenyl N-cyclohexylcarbamate
• Synonyms: Cyclohexylcarbamic acid 3′-carbamoyl-biphenyl-3-yl ester; URB597; KDS-4103; URB597; 3'-Carbamoyl-[1,1'-biphenyl]-3-yl cyclohexylcarbamate

Database IDs

• CAS Number: 546141-08-6
• MDL Number: MFCD05863934
• PubChem SID: 162035022
• PubChem CID: 1383884
• CHEMBL: 184238
• Chemspider ID: 1156960
• MeSH Name: URB597
• Wikipedia Title: URB597

CALCULATED PROPERTIES

• Acid pKa: 14.306808
• H Acceptors: 2
• H Donor: 2
• LogD (pH = 5.5): 3.767773
• LogD (pH = 7.4): 3.7677734
• Log P: 3.7677736
• Molar Refractivity: 95.9926 cm^3
• Polarizability: 38.14706 Å^3
• Polar Surface Area: 81.42 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Solubility: DMSO: soluble ~14 mg/mL
• Apperance: white powder

Safety Information

• Storage Condition: -20°C
• Storage Warning: IRRITANT
• European Hazard Symbols: Nature polluting (N)
• UN Number: 3077
• German water hazard class: 3
• Hazard Class: 9
• Packing Group: 3
• Risk Statements: 50/53
• Safety Statements: 22-24/25-60-61
• TSCA Listed: false
• GHS Pictograms: GHS07; GHS09
• GHS Signal Word: Warning
• GHS Hazard statements: H319-H410
• GHS Precautionary statements: P273-P305 + P351 + P338-P501
• Personal Protective Equipment: Eyeshields, Gloves
• RID/ADR: UN 3077 9/PG 3
• Storage Temperature: 2-8°C

Pharmacology Properties

• Target: fatty acid amide hydrolase (FAAH)

Product Information

• Purity: ≥98% (HPLC); 95+%; 97%
• Salt Data: Free Base
• Empirical Formula (Hill Notation): C20H22N2O3

DETAILS

Selleck Chemicals - S2631

Research Area

• Description: Cancer

Biological Activity

• Description: URB597 (KDS-4103) is a potent FAAH inhibitor with IC50 of 4.6 nM.
• Targets:

  FAAH

• IC50:

  4.6 nM ^[1]

• 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. ^[1] URB597 inhibits FAAH activity in human liver microsomes with IC50 of 3 nM. ^[2] URB597 reduces the expression of the LPS-induced enzymes cyclo-oxygenase 2 (COX2) 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. ^[3] 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. ^[4]
• 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. ^[5] 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. ^[6] 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. ^[7] URB597 could reverse most depressive-like symptoms induced by adolescent THC exposure in femal rats. ^[8]

Protocol

• Protocol: Kinase Assay ^[1]
• Pharmacology: Membrane fractions are prepared from brain homogenates, and FAAH activity is assayed using [^3H]anandamide (anandamide[ethanolamine-^3H], 60 Ci/mmol) as a substrate. Rat brain membranes (50 μg protein) are incubated for 30 min at 37 °C in buffer containing [^3H]anandamide and varying concentrations of URB597. At the end of the incubation period, we stopp the reactions with a mixture of chloroform/methanol and measured [^3H]ethanolamine in the aqueous phase by liquid scintillation counting.
• Protocol: Animal Study ^[5]
• Animal Models: Adult male Wistar rats (250–300 g) and C57/BL6 or FAAH-/- mice
• Formulation: sterile 0.9% sodium chloride solution
• Doses: 0.3 mg/kg
• Administration: Inject subcutaneously in a single dose 2 hours or 16 hours before killing

References

• References: [1] Mor M, et al. J Med Chem, 2004, 47(21), 4998-5008.
• References: [2] Piomelli D, et al. CNS Drug Rev, 2006, 12(1), 21-38.
• References: [3] Tham CS, et al. FEBS Lett, 2007, 581(16), 2899-2904.
• References: [4] Niforatos W, et al. Mol Pharmacol, 2007, 71(5), 1209-1216.
• References: [5] Fegley D, et al. J Pharmacol Exp Ther, 2005, 313(1), 352-358.
• References: [6] Jayamanne A, et al. Br J Pharmacol, 2006, 147(3), 281-288.
• References: [7] Bortolato M, et al. Biol Psychiatry, 2007, 62(10), 1103-1110.
• References: [8] Realini N, et al. Neuropharmacology, 2011, 60(2-3), 235-243.

Sigma Aldrich - U4133

Biochem/physiol Actions
Potent, selective fatty acid amide hydrolase (FAAH) inhibitor.

REFERENCES

• Mor M, et al. J Med Chem, 2004, 47(21), 4998-5008.
• Piomelli D, et al. CNS Drug Rev, 2006, 12(1), 21-38.
• Tham CS, et al. FEBS Lett, 2007, 581(16), 2899-2904.
• Niforatos W, et al. Mol Pharmacol, 2007, 71(5), 1209-1216.
• Fegley D, et al. J Pharmacol Exp Ther, 2005, 313(1), 352-358.
• Jayamanne A, et al. Br J Pharmacol, 2006, 147(3), 281-288.
• Bortolato M, et al. Biol Psychiatry, 2007, 62(10), 1103-1110.
• Realini N, et al. Neuropharmacology, 2011, 60(2-3), 235-243.