N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]propanamide

• ChemBase ID: 692
• Molecular Formular: C22H28N2O
• Molecular Mass: 336.47052
• Monoisotopic Mass: 336.22016353
• SMILES: O=C(N(C1CCN(CC1)CCc1ccccc1)c1ccccc1)CC
• Canonical SMILES: CCC(=O)N(c1ccccc1)C1CCN(CC1)CCc1ccccc1
• InChI: InChI=1S/C22H28N2O/c1-2-22(25)24(20-11-7-4-8-12-20)21-14-17-23(18-15-21)16-13-19-9-5-3-6-10-19/h3-12,21H,2,13-18H2,1H3
• InChIKey: PJMPHNIQZUBGLI-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]propanamide
• IUPAC Traditional name: fentanyl
• Brand Name: Actiq; Duragesic; Duragesic-100; Durogesic; Fentanest; Fentanil; Pentanyl; Phentanyl; Sentonil; Sublimaze; Nasalfent; Rapinyl
• Synonyms: N-(Phenyl)-N-(1-[2-phenylethyl]-4-piperidinyl)propanamide; 1-Phenethyl-4-(N-phenylpropionamido)piperidine; Durogesic; Durogesic D-Trans; Durotep MT; Fentanest; Fentanil; Fentora; Matrifen; Phentanyl; R 4263; Sublimase; Fentanila [INN-Spanish]; Fentanyl citrate; Fentanylum [INN-Latin]; fentanyl; Fentanyl

Database IDs

• CAS Number: 437-38-7
• PubChem SID: 46506372; 160964155
• PubChem CID: 3345
• CHEBI ID: 119915
• ATC CODE: N01AH01; N02AB03
• CHEMBL: 596
• Chemspider ID: 3228
• DrugBank ID: DB00813
• IUPHAR ligand ID: 1626
• KEGG ID: D00320
• Unique Ingredient Identifier: UF599785JZ
• Wikipedia Title: Fentanyl

CALCULATED PROPERTIES

JChem

• H Acceptors: 2
• H Donor: 0
• LogD (pH = 5.5): 0.7473339
• LogD (pH = 7.4): 2.432824
• Log P: 3.8154986
• Molar Refractivity: 103.4825 cm^3
• Polarizability: 40.300232 Å^3
• Polar Surface Area: 23.55 Å^2
• Rotatable Bonds: 6
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 4.12
• LOG S: -4.15
• Solubility (Water): 2.40e-02 g/l

PROPERTIES

Physical Property

• Solubility: 200 mg/L; Chloroform; Dichloromethane; DMSO,Hexane; MethanolDichloromethane
• Apperance: Pale Brown Solid
• Melting Point: 83-84°C; 87.5°C (189.5°F)
• Hydrophobicity(logP): 3.9

Safety Information

• Storage Condition: Controlled Substance, -20°C Freezer

Pharmacology Properties

• Admin Routes: TD, IM, IV, oral, sublingual, buccal
• Bioavailability: 92% (transdermal); 89% (intranasal); 50% (buccal); 33% (ingestion)
• Dependency Liability: Moderate - High
• Excretion: 60% Urinary (metabolites, <10% unchanged drug)
• Half Life: (IV)= 2.5 minutes ; Intranasal = 6.5 mins ; Transdermal = 7 hours (range 3–12 h)
• Metabolism: hepatic, primarily by CYP3A4
• Protein Bound: 80-85%
• Legal Status: Class A (UK); Schedule II (US)
• Pregnancy Category: C (US)

DETAILS

DrugBank - DB00813

• Drug Groups: illicit; approved; investigational
• Description: A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078)
• Indication: For the treatment of cancer patients with severe pain that breaks through their regular narcotic therapy.
• Pharmacology: Fentanyl is an opioid analgesic. Fentanyl interacts predominately with the opioid mu-receptor but also binds to kappa and delta-type opioid receptors. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, Fentanyl exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. Fentanyl may increase the patient's tolerance for pain and decrease the perception of suffering, although the presence of the pain itself may still be recognized. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Fentanyl depresses the respiratory centers, depresses the cough reflex, and constricts the pupils.
• Toxicity: Fentanyl has an LD50 of 3.1 milligrams per kilogram in rats, and, 0.03 milligrams per kilogram in monkeys. The LD50 in humans is not known.
• Affected Organisms: Humans and other mammals
• Biotransformation: Fentanyl is metabolized primarily via human cytochrome P450 3A4 isoenzyme system.
• Absorption: Bioavailability is 92% following transdermal administration and 50% following buccal administration.
• Half Life: 7 (range 3-12) hours
• Protein Binding: 80-85%
• Elimination: Fentanyl is metabolized primarily via human cytochrome P450 3A4 isoenzyme system and mostly eliminated in urine. Within 72 hours of IV fentanyl administration, approximately 75% of the dose is excreted in urine, mostly as metabolites with less than 10% representing unchanged drug.
• Distribution: * 3 to 8 L/kg [Surgical Patients]; * 0.8 to 8 [Hepatically Impaired Patients]
• Clearance: * 27 – 75 L/h [Surgical Patients receving IV administration]; * 3 – 80 L/h [Hepatically Impaired Patients receving IV administration]; * 30 – 78 L/h [Renally Impaired Patients receving IV administration]
• References: Van Bever WF, Niemegeers CJ, Janssen PA: Synthetic analgesics. Synthesis and pharmacology of the diastereoisomers of N-(3-methyl-1-(2-phenylethyl)-4-piperidyl)-N-phenylpropanamide and N-(3-methyl-1-(1-methyl-2-phenylethyl)-4-piperidyl)-N-phenylpropanamide. J Med Chem. 1974 Oct;17(10):1047-51. [Pubmed] ; Messina J, Darwish M, Fine PG: Fentanyl buccal tablet. Drugs Today (Barc). 2008 Jan;44(1):41-54. [Pubmed] ; Taylor DR: Fentanyl buccal tablet: rapid relief from breakthrough pain. Expert Opin Pharmacother. 2007 Dec;8(17):3043-51. [Pubmed] ; Simpson DM, Messina J, Xie F, Hale M: Fentanyl buccal tablet for the relief of breakthrough pain in opioid-tolerant adult patients with chronic neuropathic pain: a multicenter, randomized, double-blind, placebo-controlled study. Clin Ther. 2007 Apr;29(4):588-601. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Toronto Research Chemicals - F274990

Used as an analgesic. Controlled Substance.

REFERENCES

• Van Bever WF, Niemegeers CJ, Janssen PA: Synthetic analgesics. Synthesis and pharmacology of the diastereoisomers of N-(3-methyl-1-(2-phenylethyl)-4-piperidyl)-N-phenylpropanamide and N-(3-methyl-1-(1-methyl-2-phenylethyl)-4-piperidyl)-N-phenylpropanamide. J Med Chem. 1974 Oct;17(10):1047-51. Pubmed
• Taylor DR: Fentanyl buccal tablet: rapid relief from breakthrough pain. Expert Opin Pharmacother. 2007 Dec;8(17):3043-51. Pubmed
• Simpson DM, Messina J, Xie F, Hale M: Fentanyl buccal tablet for the relief of breakthrough pain in opioid-tolerant adult patients with chronic neuropathic pain: a multicenter, randomized, double-blind, placebo-controlled study. Clin Ther. 2007 Apr;29(4):588-601. Pubmed
• Messina J, Darwish M, Fine PG: Fentanyl buccal tablet. Drugs Today (Barc). 2008 Jan;44(1):41-54. Pubmed
• Zernig, G., et al.: Life Sci., 57, 2113 (1995)
• Bot, G., et al.: J. Pharmacol. Exper. Therap., 285, 1207 (1995)