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Identification
NameBezitramide
Accession NumberDB01459
Typesmall molecule
Groupsexperimental, illicit, withdrawn
Description

Bezitramide is a narcotic analgesic which was discovered in 1961, clinically tested around the 1970’s 1, and marketed under the name Burgodin®. After cases of fatal overdose in the Netherlands in 2004 the drug was withdrawn from the market.

In the United States Bezitramide was never been approved for clinical use. It is presently an illegal substance classified under Schedule II of the Controlled Substances Act. [wiki]

Structure
Thumb
Synonyms
SynonymLanguageCode
1-[1-(3-Cyano-3,3-diphenylpropyl)-4-piperidinyl]-1,3-dihydro-3-(1-oxopropyl)-2H-benzimidazol-2-oneNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
Burgodin Janssen Pharmceutica
Brand mixturesNot Available
Categories
CAS number15301-48-1
WeightAverage: 492.6114
Monoisotopic: 492.252526288
Chemical FormulaC31H32N4O2
InChI KeyFLKWNFFCSSJANB-UHFFFAOYSA-N
InChI
InChI=1S/C31H32N4O2/c1-2-29(36)35-28-16-10-9-15-27(28)34(30(35)37)26-17-20-33(21-18-26)22-19-31(23-32,24-11-5-3-6-12-24)25-13-7-4-8-14-25/h3-16,26H,2,17-22H2,1H3
IUPAC Name
4-[4-(2-oxo-3-propanoyl-2,3-dihydro-1H-1,3-benzodiazol-1-yl)piperidin-1-yl]-2,2-diphenylbutanenitrile
SMILES
CCC(=O)N1C(=O)N(C2CCN(CCC(C#N)(C3=CC=CC=C3)C3=CC=CC=C3)CC2)C2=CC=CC=C12
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassDiphenylacetonitriles
Direct parentDiphenylacetonitriles
Alternative parentsDiphenylmethanes; Phenylpropylamines; Benzyl Cyanides; Benzimidazoles; Carbonylimidazoles; Aminopiperidines; N-substituted Imidazoles; Tertiary Amines; Carboxylic Acid Amides; Nitriles; Polyamines; Enolates
Substituentsdiphenylmethane; phenylpropylamine; benzyl-cyanide; benzimidazole; imidazole-1-carbonyl group; 4-aminopiperidine; piperidine; n-substituted imidazole; imidazole; azole; tertiary amine; carboxamide group; polyamine; nitrile; carbonitrile; enolate; organonitrogen compound; amine
Classification descriptionThis compound belongs to the diphenylacetonitriles. These are cyclic aromatic compounds containing a diphenylacetonitrile moeity, which consists of a diphenylmethane linked to and acetonitrile to form 2,2-diphenylacetonitrile.
Pharmacology
IndicationA narcotic analgesic once used for the treatment of severe chronic pain. [1]
PharmacodynamicsBezitramide acts in the body to relieve pain with a potency 20 times that of methadone [1]. Its duration of action is relatively long, lasting up to 12 hours post oral administration, after the achievement of steady state. Its onset of action is slow, with a peak in analgesic effect noted between 2.5-3.5 hours after dosing. It is noted to illicit a strong antitussive effect, which could be of benefit to patients with bronchial carcinoma.
Mechanism of actionNot Available
AbsorptionBezitramide has poor water solubility, thus administration is restricted to the oral route. [1]
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Bezitramide is a prodrug which undergoes rapid hydrolysis of a proprionyl-group to form the major metabolite, R-4618. R-4618 has analgesic properties similar to the parent compound.[1] Metabolism occurs in the gastrointestinal tract under both acidic and alkaline conditions [1].

Route of eliminationLess than 0.3% of the dose was excreted unchanged in the urine. High concentrations in feces suggested incomplete absorption of biliary excretion. Experiments in rats demonstrated extensive (up to 70%) biliary excretion, and less than 3% urinary excretion. [1]
Half life11-24h. [1]
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9787
Caco-2 permeable - 0.5631
P-glycoprotein substrate Substrate 0.6446
P-glycoprotein inhibitor I Inhibitor 0.8347
P-glycoprotein inhibitor II Non-inhibitor 0.6466
Renal organic cation transporter Non-inhibitor 0.518
CYP450 2C9 substrate Non-substrate 0.7483
CYP450 2D6 substrate Non-substrate 0.6835
CYP450 3A4 substrate Substrate 0.6644
CYP450 1A2 substrate Non-inhibitor 0.9217
CYP450 2C9 substrate Non-inhibitor 0.5586
CYP450 2D6 substrate Non-inhibitor 0.7687
CYP450 2C19 substrate Non-inhibitor 0.8888
CYP450 3A4 substrate Inhibitor 0.584
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6976
Ames test Non AMES toxic 0.569
Carcinogenicity Non-carcinogens 0.8409
Biodegradation Not ready biodegradable 0.9939
Rat acute toxicity 3.5117 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Strong inhibitor 0.5527
hERG inhibition (predictor II) Inhibitor 0.6899
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point145-149 °CPhysProp
water solubilityPoor water solubility Meijer, D. K. F., et al. "Pharmacokinetics of the oral narcotic analgesic bezitramide and preliminary observations on its effect on experimentally induced pain." European journal of clinical pharmacology 27.5 (1984): 615-618.
logP4.80SANGSTER (1993)
Predicted Properties
PropertyValueSource
water solubility6.70e-03 g/lALOGPS
logP4.35ALOGPS
logP4.79ChemAxon
logS-4.9ALOGPS
pKa (strongest basic)8.32ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count0ChemAxon
polar surface area67.65ChemAxon
rotatable bond count7ChemAxon
refractivity155.25ChemAxon
polarizability55.58ChemAxon
number of rings5ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference

1. Meijer, D. K. F., et al. “Pharmacokinetics of the oral narcotic analgesic bezitramide and preliminary observations on its effect on experimentally induced pain.” European journal of clinical pharmacology 27.5 (1984): 615-618.

External Links
ResourceLink
PubChem Compound61791
PubChem Substance46505037
ChemSpider55675
WikipediaBezitramide
ATC CodesN02AC05
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available
Comments
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Drug created on July 31, 2007 07:09 / Updated on September 16, 2013 17:14