Bezitramide

Bezitramide is an opioid analgesic. Bezitramide itself is a prodrug which is readily hydrolyzed in the gastrointestinal tract to its active metabolite, despropionyl-bezitramide.[1] Bezitramide was discovered at Janssen Pharmaceutica in 1961.[2][3][4] It is most commonly marketed under the trade name Burgodin.

Bezitramide
Clinical data
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • CA: Schedule I
  • DE: Anlage I (Authorized scientific use only)
  • US: Schedule II
Identifiers
IUPAC name
  • 4-[4-(2-oxo-3-propanoyl-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]-2,2-diphenylbutanenitrile
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.035.744
Chemical and physical data
FormulaC31H32N4O2
Molar mass492.623 g·mol−1
3D model (JSmol)
SMILES
  • O=C(N2c1ccccc1N(C2=O)C5CCN(CCC(C#N)(c3ccccc3)c4ccccc4)CC5)CC
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 Y
  • Key:FLKWNFFCSSJANB-UHFFFAOYSA-N Y
  (verify)

The drug was pulled from the shelves in the Netherlands in 2004 after fatal overdose cases, including one where a five-year-old child took one tablet from his mother's purse, ate it, and promptly died.[5]

Bezitramide is regulated much the same as morphine in all known jurisdictions and is a Schedule II substance under the United States' Controlled Substances Act of 1970, with an ACSCN of 9800 and zero annual manufacturing quota.[6] However, as of May 2021, it has never been marketed in the United States.

Synthesis
Synthesis:[7] Patent:[8] Prec:[9]

The Sn2 alkylation between 4-bromo-2,2-diphenylbutyronitrile [39186-58-8] (1) and 4-(2-oxo-1-benzimidazolinyl)-piperidine [20662-53-7] (2) with affords depropionylbezitramide [83898-28-6] (3). Acylation with propanoic anhydride then completed the synthesis of Bezitramide (4).

See also

References
  1. Meijer DK, Hovinga G, Versluis A, Bröring J, van Aken K, Moolenaar F, Wesseling H (1984). "Pharmacokinetics of the oral narcotic analgesic bezitramide and preliminary observations on its effect on experimentally induced pain". European Journal of Clinical Pharmacology. 27 (5): 615–8. doi:10.1007/BF00556902. PMID 6519169. S2CID 23978449.
  2. US patent 3196157, Janssen PA, "Benzimidalinyl Piperidines", published 1963-06-11, issued 1965-07-20
  3. Janssen PA, Niemegeers CJ, Schellekens KH, Marsboom RH, Herin VV, Amery WK, et al. (June 1971). "Bezitramide (R 4845), a new potent and orally long-acting analgesic compound". Arzneimittel-Forschung. 21 (6): 862–7. PMID 5109278.
  4. Knape H (April 1970). "Bezitramide, an orally active analgesic. An investigation on pain following operations for lumbar disc protrusion (preliminary report)". British Journal of Anaesthesia. 42 (4): 325–8. doi:10.1093/bja/42.4.325. PMID 4913411.
  5. de Vos JC, Rohof OJ, Bernsen PJ, Conemans JM, van Unnik AJ (August 1983). "[Death caused by one tablet of Burgodin]". Nederlands Tijdschrift voor Geneeskunde. 127 (34): 1552–3. PMID 6633692.
  6. Title 21 United States Code (USC) Controlled Substances Act
  7. Janssen, P. A.; Niemegeers, C. J.; Schellekens, K. H.; Marsboom, R. H.; Herin, V. V.; Amery, W. K.; Admiraal, P. V.; Bosker, J. T.; Crul, J. F.; Pearce, C.; Zegveld, C. (1971). "Bezitramide (R 4845), a new potent and orally long-acting analgesic compound". Arzneimittel-Forschung 21 (6): 862–867. PMID 5109278.
  8. BE633495 idem Janssen Paul Adriaan Jan, U.S. Patent 3,196,157 (1965 to Res Lab Dr C Janssen N V).
  9. Jinchun Tang & Sunan Wang, CN1 02030682A (2010 to Changzhou Kangpu Pharmaceutical Co Ltd).
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