Butaclamol

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Wikipedia

Butaclamol
Clinical data
ATC code
  • none
Identifiers
  • (3S,4aS,13bS)-3-(2-Methyl-2-propanyl)-2,3,4,4a,8,9,13b,14-octahydro-1H-benzo[6,7]cyclohepta[1,2,3-de]pyrido[2,1-a]isoquinolin-3-ol
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC25H31NO
Molar mass361.529 g·mol−1
3D model (JSmol)
  • CC(C)(C)C1(CCN2CC3C4=CC=CC=C4CCC5=C3C(=CC=C5)C2C1)O

Butaclamol (AY-23,028) is a type of antipsychotic which was never marketed.[1] Sold as the hydrochloride salt for use in research, the compound acts as a dopamine receptor antagonist.[2]

Discussion

pKa = 7.15 (uncorrected for ionic strength)[3]

McN-4171 is an analog of butaclamol.[3][4] McN-4612-Y is also described in the attached article. This is similar to McN 4612-z except it is the opposite optical antipode. It is therefore supposedly an antipsychotic.

Synthesis

The synthesis has been reported:[5][6][7] Patent:[8]

  • The starting material is made by a Favorskii reaction of dibenzosuberone with acetylene followed by a Meyer–Schuster rearrangement to the aldehyde and oxidation to the acid. Another method is Reformatsky reaction with bromoethylacetate and catalytic hydrogenation of the olefin in the ester that follows dehydration.
  • The starting material is called 10,11-Dihydro-5H-dibenzo-[a,d]cycloheptene-5-acetic acid, PC12669091 (1). FGI by any of a number of methods to the isocyanate (NCO) gives (2). Addition of one equivalent of water gives N-formyl-10,11-dihydro-5H-dibenzo(a,d)cycloheptene-5-methylamine (3). Cyclization gives 1,7,8,12b-tetrahydrobenzo(6,7)cyclohept(1,2,3-de)isoquinoline [7574-72-3] (4). A modified Robinson annulation with methylvinylketone gave PC21397166 (5).

See also

References

  1. ↑ Buckingham J (1985). Dictionary of organic compounds - Google Books. CRC Press. ISBN 978-0-412-54090-5.
  2. ↑ Hall DA, Strange PG (June 1997). "Evidence that antipsychotic drugs are inverse agonists at D2 dopamine receptors". British Journal of Pharmacology. 121 (4): 731–6. doi:10.1038/sj.bjp.0701196. PMC 1564749. PMID 9208141.
  3. 1 2 Chrzanowski FA, McGrogan BA, Maryanoff BE (March 1985). "The pKa of butaclamol and the mode of butaclamol binding to central dopamine receptors". Journal of Medicinal Chemistry. 28 (3): 399–400. doi:10.1021/jm00381a022. PMID 2579238.
  4. ↑ Kukla, M. J., Bloss, J. L., Brougham, L. R. (April 1979). "Use of the butaclamol template in a search for antipsychotic agents with lessened side effects". Journal of Medicinal Chemistry. 22 (4): 401–406. doi:10.1021/jm00190a009.
  5. ↑ Chronicles of Drug Discovery, Volume 1, Edited by Jasjit S. Bindra and Daniel Lednicer, page 61, (L. G. Humber).
  6. ↑ Castañer, J., Chatterjee, S. S. (1976). "Butaclamol". Drugs of the Future. 1 (4): 171. doi:10.1358/dof.1976.001.04.64761.
  7. ↑ Bruderlein, F. T., Humber, L. G., Voith, K. (February 1975). "Neuroleptic agents of the benzocycloheptapyridoisoquinoline series. 1. Syntheses and stereochemical and structural requirements for activity of butaclamol and related compounds". Journal of Medicinal Chemistry. 18 (2): 185–188. doi:10.1021/jm00236a016. PMID 1168258.
  8. ↑ Francois T. Bruderlein, US4059585 (1977 to Wyeth Canada ULC).