Chemistry:Butaclamol
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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
- ↑ Dictionary of organic compounds - Google Books. CRC Press. 1985. ISBN 978-0-412-54090-5. https://books.google.com/books?id=wZawOvjGME0C&q=butaclamol&pg=PA1131.
- ↑ "Evidence that antipsychotic drugs are inverse agonists at D2 dopamine receptors". British Journal of Pharmacology 121 (4): 731–6. June 1997. doi:10.1038/sj.bjp.0701196. PMID 9208141.
- ↑ 3.0 3.1 "The pKa of butaclamol and the mode of butaclamol binding to central dopamine receptors". Journal of Medicinal Chemistry 28 (3): 399–400. March 1985. doi:10.1021/jm00381a022. PMID 2579238.
- ↑ "Use of the butaclamol template in a search for antipsychotic agents with lessened side effects". Journal of Medicinal Chemistry 22 (4): 401–406. April 1979. doi:10.1021/jm00190a009. https://pubs.acs.org/doi/abs/10.1021/jm00190a009.
- ↑ Chronicles of Drug Discovery, Volume 1, Edited by Jasjit S. Bindra and Daniel Lednicer, page 61, (L. G. Humber).
- ↑ "Butaclamol". Drugs of the Future 1 (4): 171. 1976. doi:10.1358/dof.1976.001.04.64761.
- ↑ "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. February 1975. doi:10.1021/jm00236a016. PMID 1168258.
- ↑ Francois T. Bruderlein, US4059585 (1977 to Wyeth Canada ULC).
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