Binedaline
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| Routes of administration | Oral |
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| Formula | C19H23N3 |
| Molar mass | 293.414 g·mol−1 |
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Binedaline (also called binodaline or binedaline hydrochloride[1]) is a drug that was investigated as an antidepressant in the 1980s but was never marketed.[2][3] It acts as a selective norepinephrine reuptake inhibitor (Ki = 25 nM), with relatively insignificant influence on the serotonin (Ki = 847 nM) and dopamine (Ki >= 2 μM) transporters.[4] It has negligible affinity for the α-adrenergic, mACh, H1, or 5-HT2 receptors.[4]
Synthesis
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Grignard reaction of 2-aminobenzophenone (1) with methylmagnesium bromide and dehydration of the tertiary carbinol gives 2-(1-phenylvinyl)aniline (2). In an example of the Widman-Stoermer synthesis, treatment with nitrous acid followed by basification of the diazonium species with ammonia causes an intramolecular cyclization to afford 4-phenylcinnoline (3). Hydrogenation gives 4-phenyl-1,4-dihydrocinnoline (4). The presence of acetic acid gives (5). The reaction with methyl p-toluenesulfonate leads to (6). Acid hydrolysis gives N-methyl-3-phenylindol-1-amine (7). Sodamide is then used to abstract the amine proton; alkylation of then anionic species with 2-dimethylaminoethylchloride (8) then concludes the synthesis of binedaline (9).
Widman-Stoermer synthesis also used for the synthesis of cintazone.
References
[edit]- ↑ Milne GW (2017). "3043: Binedaline hydrochloride". In Milne GW (ed.). Drugs: Synonyms and Properties. Routledge. ISBN 9781351755092.
- ↑ Faltus F, Geerling FC (1984). "A controlled double-blind study comparing binedaline and imipramine in the treatment of endogenous depression". Neuropsychobiology. 12 (1): 34–38. doi:10.1159/000118107. PMID 6239991.
- ↑ Triggle DJ (1996). Dictionary of Pharmacological Agents. Boca Raton: Chapman & Hall/CRC. ISBN 0-412-46630-9.
- 1 2 Morin D, Zini R, Urien S, Tillement JP (April 1989). "Pharmacological profile of binedaline, a new antidepressant drug". The Journal of Pharmacology and Experimental Therapeutics. 249 (1): 288–296. PMID 2540319.
- ↑ Schatz F, Jahn U, Wagner-Jauregg T, Zirngibl L, Thiele K (1980). "1-amino-3-phenylindoles with antidepressant activity. Binodaline hydrochloride and related substances". Arzneimittel-Forschung. 30 (6): 919–923. doi:10.1002/chin.198038207. PMID 7191264.
- ↑ DE 2512702, Fischer K, Jahn U, Schatz F, Stammbach C, Thiele K, Wagner-Jauregg T. Zirngibl L, "New Hydrazines and Methods of Manufacturing Them", issued 23 September 1982, assigned to Siegfried AG
- ↑ US 4204998, Schatz F, Stammbach C, Thiele K, Theodor W. Wagner-Jauregg, Zirngibl L, Fischer J, Jahn U, "N-Amino indole derivatives having pharmacological activity", issued 27 May 1980, assigned to Siegfried AG