Binedaline (also called binodaline or binedaline hydrochloride) is a drug that was investigated as an antidepressant in the 1980s but was never marketed. 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. It has negligible affinity for the α-adrenergic, mACh, H1, or 5-HT2 receptors.
Synthesis
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.
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