Binedaline

Last updated
Binedaline
Binedaline.png
Clinical data
Routes of
administration 		Oral
ATC code
  • None
Legal status
Legal status
  • In general: unscheduled
Identifiers
  • N,N,N-Trimethyl-N-(3-phenylindol-1-yl)ethane-1,2-diamine
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C19H23N3
Molar mass 293.414 g·mol−1
3D model (JSmol)
  • c1cccc2c1c(cn2N(CCN(C)C)C)c3ccccc3
  • InChI=1S/C19H23N3/c1-20(2)13-14-21(3)22-15-18(16-9-5-4-6-10-16)17-11-7-8-12-19(17)22/h4-12,15H,13-14H2,1-3H3 Yes check.svgY
  • Key:SXYFFMXPDDGOEK-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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

Thieme Synthesis: Patents: Binedaline synthesis.svg
Thieme Synthesis: Patents:

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

  1. ↑ Milne GW (2017). "3043: Binedaline hydrochloride". In Milne GW (ed.). Drugs: Synonyms and Properties. Routledge. ISBN   9781351755092.
  2. ↑ 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.
  3. ↑ Triggle DJ (1996). Dictionary of Pharmacological Agents. Boca Raton: Chapman & Hall/CRC. ISBN   0-412-46630-9.
  4. 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.
  5. ↑ 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.
  6. ↑ 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
  7. ↑ 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
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