Binospirone

Binospirone (MDL-73,005-EF) is a drug which acts as a partial agonist at 5-HT1A somatodendritic autoreceptors but as an antagonist at postsynaptic 5-HT1A receptors.[1] It has anxiolytic effects.[2]

Binospirone
Clinical data
ATC code
  • none
Identifiers
IUPAC name
  • 8-[2-(2,3-dihydro-1,4-benzodioxin-2-ylmethylamino)ethyl]-8-azaspiro[4.5]decane-7,9-dione
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC20H26N2O4
Molar mass358.438 g·mol−1
3D model (JSmol)
SMILES
  • O=C1N(C(=O)CC2(C1)CCCC2)CCNCC3Oc4ccccc4OC3
InChI
  • InChI=1S/C20H26N2O4/c23-18-11-20(7-3-4-8-20)12-19(24)22(18)10-9-21-13-15-14-25-16-5-1-2-6-17(16)26-15/h1-2,5-6,15,21H,3-4,7-14H2
  • Key:BVMYCHKQPGEOSI-UHFFFAOYSA-N
  (verify)

Synthesis
Patent (Ex 1 & Ex 9):[3]

The reaction between catechol (1) and 2-chloroacrylonitrile [920-37-6] (2) gives 1,4-Benzodioxin-2-Carbonitrile [91889-45-1] (3). The reduction of the nitrile group with lithium aluminium hydride gives 2,3-dihydro-1,4-benzodioxin-3-ylmethanamine [4442-59-5] (4).

Alkylation of 3,3-Tetramethyleneglutarimide [1075-89-4] (5) with (for example) 2-chloroethanol gives 8-(2-hydroxyethyl)-8-azaspiro[4.5]decane-7,9-dione [21098-04-4] (6). FGI of the alcohol to a better leaving group by reaction with tosyl chloride gives CID:14839216 (7).

Convergent synthesis now completes the synthesis of Binospirone (8).

See also

References
  1. Bertrand F, Lehmann O, Galani R, Lazarus C, Jeltsch H, Cassel JC (April 2001). "Effects of MDL 73005 on water-maze performances and locomotor activity in scopolamine-treated rats". Pharmacology, Biochemistry, and Behavior. 68 (4): 647–60. doi:10.1016/S0091-3057(01)00448-8. PMID 11526961. S2CID 8595441.
  2. Moser PC, Tricklebank MD, Middlemiss DN, Mir AK, Hibert MF, Fozard JR (February 1990). "Characterization of MDL 73005EF as a 5-HT1A selective ligand and its effects in animal models of anxiety: comparison with buspirone, 8-OH-DPAT and diazepam". British Journal of Pharmacology. 99 (2): 343–9. doi:10.1111/j.1476-5381.1990.tb14706.x. PMC 1917389. PMID 1970269.
  3. Marcel Hibert, Maurice W. Gittos, U.S. Patent 4,612,312 (1986 to Merrell Dow Pharmaceuticals Inc.).
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