Indantadol

Indantadol (CHF-3381, V-3381) is a drug which was formerly being investigated as an anticonvulsant and neuroprotective and is now under development for the treatment of neuropathic pain and chronic cough in Europe by Vernalis and Chiesi.[1][2][3][4][5][6][7][8] It acts as a competitive, reversible, and non-selective monoamine oxidase inhibitor,[5][6][9] and as a low affinity, non-competitive NMDA receptor antagonist.[1][2][10] A pilot study of indantadol for chronic cough was initiated in October 2009 and in April 2010 it failed to achieve significant efficacy in neuropathic pain in phase IIb clinical trials.[7][8][11][12]

Indantadol
Clinical data
Routes of
administration		Oral
ATC code
  • none
Legal status
Legal status
  • In general: uncontrolled
Identifiers
IUPAC name
  • N-(2,3-dihydro-1H-inden-2-yl)glycinamide
CAS Number
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC11H14N2O
Molar mass190.246 g·mol−1
3D model (JSmol)
SMILES
  • NCC(=O)NC1Cc2ccccc2C1

Synthesis
Patent[13]

Ex 8: The reductive amination between 2-indanone [615-13-4] (1) and Glycine methyl ester [616-34-2] (2) with sodium cyanoborohydride in ethanol gives CID:22080528 (3). Ammonolysis of the ester gives the primary amide product, i.e. indantadol (4).

See also

References
  1. Villetti G, Bregola G, Bassani F, et al. (June 2001). "Preclinical evaluation of CHF3381 as a novel antiepileptic agent". Neuropharmacology. 40 (7): 866–78. doi:10.1016/S0028-3908(01)00026-0. PMID 11378157. S2CID 23709155.
  2. Gandolfi O, Bonfante V, Voltattorni M, et al. (September 2001). "Anticonvulsant preclinical profile of CHF 3381: dopaminergic and glutamatergic mechanisms". Pharmacology Biochemistry and Behavior. 70 (1): 157–66. doi:10.1016/S0091-3057(01)00591-3. PMID 11566153. S2CID 24029988.
  3. Zucchini S, Buzzi A, Bergamaschi M, Pietra C, Villetti G, Simonato M (November 2002). "Neuroprotective activity of CHF3381, a putative N-methyl-D-aspartate receptor antagonist". NeuroReport. 13 (16): 2071–4. doi:10.1097/00001756-200211150-00016. PMID 12438928. S2CID 32235961.
  4. Villetti G, Bergamaschi M, Bassani F, et al. (August 2003). "Antinociceptive activity of the N-methyl-D-aspartate receptor antagonist N-(2-Indanyl)-glycinamide hydrochloride (CHF3381) in experimental models of inflammatory and neuropathic pain". The Journal of Pharmacology and Experimental Therapeutics. 306 (2): 804–14. doi:10.1124/jpet.103.050039. PMID 12750440. S2CID 12703264.
  5. "CHF 3381". Drugs in R&D. 5 (1): 28–30. 2004. doi:10.2165/00126839-200405010-00005. PMID 14725488. S2CID 29253197.
  6. Mattia C, Coluzzi F (September 2007). "Indantadol, a novel NMDA antagonist and nonselective MAO inhibitor for the potential treatment of neuropathic pain". IDrugs: The Investigational Drugs Journal. 10 (9): 636–44. PMID 17786847.
  7. "IN-STEP Phase IIb study results". Archived from the original on 2014-08-13.
  8. "Vernalis initiates Pilot Study of V3381 in patients with chronic cough". Archived from the original on 2014-08-13.
  9. Mathiesen O, Imbimbo BP, Hilsted KL, Fabbri L, Dahl JB (August 2006). "CHF3381, a N-methyl-D-aspartate receptor antagonist and monoamine oxidase-A inhibitor, attenuates secondary hyperalgesia in a human pain model". The Journal of Pain. 7 (8): 565–74. doi:10.1016/j.jpain.2006.02.004. PMID 16885013.
  10. Barbieri M, Bregola G, Buzzi A, et al. (August 2003). "Mechanisms of action of CHF3381 in the forebrain". British Journal of Pharmacology. 139 (7): 1333–41. doi:10.1038/sj.bjp.0705381. PMC 1573965. PMID 12890713.
  11. "V3381CC". Archived from the original on 2014-08-13.
  12. "Vernalis completes recruitment in V3381 Phase II IN-STEP study for neuropathic pain". Archived from the original on 2014-08-13.
  13. Paolo Chiesi, et al. WO 1998003472 (1998 to Chiesi Farmaceutici SpA).
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