Befiradol

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Befiradol
F-13640 structure.png
Systematic (IUPAC) name
3-chloro-4-fluorophenyl-[4-fluoro-4-([(5-methylpyridin-2-yl)methylamino]methyl)piperidin-1-yl]methanone
Clinical data
Legal status Uncontrolled
Identifiers
CAS number 208110-64-9 N
ATC code None
PubChem CID 9865384
ChemSpider 8041076 YesY
UNII RAT9OHA1YH YesY
ChEMBL CHEMBL45305 YesY
Chemical data
Formula C20H22ClF2N3O 
Mol. mass 393.857 g/mol
 N (what is this?)  (verify)

Befiradol (F-13,640; NLX-112) is a very potent and highly selective 5-HT1A receptor full agonist. It has powerful analgesic and antiallodynic effects comparable to those of high doses of opioid painkillers, but with fewer and less prominent side effects, as well as little or no development of tolerance with repeated use.[1][2][3][4][5][6] A SAR study revealed that replacement of the dihalophenyl moiety by 3-benzothienyl increases maximal efficacy from 84% to 124% (Ki=2.7 nM).[7]

Befiradol was discovered and developed by Pierre Fabre Médicament, a French pharmaceuticals company. In September 2013, befiradol was out-licensed to Neurolixis, a California-based biotechnology company. Neurolixis announced that it intends to re-purpose befiradol for the treatment of Levodopa-induced dyskinesia in Parkinson's disease.[8]

See also[edit]

References[edit]

  1. ^ Bardin L, Tarayre JP, Malfetes N, Koek W, Colpaert FC (April 2003). "Profound, non-opioid analgesia produced by the high-efficacy 5-HT(1A) agonist F 13640 in the formalin model of tonic nociceptive pain". Pharmacology 67 (4): 182–94. doi:10.1159/000068404. PMID 12595749. 
  2. ^ Bruins Slot LA, Koek W, Tarayre JP, Colpaert FC (April 2003). "Tolerance and inverse tolerance to the hyperalgesic and analgesic actions, respectively, of the novel analgesic, F 13640". European Journal of Pharmacology 466 (3): 271–9. doi:10.1016/S0014-2999(03)01566-8. PMID 12694810. 
  3. ^ Bardin L, Assié MB, Pélissou M, Royer-Urios I, Newman-Tancredi A, Ribet JP, Sautel F, Koek W, Colpaert FC (March 2005). "Dual, hyperalgesic, and analgesic effects of the high-efficacy 5-hydroxytryptamine 1A (5-HT1A) agonist F 13640 [(3-chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl)-amino]-methyl}piperidin-1-yl]methanone, fumaric acid salt]: relationship with 5-HT1A receptor occupancy and kinetic parameters". The Journal of Pharmacology and Experimental Therapeutics 312 (3): 1034–42. doi:10.1124/jpet.104.077669. PMID 15528450. 
  4. ^ Colpaert FC, Deseure K, Stinus L, Adriaensen H (February 2006). "High-efficacy 5-hydroxytryptamine 1A receptor activation counteracts opioid hyperallodynia and affective conditioning". The Journal of Pharmacology and Experimental Therapeutics 316 (2): 892–9. doi:10.1124/jpet.105.095109. PMID 16254131. 
  5. ^ Deseure K, Bréand S, Colpaert FC (July 2007). "Curative-like analgesia in a neuropathic pain model: parametric analysis of the dose and the duration of treatment with a high-efficacy 5-HT(1A) receptor agonist". European Journal of Pharmacology 568 (1–3): 134–41. doi:10.1016/j.ejphar.2007.04.022. PMID 17512927. 
  6. ^ Bernard Vacher, Bernard Bonnaud, Wouter Koek. Pyridin-2-yl-methylamine derivatives, method of preparing and application as medicine. US Patent 6020345, May 21, 1999.
  7. ^ Bollinger S, Hübner H, Heinemann FW, Meyer K, Gmeiner P (October 2010). "Novel pyridylmethylamines as highly selective 5-HT(1A) superagonists". J. Med. Chem. 53 (19): 7167–79. doi:10.1021/jm100835q. PMID 20860381. 
  8. ^ http://neurolixis.com/images/stories/nlx_pf_license_23sept13.pdf