Eplivanserin

Summary

Eplivanserin (SR-46,349; planned trade name Ciltyri) was an experimental drug for the treatment of insomnia which was being developed by Sanofi Aventis.[1]

Eplivanserin
Clinical data
Routes of
administration
Oral
ATC code
  • none
Identifiers
  • (Z,E)-1-(2-fluorophenyl)-3-(4-hydroxyphenyl)-2-propen-1-one O-[2-(dimethylamino)ethyl]oxime
CAS Number
PubChem CID
  • 5493160
ChemSpider
  • 13267837 ☒N
UNII
  • 3CO94WO6DJ
KEGG
  • D10006 ☒N
ECHA InfoCard100.189.857 Edit this at Wikidata
Chemical and physical data
FormulaC19H21FN2O2
Molar mass328.387 g·mol−1
3D model (JSmol)
  • Interactive image
  • c2cc(O)ccc2\C=C\C(=N\OCCN(C)C)\c1ccccc1F
  • InChI=1S/C19H21FN2O2/c1-22(2)13-14-24-21-19(17-5-3-4-6-18(17)20)12-9-15-7-10-16(23)11-8-15/h3-12,23H,13-14H2,1-2H3/b12-9+,21-19- ☒N
  • Key:VAIOZOCLKVMIMN-PRJWTAEASA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Sanofi Aventis announced in December 2009 that it was withdrawing its application for approval of eplivanserin from both the U.S. Food and Drug Administration and the European Medicines Agency.[2]

Mechanism of action edit

Eplivanserin is an inverse agonist on the serotonin receptor subtype 5-HT2A. In contrast to older sedating drugs acting on 5-HT2A receptors (e.g., mirtazapine, clozapine, risperidone), eplivanserin has practically no affinity to dopamine, histamine and adrenergic receptors.[3]

Study results edit

In a placebo controlled Phase II clinical trial with 351 subjects, eplivanserin reduced the sleep latency by 39 minutes (versus 26 minutes under placebo).[3]

Synthesis edit

 
Patent:[4] Chinese

The condensation between 2'-Fluoroacetophenone [445-27-2] (5) & 4-hydroxybenzaldehyde [123-08-0] (6) give a chalcone intermediate (also an enone), i.e. CID:53982926 (7).

(2-chloroethyl)dimethylamine (CDMA) & acetone oxime are reacted together to give dimethylaminoacetoxime (DMA acetoxime), CID:16641114 (3).

Convergent synthesis gives the product as a mixture of isomers.

See also edit

References edit

  1. ^ "Future Treatments for Depression, Anxiety, Sleep Disorders, Psychosis, and ADHD". Neurotransmitter.net.
  2. ^ Spencer M, Berton E (21 December 2009). "Sanofi-Aventis Discontinues Eplivanserin For Insomnia". Dow Jones & Co. Archived from the original on 21 July 2011. Retrieved 27 January 2010.
  3. ^ a b Teegarden BR, Al Shamma H, Xiong Y (2008). "5-HT(2A) inverse-agonists for the treatment of insomnia". Current Topics in Medicinal Chemistry. 8 (11): 969–76. doi:10.2174/156802608784936700. PMID 18673166.
  4. ^ Eric Garcia, Christian Hoff, U.S. patent 20,120,022,292 (2012 to Sanofi-Aventis).