Eplivanserin

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
IUPAC name
  • (Z,E)-1-(2-fluorophenyl)-3-(4-hydroxyphenyl)-2-propen-1-one O-[2-(dimethylamino)ethyl]oxime
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ECHA InfoCard100.189.857
Chemical and physical data
FormulaC19H21FN2O2
Molar mass328.387 g·mol−1
3D model (JSmol)
SMILES
  • c2cc(O)ccc2\C=C\C(=N\OCCN(C)C)\c1ccccc1F
InChI
  • 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
 NY (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

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

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
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

References
  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. 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).
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