Volinanserin

Today we will take a look at Volinanserin, a topic that has captured the attention of millions of people around the world. Since its emergence, Volinanserin has had a significant impact on different aspects of society, provoking debates, controversies and significant changes. Over the years, Volinanserin has evolved and adapted to changing circumstances, maintaining its relevance in different spheres of life. In this article, we will explore the history, impact and future of Volinanserin, looking at how it has shaped and will continue to shape the world we live in.

Volinanserin
Clinical data
Other namesMDL-100,907; M100907
ATC code
  • None
Identifiers
  • (R)-(2,3-dimethoxyphenyl)--4-piperidyl]methanol
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.123.797 Edit this at Wikidata
Chemical and physical data
FormulaC22H28FNO3
Molar mass373.468 g·mol−1
3D model (JSmol)
  • c3cc(F)ccc3CCN(CC2)CCC2C(O)c(c1OC)cccc1OC

Volinanserin (INN) (developmental code name MDL-100,907) is a highly selective 5-HT2A receptor antagonist that is frequently used in scientific research to investigate the function of the 5-HT2A receptor. It was also tested in clinical trials as a potential antipsychotic, antidepressant, and treatment for insomnia but was never marketed.

Synthesis

Synthesis: Patent: Precursor: Compositions:

The protection of Ethyl isonipecotate (1) with Boc anhydride gives ethyl n-boc-4-piperidinecarboxylate (2). Ester-amide interchange with N-Methoxymethylamine HCl: in the presence of CDI coupling agent gives 1-Boc-4-piperidine (3). Weinreb ketone synthesis occurs upon benzoylation with 1,2-Dimethoxybenzene (4) to give 1-Boc-4-(3,4-dimethoxybenzoyl)piperidine, CID:139510111 (5). Acid removal of the urethane protecting group gives (3,4-dimethoxyphenyl)-piperidin-4-ylmethanone (6). The reduction of the ketone with sodium borohydride leads to (3,4-Dimethoxyphenyl)-piperidin-4-ylmethanol, CID:24261124 (7). Resolution of the alcohol gives (8). Sn2 alkylation of the secondary nitrogen with 4-Fluorophenethyl bromide (9) completed the synthesis of Volinanserin (10).

See also

References

  1. ^ Schmidt CJ, Fadayel GM, Sullivan CK, Taylor VL (November 1992). "5-HT2 receptors exert a state-dependent regulation of dopaminergic function: studies with MDL 100,907 and the amphetamine analogue, 3,4-methylenedioxymethamphetamine". European Journal of Pharmacology. 223 (1): 65–74. doi:10.1016/0014-2999(92)90819-P. PMID 1362159.
  2. ^ Herth MM, Kramer V, Piel M, Palner M, Riss PJ, Knudsen GM, Rösch F (April 2009). "Synthesis and in vitro affinities of various MDL 100907 derivatives as potential 18F-radioligands for 5-HT2A receptor imaging with PET". Bioorganic & Medicinal Chemistry. 17 (8): 2989–3002. CiteSeerX 10.1.1.519.5663. doi:10.1016/j.bmc.2009.03.021. PMID 19329329.
  3. ^ Nic Dhonnchadha BA, Fox RG, Stutz SJ, Rice KC, Cunningham KA (April 2009). "Blockade of the serotonin 5-HT2A receptor suppresses cue-evoked reinstatement of cocaine-seeking behavior in a rat self-administration model". Behavioral Neuroscience. 123 (2): 382–96. doi:10.1037/a0014592. PMC 3830454. PMID 19331461.
  4. ^ Offord SJ, Wong DF, Nyberg S (August 1999). "The role of positron emission tomography in the drug development of M100907, a putative antipsychotic with a novel mechanism of action". Journal of Clinical Pharmacology. 39 (S1): 17S–24S. doi:10.1002/j.1552-4604.1999.tb05933.x. PMID 10434243. S2CID 21311671.
  5. ^ Charney DS, Nestler PS, Sklar P, Buxbaum JD (July 2013). Neurobiology of Mental Illness. OUP USA. p. 767. ISBN 9780199934959.
  6. ^ Marek GJ, Martin-Ruiz R, Abo A, Artigas F (December 2005). "The selective 5-HT2A receptor antagonist M100907 enhances antidepressant-like behavioral effects of the SSRI fluoxetine". Neuropsychopharmacology. 30 (12): 2205–15. doi:10.1038/sj.npp.1300762. PMID 15886717.
  7. ^ 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.
  8. ^ Németh, Krisztina; Palkó, Roberta; Kovács, Péter; Visy, Júlia (2014). "Development of novel chiral capillary electrophoresis methods for the serotonin receptor (5-HT2A) antagonist MDL 100,907 (volinanserin) and for its key intermediate compound". Journal of Pharmaceutical and Biomedical Analysis. 88: 579–583. doi:10.1016/j.jpba.2013.10.017.
  9. ^ Albert A. Carr, John M. Kane, & David A. Hay, WO1991018602 (to Aventis Pharmaceuticals Inc).
  10. ^ Huang, Yiyun; Mahmood, Khalid; Mathis, Chester A. (1999). "An efficient synthesis of the precursors of MDL 100907 labeled in two specific positions". Journal of Labelled Compounds and Radiopharmaceuticals. 42 (10): 949–957. doi:10.1002/(SICI)1099-1344(199910)42:10<949::AID-JLCR253>3.0.CO;2-S.
  11. ^ Thomas Paul Blackburn, WO1998004289 (to SmithKline Beecham Ltd).
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