Chemistry:Adatanserin

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Adatanserin (WY-50,324, SEB-324) is a mixed 5-HT1A receptor partial agonist and 5-HT2A and 5-HT2C receptor antagonist.[1][2][3] It was under development by Wyeth as an antidepressant but was ultimately not pursued.[3][4]

Adantaserin has been shown to be neuroprotective against ischemia-induced glutamatergic excitotoxicity, an effect which appears to be mediated by blockade of the 5-HT2A receptor.[5]

Synthesis

2-Chloropyrimidine (1) reacts with piperazine (2), forming 2-(1-piperazinyl)pyrimidine (3). Treatment with the phthalimide derivative N-(2-bromoethyl)phthalimide (4) in an alkylation reaction produces (5), which is deprotected using hydrazine to give the primary amine (6). Amide formation with the acid chloride of 1-adamantanecarboxylic acid yields adatanserin.[6][3]

See also

References

  1. ↑ "Antidepressant-like activity of compounds with varying efficacy at 5-HT1A receptors". Neuropharmacology 32 (4): 331–40. April 1993. doi:10.1016/0028-3908(93)90153-T. PMID 8497336. 
  2. ↑ "Pharmacological characterization of in vivo properties of putative mixed 5-HT1A agonist/5-HT2A/2C antagonist anxiolytics. I. Antipunishment effects in the pigeon". The Journal of Pharmacology and Experimental Therapeutics 276 (2): 388–97. February 1996. doi:10.1016/S0022-3565(25)12286-6. PMID 8632301. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8632301. 
  3. ↑ 3.0 3.1 3.2 "Synthesis and SAR of adatanserin: novel adamantyl aryl- and heteroarylpiperazines with dual serotonin 5-HT(1A) and 5-HT(2) activity as potential anxiolytic and antidepressant agents". Journal of Medicinal Chemistry 42 (25): 5077–94. December 1999. doi:10.1021/jm9806704. PMID 10602693. 
  4. ↑ Stahl, S. M. (2000). Essential psychopharmacology: neuroscientific basis and practical application. Cambridge, UK: Cambridge University Press. p. 262. ISBN 0-521-64615-4. https://archive.org/details/essentialpsychop00step. "adatanserin." 
  5. ↑ "Attenuation of ischemic efflux of endogenous amino acids by the novel 5-HT(1A)/5-HT(2) receptor ligand adatanserin". Neurochemistry International 40 (3): 203–9. March 2002. doi:10.1016/S0197-0186(01)00082-1. PMID 11741003. 
  6. ↑ Magid A.-M., et al., "Use of aryl- and heteroaryl piperazinyl carboxamides in the treatment of various central nervous system disorders", US patent 5482940, issued 1996-01-09, assigned to American Home Products Corp




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