Adatanserin

Adatanserin

Clinical data
Drug class	Serotonin 5-HT1A receptor agonist; Serotonin 5-HT2A receptor antagonist; Serotonin 5-HT2C receptor antagonist
ATC code	none
Identifiers
IUPAC name N-[2-(4-pyrimidin-2-ylpiperazin-1-yl)ethyl]adamantane-1-carboxamide
CAS Number	127266-56-2  Y
PubChem CID	130918
ChemSpider	115774  Y
UNII	W5U6WQM26H
ChEMBL	ChEMBL2107510  Y
CompTox Dashboard (EPA)	DTXSID90869749
Chemical and physical data
Formula	C21H31N5O
Molar mass	369.513 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C(NCCN2CCN(c1ncccn1)CC2)C35CC4CC(CC(C3)C4)C5
InChI InChI=1S/C21H31N5O/c27-19(21-13-16-10-17(14-21)12-18(11-16)15-21)22-4-5-25-6-8-26(9-7-25)20-23-2-1-3-24-20/h1-3,16-18H,4-15H2,(H,22,27) Y Key:HPFLVTSWRFCPCV-UHFFFAOYSA-N Y

Adatanserin (WY-50,324, SEB-324) is a mixed 5-HT_1A receptor partial agonist and 5-HT_2A and 5-HT_2C 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-HT_2A 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

• Flibanserin

References

1. Singh A, Lucki I (April 1993). "Antidepressant-like activity of compounds with varying efficacy at 5-HT1A receptors". Neuropharmacology. 32 (4): 331–40. doi:10.1016/0028-3908(93)90153-T. PMID   8497336. S2CID   38611829.
2. Kleven MS, Koek W (February 1996). "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. doi:10.1016/S0022-3565(25)12286-6. PMID   8632301.
3. Abou-Gharbia MA, Childers WE, Fletcher H, et al. (December 1999). "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. 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. adatanserin.
5. Dawson LA, Galandak J, Djali S (March 2002). "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. doi:10.1016/S0197-0186(01)00082-1. PMID   11741003. S2CID   24104458.
6. USpatent 5482940,Magid A.-M., et al.,"Use of aryl- and heteroaryl piperazinyl carboxamides in the treatment of various central nervous system disorders",issued 1996-01-09, assigned to American Home Products Corp