Sunepitron

Sunepitron
Clinical data
Other namesCP-93,393
Routes of
administration		Oral
ATC code
  • none
Identifiers
IUPAC name
  • 1-{[2-(pyrimidin-2-yl)octahydro-2H-pyrido[1,2-a]pyrazin-7-yl]methyl}pyrrolidine-2,5-dione
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC17H23N5O2
Molar mass329.404 g·mol−1
3D model (JSmol)
SMILES
  • O=C1N(C(=O)CC1)CC4CCC3N(CCN(c2ncccn2)C3)C4

Sunepitron (developmental code name CP-93,393) is a combined 5-HT1A receptor agonist and α2-adrenergic receptor antagonist.[1][2] It was previously under development by Pfizer for the treatment of depression and anxiety.[3] It made it to phase III clinical trials before being discontinued.[2][3]

Chemistry

Synthesis

Sunepitron synthesis: G.N. Bright, K.A. Desai, U.S. Patent 5,122,525 (1992).

The synthesis starts by conversion of the pyridine dicarboxylic acid (1) to its acid chloride; rxn with MeOH then affords the ester (2). Catalytic hydrogenation serves to reduce the pyridine ring to a piperidine of undefined stereochemistry (3). Alkylation of this intermediate with chloroacetonitrile affords (4). Treatment of that intermediate with Raney nickel reduces the cyano group to the corresponding primary amine; this product then undergoes an internal ester-amine interchange to yield the cyclized lactam (5). LAH serves to reduce the lactam to an amine; the ester on the other ring is reduced to a carbinol in the process, affording the aminoalcohol (7). The basic function is next alkylated with 2-chloropyrimidine (7). Rxn of the alcoholin (8) with MsCl leads to the mesylate; that group is next displaced by sodium azide (9); the azide group is next reduced to the primary amine. Resolution of this product as its mandelate salt then yields (10) as a single enantiomer. Rxn of that product with succinic anhydride converts the pendant amine to a succinimide, affording the anxiolytic agent sunepitron (1).

See also

References

  1. ↑ Goodnick PJ (July 1999). "Psychopharmacology of depression in the next millennium". CNS Spectrums. 4 (7): 21–35. doi:10.1017/s1092852900011998. PMID 18438295.
  2. 1 2 Stahl SM (2000). Essential psychopharmacology: neuroscientific basis and practical application. Cambridge, UK: Cambridge University Press. p. 265. ISBN 0-521-64615-4.
  3. 1 2 Kaplan EP, Turkington C (2001). Making the antidepressant decision: how to choose the right treatment option for you and your loved ones. Chicago, Ill: Contemporary Books. ISBN 0-7373-0417-0.
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