Sunepitron

IdentifiersCAS NumberPubChem CIDChemSpiderUNIIKEGGChEMBLChemical and physical dataFormulaC₁₇H₂₃N₅O₂Molar mass329.404 g·mol⁻¹3D model (JSmol)

Sunepitron (developmental code name CP-93,393) is a combined 5-HT_1A 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

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

• Lesopitron

References