Sunepitron

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]

Sunepitron

Clinical data
Other names	CP-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	131831-03-3 Y HCl: 148408-65-5 Y
PubChem CID	9799246
ChemSpider	7975011
UNII	2GT50C8U60 HCl: 1NYW5HLO1E Y
KEGG	D02569
ChEMBL	ChEMBL380369
Chemical and physical data
Formula	C17H23N5O2
Molar mass	329.404 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C1N(C(=O)CC1)CC4CCC3N(CCN(c2ncccn2)C3)C4

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

• Lesopitron