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

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

and α₂-adrenergic receptor

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain. It was previously under development by

Pfizer Pfizer Inc. ( ) is an American Multinational corporation, multinational Pharmaceutical industry, pharmaceutical and biotechnology corporation headquartered at The Spiral (New York City), The Spiral in Manhattan, New York City. Founded in 184 ...

for the treatment of depression and

anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

. It made it to phase III

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

s before being discontinued.

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 Raney nickel , also called spongy nickel, is a fine-grained solid composed mostly of nickel derived from a nickel–aluminium alloy. Several grades are known, of which most are gray solids. Some are pyrophoric, but most are used as air-stable s ...

reduces the cyano group to the corresponding primary amine; this product then undergoes an internal ester-amine interchange to yield the cyclized

lactam A lactam is a Cyclic compound, cyclic amide, formally derived from an amino alkanoic acid through cyclization reactions. The term is a portmanteau of the words ''lactone'' + ''amide''. Nomenclature Greek_alphabet#Letters, Greek prefixes in alpha ...

(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 Sodium azide is an inorganic compound with the formula . This colorless salt is the gas-forming component in some car airbag systems. It is used for the preparation of other azide compounds. It is highly soluble in water and is acutely poisonou ...

(9); the azide group is next reduced to the primary amine. Resolution of this product as its

mandelate Mandelic acid is an aromatic alpha hydroxy acid with the molecular formula C6H5CH(OH)CO2H. It is a white crystalline solid that is soluble in water and polar organic solvents. It is a useful precursor to various drugs. The molecule is chiral. The ...

salt then yields (10) as a single enantiomer. Rxn of that product with

succinic anhydride Succinic anhydride, is an organic compound with the molecular formula (CH2CO)2O. This colorless solid is the acid anhydride of succinic acid. Preparation In the laboratory, this material can be prepared by dehydration of succinic acid. Such dehy ...

converts the pendant amine to a succinimide, affording the anxiolytic agent sunepitron (1).

References

{{Serotonin receptor modulators 5-HT1A agonists Abandoned drugs Alpha-2 blockers Pyrimidines Succinimides

Chemistry

Synthesis

See also

References