Syntheses of Cinacalcet: An Enantiopure Active Pharmaceutical Ingredient (API)

Cinacalcet hydrochloride is the only approved drug acting as calcimimetic, a new class of compounds used in the therapy of secondary hyperparathyroidism and parathyroid carcinoma. Several generic drug manufacturers and research groups from academia have reported alternative approaches to this molecule, mainly from (R)-(+)-1-(1-naphthyl)ethylamine. There are mainly three strategies that have been used to couple this readily accessible enantiopure amine to the other part of the molecule: amide formation followed by reduction, reaction with an aldehyde and reduction of the resulting imine, and nucleophilic substitution with a suitable partner that carries a leaving group. More exotic approaches have also been disclosed. In the present review all of them are discussed.