1-(4-Chlorobenzhydryl)piperazine is an inactive metabolite of meclizine and chlorcyclizine .1,2 It has also been found as an impurity in commercial preparations of hydroxyzine and cetirizine .3,4 1-(4-Chlorobenzhydryl)piperazine has been used in the synthesis of voltage-gated sodium channel 1.7 (Nav1.7) inhibitors, anticancer agents, and antihistamines.5,6,7
1.Gaertner, H.J., Breyer, U., and Liomin, G.Chronic administration of chlorcyclizine and meclizine to rats: Accumulation of a metabolite formed by piperazine ring cleavageJ. Pharmacol. Exp. Ther.185(2)195-201(1973) 2.Kuntzman, R., Klutch, A., Tsai, I., et al.Physiological distribution and metabolic inactivation of chlorcyclizine and cyclizineJ. Pharmacol. Exp. Ther.149(1)29-35(1965) 3.Simpson, D., Skellern, G.G., and Miller, J.H.Method for the control of known impurities in hydroxyzine hydrochlorideJ. Pharm. Biomed. Anal.14(8-10)1371-1375(1996) 4.Javid, F.S., Shafaat, A., and Zarghi, A.Determination of cetirizine and its impurities in bulk and tablet formulation using a validated capillary zone electrophoretic methodJ. Anal. Chem.69(5)442-447(2014) 5.Back, S.K., Kam, Y.L., Oh, J.A., et al.Synthesis and evaluation of (4-chlorobenzhydryl) piperazine amides as sodium channel Nav1.7 inhibitorsBull. Korean Chem. Soc.36(9)2290-2297(2015) 6.Yarim, M., Koksal, M., Durmaz, I., et al.Cancer cell cytotoxicities of 1-(4-substitutedbenzoyl)-4-(4-chlorobenzhydryl)piperazine derivativesInt. J. Mol. Sci.13(7)8071-8085(2012) 7.Narsaiah, A.V., and Narssimha, P.Efficient synthesis of antihistamines clocinizine and chlorcyclizineMed. Chem. Res.21538-541(2012)