Asymmetric synthesis and biological evaluation of N-cyclohexyl-4-[1-(2,4-dichlorophenyl)-1-(p-tolyl)methyl]piperazine-1-carboxamide as hCB1 receptor antagonists

► We synthesized the enantiomers of hCB1 inverse agonist 13R and 13S. ► Results indicated that the (R)-enantiomer is more active. ► In vivo study showed enhanced antagonistic activity for hCB1, and better bio-efficacy.