Structure-Activity Study of L-Cysteine-Based N-Type Calcium Channel Blockers: Optimization of N- and C-Terminal Substituents.

Abstract Synthesis and structure–activity relationship (SAR) studies of l -cysteine-based N-type calcium channel blockers are described. In the course of exploring SAR of the N- and C-terminal substituents, the l -cysteine derivative 4b was found to be a potent N-type calcium channel blocker with an IC 50 value of 0.14 μM on IMR-32 assay. Compound 4b showed 12-fold selectivity for N-type over L-type calcium channels on AtT-20 assay.