Synthesis and evaluation of aminobenzothiazoles as blockers of N- and T-type calcium channels

Abstract Both N- and T-type calcium ion channels have been implicated in pain transmission and the N-type channel is a well-validated target for the treatment of neuropathic pain. An SAR investigation of a series of substituted aminobenzothiazoles identified a subset of five compounds with comparable activity to the positive control Z160 in a FLIPR-based intracellular calcium response assay measuring potency at both Ca V 2.2 and Ca V 3.2 channels. These compounds may form the basis for the development of drug leads and tool compounds for assessing in vivo effects of variable modulation of Ca V 2.2 and Ca V 3.2 channels.