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. Crown Copyright (C) 2018 Published by Elsevier Ltd. All rights reserved.