Discovery of thiazole salt AChE inhibitors and development of thiamine disulfide prodrugs targeting the central nervous system

•A novel class of thiazolate type AChE inhibitors was revealed, and the optimized compounds Tat2 achieved nanomolar levels against hAChE.•A series of differently substituted thiamine disulfide prodrugs was discovered based on the obtained thiazolate AChE inhibitors.•Thiazolate AChE inhibitor Tat2 in the brain at levels consistent with plasma up to 500 ng/g after intraperitoneal administration of prodrug Tap4 in ICR mice.