Synthesis of Four SIRT1 Activators Based on an Imidazo(1,2-b)thiazole Structure, in vitro Derived Metabolites and Deuterated Analogs

The enzyme sirtuin 1 (SIRT1) is a major target for the treatment of various metabolic disorders. Herein, a practical synthesis of imidazo(1,2-b)thiazole derivatives, one of the most comprehensively studied class of synthetic SIRT1 activators, is presented. The synthesized SIRT1 activators, the in vitro-identified metabolite of SRT1720, and the eightfold deuterated analytical standards were obtained through a six-step protocol yielding model compounds with a conserved core structure and two variable moieties. A multiplicity of potential SIRT1 activators and metabolites can be prepared with substituents enabling the modification of biological effects.