The Open Organic Chemistry Journal

2014, 8 : 19-23
Published online 2014 November 14. DOI: 10.2174/1874095201408010019
Publisher ID: TOOCJ-8-19

Synthesis of Four SIRT1 Activators Based on an Imidazo[1,2-b]thiazole Structure, Derived Metabolites and Deuterated Analogs

Sebastian Höppner , Nils Schlörer , Wilhelm Schänzer and Mario Thevis
Center for Preventive Doping Research/Institute of Biochemistry, German Sport University Cologne, Germany.

ABSTRACT

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.

Keywords:

Isotope labeling, metabolite, SIRT1 activator, SRT1720, SRT2104.