Novel 4-Oxothienopyrimidinyl Propanoic Acid Derivatives as AMPActivated Protein Kinase (AMPK) Activators

Adenosine 5’-monophosphate (AMP) activated protein kinase (AMPK) is a highly conserved sensor of cellular energy. AMPK has been recognized as a key regulator of mammalian metabolic function and has emerged as an attractive target for the treatment of metabolic disorders, including obesity and type 2 diabetes. The synthesis and biological evaluation of novel 3-(4-oxothieno[2,3-d]pyrimidin-3(4H)-yl)propanoic acid derivatives as AMPK activators are described. The in vivo proof of principle for plasma glucose lowering effect is exemplified with a lead compound from this series. Keywords: AMP-activated protein kinase (AMPK), AMPK activators, Thienopyrimidinone derivatives, Type-2 diabetes mellitus, db/db mice model.