Bicyclic inhibitors of glycogen synthase kinase 3

Abstract

Bicyclic based compounds of the formula (I), compositions and methods of inhibiting the activity of glycogen synthase kinase (GSK3) in vitro and a treatment of GSK3 mediated disorders in vivo are provided. The methods, compounds and compositions of the invention may be employed alone, or in combination with other pharmacologically active agents in the treatment of disorders mediated by GSK3 activity, such as in the treatment of diabetes, Alzheimer's disease and other neurodegenerative disorders, obesity, atherosclerotic cardiovascular disease, essential hypertension, polycystic ovary syndrome, syndrome X, ischemia, traumatic brain injury, bipolar disorder, immunodeficiency or cancer.

Description

field of invention

[0001] The present invention relates to novel bicyclic compounds that inhibit the activity of glycogen synthase kinase 3 (GSK3), pharmaceutical compositions containing these compounds, and the use of the compounds and compositions alone or in combination with other pharmaceutically active agents. The compounds and compositions provided by the present invention are effective in treating diseases mediated by GSK3 activity, such as diabetes, Alzheimer's disease and other neurodegenerative diseases, obesity, arteriosclerotic cardiovascular disease, essential hypertension, Utility in diseases such as polycystic ovary syndrome, syndrome X, ischemia (especially cerebral ischemia), traumatic brain injury, bipolar disorder, immunodeficiency or cancer. Background of the invention

[0002] Glycogen synthase kinase 3 (GSK3) is a serine / threonine kinase for which two isoforms have been identified: alpha and beta. Woodgett, Trends Biochem Sci., 16:177-81 (1991). Both ...