(3-oxo-3, 4-dihydro-quinoxalin-2-yl-amino) -benzamide derivatives and related compound as glycogen phosphorylase inhibitors for the treatment of diabetes and obesity

Abstract

The invention features pharmaceutically active quinoxalinones of formula (1), compositions containing them, and methods of making and using theme: Formula (I) wherein R<1> is H, C 1-6 alkyl, or halo; R<2> is H or halo; R<3> is H, C 1-6 alkyl, X is N or CH; Y is a covalent bond, -NHCO- or -CONH-; Z is phenyl or a 5 or 6-membered heterocyclyl with between l and 2 heteroatoms independently selected from N, O, and S; and n is 0, 1 or 2; or a pharmaceutically acceptable salt, ester, amide, hydrate, or solvate thereof; as well as their use as glycogen phosphorylase inhibitors for the treatment of i diabetes and obesity.

Description

Background of the invention [0001] Non-insulin-dependent diabetes mellitus (NIDDM) is a polygenic disease characterized by defective insulin function in multiple target tissues including muscle, fat and liver. It is well established that normal glucose homeostasis requires accurate metabolic control in all insulin-responsive tissues; however the relative importance of each of these tissues to the pathogenesis of NIDDM is unclear. [0002] More specifically, maintenance of normal glucose homeostasis involves a highly coordinated series of events mediated by a variety of cellular proteins that catalyze 1) the transport and phosphorylation of glucose, 2) the phosphorylation of The combination of glucose monosaccharides into glycogen, and 3) glycogen hydrolysis and hepatic glucose production. Each of these processes represents a site of possible therapeutic intervention. Several pathways regulating hepatic glucose production (HGP) are involved in the regulation of circulating bl...

AI Technical Summary

Problems solved by technology

Alternative approaches to inhibiting glycogenolysis to reduce HGP have not been fully explored

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