Oxymethylene aryl compounds and uses thereof

Abstract

Use of oxymethylene aryl GPR119 agonists and DPP IV inhibitors for the treatment of diabetic diseases, including Type II diabetes and other diseases associated with poor glycemic control are provided.

Description

Background technique [0001] Diabetes can be divided into two clinical syndromes: type I diabetes and type II diabetes. Type I diabetes or insulin-dependent diabetes mellitus is a chronic autoimmune disease characterized by insulin-producing beta-cells (hereinafter referred to as "islet cells" or "islet cells") in the islets of Langerhans of the pancreas. ) are lost in large numbers. As these cells are progressively destroyed, the amount of insulin secreted decreases, eventually leading to hyperglycemia (abnormally high levels of glucose in the blood) when the amount secreted falls below that required for euglycemia (normal levels of blood sugar). content). Although the exact trigger of this immune response is unknown, type 1 diabetics have high levels of antibodies directed against pancreatic β-cells (hereinafter referred to as "β-cells"). However, not all patients with high levels of these antibodies develop type 1 diabetes. [0002] Type II diabetes, or non-insulin depen...

AI Technical Summary

Problems solved by technology

The second component is the failure to respond to a hyperglycemic challenge to increase insulin release above an already elevated basal output

Inhibitors of cAMP phosphodiesterases have been shown to increase insulin secretion in vitro and in vivo, including PDE1C, PDE3B, PDE10 (Han P et al., J Biol Chem. 6 Aug 1999; 274(32):22337-44; Harndahl L et al., J Biol Chem. 2002 Oct 4; 277(40):37446-55; WalzHA et al People, J Endocrinol. 2006 Jun;189(3):629-41; Choi YH et al., J Clin Invest. 2006 Dec;116(12) : 3240-51; and Cantin LD et al., Bioorg Med Chem Lett. 2007 May 15; 17(10): 2869-73), but so far, PDEs not found to have the cell-type selectivity necessary to avoid undesired effects

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