Fatima Z. Basha

HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi-75270, Pakistan

Abstract:

The prevalence of type-2 diabetes and the associated serious complications continues to grow rapidly. Although there are several classes of anti-diabetic drugs presently available, long-term management of the disease with current agents have treatment-limiting side effects. Thus, there is a dire need for novel anti-diabetic drugs today.

Inhibition of dipeptidyl peptidase IV (DPP-IV) is currently under development as a new approach for the treatment of type-2 diabetes. Recently, the FDA has approved DPP-IV inhibitors (sitagliptin 1, vildagliptin 2, saxagliptin 3, and linagliptin 4) as antidiabetic agents. These inhibitors have shown great promise as a new class of therapeutic agents. ABT-279, is awaiting regulatory approval (Figure 1). DPP-IV inhibitors offer several advantages over existing therapies: 1) Low risk of hypoglycemia; 2) body weight neutrality; 3) potential for disease reversal with restoration of -cell function. In this presentation, we describe the design,bpancreatic  discovery, synthesis, SAR and in vivo activity of some of the best proven DPP-IV Inhibitors.