Dipeptidyl peptidase inhibitors

ORGN 667

Michael B. Wallace, Department of Medicinal Chemistry, Takeda San Diego, 10410 Science Center Drive, San Diego, CA 92121
Inhibition of dipeptidyl peptidase IV (DPP-IV), an enzyme that rapidly inactivates GLP-1, has been shown to increase the secretion of insulin and effectively regulate elevated blood glucose levels. Takeda San Diego has developed several novel series of compounds as inhibitors of DPP-IV for the treatment of type 2 diabetes. Multiple compounds are currently being evaluated in clinical trials, including SYR-322, which has progressed to Phase III. The role of a structure-based approach in the design and synthesis of highly potent and selective non-covalent DPP-IV inhibitors will be presented.