Structure-activity-relationship of amide and sulfonamide analogs of omarigliptin

  • Bioorg Med Chem Lett. 2015 Dec 15;25(24):5767-71. doi: 10.1016/j.bmcl.2015.10.070.
Ping Chen  1 ,  Dennis Feng  1 ,  Xiaoxia Qian  1 ,  James Apgar  1 ,  Robert Wilkening  1 ,  Jeffrey T Kuethe  1 ,  Ying-Duo Gao  1 ,  Giovanna Scapin  1 ,  Jason Cox  1 ,  George Doss  2 ,  George Eiermann  3 ,  Huaibing He  2 ,  Xiaohua Li  2 ,  Kathryn A Lyons  2 ,  Joseph Metzger  4 ,  Aleksandr Petrov  3 ,  Joseph K Wu  4 ,  Shiyao Xu  2 ,  Ann E Weber  1 ,  Youwei Yan  1 ,  Ranabir Sinha Roy  4 ,  Tesfaye Biftu  1
Affiliations
  • 1. Department of Discovery Chemistry, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States.
  • 2. Department of Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States.
  • 3. Department of Pharmacology, Screening & Protein Sciences, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States.
  • 4. Department of Cardiometabolic Diseases, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States.
PMID: 26546218 DOI: 10.1016/j.bmcl.2015.10.070
Abstract

A series of novel substituted-[(3R)-amino-2-(2,5-difluorophenyl)]tetrahydro-2H-pyran analogs have been prepared and evaluated as potent, selective and orally active DPP-4 inhibitors. These efforts lead to the discovery of a long acting DPP-4 Inhibitor, omarigliptin (MK-3102), which recently completed phase III clinical development and has been approved in Japan.

Keywords
DPP-4 inhibitor; DPP-8; DPP-9; Omarigliptin; Pyrazolopyrolidine; Sitagliptin; Type 2 diabetes; X-ray.