2. Academic Validation
  3. Structure-activity-relationship of amide and sulfonamide analogs of omarigliptin

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

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.

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