title: Omarigliptin (MK-3102): a novel long-acting DPP-4 inhibitor for once-weekly treatment of type 2 diabetes.
abstract: In our effort to discover DPP-4 inhibitors with added benefits over currently commercially available DPP-4 inhibitors, MK-3102 (omarigliptin), was identified as a potent and selective dipeptidyl peptidase 4 (DPP-4) inhibitor with an excellent pharmacokinetic profile amenable for once-weekly human dosing and selected as a clinical development candidate. This manuscript summarizes the mechanism of action, scientific rationale, medicinal chemistry, pharmacokinetic properties, and human efficacy data for omarigliptin, which is currently in phase 3 clinical development.
authors.affiliation: Department of Discovery Chemistry, ‡Department of Metabolic Disorders, §Department of Pharmacology, ∥Department of Drug Metabolism, ⊥Basic Pharmaceutical Sciences, and #Department of Safety Assessment and Animal Resources, Merck & Co., Inc. , Whitehouse Station, New Jersey 08889, United States.
authors.forename: Tesfaye
authors.initials: T
authors.lastname: Biftu
authors.forename: Ranabir
authors.initials: R
authors.lastname: Sinha-Roy
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Qian
authors.forename: Dennis
authors.initials: D
authors.lastname: Feng
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Kuethe
authors.forename: Giovanna
authors.initials: G
authors.lastname: Scapin
authors.forename: Ying Duo
authors.initials: YD
authors.lastname: Gao
authors.forename: Youwei
authors.initials: Y
authors.lastname: Yan
authors.forename: Davida
authors.initials: D
authors.lastname: Krueger
authors.forename: Annette
authors.initials: A
authors.lastname: Bak
authors.forename: George
authors.initials: G
authors.lastname: Eiermann
authors.forename: Jiafang
authors.initials: J
authors.lastname: He
authors.forename: Jason
authors.initials: J
authors.lastname: Cox
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Hicks
authors.forename: Kathy
authors.initials: K
authors.lastname: Lyons
authors.forename: Huaibing
authors.initials: H
authors.lastname: He
authors.forename: Gino
authors.initials: G
authors.lastname: Salituro
authors.forename: Sharon
authors.initials: S
authors.lastname: Tong
authors.forename: Sangita
authors.initials: S
authors.lastname: Patel
authors.forename: George
authors.initials: G
authors.lastname: Doss
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Petrov
authors.forename: Joseph
authors.initials: J
authors.lastname: Wu
authors.forename: Shiyao Sherrie
authors.initials: SS
authors.lastname: Xu
authors.forename: Charles
authors.initials: C
authors.lastname: Sewall
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.forename: Bei
authors.initials: B
authors.lastname: Zhang
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Thornberry
authors.forename: Ann E
authors.initials: AE
authors.lastname: Weber
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D006574:Heterocyclic Compounds, 2-Ring / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D011714:Pyrans / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: C587539:2-(2,5-difluorophenyl)-5-(2-(methylsulfonyl)-2,6-dihydropyrrolo(3,4-c)pyrazol-5(4H)-yl)tetrahydro-2H-pyran-3-amine; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006574:Heterocyclic Compounds, 2-Ring; D007004:Hypoglycemic Agents; D011714:Pyrans