Omarigliptin (MK-3102): A Novel Long-Acting DPP-4 Inhibitor for Once-Weekly Treatment of Type 2 Diabetes

被引：152

作者：

Biftu, Tesfaye ^{[1
]}

Sinha-Roy, Ranabir ^{[2
]}

Chen, Ping ^{[1
]}

Qian, Xiaoxia ^{[1
]}

Feng, Dennis ^{[1
]}

Kuethe, Jeffrey T. ^{[1
]}

Scapin, Giovanna ^{[1
]}

Gao, Ying Duo ^{[1
]}

Tan, Youwei ^{[1
]}

Krueger, Davida ^{[5
]}

Bak, Annette ^{[5
]}

Eiermann, George ^{[3
]}

He, Jiafang ^{[1
]}

Cox, Jason ^{[1
]}

Hicks, Jacqueline ^{[1
]}

Lyons, Kathy ^{[4
]}

He, Huaibing ^{[4
]}

Salituro, Gino ^{[4
]}

Tong, Sharon ^{[4
]}

Patel, Sangita ^{[1
]}

Doss, George ^{[1
]}

Petrov, Aleksandr ^{[3
]}

Wu, Joseph ^{[2
]}

Xu, Shiyao Sherrie ^{[4
]}

Sewall, Charles ^{[6
]}

Zhang, Xiaoping ^{[2
]}

Zhang, Bei ^{[2
]}

Thornberry, Nancy A. ^{[2
]}

Weber, Ann E. ^{[1
]}

机构：

[1] Merck & Co Inc, Dept Discovery Chem, Whitehouse Stn, NJ 08889 USA

[2] Merck & Co Inc, Dept Metab Disorders, Whitehouse Stn, NJ 08889 USA

[3] Merck & Co Inc, Dept Pharmacol, Whitehouse Stn, NJ 08889 USA

[4] Merck & Co Inc, Dept Drug Metab, Whitehouse Stn, NJ 08889 USA

[5] Merck & Co Inc, Basic Pharmaceut Sci, Whitehouse Stn, NJ 08889 USA

[6] Merck & Co Inc, Dept Safety Assessment & Anim Resources, Whitehouse Stn, NJ 08889 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 57卷 / 08期

关键词：

DIPEPTIDYL-PEPTIDASE-IV; RATIONAL DESIGN; IDENTIFICATION; HOMOLOG; CLONING; POTENT;

D O I：

10.1021/jm401992e

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

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.

引用

页码：3205 / 3212

页数：8

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