Fluoroolefins as amide bond mimics in dipeptidyl peptidase IV inhibitors

被引：96

作者：

Edmondson, Scott D. ^{[1
]}

Wei, Lan ^{[1
]}

Xu, Jinyou ^{[1
]}

Shang, Jackie ^{[2
]}

Xu, Shiyao ^{[2
]}

Pang, Jianmei ^{[2
]}

Chaudhary, Ashok ^{[3
]}

Dean, Dennis C. ^{[3
]}

He, Huaibing ^{[1
]}

Leiting, Barbara ^{[4
]}

Lyons, Kathryn A. ^{[1
]}

Patel, Reshma A. ^{[4
]}

Patel, Sangita B. ^{[5
]}

Scapin, Giovanna ^{[5
]}

Wu, Joseph K. ^{[4
]}

Beconi, Maria G. ^{[6
]}

Thornberry, Nancy A. ^{[4
]}

Weber, Ann E. ^{[1
]}

机构：

[1] Merck & Co Inc, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck & Co Inc, Preclin Drug Metab & Pharmacokinet, Rahway, NJ 07065 USA

[3] Merck & Co Inc, DMPK Global Technol, Rahway, NJ 07065 USA

[4] Merck & Co Inc, Dept Metab Disorders, Rahway, NJ 07065 USA

[5] Merck & Co Inc, Global Struct Biol, Rahway, NJ 07065 USA

[6] Abbott Labs, Dept Drug Metab, Abbott Pk, IL 60045 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 07期

关键词：

fluoroolefin; DPP-4; dipeptidyl peptidase IV; oxadiazole; amide bond mimic; amide bond mimetic; amide bond bioisostere; QPP; DPP-II;

D O I：

10.1016/j.bmcl.2008.02.050

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis, selectivity, rat pharmacokinetic profile, and drug metabolism profiles of a series of potent fluoroolefin-derived DPP-4 inhibitors (4) are reported. A radiolabeled fluoroolefin 33 was shown to possess a high propensity to form reactive metabolites, thus revealing a potential liability for this class of DPP-4 inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：2409 / 2413

页数：5

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