Synthesis and evaluation of [(1R)-1-amino-2-(2,5-difluorophenyl)ethyl] cyclohexanes and 4-[(1R)-1-amino-2-(2,5-difluorophenyl)ethyl]piperidines as DPP-4 inhibitors

被引：15

作者：

Chen, Ping ^{[1
]}

Caldwell, Charles G. ^{[1
]}

Ashton, Wallace ^{[1
]}

Wu, Joseph K. ^{[2
]}

He, Huaibing ^{[1
]}

Lyons, Kathryn A. ^{[1
]}

Thornberry, Nancy A. ^{[2
]}

Weber, Ann E. ^{[1
]}

机构：

[1] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck Res Labs, Dept Metab Disorders Diabet, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 06期

关键词：

DIPEPTIDYL-PEPTIDASE-IV; GLUCAGON-LIKE PEPTIDE-1; SITAGLIPTIN; DISCOVERY; HOMOLOG; POTENT;

D O I：

10.1016/j.bmcl.2010.12.060

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 4-amino cyclohexanes and 4-substituted piperidines were prepared and evaluated for inhibition of DPP-4. Analog 20q displayed both good DPP-4 potency and selectivity against other proteases, while derivative 20k displayed long half life and modest oral bioavailability in rat. The most potent analog, 3-(5-aminocarbonylpyridyl piperidine 53j, displayed excellent DPP-4 activity with good selectivity versus other proline enzymes. Published by Elsevier Ltd.

引用

页码：1880 / 1886

页数：7

共 22 条

[1] Cloning, expression and chromosomal localization of a novel human dipeptidyl peptidase (DPP) IV homolog, DPP8 [J].