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Design, Synthesis, and Pharmacological Evaluation of Fused ?-Homophenylalanine Derivatives as Potent DPP-4 Inhibitors.

ABSTRACT: Dipeptidyl peptidase-4 (DPP-4) inhibitors are accepted as a favorable class of agents for the treatment of type 2 diabetes. Herein, a series of fused ?-homophenylalanine derivatives as novel DPP-4 inhibitors were designed, synthesized, and evaluated for their inhibitory activities against DPP-4. Most of them displayed excellent DPP-4 inhibitory activities and good selectivity. Among them, 9aa, 18a, and 18m also showed good efficacy in an oral glucose tolerance test (OGTT) in ICR mice. Moreover, when dosed 8 h prior to glucose challenge, 18m showed significantly greater potency than sitagliptin. It thus provides potential candidates for the further development into potent drugs targeting DPP-4.

SUBMITTER: Jiang T

PROVIDER: S-EPMC4434481 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Design, Synthesis, and Pharmacological Evaluation of Fused β-Homophenylalanine Derivatives as Potent DPP-4 Inhibitors.

Jiang Tao T Zhou Yuren Y Chen Zhuxi Z Sun Peng P Zhu Jianming J Zhang Qiang Q Wang Zhen Z Shao Qiang Q Jiang Xiangrui X Li Bo B Chen Kaixian K Jiang Hualiang H Wang Heyao H Zhu Weiliang W Shen Jingshan J

ACS medicinal chemistry letters 20150408 5

Dipeptidyl peptidase-4 (DPP-4) inhibitors are accepted as a favorable class of agents for the treatment of type 2 diabetes. Herein, a series of fused β-homophenylalanine derivatives as novel DPP-4 inhibitors were designed, synthesized, and evaluated for their inhibitory activities against DPP-4. Most of them displayed excellent DPP-4 inhibitory activities and good selectivity. Among them, 9aa, 18a, and 18m also showed good efficacy in an oral glucose tolerance test (OGTT) in ICR mice. Moreover, ...[more]

PMID: 26005541

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