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

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

  • ACS Med Chem Lett. 2015 Apr 8;6(5):602-6. doi: 10.1021/acsmedchemlett.5b00074.
Tao Jiang 1,  Yuren Zhou 1,  Zhuxi Chen 1,  Peng Sun 1,  Jianming Zhu 1,  Qiang Zhang 1,  Zhen Wang 1,  Qiang Shao 1,  Xiangrui Jiang 1,  Bo Li 1,  Kaixian Chen 1,  Hualiang Jiang 1,  Heyao Wang 1,  Weiliang Zhu 1,  Jingshan Shen 1
Affiliations

Affiliation

  • 1 Drug Discovery and Design Center, Key Laboratory for Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203, China.
PMID: 26005541 DOI: 10.1021/acsmedchemlett.5b00074
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 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, 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.

Keywords

DPP-4 inhibitor; Diabetes; sitagliptin; β-homophenylalanine derivatives.

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