title: Design, synthesis, biological evaluation, and docking studies of (s)-phenylalanine derivatives with a 2-cyanopyrrolidine moiety as potent dipeptidyl peptidase 4 inhibitors.
abstract: A novel series of (S)-phenylalanine derivatives with a 2-cyanopyrrolidine moiety were designed and synthesized through a rational drug design strategy. Biological evaluation revealed that most tested compounds were potent dipeptidyl peptidase 4 (DPP-4) inhibitors; among them, the cyclopropyl-substituted phenylalanine derivative 11h displayed the most potent DPP-4 inhibitory activity with an IC50 value of 0.247 μm. In addition, molecular docking analysis of the representative compounds 11h, 11k, and 15a were performed, which not only revealed the impact of binding modes on DPP-4 inhibitory activity but also provided additional methodological values for design and optimization.
authors.affiliation: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Yizhe
authors.initials: Y
authors.lastname: Wu
authors.forename: Haoshu
authors.initials: H
authors.lastname: Wu
authors.forename: Li
authors.initials: L
authors.lastname: Tang
authors.forename: Peng
authors.initials: P
authors.lastname: Wu
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Yongzhou
authors.initials: Y
authors.lastname: Hu
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000201:enzymology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D062105:Molecular Docking Simulation; D010649:Phenylalanine / Q000737:chemistry* / Q000494:pharmacology*; D011759:Pyrrolidines / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D011759:Pyrrolidines; D010649:Phenylalanine; D018819:Dipeptidyl Peptidase 4
keywords: (S)-phenylalanine; 1,2,3-triazole; 2-cyanopyrrolidine; Dipeptidyl peptidase 4 inhibitors; type 2 diabetes