Design, Synthesis, Biological Evaluation, and Docking Studies of (S)-Phenylalanine Derivatives with a 2-Cyanopyrrolidine Moiety as Potent Dipeptidyl Peptidase 4 Inhibitors

Yang Liu, Yizhe Wu, Haoshu Wu, Li Tang, Peng Wu, Tao Liu, Yongzhou Hu

Research output: Contribution to journalJournal articleResearchpeer-review

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 0.247m. 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.
Original languageEnglish
JournalChemical Biology & Drug Design (Online)
Volume82
Issue number2
Pages (from-to)140-146
ISSN1747-0285
DOIs
Publication statusPublished - 2013
Externally publishedYes

Keywords

  • Biochemistry
  • Molecular Medicine
  • (S)-phenylalanine
  • 1,2,3-triazole
  • 2-cyanopyrrolidine
  • Dipeptidyl peptidase 4 inhibitors
  • Type 2 diabetes
  • 2 cyanopyrrolidine derivative
  • Dipeptidyl peptidase IV inhibitor
  • Phenylalanine derivative
  • Pyrrolidine derivative
  • Unclassified drug
  • Binding kinetics
  • Drug binding
  • Drug design
  • Drug potency
  • Drug screening
  • Drug synthesis
  • IC 50
  • Molecular docking
  • Priority journal
  • Diabetes Mellitus, Type 2
  • Dipeptidyl Peptidase 4
  • Dipeptidyl-Peptidase IV Inhibitors
  • Humans
  • Molecular Docking Simulation
  • Phenylalanine
  • Pyrrolidines
  • Chemistry
  • GLUCAGON-LIKE PEPTIDE-1
  • IV INHIBITORS
  • Medicinal chemistry
  • AMINO-ACIDS
  • PROTEIN
  • Management
  • SERINE
  • AZIDES
  • 3-triazole
  • Drug optimization
  • 2-cyanopyrrolidine moiety containing (S)-phenylalanine derivatives enzyme inhibitor-drug, antidiabetic-drug synthesis pharmacodynamics
  • Dipeptidyl peptidase-4 DPP-4
  • 12512, Pathology - Therapy
  • 22002, Pharmacology - General
  • 22016, Pharmacology - Endocrine system
  • Molecular docking laboratory techniques
  • Pharmacology
  • 47E5O17Y3R Phenylalanine
  • EC 3.4.14.5 Dipeptidyl Peptidase 4
  • PHENYLALANINE
  • Derivatives
  • Research

Fingerprint Dive into the research topics of 'Design, Synthesis, Biological Evaluation, and Docking Studies of (S)-Phenylalanine Derivatives with a 2-Cyanopyrrolidine Moiety as Potent Dipeptidyl Peptidase 4 Inhibitors'. Together they form a unique fingerprint.

Cite this