Identification of novel aminopiperidine derivatives for antibacterial activity against Gram-positive bacteria

Bioorg Med Chem Lett. 2016 Jul 1;26(13):3148-3152. doi: 10.1016/j.bmcl.2016.04.086. Epub 2016 Apr 30.

Abstract

We have previously reported amidopiperidine derivatives as a novel peptide deformylase (PDF) inhibitor and evaluated its antibacterial activity against Gram-positive bacteria, but poor pharmacokinetic profiles have resulted in low efficacy in in vivo mouse models. In order to overcome these weaknesses, we newly synthesized aminopiperidine derivatives with remarkable antimicrobial properties and oral bioavailability, and also identified their in vivo efficacy against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE) and penicillin-resistant Streptococcus pneumoniae (PRSP).

Keywords: Aminopiperidine; Antibacterial; Gram-positive; Peptide deformylase; Resistant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Amidohydrolases / antagonists & inhibitors
  • Amidohydrolases / metabolism
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Gram-Positive Bacteria / drug effects*
  • Gram-Positive Bacteria / enzymology
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Piperidines / administration & dosage
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Piperidines
  • Amidohydrolases
  • peptide deformylase