Bipiperidinyl carboxylic acid amides as potent, selective, and functionally active CCR4 antagonists

Chem Biol Drug Des. 2007 Sep;70(3):268-72. doi: 10.1111/j.1747-0285.2007.00551.x.

Abstract

A cell-based assay for the chemokine G-protein-coupled receptor CCR4 was developed, and used to screen a small-molecule compound collection in a multiplex format. A series of bipiperidinyl carboxylic acid amides amenable to parallel chemistry were derived that were potent and selective antagonists of CCR4. One prototype compound was shown to be active in a functional model of chemotaxis, making it a useful chemical tool to explore the role of CCR4 in asthma, allergy, diabetes, and cancer.

MeSH terms

  • Amides / chemistry*
  • Amides / pharmacology*
  • Biperiden / chemistry*
  • Carboxylic Acids / chemistry*
  • Inhibitory Concentration 50
  • Molecular Structure
  • Receptors, CCR4
  • Receptors, Chemokine / antagonists & inhibitors*
  • Receptors, Chemokine / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Amides
  • Carboxylic Acids
  • Receptors, CCR4
  • Receptors, Chemokine
  • Biperiden