Ligand-based molecular design of 4-benzylpiperidinealkylureas and amides as CCR3 antagonists

J Mol Model. 2010 Apr;16(4):669-76. doi: 10.1007/s00894-009-0621-z. Epub 2009 Dec 4.

Abstract

Asthma is an inflammatory disease of the lungs. Clinical studies suggest that eotaxin and chemokine receptor-3 (CCR3) play a primary role in the recruitment of eosinophils in allergic asthma. Development of novel and potent CCR3 antagonists could provide a novel mechanism for inhibition of this recruitment process, thereby preventing asthma. With the intention of designing new ligands with enhanced inhibitor potencies against CCR3, a 3D-QSAR CoMFA study was carried out on 41 4-benzylpiperidinealkylureas and amide derivatives. The best statistics of the developed CoMFA model were r (2) = 0.960, r(2)cv, n = 32 for the training set and r(2)pred, n = 9 for the test set. The generated 3D-QSAR contribution maps shed some light on the effects of the substitution pattern related to CCR3 antagonist activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry
  • Amides / pharmacology*
  • Asthma / pathology
  • Asthma / prevention & control
  • Benzene Derivatives
  • Drug Design
  • Humans
  • Ligands
  • Quantitative Structure-Activity Relationship*
  • Receptors, CCR3 / antagonists & inhibitors*
  • Urea / chemistry
  • Urea / pharmacology*

Substances

  • Amides
  • Benzene Derivatives
  • CCR3 protein, human
  • Ligands
  • Receptors, CCR3
  • Urea