The discovery of CCR3/H1 dual antagonists with reduced hERG risk

  • Bioorg Med Chem Lett. 2012 Nov 1;22(21):6688-93. doi: 10.1016/j.bmcl.2012.08.124.
Ash Bahl  1 ,  Patrick Barton ,  Keith Bowers ,  Steven Brough ,  Richard Evans ,  Christopher A Luckhurst ,  Tobias Mochel ,  Matthew W D Perry ,  Aaron Rigby ,  Robert J Riley ,  Hitesh Sanganee ,  Adam Sisson ,  Brian Springthorpe
Affiliations
  • 1. Department of Bioscience, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough LE11 5RH, United Kingdom.
PMID: 23031591 DOI: 10.1016/j.bmcl.2012.08.124
Abstract

A series of dual CCR3/H(1) antagonists based on a bispiperidine scaffold were discovered. Introduction of an acidic group overcame hERG liability. Bioavailability was optimised by modulation of physico-chemical properties and physical form to deliver a compound suitable for clinical evaluation.

Products