Scaffold-hopping with zwitterionic CCR3 antagonists: identification and optimisation of a series with good potency and pharmacokinetics leading to the discovery of AZ12436092

Ash Bahl; Patrick Barton; Keith Bowers; Moya V Caffrey; Rebecca Denton; Peter Gilmour; Shaun Hawley; Tero Linannen; Christopher A Luckhurst; Tobias Mochel; Matthew W D Perry; Robert J Riley; Emma Roe; Brian Springthorpe; Linda Stein; Peter Webborn

doi:10.1016/j.bmcl.2012.08.103

Scaffold-hopping with zwitterionic CCR3 antagonists: identification and optimisation of a series with good potency and pharmacokinetics leading to the discovery of AZ12436092

Bioorg Med Chem Lett. 2012 Nov 1;22(21):6694-9. doi: 10.1016/j.bmcl.2012.08.103. Epub 2012 Sep 11.

Authors

Ash Bahl¹, Patrick Barton, Keith Bowers, Moya V Caffrey, Rebecca Denton, Peter Gilmour, Shaun Hawley, Tero Linannen, Christopher A Luckhurst, Tobias Mochel, Matthew W D Perry, Robert J Riley, Emma Roe, Brian Springthorpe, Linda Stein, Peter Webborn

Affiliation

¹ Department of Bioscience, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough LE11 5RH, United Kingdom.

PMID: 23021991
DOI: 10.1016/j.bmcl.2012.08.103

Abstract

The discovery and optimisation of a series of zwitterionic CCR3 antagonists is described. Optimisation of the structure led to AZ12436092, a compound with excellent selectivity over activity at hERG and outstanding pharmacokinetics in preclinical species.

MeSH terms

Animals
Drug Discovery*
Humans
Inhibitory Concentration 50
Molecular Structure
Piperidines / chemistry*
Piperidines / pharmacokinetics*
Rats
Receptors, CCR3 / antagonists & inhibitors*

Substances

AZ12436092
Piperidines
Receptors, CCR3