1.
Bioorg Med Chem Lett
; 22(21): 6694-9, 2012 Nov 01.
Article
in English
| MEDLINE
| ID: mdl-23021991
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.
Subject(s)
Drug Discovery , Piperidines/chemistry , Piperidines/pharmacokinetics , Receptors, CCR3/antagonists & inhibitors , Animals , Humans , Inhibitory Concentration 50 , Molecular Structure , Rats
2.
Bioorg Med Chem Lett
; 22(21): 6688-93, 2012 Nov 01.
Article
in English
| MEDLINE
| ID: mdl-23031591
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.