1.
Bioorg Med Chem Lett
; 22(21): 6688-93, 2012 Nov 01.
Artículo
en Inglés
| MEDLINE
| ID: mdl-23031591
RESUMEN
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.
Asunto(s)
Descubrimiento de Drogas , Antagonistas de los Receptores Histamínicos H1/química , Receptores CCR3/antagonistas & inhibidores , Animales , Interacciones Farmacológicas , Canales de Potasio Éter-A-Go-Go/antagonistas & inhibidores , Antagonistas de los Receptores Histamínicos H1/farmacocinética , Estructura Molecular , Piperidinas/química , Ratas , Factores de Riesgo
2.
Bioorg Med Chem Lett
; 22(21): 6694-9, 2012 Nov 01.
Artículo
en Inglés
| MEDLINE
| ID: mdl-23021991
RESUMEN
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.