Development of CXCR3 antagonists. Part 2: Identification of 2-amino(4-piperidinyl)azoles as potent CXCR3 antagonists

Robert J Watson; Daniel R Allen; Helen L Birch; Gayle A Chapman; Duncan R Hannah; Roland L Knight; Johannes W G Meissner; David A Owen; Elizabeth J Thomas

doi:10.1016/j.bmcl.2007.10.029

Development of CXCR3 antagonists. Part 2: Identification of 2-amino(4-piperidinyl)azoles as potent CXCR3 antagonists

Bioorg Med Chem Lett. 2007 Dec 15;17(24):6806-10. doi: 10.1016/j.bmcl.2007.10.029. Epub 2007 Oct 17.

Authors

Robert J Watson¹, Daniel R Allen, Helen L Birch, Gayle A Chapman, Duncan R Hannah, Roland L Knight, Johannes W G Meissner, David A Owen, Elizabeth J Thomas

Affiliation

¹ UCB Inflammation Discovery, Granta Park, Great Abington, Cambridge CB21 6GS, United Kingdom.

PMID: 17964154
DOI: 10.1016/j.bmcl.2007.10.029

Abstract

Development of a lead series of piperidinylurea CXCR3 antagonists has led to the identification of molecules with alternative linkages which retain good potency. A novel 5-(piperidin-4-yl)amino-1,2,4-thiadiazole derivative was found to have satisfactory in vitro metabolic stability and to be orally bioavailable in mice, giving high plasma concentrations and a half life of 5.4h.

MeSH terms

Amination
Animals
Azoles / chemical synthesis*
Azoles / chemistry
Azoles / pharmacology*
CHO Cells
Cricetinae
Cricetulus
Humans
Mice
Models, Molecular
Molecular Structure
Piperidines / chemistry*
Receptors, CXCR3 / antagonists & inhibitors*
Receptors, CXCR3 / metabolism
Structure-Activity Relationship
Water / chemistry

Substances

Azoles
Piperidines
Receptors, CXCR3
Water
piperidine