Optimization of 2-aminothiazole derivatives as CCR4 antagonists

Xuemei Wang; Feng Xu; Qingge Xu; Hossen Mahmud; Jonathan Houze; Liusheng Zhu; Michelle Akerman; George Tonn; Liang Tang; Brian E McMaster; Daniel J Dairaghi; Thomas J Schall; Tassie L Collins; Julio C Medina

doi:10.1016/j.bmcl.2006.01.126

Optimization of 2-aminothiazole derivatives as CCR4 antagonists

Bioorg Med Chem Lett. 2006 May 15;16(10):2800-3. doi: 10.1016/j.bmcl.2006.01.126. Epub 2006 Feb 23.

Authors

Xuemei Wang¹, Feng Xu, Qingge Xu, Hossen Mahmud, Jonathan Houze, Liusheng Zhu, Michelle Akerman, George Tonn, Liang Tang, Brian E McMaster, Daniel J Dairaghi, Thomas J Schall, Tassie L Collins, Julio C Medina

Affiliation

¹ Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.

PMID: 16497499
DOI: 10.1016/j.bmcl.2006.01.126

Abstract

A series of 2-aminothiazole-derived antagonists of the CCR4 receptor has been synthesized and their affinity for the receptor evaluated using a [(125)I]TARC (CCL17) displacement assay. Optimization of these compounds for potency and pharmacokinetic properties led to the discovery of potent, orally bioavailable antagonists.

MeSH terms

Cell Line
Humans
Receptors, CCR4
Receptors, Chemokine / antagonists & inhibitors*
Thiazoles / pharmacokinetics
Thiazoles / pharmacology*

Substances

CCR4 protein, human
Receptors, CCR4
Receptors, Chemokine
Thiazoles