Optimization of CCR4 antagonists: side-chain exploration

Ashok V Purandare; Honghe Wan; Aiming Gao; John Somerville; Christine Burke; Wayne Vaccaro; Xiaoxia Yang; Kim W McIntyre; Michael A Poss

doi:10.1016/j.bmcl.2005.09.022

Optimization of CCR4 antagonists: side-chain exploration

Bioorg Med Chem Lett. 2006 Jan 1;16(1):204-7. doi: 10.1016/j.bmcl.2005.09.022. Epub 2005 Oct 19.

Authors

Ashok V Purandare¹, Honghe Wan, Aiming Gao, John Somerville, Christine Burke, Wayne Vaccaro, Xiaoxia Yang, Kim W McIntyre, Michael A Poss

Affiliation

¹ Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA. ashok.purandare@bms.com

PMID: 16236499
DOI: 10.1016/j.bmcl.2005.09.022

Abstract

The design, synthesis, and activity of novel and selective small molecule antagonists of the CC chemokine receptor-4 (CCR4) are presented. Compound 8c was efficacious in a murine allergic inflammation model (ED(50) 30 mg/kg).

MeSH terms

Animals
Chemistry, Pharmaceutical / methods
Chemokines / metabolism
Chemotaxis
Dose-Response Relationship, Drug
Drug Design
Drug Evaluation, Preclinical
Eosinophils / metabolism
Hypersensitivity
Inflammation
Inhibitory Concentration 50
Leukocytes / cytology
Mice
Models, Chemical
Receptors, CCR4
Receptors, Chemokine / antagonists & inhibitors*
Signal Transduction
Structure-Activity Relationship

Substances

Ccr4 protein, mouse
Chemokines
Receptors, CCR4
Receptors, Chemokine