Core exploration in optimization of chemokine receptor CCR4 antagonists

Ashok V Purandare; Honghe Wan; John E Somerville; Christine Burke; Wayne Vaccaro; XiaoXia Yang; Kim W McIntyre; Michael A Poss

doi:10.1016/j.bmcl.2006.10.091

Core exploration in optimization of chemokine receptor CCR4 antagonists

Bioorg Med Chem Lett. 2007 Feb 1;17(3):679-82. doi: 10.1016/j.bmcl.2006.10.091. Epub 2006 Nov 2.

Authors

Ashok V Purandare¹, Honghe Wan, John E 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. [email protected]

PMID: 17098428
DOI: 10.1016/j.bmcl.2006.10.091

Abstract

The design, synthesis, and SAR studies of 'core' variations led to identification of novel, selective, and potent small molecule antagonist (22) of the CC chemokine receptor-4 (CCR4) with improved in vitro activity and liability profile. Compound 22 was efficacious in a murine allergic inflammation model (ED50 approximately 10 mg/kg).

MeSH terms

Animals
Benzyl Compounds / chemical synthesis
Benzyl Compounds / pharmacology
Cell Line
Chemotaxis / drug effects
Dose-Response Relationship, Drug
Indicators and Reagents
Mice
Ovalbumin
Pneumonia / chemically induced
Pneumonia / drug therapy
Quinolines / chemical synthesis
Quinolines / pharmacology
Receptors, CCR4
Receptors, Chemokine / antagonists & inhibitors*
Respiratory Hypersensitivity / drug therapy
Respiratory Hypersensitivity / pathology
Structure-Activity Relationship

Substances

Benzyl Compounds
Ccr4 protein, mouse
Indicators and Reagents
Quinolines
Receptors, CCR4
Receptors, Chemokine
Ovalbumin