Recent developments in CCR2 antagonists.
Monocyte chemoattractant protein-1 (MCP-1) is a major chemoattractant for monocytes and memory T cells by means of their binding to its specific cell-surface receptor, CC-chemokine receptor-2 (CCR2). CCR2 belongs to the G-protein-coupled seven-transmembrane receptor superfamily. The evidence in favor of CCR2 and MCP-1 having dominant roles in monocyte chemotaxis and chronic inflammation was provided by CCR2 and MCP-1 knockout mice. It has been recognized that CCR2 antagonists are potential therapeutic agents in preventing, treating, or ameliorating a CCR2-mediated inflammatory syndrome or disease such as psoriasis, uveitis, rheumatoid arthritis, multiple sclerosis, asthma, obesity, and chronic obstructive pulmonary disease. This review summarizes recent developments in small-molecule CCR2 antagonists disclosed by patent applications published between 2005 and 2008 and related publications.
Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development LLC, Cranbury, NJ 08512, USA. mxia@its.jnj.com
Mingde
M
Xia
Zhihua
Z
Sui
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology; D004195:Disease Models, Animal; D015195:Drug Design; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D009000:Monocytes / Q000378:metabolism; D010330:Patents as Topic; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors*
D000893:Anti-Inflammatory Agents; C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D054390:Receptors, CCR2