Analide derivatives as monocyte chemoattractant protein-1 receptor antagonists

Monocyte chemoattractant protein-1 (MCP-1) is a potent and specific chemotactic agent for monocytes and T-lymphocytes in vitro. Its expression in conditions such as atherosclerosis and rheumatoid arthritis, which are characterised by mononuclear cell infiltrates, suggest that MCP-1 might contribute to the inflammatory component of these diseases. In murine models of early atherosclerotic disease, in which the gene for MCP-I or its receptor is also deleted, lesion development and monocyte accumulation are markedly reduced. There is an apparent causal relationship between mononuclear cell recruitment and disease progression. One interventionist approach would be the use of MCP-1 receptor antagonists to abrogate inflammatory cell recruitment. Takeda has disclosed a series of novel analide derivatives, which act as MCP-1 receptor antagonists. These analide derivatives are shown to inhibit chemotaxis in vitro. The absence of any data to support efficacy in vivo makes assessment of the full therapeutic value of these compounds difficult.