Smithkline Beecham Corporation

Frank E Blaney

William Edward Bondinell

James A Chan

This invention relates to substituted benzo&lsqb;1,2-b:5,4-b&prime;&rsqb;dipyran-4-amines which are modulators, agonists or antagonists, of the CCR5 receptor. In addition, this invention relates to the treatment and prevention of disease states mediated by CCR5, including, but not limited to, asthma and a topic disorders (for example, a topic dermatitis and allergies), rheumatoid arthritis, sarcoidosis and other fibrotic diseases, atherosclerosis, psoriasis, autoimmune diseases such as multiple sclerosis, and inflammatory bowel disease, all in mammals, by the use of substituted benzo&lsqb;1,2-b:5,4-b&prime;&rsqb;dipyran-4-amines which are CCR5 receptor antagonists. Furthermore, since CD8&plus;T cells have been implicated in COPD, CCR5 may play a role in their recruitment and therefore antagonists to CCR5 could provide potential therpeutic in the treatment of COPD. Also, since CCR5 is a co-receptor for the entry of HIV into cells, selective receptor modulators may be useful in the treatment of HIV infection.

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Harlow, United Kingdom

Frank E Blaney