Smithkline Beecham Corporation

Other

James A Chan

William Edward Bondinell

Juan I Luengo

Roderick Alan Porter

David Thomas Davies

Steven Dabbs

Joseph W Venslavsky

Ann L Breen

Frank E Blaney

This invention relates to substituted benzanilides which are ligands, 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 atopic disorders (for example, atopic 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 benzanilides 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 therapeutic in the treatment of COPD. Also, since CCR5 is a co-receptor for the entry of HIV into cells, selective receptor ligands may be useful in the treatment of HIV infection.

Substituted benzanilides as CCR5 receptors ligands, antiinflammatory agents and antiviral agents

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.

Compounds and methods

A method of treating a CCR5-mediated disease state in mammals which comprises administering to a mammal in need of such treatment, an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof.

2,5-diimino-3a,6a-diaryl-1,2,3,3a,4,5,6,6a-octahydroim

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West Chester, PA, United States of America

James A Chan