Compounds, compositions and methods for the treatment of inflammatory diseases

Abstract

The use of a composition comprising a compound:

where R is a C₁-C₁₀ alkylene group, in which, when the number of carbon atoms is at least 2, there are optionally 1 or 2 non-adjacent double bonds; 1 to 3 non-adjacent methylene groups are optionally replaced by NR¹ (where R¹ is H, alkyl, or acyl), O, or S; and 1 or 2 methylene groups are optionally replaced by a carbonyl or hydroxymethylene group for the preparation of a medicament or a pharmaceutical for the treatment of inflammatory diseases.

Description

[0001] This application is a Continuation-in-Part of U.S. application Ser. No. 11 / 503,400 filed Aug. 10, 2006, now abandoned, which claimed priority to U.S. Provisional Application No. 60 / 707,567 filed Aug. 10, 2005. This application is also a Continuation-in-Part of U.S. application Ser. No. 10 / 077,596 filed Feb. 15, 2002, which is a Continuation-in-Part of application Ser. No. 10 / 053,625, now issued as U.S. Pat. No. 6,929,808 on Aug. 16, 2005.TECHNICAL FIELD [0002] This invention relates to bis- and tris-dihydroxyaryl compounds and their methylenedioxy analogs and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of inflammatory diseases such as arthritis, and in the manufacture of medicaments for such treatment. BACKGROUND OF THE INVENTION [0003] Various forms of inflammation are characterized by activation of macrophages. Macrophages are thought to induce and maintain inflammatory processes mainly by ...

AI Technical Summary

Benefits of technology

[0014] The various compounds disclosed herein inhibit lipopolysaccharide(LPS) / interferon gamma (IFNγ) induced NO release by microglia. This release by the microglia is in response to LPS / IFNγ pro-inflammatory stimulation. These compounds may prevent oxidative stress induced cell death in addition to the inhibition of NO and TNF-α release by microglia and subsequent inhibition of the inflammatory cascade.

Problems solved by technology

Macrophage products are more generally involved in pathophysiological mechanisms, such as plasma extravasation, inflammatory cell diapedesis, release of toxic free radicals such as nitric oxide, endothelial injury, and release of tissue degrading enzymes, which result in tissue injury and, ultimately, organ failure.

It is suspected that certain infections or factors in the environment might trigger the immune system to attack the body's own tissues, resulting in inflammation in various organs of the body.

In some patients with rheumatoid arthritis, chronic inflammation leads to the destruction of the cartilage, bone and ligaments causing deformity of the joints.

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