Inflammatory cytokine release inhibitor

Abstract

A medicament having inhibitory activity against NF-κB activation, which comprises a compound represented by the following general formula (I) or a pharmacologically acceptable salt as an active ingredient:wherein X represents a connecting group, A represents hydrogen atom or acetyl group, E represents an aryl group or a heteroaryl group, and ring X represents an arene or a heteroarene.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]The present application is a Divisional of U.S. application Ser. No. 10 / 433,619, which is a National Stage of PCT / JP2001 / 011084, filed Dec. 18, 2001, which was not published in English under PCT Article 21(2), and which claims priority of Japanese Application No. 2000-383202, filed Dec. 18, 2000. The entire disclosure of application Ser. No. 10 / 433,619 is considered as being part of this application, and the entire disclosure of application Ser. No. 10 / 433,619 is expressly incorporated by reference herein in its entirety.FIELD OF INVENTION[0002]The present invention relates to pharmaceutical compositions having inhibitory activity against the production and release of inflammatory cytokines such as interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor (TNF-α), and having inhibitory activity against the activation of NF-κ K B.BACKGROUND ART[0003]Inflammation is a basic defense mechanism to various infestations, where inflammatory cytoki...

AI Technical Summary

Benefits of technology

"The present invention provides medications for the preventive and therapeutic treatment of inflammatory disorders, autoimmune diseases, and bone diseases. The medications contain compounds that specifically inhibit IKK-β, a protein that plays a role in the production and release of inflammatory cytokines. These compounds are expected to have inhibitory activity against NF-κB activation without causing serious side effects. The invention is based on the use of computerized molecular design technology to select compounds with inhibitory action against NF-κB activation by targeting IKK-β. The compounds were tested using a reporter assay method and found to have inhibitory activity against NF-κB activation. The medicament is a pharmaceutical composition containing one or more of the compounds as an active ingredient."

Problems solved by technology

However, since huge amount of aspirin needs to be administered to sufficiently suppress NF-κ B activation, and as a result, since possibility of side effects such as gastrointestinal disorders by prostaglandin synthesis inhibition and increase of bleeding tendency by anticoagulation is expected with high probability, aspirin is not suitable for long term application.

However, long term use is not suitable, because they have serious side effects such as aggravation of an infectious disease, generation of peptic ulcer, degradation of bone density, and central action.

Leflunomide as an immunosuppressive agent, as an isoxazole-type agent, also has NF-κ B inhibitory action (Manna S., et al., J. Immunol., 164, 2095-2102 (1999)), however, the drug is also not suitable for long term use due to serious side effects.

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