Methods for treating inflammatory conditions or inhibiting JNK

Abstract

This invention is generally directed to methods for treating or preventing a disease or disorder comprising administering to a patient in need thereof an effective amount of a Jun N-terminal kinase (JNK) inhibitor, such as an isothiazoloanthrone, isoxazoloanthrone, isoindolanthrone, or derivative thereof having the general formula: and pharmaceutically acceptable salts thereof, wherein Ro is -CH2-, -SO-, -O-, -SO2-, or -S-.

Description

[0001] This application is a continuation-in-part of U.S. application Ser. No. 10 / 071,390 filed Feb. 7, 2002 which claims the benefit of U.S. Provisional Application No. 60 / 269,013 filed Feb. 15, 2001, each of which is incorporated by reference herein in its entirety.1. FIELD OF THE INVENTION[0002] This invention is generally directed to methods for treating or preventing a disease or disorder comprising administering to a patient in need thereof an effective amount of a Jun N-terminal kinase ("JNK") inhibitor, such as an isothiazoloanthrone, isoxazoloanthrone, isoindolanthrone, or derivative thereof, including pharmaceutically acceptable salts thereof.2. BACKGROUND OF THE INVENTION[0003] The Jun N-terminal kinase pathway is activated by exposure of cells to environmental stress or by treatment of cells with pro-inflammatory cytokines. Targets of the JNK pathway include the transcription factors c-jun and ATF2 (Whitmarsh A. J., and Davis R. J. J. Mol. Med. 74:589-607, 1996). These t...

AI Technical Summary

Benefits of technology

The present invention relates to methods for treating or preventing various conditions such as inflammatory conditions, liver disease, cardiovascular disease, neurodegenerative disease, or cancer, by administering to a patient in need thereof a compound of Formula I or a pharmaceutically acceptable salt thereof. The compounds of Formula I have specific structures and can have various substituents, which can influence their biological activity. The invention provides effective treatment or prevention methods for these conditions by administering the appropriate compound or salt.

Problems solved by technology

Deletion of either JNK1 or JNK2 in mice resulted in a selective defect in the ability of Th1 effector cells to express IFNg.

Ischemia and ischemia coupled with reperfusion in the heart, kidney, or brain results in cell death and scar formation, which can ultimately lead to congestive heart failure, renal failure, or cerebral dysfunction.

In organ transplantation, reperfusion of previously ischemic donor organs results in acute leukocyte-mediated tissue injury and delay of graft function.

Thus, JNK inhibitors may block transformation and tumor cell growth.

Stroke is the 3.sup.rd leading cause of death and a leading cause of disability in the U.S. Stroke, along with neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's disease (PD) impose a huge burden on the health care industry by impacting the quality of life of those affected.

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