Treatment methods using triaryl methane compounds

Abstract

The use of novel inhibitors of potassium flux is disclosed for the treatment of inflammatory processes, such as multiple sclerosis, insulin-dependent (type I) diabetes mellitus, rheumatoid arthritis, peripheral neuritis and pulmonary hypertension. The compounds are also of use in treating and preventing stroke. These inhibitors have a high specificity for the IK1 channel and greater stability relative to non-fluorine substituted homologues.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Application 60 / 752,935, filed December 20, 2005, the disclosure of which is incorporated herein in its entirety for all purposes. Background of the invention [0003] One aspect of the invention relates to methods of treating or preventing inflammatory processes, including in particular multiple sclerosis and pulmonary hypertension. [0004] Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Individuals with MS experience deficits in neurological function, including vision loss, motor deterioration, sensory impairment, incontinence, and other events related to central nervous system deficits; however, MS does not impair cognitive function. MS disease progression has a highly variable course, with patients experiencing acute symptoms, followed by periods of remission of symptoms, and later progression to chronic and degenerative cond...

AI Technical Summary

Problems solved by technology

While having demonstrable efficacy, the imidazolyl-based Kv1.3 and / or IK1 channel inhibitors studied to date have been limited by several drawbacks including a well-documented potential for hepatotoxicity

This toxicity is exacerbated by the inhibitor's low potency, nonspecific interaction with calcium-activated potassium channels rather than Kv1.3 and / or IK1 channels, and low bioavailability, each of which contributes to inhibition higher doses and more frequent dosing of

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