Benzimidazole derivatives as modulators of IgE

Abstract

This invention relates to a family of benzimidazole analogs, which are inhibitors of the IgE response to allergens. These compounds are useful in the treatment of allergy, asthma, or any diseases where IgE is pathogenic.

Description

BACKGROUND OF THE INVENTION This invention relates to small molecule inhibitors of the IgE response to allergens that are useful in the treatment of allergy and / or asthma or any diseases where IgE is pathogenic. An estimated 10 million persons in the United States have asthma, about 5% of the population. The estimated cost of asthma in the United States exceeds $6 billion. About 25% of patients with asthma who seek emergency care require hospitalization, and the largest single direct medical expenditure for asthma has been inpatient hospital services (emergency care), at a cost of greater than $1.6 billion. The cost for prescription medications, which increased 54% between 1985 and 1990, was close behind at $1.1 billion (Kelly, Pharmacotherapy 12:13S-21S (1997)). According to the National Ambulatory Medical Care Survey, asthma accounts for 1% of all ambulatory care visits, and the disease continues to be a significant cause of missed school days in children. Despite improved unde...

AI Technical Summary

Benefits of technology

Other variations within the scope of the present invention may be more fully understood with reference to the following detailed description.

Problems solved by technology

According to the National Ambulatory Medical Care Survey, asthma accounts for 1% of all ambulatory care visits, and the disease continues to be a significant cause of missed school days in children.

Thus, asthma constitutes a significant public health problem.

However, because the β2-agonists do not possess significant antiinflammatory activity, they have no effect on bronchial hyperreactivity.

Some of the newer antihistamines, such as azelastine and ketotifen, may have both antiinflammatory and weak bronchodilatory effects, but they currently do not have any established efficacy in asthma treatment.

Phosphodiesterase inhibitors, like theophylline / xanthines, may attenuate late inflammatory responses, but there is no evidence that these compounds decrease bronchial hyperreactivity.

Unfortunately, these antiinflammatory agents do not produce bronchodilation.

Thus, while numerous drugs are currently available for the treatment of asthma, these compounds are primarily palliative and / or have significant side effects.

None of the current therapies eliminate the excess circulating IgE.

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