Patent Evaluation: Tricyclic-ylidene acetic acids as anti-eosinophil agents

Summary

Novelty: Compounds potentially useful in the treatment of disorders resulting from eosinophil accumulation/activation are disclosed (e.g. obstructive and inflammatory airway diseases, allergic and non-allergic eosinophil-related conditions).

Biology: Suppression of eosinophil accumulation is measured in guinea pigs; the animals are sensitized to ovalbumin and challenged via administration of a 0.1% ovalbumin nebulized solution. Preferred compounds significantly reduce eosinophil accumulation (relative to controls) at 10–50 mg/kg/day via inhalation or sc administration. The efficacy of the compounds in pneumoconiosis/bronchitis and other eosinophil related disorders is measured in clinical studies. Preferred embodiments of the invention result in improved lung function and reduced eosinophil counts.

Chemistry: The use of the (Z)-isomer of α-[10-oxy-4H-benzo[4,5]cycloheptal[1,2-b]-thiophen-4-ylidene]-acetic acid is specifically claimed and is one of eleven compounds exemplified. Preparative details are not presented.