Platelet-activating factor (PAF) has recently been identified as an acetyl glyceryl ether phosphorylcholine (AGEPC), i.e., 1O-hexadecyl/octadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine (Hanahan, D. S. et al., J. Biol. Chem., 255:5514, 1980). Even before its chemical identification, PAF has been linked to various biologic activities and pathways making it one of the important mediators responsible for a variety of physiological processes including activation or coagulation of platelets, pathogenesis of immune complex deposition, smooth muscle contraction, inflammation as well as respiratory, cardiovascular and intravascular alterations. These physiological processes are known to be associated with a large group of diseases, for example, inflammatory diseases, cardiovascular disorders, asthma, lung edema, and adult respiratory distress syndrome. It is therefore only natural that more and more scientific investigators are focusing their work on the search of a PAF-antagonist or inhibitor for the treatment and/or the prevention of these common diseases.
The novel compound of the present invention, 5-allyl-2-(3,4-dimethoxyphenyl)-3a,.alpha.-methoxy-3-methyl-2,3,3a,6-tetra hydro-6-oxobenzofuran (I), is a potent and specific PAF-antagonist isolated from the Chinese herbal plant Piper futokadsura Sieb. et Zucc. ##STR1## Although the plant Piper futokadsura Sieb. et Zucc. itself has been used by the Chinese as an herb medicine for the treatment of arthritis conditions, we have for the first time isolated compound (I) from this herb and discovered its property as a specific PAF-antagonist useful not only for the treatment of arthritic conditions but also for other diseases including asthma, hypertension, lung-edema, adult distress syndrome and the like.
Accordingly, it is the object of the present invention to provide compound (I) as a specific PAF-antagonist.
Another object of this invention is to provide processes for the isolation of compound (I).
A further object of this invention is to provide a pharmaceutically acceptable composition containing compound (I) as the active ingredient for the treatment of diseases which are subject to the mediation of a PAF-antagonist.
Still a further object of this invention is to provide a method of treatment comprising the administration of a therapeutically sufficient amount of compound (I) to a patient suffering from various skeletal-muscular disorders including but not limited to inflammation, e.g., osteoarthritis, rheumatoid arthritis and gout; hypertension; cardiovascular disorder; asthma; lung edema; or adult respiratory distress syndrome.
USPTO Backgrounds
USPTO Backgrounds