Abstract
SummarySummaryNovelty: Novel 1-oxa-2,9-diphenyl-spiro[4.4]nonane derivatives are claimed as PAF antagonists. They are potentially useful for the treatment of inflammatory disorders.Biology: The inhibition of [3H]-PAF binding to human platelet plasma membrane was determined by isotopic labelling and filtration techniques. Results were given for eight compounds; IC50 values were in the range 1.0-12.0μM. In vivo, the ability of the compounds to reverse hypotension caused by an infusion of PAF in male Sprague Dawley rats was demonstrated. 1-Oxa-6-oxo-7-(3-pyridyl)methylene-2,9-di(3,4-dimethoxyphenyl)spiro[4.4]nonane had an ED50 value of 800 μg/kg iv.Chemistry: Nineteen compounds are specifically claimed and are exemplified by synthesis; yields, mp, elemental analyses, IR and 1H nmr data are reported. One of the specifically claimed compounds is 1-oxa-6-oxo-2,9-di(3,4-dimethoxyphenyl)spirone[4.4]nonane.Structure:
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