Patent Evaluation: Spirononane Derivatives as PAF Antagonists

Summary

Novelty: 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: