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Chemical and biochemical characterization of lignan analogs as novel PAF receptor antagonists
Author(s) -
Shen T. Y.
Publication year - 1991
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02536521
Subject(s) - chemistry , stereochemistry , platelet activating factor , antagonist , lignan , enantiomer , tetrahydrofuran , receptor , biochemistry , medicine , solvent
Various derivatives and isosteres of neolignans of the 2,5‐diaryl tetrahydrofuran type have been synthesized as antagonists of platelet‐activating factor (PAF). A detailed analysis of their structure‐activity relationship (SAR) has revealed a clear preference for an asymmetrical molecular configuration with a high degree of stereo and chiral specificity associated with greater potency. The trans ‐2S,5S enantiomers are generally 10–200 times more potent in vitro than their corresponding cis or trans ‐2R,5R isomers. A similar stereochemical preference is indicated by the recently reported PAF antagonist MK‐287 which has undergone clinical evaluation. An azido derivative L‐662,025 has been characterized as a photolabile irreversible antagonist of PAF for the investigation of solubilized and partially purified PAF binding proteins from cell membranes. The biological justification for concomitant inhibition of both PAF receptor and 5‐lipoxygenase in inflammation is well recognized. The feasibility of developing such dual‐functional agents has been demonstrated by a group of dithiolane analogs of neolignans and several derivatives of futoenone.