ABSTRACT
The structure of natural platelet-activating factor (PAF) was established in 1979 by three independent research groups to be a mixture of 1-hexadecyl and 1 -octadecyl-2-acety-sn-glycero-3-phosphocholine. Subsequent work by Godfroid4 determined that the absolute configuration of natural PAF as the R-enantiomer. The ease of measuring PAF-induced human or rabbit platelet aggregation has led to the use of the assay as a primary laboratory screen for detecting potential PAF antagonists. The initial attempts to find antagonists of PAF focused on the open-chain analogs of PAF. The structure activity findings in the open-chain PAF antagonists served as a basis for the design of most of the reported cyclic PAF antagonists. PAF-antagonist inhibition against rabbit platelets has been reported for a series of 1,4-dioxanes. A series of compounds where the phosphate group is conformationally restricted by being incorporated into a 1,3,2-dioxaphosphorinane ring system have been reported.
