ABSTRACT
Platelet-activating factor (PAF) is an endogenous ether phospholipid mediator with a wide range of biological activities. This autacoid is generated in inflammatory and allergic responses, and promotes platelet and neutrophil aggregation, induces bronchoconstriction and hypotension and increases vascular permeability. An intensive effort to find products blocking PAF effect has resulted in the discovery of a number of specific PAF antagonists, the first antagonist described being CV 3988. The chapter analyses the synthesis and biological activity of new PAF-related antagonists with a constrained framework: aminoacylates and aminocarbamates of 2-sub-stituted 4-hydroxymethyl dioxolans. The compounds were tested in vitro for their ability to inhibit platelet aggregation induced by PAF. A structure activity relationship was established. Only the most active were tested on other aggregating agents. PAF induces aggregation and degranulation of neutrophils. PAF induced Polymorphonuclear Leukocyte activation as measured by aggregation is reduced by PAF antagonists.
