N-[ω-(Heteroaryl)Alkyl]Carboxamide Derivatives as Platelet Activating Factor Antagonists: Structure-Activity Relationships and Biological Data

Platelet-activating factor (PAF) is a phospholipid mediator generated in a variety of inflammatory and allergic reactions. It exerts a vast array of biological activities including induction of platelet and neutrophil aggregation, bronchoconstriction, increased vascular permeability, and hypotension. An intensive effort to find drugs which attenuate the effects of PAF has resulted in the discovery of a number of specific PAF antagonists, some of which are currently undergoing clinical trials. In order to determine the contribution of the heterocyclic moiety to binding, a variety of analogs with four carbon connecting chains and differing heteroaromatic species were investigated. The aggregation of canine platelets in whole blood was induced by addition of PAF. The inhibitory effect of the compounds was tested by adding them to a volume of 500 µl whole blood 1 min before addition of the aggregating agent.