ABSTRACT
Platelet-activating factor (PAF), an endogenous phospholipid generated and secreted by a number of different cell types, i.e., neutrophil, mast cell, platelet, and basophil, was first discovered and characterized as a potent platelet-aggregating agent. This chapter discusses the structure-activity relationship of the novel natural products and related compounds which contain diketopi-perazine as a common structural unit. It suggests that the vinylogous diketopiperazine moiety might contribute to the ability of the molecule to bind to PAF receptor sites. The chapter examines the possibility of replacement of oxindole to the other simpler aromatic nuclei. Some diketopiperazines were synthesized from D-methionine and aromatic D-amino acid such as D-phenylalanine, D-naphthylalanine, and D-tryptophan. The chapter concludes that the stereochemistry of the diketopiperazine moiety is an important factor for PAF inhibitory activity and that the hydrophobic aromatic portion plays an important role for the binding of diketopiperazines to the PAF receptor in this series.
