Structure Activity Relationships in 5-Aryl-2,3-Dihydroimidazo[2,1a]Isoquinoline PAF Antagonists

The search for substances that can antagonize PAF (Figure 1) by a receptor-mediated mechanism has resulted in the discovery of a variety of compounds that can be classified as charged and non-charged PAF receptor antagonists. ^1-9 The charged antagonists contain a formal positive charge as a zwitterion, quaternary alkyl ammonium, or heterocyclic group and were designed using the PAF molecule as a template. Some examples of charged PAF antagonists are CV-3988, CV-6209, and SRI 63-441 (Figure 2). Non-charged PAF antagonists, of which ginkgolide B and brotizolam (Figure 3) are representative examples, lack a formal charge and were discovered by screening of natural products, known pharmacological agents, and synthetic compounds. The imidazo[2,1-a]isoquinolines ^{10 , 11} represent the first class of non-charged PAF receptor antagonists that were designed using the PAF molecule as a template. ^{12 , 13}