N-1 Substituted Pyrimidin-4-Ones: Novel, Orally Active Inhibitors Of Lipoprotein-Associated Phospholipase A(2)

From two related series of 2-(alkylthio)-pyrimidones, a novel series of 1-((amidolinked)-alkyl)-pyrimidones has been designed as nanomolar inhibitors of human lipoprotein-associated phopholipase A(2). These compounds show greatly enhanced activity in isolated plasma. Selected derivatives such as compounds 51 and 52 are orally active with a good duration of action. (C) 2000 Elsevier Science Ltd. All rights reserved.