1. Design, synthesis, and structure-activity relationship of new isobenzofuranone ligands of protein kinase C.
- Author
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Baba Y, Ogoshi Y, Hirai G, Yanagisawa T, Nagamatsu K, Mayumi S, Hashimoto Y, and Sodeoka M
- Subjects
- Benzofurans chemical synthesis, Binding Sites, Dose-Response Relationship, Drug, Drug Design, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors pharmacology, Humans, Hydrogen Bonding, Ligands, Molecular Structure, Protein Binding, Protein Kinase C chemistry, Structure-Activity Relationship, Benzofurans pharmacology, Protein Kinase C antagonists & inhibitors
- Abstract
Protein kinase C (PKC) is a family of enzymes, which play important roles in intracellular signal transduction. We have designed novel PKC ligands having an isobenzofuranone template, based on the proposed interaction of DAG (1,2-diacyl-sn-glycerol) with the PKCdelta C1B ligand-binding domain. Several isobenzofuranone derivatives were synthesized and their PKCalpha binding activities were evaluated. The pivaloyl derivative 1f was found to be a strong PKCalpha ligand, and the structure-activity relationship is well explained by our proposed binding model.
- Published
- 2004
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