Phenyl β-Methoxyacrylates: A New Antimalarial Pharmacophore

摘要: Phenyl beta-methoxyacrylates, linked to an aromatic ring via olefinic bridge, have been identified as novel, potentially inexpensive, antimalarial agents. The compounds are believed exert their activity by inhibition of mitochondrial electron transport at the cytochrome bc(1) complex. A series synthesized define structure-activity relationships affecting activity. It was found that beta-methoxyacrylate required ortho linker and optimal bridge (E,E)-butadiene. Compounds in which second ortho-substituted or ortho,para-disubstituted gave potency. Several were with potency is superior chloroquine both culture a murine malaria model.