Casagrande Manolo, Basilico Nicoletta, Parapini Silvia, Romeo Sergio, Taramelli Donatella, Sparatore Anna
Istituto di Chimica Farmaceutica e Tossicologica 'Pietro Pratesi', University of Milan, Via Mangiagalli 25, 20133 Milan, Italy.
Bioorg Med Chem. 2008 Jul 15;16(14):6813-23. doi: 10.1016/j.bmc.2008.05.068. Epub 2008 Jun 16.
To develop new classes of antimalarial agents, the possibility of replacing the phenolic ring of amodiaquine, tebuquine, and isoquine with other aromatic nuclei was investigated. Within a first set of pyrrole analogues, several compounds displayed high activity against both D10 (CQ-S) and W-2 (CQ-R) strains of Plasmodium falciparum. The isoquine structure was also modified by replacing the diethylamino group with more metabolically stable bicyclic moieties and by replacing the aromatic hydroxyl function with a chlorine atom. Among these compounds, two quinolizidinylmethylamino derivatives (6f and 7f) displayed high activity against both CQ-S and CQ-R strains.
为开发新型抗疟药，研究了用其他芳环取代阿莫地喹、替布喹和异喹啉酚环的可能性。在第一组吡咯类似物中，几种化合物对恶性疟原虫的D10（氯喹敏感）和W-2（氯喹耐药）菌株均表现出高活性。异喹啉结构也进行了修饰，用代谢更稳定的双环部分取代二乙氨基，并用氯原子取代芳族羟基官能团。在这些化合物中，两种喹嗪基甲基氨基衍生物（6f和7f）对氯喹敏感和氯喹耐药菌株均表现出高活性。
