Organic Chemistry Division II, Indian Institute of Chemical Technology, Uppal Road Tarnaka, Hyderabad 500607, India.
Bioorg Med Chem Lett. 2012 Jan 15;22(2):1103-6. doi: 10.1016/j.bmcl.2011.11.108. Epub 2011 Dec 13.
An efficient synthesis of antischistosomal drug praziquantel and analogues was achieved and the synthetic route designed was to afford structurally diverse analogues for better structure-activity relationship understanding. Total of nineteen PZQ analogues with structural variations at amide, piperazine and aromatic moieties have been synthesized and fully characterized. Among all the new analogues tested for antischistosomal activity, one dimethoxy tetrahydroisoquinoline analogue and two tetrahydro-β-carboline analogues exhibited moderate activity against adult Schistosoma mansoni. Tetrahydro-β-carboline analogues showed moderate activity whereas the presence of p-trifluoromethylbenzoyl and p-toluenesulphonyl moieties resulted in complete suppression of antischistosomal activity.
实现了抗血吸虫病药物吡喹酮及其类似物的高效合成，所设计的合成路线旨在提供结构多样的类似物，以更好地了解结构-活性关系。共合成并充分表征了 19 种具有酰胺、哌嗪和芳基结构变化的 PZQ 类似物。在所有测试抗血吸虫活性的新类似物中，一种二甲氧基四氢异喹啉类似物和两种四氢-β-咔啉类似物对曼氏血吸虫成虫表现出中等活性。四氢-β-咔啉类似物表现出中等活性，而存在对三氟甲基苯甲酰基和对甲苯磺酰基部分则完全抑制抗血吸虫活性。
