Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, Punjab, India.
Department of Medicine, University of California, San Francisco, CA, USA.
Bioorg Chem. 2019 Jul;88:102912. doi: 10.1016/j.bioorg.2019.04.006. Epub 2019 Apr 11.
Synthesis of C-5-substituted 1,3-dioxoisoindoline-4-aminoquinolines having amide group as a spacer was developed with an intent to evaluate their antiplasmodial activities. The synthesized dioxoisoindoline-aminoquinolines tethered with β-alanine as a spacer and secondary amine as substituent displayed good anti-plasmodial activities. Compound 7j, with an optimum combination of β-alanine and an ethyl chain length as linker along with diethylamine as the secondary amine counterpart at dioxoisoindoline proved to be most potent and non-cytotoxic with IC of 0.097 µM against W2 strain of P. falciparum and a selective index of >2000.
我们开发了一种 C-5 取代的 1,3-二氧代异吲哚啉-4-氨基喹啉，其中酰胺基作为间隔基，旨在评估它们的抗疟活性。合成的二氧代异吲哚啉-氨基喹啉与 β-丙氨酸作为间隔基和仲胺作为取代基相连，表现出良好的抗疟活性。化合物 7j，在二氧代异吲哚啉上具有最佳的 β-丙氨酸和乙基链长组合作为连接子，以及二乙胺作为仲胺对应物，对 W2 株疟原虫的 IC 为 0.097 µM，具有最高的活性和非细胞毒性，选择性指数>2000。
