Computational modelling was used to identify scaffolds with the potential to disrupt the interaction between HIV-1 integrase and lens epithelium-derived growth factor (HIV-1-IN-LEDGF/p75). Virtual screening of commercial library collections led to the identification of N-(4-chlorophenyl)-7,7-dimethyl-2,5-dioxo-1,2,5,6,7,8-hexahydroquinoline-3-carboxamide as a promising candidate. The synthesis of this compound and its derivatives involved the reaction of the corresponding carboxylic acid derivatives with aniline in the presence of coupling agent carbonyldiimidazole (CDI). This gave rise to N-2,5-dioxo-1,2,5,6,7,8-hexahydroquinoline-3-carboxamides in yields of 71-85%. These compounds were found to be non-toxic in an MT4 cell line at 100 μM and were subsequently evaluated for antiviral activity in infected MT4 cells at a single dose concentration of 100 μM.

中文翻译：

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六氢喹啉-3-甲酰胺衍生物的合成及其HIV-1抗病毒活性

计算模型用于识别具有破坏 HIV-1 整合酶和晶状体上皮衍生生长因子 (HIV-1-IN-LEDGF/p75) 之间相互作用的潜力的支架。对商业图书馆馆藏进行虚拟筛选，鉴定出N- (4-chlorophenyl)-7,7-dimethyl-2,5-dioxo-1,2,5,6,7,8-hexahydroquinoline-3-carboxamide有前途的候选人。该化合物及其衍生物的合成涉及相应的羧酸衍生物与苯胺在偶联剂羰基二咪唑 (CDI) 存在下的反应。这产生了N -2,5-dioxo-1,2,5,6,7,8-hexahydroquinoline-3-carboxamides 的产率为 71-85%。发现这些化合物在 100 μM 的 MT4 细胞系中是无毒的，随后在 100 μM 的单剂量浓度下评估了受感染的 MT4 细胞的抗病毒活性。