Background: High attrition rate in late drug discovery and development stages leads to financial loss to industries and Governments. Despite the global prevalence of HIV infection and lack of promising treatment for AIDS patients, there are only a few drugs approved for the management of infected patients. There is an urgent need to discover newer anti-HIV drugs with novel mechanism of action and with efforts to reduce attrition rate in early drug discovery stages.

Objective: Prioritization of reported potential anti-HIV-1 leads according to their quantitative estimation of druglikeness (QED), carcinogenicity, mutagenicity, absorption, metabolism and toxic properties. Synthesis of analogs of the best lead and evaluation of their anti-HIV-1 activity is shown.

Methods: In silico anti-HIV lead prioritization was performed on a set of known anti-HIV natural products in order to obtain a lead with better druglikeness and ADMET properties. Prioritized lead tembamide and its four analogs were synthesized and their anti-HIV-1 activity was evaluated.

Results: Tembamide was found to be a lead with better QED, absorption and metabolism properties and with no carcinogenicity, mutagenicity and toxic potential. (+)-Tembamide is previously reported to show potent anti-HIV-1 activity against laboratory adapted strains HIV-1IIIB (X4, subtype B) and HIV-1Ada5 (R5, subtype B) in H9 cell line. It was observed during this study that synthesized tembamide and its four analogs were weakly active against primary isolates HIV-1UG070 (X4, subtype D) and HIV-1VB59 (R5, subtype C) in TZM-bl cell line.

Conclusion: The results showed that there is scope for the improvement of activity of tembamide analogs to discover a potent anti-HIV compound.

背景：药物研发后期的人员流失率高，导致行业和政府蒙受经济损失。尽管全球范围内普遍存在HIV感染并且对AIDS患者缺乏有希望的治疗方法，但只有少数几种药物被批准用于治疗感染患者。迫切需要发现具有新颖作用机制并努力降低早期药物发现阶段的消耗率的新型抗HIV药物。

目的：根据已报道的潜在抗HIV-1线索对药物相似性（QED），致癌性，致突变性，吸收，代谢和毒性特性的定量估计，对它们进行优先排序。显示了最佳铅的类似物的合成及其抗HIV-1活性的评估。

方法：对一组已知的抗HIV天然产物进行计算机抗HIV铅优先排序，以获取具有更好的药物相似性和ADMET特性的铅。合成了优先的戊酰胺铅及其四个类似物，并评估了它们的抗HIV-1活性。

结果：发现甲酰胺是具有更好的QED，吸收和代谢特性且没有致癌性，诱变性和毒性潜力的铅。先前报道（+）-氨甲酰胺在H9细胞系中对实验室适应的菌株HIV-1IIIB（X4，B型）和HIV-1Ada5（R5，B型）显示出有效的抗HIV-1活性。在该研究过程中观察到，合成的Tembamide及其四个类似物在TZM-b1细胞系中对主要分离株HIV-1UG070（X4，D型）和HIV-1VB59（R5，C型）具有弱活性。

结论：结果表明，仍有必要改善Tembamide类似物的活性，以发现有效的抗HIV化合物。