Design, synthesis, and biological evaluation of piperidinyl-substituted [1,2,4]triazolo[1,5-a]pyrimidine derivatives as potential anti-HIV-1 agents with reduced cytotoxicity.,Chemical Biology & Drug Design

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Design, synthesis, and biological evaluation of piperidinyl-substituted [1,2,4]triazolo[1,5-a]pyrimidine derivatives as potential anti-HIV-1 agents with reduced cytotoxicity.
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2020-07-28 , DOI: 10.1111/cbdd.13760
Boshi Huang ₁ , Dongwei Kang ₁ , Ye Tian ₁ , Dirk Daelemans ₂ , Erik De Clercq ₂ , Christophe Pannecouque ₂ , Peng Zhan ₁ , Xinyong Liu ₁

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Taking the previously reported compound BH‐7d as the lead, we designed and synthesized a series of piperidinyl‐substituted [1,2,4]triazolo[1,5‐a]pyrimidines, and their anti‐HIV activities as well as cytotoxicities were evaluated. Several compounds exhibited moderate anti‐HIV (IIIB) potency, among which 2b was the most active one (EC₅₀ = 4.29 μM). Structure–activity relationships derived from the antiretroviral results were analyzed. Additionally, most compounds demonstrated reduced cytotoxicity (CC₅₀ > 200 μM) compared with those of BH‐7d and etravirine. Molecular docking study further revealed the binding conformation of 2b in the binding pocket of HIV‐1 reverse transcriptase.

中文翻译：

哌啶基取代的 [1,2,4] 三唑并 [1,5-a] 嘧啶衍生物作为具有降低细胞毒性的潜在抗 HIV-1 药物的设计、合成和生物学评价。

以先前报道的化合物BH-7d为先导，我们设计合成了一系列哌啶基取代的[1,2,4]三唑并[1,5-a]嘧啶类化合物，其抗HIV活性和细胞毒性均在评估。几种化合物表现出中等的抗 HIV (IIIB) 效力，其中2b是最活跃的一种 (EC ₅₀ = 4.29 μM)。分析了源自抗逆转录病毒结果的构效关系。此外，与BH-7d和依曲韦林相比，大多数化合物表现出降低的细胞毒性（CC ₅₀ > 200 μM）。分子对接研究进一步揭示了HIV-1 逆转录酶结合口袋中2b的结合构象。

更新日期：2020-07-28

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