4-((6-chloro-4-(mesityloxy)pyridin-2-yl)amino)benzonitrile

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-((6-chloro-4-(mesityloxy)pyridin-2-yl)amino)benzonitrile
• 英文别名: 4-[[6-Chloro-4-(2,4,6-trimethylphenoxy)-2-pyridyl]amino]benzonitrile；4-[[6-chloro-4-(2,4,6-trimethylphenoxy)pyridin-2-yl]amino]benzonitrile
• 化学式: C₂₁H₁₈ClN₃O
• 分子量: 363.846
• InChiKey: OABIRUFMVLLFCR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  57.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-((6-chloro-4-(mesityloxy)pyridin-2-yl)amino)benzonitrile 在 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 4-((4-(mesityloxy)-6-((2-(piperazin-1-yl)ethyl)amino)pyridin-2-yl)amino)benzonitrile
  参考文献：
  名称：

  Design, synthesis and anti-HIV evaluation of novel diarylpyridine derivatives targeting the entrance channel of NNRTI binding pocket

  摘要：

  The development of novel NNRTIs with activity against variants of HIV-1RT is crucial for overcoming treatment failure. In the present study, a series of novel 6-substituted diarylpyridine derivatives targeting the entrance channel of the NNIBP of RT were designed through a molecular hybridization strategy. Encouragingly, these new diarylpyridine derivatives were found to be active against wild-type (WT) HIV-1 with an EC50 values ranging from 0.035 mu M to 1.99 mu M. Nearly half of them exhibited more potent inhibitory activities in cellular assays than the control drug nevirapine (NVP). Notably, three most promising compounds If (EC50 = 35 nM), la (EC50 = 43 nM) and Ila (EC50 = 41 nM) showed high potency against WT and were comparable to the reference drug delavirdine (DLV) (EC50 = 33 nM). Moreover, compounds Ib, Ilb and Ilh displayed effective activity against the most common clinically observed single and double-mutated HIV-1 strains in micromolar concentrations. In particular, the inhibition of 1lb against the K103N mutation (EC50 = 49 nM), which confers resistance to a wide variety of NNRTIs, was about 140 times more effective than NVP (EC50 = 6.78 mu M), 50 times more than DLV (EC50 = 2.48 mu M) and about 3 times more than ER/(EC50 = 0.12 M), indicating that the newly designed compounds have great potential to be further developed as new anti-HIV-1 agents. Preliminary structure-activity relationships (SARs) and molecular modeling of the new diarylpyridine derivatives were discussed in detail. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.11.039
• 作为产物：
  描述：

  2,4,6-三氯吡啶 在 palladium diacetate 、 potassium carbonate 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.25h， 生成 4-((6-chloro-4-(mesityloxy)pyridin-2-yl)amino)benzonitrile
  参考文献：
  名称：

  6-取代二芳基吡啶衍生物及其制备方法与应 用

  摘要：

  本发明公开了一种6‑取代二芳基吡啶衍生物及其制备方法和应用。所述化合物具有式I所示的结构。本发明还涉及含有式I结构化合物的药物组合物以及提供上述化合物在制备抗HIV药物中的应用。

  公开号：

  CN105294550B

文献信息

• 6-取代二芳基吡啶衍生物及其制备方法与应 用
  申请人：山东大学

  公开号：CN105294550B

  公开（公告）日：2018-06-05

  本发明公开了一种6‑取代二芳基吡啶衍生物及其制备方法和应用。所述化合物具有式I所示的结构。本发明还涉及含有式I结构化合物的药物组合物以及提供上述化合物在制备抗HIV药物中的应用。
• Design, synthesis and anti-HIV evaluation of novel diarylpyridine derivatives targeting the entrance channel of NNRTI binding pocket
  作者：Jiapei Yang、Wenmin Chen、Dongwei Kang、Xueyi Lu、Xiao Li、Zhaoqiang Liu、Boshi Huang、Dirk Daelemans、Christophe Pannecouque、Erik De Clercq、Peng Zhan、Xinyong Liu

  DOI：10.1016/j.ejmech.2015.11.039

  日期：2016.2

  The development of novel NNRTIs with activity against variants of HIV-1RT is crucial for overcoming treatment failure. In the present study, a series of novel 6-substituted diarylpyridine derivatives targeting the entrance channel of the NNIBP of RT were designed through a molecular hybridization strategy. Encouragingly, these new diarylpyridine derivatives were found to be active against wild-type (WT) HIV-1 with an EC50 values ranging from 0.035 mu M to 1.99 mu M. Nearly half of them exhibited more potent inhibitory activities in cellular assays than the control drug nevirapine (NVP). Notably, three most promising compounds If (EC50 = 35 nM), la (EC50 = 43 nM) and Ila (EC50 = 41 nM) showed high potency against WT and were comparable to the reference drug delavirdine (DLV) (EC50 = 33 nM). Moreover, compounds Ib, Ilb and Ilh displayed effective activity against the most common clinically observed single and double-mutated HIV-1 strains in micromolar concentrations. In particular, the inhibition of 1lb against the K103N mutation (EC50 = 49 nM), which confers resistance to a wide variety of NNRTIs, was about 140 times more effective than NVP (EC50 = 6.78 mu M), 50 times more than DLV (EC50 = 2.48 mu M) and about 3 times more than ER/(EC50 = 0.12 M), indicating that the newly designed compounds have great potential to be further developed as new anti-HIV-1 agents. Preliminary structure-activity relationships (SARs) and molecular modeling of the new diarylpyridine derivatives were discussed in detail. (C) 2015 Elsevier Masson SAS. All rights reserved.