2,6-dichloro-4-(2,4,6-trimethylphenoxy)pyridine | 1580001-94-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,6-dichloro-4-(2,4,6-trimethylphenoxy)pyridine
• 英文别名: 2,6-dichloro-4-(mesityloxy)pyridine
• CAS: 1580001-94-0
• 化学式: C₁₄H₁₃Cl₂NO
• 分子量: 282.169
• InChiKey: LVLZQEKPZOETSY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.11
• 重原子数：
  18.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  22.12
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  2,6-dichloro-4-(2,4,6-trimethylphenoxy)pyridine 在 sodium methylate 、 palladium diacetate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 为溶剂， 反应 4.0h， 生成 4-((4-(mesityloxy)-6-methoxypyridin-2-yl)amino)benzonitrile
  参考文献：
  名称：

  Discovery of 2-pyridone derivatives as potent HIV-1 NNRTIs using molecular hybridization based on crystallographic overlays

  摘要：

  Based on crystallographic overlays of the known inhibitors TMC125 and R221239 complexed in RT, we designed a novel series of 4-phenoxy-6-(phenylamino) pyridin-2(1H)-one derivatives as HIV NNRTIs by molecular hybridization approach. The biological testing results indicated that 2-pyridone scaffold of these inhibitors was indispensable for their anti-HIV-1 activity, and substitution of halogen at the 3-position of the 2-pyridone ring would decrease the anti-HIV activity. Four most potent compounds had anti-HIV-1 IIIB activities at low micromolar concentrations (EC50 = 0.15-0.84 mu M), comparable to that of nevirapine and delavidine. Some compounds were selected to test their anti-HIV-1 RT inhibitory action and to perform molecular modeling studies to predict the binding mode of these 2-pyridone derivatives. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.01.054
• 作为产物：
  描述：

  2,6-二氯吡啶N-氧化物 在 potassium carbonate 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.25h， 生成 2,6-dichloro-4-(2,4,6-trimethylphenoxy)pyridine
  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

• 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.
• Structural optimization of pyridine-type DAPY derivatives to exploit the tolerant regions of the NNRTI binding pocket
  作者：Wenmin Chen、Peng Zhan、Dirk Daelemans、Jiapei Yang、Boshi Huang、Erik De Clercq、Christophe Pannecouque、Xinyong Liu

  DOI：10.1016/j.ejmech.2016.05.054

  日期：2016.10

  Based on the crystallographic studies of diarylpyrimidines (DAPYs), we embarked on incorporating the hydrophilic piperidyl or morpholinyl group into the known DAPY derivatives bearing the pyridine moiety as a core structure, with the double aim to exploit additional interactions with the HIV-1 NNRTI binding pocket (NNIBP), as well as to improve the compound solubility. The antiviral evaluation result show that the most potent compounds I-8b2, I-8b3, I-8b4 and I-8c3 exhibited anti-HIV-1 (IIIB) strain activity ranging from 7.4 nM to 9.4 nM (SI = 168-1283), superior to FDA-approved drugs of nevirapine (NVP), lamivudine (3TC) and delavirdine (DLV), and comparable to etravirine (ETV), zidovudine (AZT) and efavirenz (EFV). Additionally, compounds I-8c2 and I-8c3 showed moderate activity against NNRTI resistant strains baring mutations K103N and Y181C with EC50 values of 6.2 mu M and 6.8 mu M, respectively. Preliminary structure-activity relationships (SARs), reverse transcriptase inhibition efficacy and molecular modeling of selected compounds are also presented. These outcomes support our design hypothesis and demonstrate that the piperidyl group modified pyridine-typed DAPY derivatives are highly potent NNRTIs with improved water solubility. (C) 2016 Elsevier Masson SAS. All rights reserved.