2-chloro-4-(4-cyano-2,6-dimethylphenoxy)-6-methoxypyridin | 1580002-04-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-chloro-4-(4-cyano-2,6-dimethylphenoxy)-6-methoxypyridin
• 英文别名: 2-chloro-6-methoxy-4-(4-cyano-2,6-dimethylphenoxy)
• CAS: 1580002-04-5
• 化学式: C₁₅H₁₃ClN₂O₂
• 分子量: 288.733
• InChiKey: PPSOMHJJXQSVOT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.02
• 重原子数：
  20.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  55.14
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-chloro-4-(4-cyano-2,6-dimethylphenoxy)-6-methoxypyridin 在 三甲基氯硅烷 、 palladium diacetate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 sodium iodide 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 生成 4-((6-((4-cyanophenyl)amino)-2-oxo-1,2-dihydropyridin-4-yl)oxy)-3,5-dimethylbenzonitrile
  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 sodium methylate 、 potassium carbonate 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-chloro-4-(4-cyano-2,6-dimethylphenoxy)-6-methoxypyridin
  参考文献：
  名称：

  Structural optimization of pyridine-type DAPY derivatives to exploit the tolerant regions of the NNRTI binding pocket

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2016.05.054