N-(3-chlorophenyl)-2-((4-(4-cyano-2,6-dimethylphenoxy)pyrimidin-2-yl)thio)acetamide

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(3-chlorophenyl)-2-((4-(4-cyano-2,6-dimethylphenoxy)pyrimidin-2-yl)thio)acetamide
• 英文别名: N-(3-chlorophenyl)-2-[4-(4-cyano-2,6-dimethyl-phenoxy)pyrimidin-2-yl]sulfanyl-acetamide；N-(3-chlorophenyl)-2-[4-(4-cyano-2,6-dimethylphenoxy)pyrimidin-2-yl]sulfanylacetamide
• 化学式: C₂₁H₁₇ClN₄O₂S
• 分子量: 424.911
• InChiKey: KPXLNQVBDLLQPQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(3-chlorophenyl)-2-((4-(4-cyano-2,6-dimethylphenoxy)pyrimidin-2-yl)thio)acetamide 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 以59%的产率得到N-(3-chlorophenyl)-2-((4-(4-cyano-2,6-dimethylphenoxy)pyrimidin-2-yl)sulfonyl)acetamide
  参考文献：
  名称：

  Pyrimidine sulfonylacetanilides with improved potency against key mutant viruses of HIV-1 by specific targeting of a highly conserved residue

  摘要：

  Based on molecular simulation, the etravirine-VRX-480773 hybrids previously disclosed by our group were optimized to yield novel pyrimidine sulfonylacetanilides 8 with improved activity against a panel of seven clinically relevant single and double mutant strains of HIV-1. The improvement in potency in this in vitro model of HIV RNA replication partly validates the mechanism by which this class of allosteric pyrimidine derivatives inhibits the reverse transcriptase (RT), and represents a remarkable step forward in the development of anti-HIV drugs. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.08.007
• 作为产物：
  描述：

  4-((2-chloropyrimidin-4-yl)oxy)-3,5-dimethylbenzonitrile 在 potassium tert-butylate 、 硫脲 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 N-(3-chlorophenyl)-2-((4-(4-cyano-2,6-dimethylphenoxy)pyrimidin-2-yl)thio)acetamide
  参考文献：
  名称：

  Hybrid chemistry. Part 4: Discovery of etravirine–VRX-480773 hybrids as potent HIV-1 non-nucleoside reverse transcriptase inhibitors

  摘要：

  A novel series of etravirine-VRX-480773 hybrids were designed using structure-guided molecular hybridization strategy and fusing the pharmacophore templates of etravirine and VRX-480773. The anti-HIV-1 activity and cytotoxicity was evaluated in MT-4 cell cultures. The most active hybrid compound in this series, N-(2-chlorophenyl)-2-((4-(4-cyano-2,6-dimethylphenoxy) pyrimidin-2-yl) thio) acetamide 3d (EC50 = 0.24, SI > 1225), was more potent than delavirdine (EC50 = 0.66 mu M, SI > 67) in the anti-HIV-1 in vitro cellular assay. Studies of structure-activity relationships established a correlation between anti-HIV activity and the substitution pattern of the acetanilide group. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.06.048

文献信息

• Hybrid chemistry. Part 4: Discovery of etravirine–VRX-480773 hybrids as potent HIV-1 non-nucleoside reverse transcriptase inhibitors
  作者：Zheng-Yong Wan、Yuan Tao、Ya-Feng Wang、Tian-Qi Mao、Hong Yin、Fen-Er Chen、Hu-Ri Piao、Erik De Clercq、Dirk Daelemans、Christophe Pannecouque

  DOI：10.1016/j.bmc.2015.06.048

  日期：2015.8

  A novel series of etravirine-VRX-480773 hybrids were designed using structure-guided molecular hybridization strategy and fusing the pharmacophore templates of etravirine and VRX-480773. The anti-HIV-1 activity and cytotoxicity was evaluated in MT-4 cell cultures. The most active hybrid compound in this series, N-(2-chlorophenyl)-2-((4-(4-cyano-2,6-dimethylphenoxy) pyrimidin-2-yl) thio) acetamide 3d (EC50 = 0.24, SI > 1225), was more potent than delavirdine (EC50 = 0.66 mu M, SI > 67) in the anti-HIV-1 in vitro cellular assay. Studies of structure-activity relationships established a correlation between anti-HIV activity and the substitution pattern of the acetanilide group. (C) 2015 Elsevier Ltd. All rights reserved.
• Pyrimidine sulfonylacetanilides with improved potency against key mutant viruses of HIV-1 by specific targeting of a highly conserved residue
  作者：Zheng-Yong Wan、Jin Yao、Tian-Qi Mao、Xin-Long Wang、Hai-Feng Wang、Wen-Xue Chen、Hong Yin、Fen-Er Chen、Erik De Clercq、Dirk Daelemans、Christophe Pannecouque

  DOI：10.1016/j.ejmech.2015.08.007

  日期：2015.9

  Based on molecular simulation, the etravirine-VRX-480773 hybrids previously disclosed by our group were optimized to yield novel pyrimidine sulfonylacetanilides 8 with improved activity against a panel of seven clinically relevant single and double mutant strains of HIV-1. The improvement in potency in this in vitro model of HIV RNA replication partly validates the mechanism by which this class of allosteric pyrimidine derivatives inhibits the reverse transcriptase (RT), and represents a remarkable step forward in the development of anti-HIV drugs. (C) 2015 Elsevier Masson SAS. All rights reserved.