3-chloro-5-{2-chloro-4-nitro-5-[(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)amino]phenoxy}benzonitrile | 1345337-31-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-chloro-5-{2-chloro-4-nitro-5-[(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)amino]phenoxy}benzonitrile
• 英文别名: 3-chloro-5-[2-chloro-4-nitro-5-(2H-pyrazolo[3,4-b]pyridin-3-ylmethylamino)phenoxy]benzonitrile
• CAS: 1345337-31-6
• 化学式: C₂₀H₁₂Cl₂N₆O₃
• 分子量: 455.26
• InChiKey: PYYJDQGKZPQLLR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  132
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-chloro-5-{2-chloro-4-nitro-5-[(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)amino]phenoxy}benzonitrile 在 tin(ll) chloride 作用下， 以 水 为溶剂， 反应 1.0h， 以40%的产率得到3-{4-amino-2-chloro-5-[(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)amino]phenoxy}-5-chlorobenzonitrile
  参考文献：
  名称：

  Design and Synthesis of Conformationally Constrained Inhibitors of Non-Nucleoside Reverse Transcriptase

  摘要：

  Highly active antiretroviral therapy (HAART) significantly reduces human immunodeficiency virus (HIV) viral load and has led to a dramatic decrease in acquired immunodeficiency syndrome (AIDS) related mortality. Despite this success, there remains a critical need for new HIV therapies to address the emergence of drug resistant viral strains. Next generation NNRTIs are sought that are effective against these mutant forms of the HIV virus. The bound conformations of our lead inhibitors, MK-1107 (1) and MK-4965 (2), were divergent about the oxymethylene linker, and each of these conformations was rigidified using two isomeric cyclic constraints. The constraint derived from the bioactive conformation of 2 provided novel, highly potent NNRTIs that possess broad spectrum antiviral activity and good pharmacokinetic profiles. Systematic SAR led to the identification of indazole as the optimal conformational constraint to provide MK-6186 (3) and MK-7445 (6). Despite their reduced flexibility, these compounds had potency comparable to that of the corresponding acyclic ethers in both recombinant enzyme and cell based assays against both the wild-type and the clinically relevant mutant strains.

  DOI：

  10.1021/jm2010173
• 作为产物：
  描述：

  3-溴-5-氯苯酚 在 四(三苯基膦)钯 、 potassium carbonate 、 caesium carbonate 、 三氟乙酸 作用下， 以 N-甲基吡咯烷酮 、 N,N-二甲基甲酰胺 为溶剂， 反应 100.5h， 生成 3-chloro-5-{2-chloro-4-nitro-5-[(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)amino]phenoxy}benzonitrile
  参考文献：
  名称：

  Design and Synthesis of Conformationally Constrained Inhibitors of Non-Nucleoside Reverse Transcriptase

  摘要：

  Highly active antiretroviral therapy (HAART) significantly reduces human immunodeficiency virus (HIV) viral load and has led to a dramatic decrease in acquired immunodeficiency syndrome (AIDS) related mortality. Despite this success, there remains a critical need for new HIV therapies to address the emergence of drug resistant viral strains. Next generation NNRTIs are sought that are effective against these mutant forms of the HIV virus. The bound conformations of our lead inhibitors, MK-1107 (1) and MK-4965 (2), were divergent about the oxymethylene linker, and each of these conformations was rigidified using two isomeric cyclic constraints. The constraint derived from the bioactive conformation of 2 provided novel, highly potent NNRTIs that possess broad spectrum antiviral activity and good pharmacokinetic profiles. Systematic SAR led to the identification of indazole as the optimal conformational constraint to provide MK-6186 (3) and MK-7445 (6). Despite their reduced flexibility, these compounds had potency comparable to that of the corresponding acyclic ethers in both recombinant enzyme and cell based assays against both the wild-type and the clinically relevant mutant strains.

  DOI：

  10.1021/jm2010173

文献信息

• Design and Synthesis of Conformationally Constrained Inhibitors of Non-Nucleoside Reverse Transcriptase
  作者：Robert Gomez、Samson J. Jolly、Theresa Williams、Joseph P. Vacca、Maricel Torrent、Georgia McGaughey、Ming-Tain Lai、Peter Felock、Vandna Munshi、Daniel DiStefano、Jessica Flynn、Mike Miller、Youwei Yan、John Reid、Rosa Sanchez、Yuexia Liang、Brenda Paton、Bang-Lin Wan、Neville Anthony

  DOI：10.1021/jm2010173

  日期：2011.11.24

  Highly active antiretroviral therapy (HAART) significantly reduces human immunodeficiency virus (HIV) viral load and has led to a dramatic decrease in acquired immunodeficiency syndrome (AIDS) related mortality. Despite this success, there remains a critical need for new HIV therapies to address the emergence of drug resistant viral strains. Next generation NNRTIs are sought that are effective against these mutant forms of the HIV virus. The bound conformations of our lead inhibitors, MK-1107 (1) and MK-4965 (2), were divergent about the oxymethylene linker, and each of these conformations was rigidified using two isomeric cyclic constraints. The constraint derived from the bioactive conformation of 2 provided novel, highly potent NNRTIs that possess broad spectrum antiviral activity and good pharmacokinetic profiles. Systematic SAR led to the identification of indazole as the optimal conformational constraint to provide MK-6186 (3) and MK-7445 (6). Despite their reduced flexibility, these compounds had potency comparable to that of the corresponding acyclic ethers in both recombinant enzyme and cell based assays against both the wild-type and the clinically relevant mutant strains.