4-chloro-3-(3-chlorophenoxy)aniline | 1333950-35-8

• 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: 4-chloro-3-(3-chlorophenoxy)aniline
• 英文别名: 4-Chloro-3-(3-chlorophenoxy)aniline
• CAS: 1333950-35-8
• 化学式: C₁₂H₉Cl₂NO
• 分子量: 254.116
• InChiKey: JETTZZRGGQWDJU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-氯-4-甲氧基嘧啶 、 4-chloro-3-(3-chlorophenoxy)aniline 在 对甲苯磺酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 5.0h， 生成 N-[4-chloro-3-(3-chlorophenoxy)phenyl]-4-methoxy-pyrimidin-2-amine
  参考文献：
  名称：

  Efficient Discovery of Potent Anti-HIV Agents Targeting the Tyr181Cys Variant of HIV Reverse Transcriptase

  摘要：

  Non-nucleoside reverse transcriptase inhibitors (NNRTIs) that interfere with the replication of human immunodeficiency virus (HIV) are being pursued with guidance from molecular modeling including free-energy perturbation (FEP) calculations for protein inhibitor binding affinities. The previously reported pyrimidinylphenylamine 1 and its chloro analogue 2 are potent anti-HIV agents; they inhibit replication of wild-type HIV-1 in infected human T-cells with EC50 values of 2 and 10 nM, respectively. However, they show no activity against viral strains containing the Tyr181Cys (Y181C) mutation in HIV-RT. Modeling indicates that the problem is likely associated with extensive interaction between the dimethylallyloxy substituent and Tyr181. As an alternative, a phenoxy group is computed to be oriented in a manner diminishing the contact with Tyr181. However, this replacement leads to a roughly 1000-fold loss of activity for 3 (2.5 mu M). The present report details the efficient, computationally driven evolution of 3 to novel NNRTIs with sub-10 nM potency toward both wild-type HIV-1 and Y181C-containing variants. The critical contributors were FEP substituent scans for the phenoxy and pyrimidine rings and recognition of potential benefits of addition of a cyanovinyl group to the phenoxy ring.

  DOI：

  10.1021/ja2058583
• 作为产物：
  描述：

  1-氯-3-碘苯 、 2-氯-5-氨基苯酚 在 2-吡啶甲酸 、 potassium phosphate 、 copper(l) iodide 作用下， 以 二甲基亚砜 为溶剂， 反应 24.0h， 生成 4-chloro-3-(3-chlorophenoxy)aniline
  参考文献：
  名称：

  [EN] CYCLIC SULFONAMIDE CONTAINING DERIVATIVES AS INHIBITORS OF HEDGEHOG SIGNALING PATHWAY
  [FR] DÉRIVÉS CONTENANT UN SULFONAMIDE CYCLIQUE EN TANT QU'INHIBITEURS DE LA VOIE DE SIGNALISATION HEDGEHOG

  摘要：

  该发明通常涉及含有环磺酰胺衍生物的创造和使用，用于抑制刺猬信号通路，并将这些化合物用于治疗高增殖性疾病和介导血管生成的疾病。

  公开号：

  WO2014071298A1

文献信息

• [EN] CYCLIC SULFONAMIDE CONTAINING DERIVATIVES AS INHIBITORS OF HEDGEHOG SIGNALING PATHWAY<br/>[FR] DÉRIVÉS CONTENANT UN SULFONAMIDE CYCLIQUE EN TANT QU'INHIBITEURS DE LA VOIE DE SIGNALISATION HEDGEHOG
  申请人：NANT HOLDINGS IP LLC

  公开号：WO2014071298A1

  公开（公告）日：2014-05-08

  The invention relates generally to the creation and use of cyclic sulfonamide containing derivatives to inhibit the hedgehog signaling pathway and to the use of those compounds for the treatment of hyperproliferative diseases and angiogenesis mediated diseases.

  该发明通常涉及含有环磺酰胺衍生物的创造和使用，用于抑制刺猬信号通路，并将这些化合物用于治疗高增殖性疾病和介导血管生成的疾病。
• CYCLIC SULFONAMIDE CONTAINING DERIVATIVES AS INHIBITORS OF HEDGEHOG SIGNALING PATHWAY
  申请人：NANT HOLDINGS IP, LLC

  公开号：US20150299190A1

  公开（公告）日：2015-10-22

  The invention relates generally to the creation and use of cyclic sulfonamide containing derivatives to inhibit the hedgehog signaling pathway and to the use of those compounds for the treatment of hyperproliferative diseases and angiogenesis mediated diseases.

  本发明通常涉及使用含环磺酰胺基衍生物的创建和使用以抑制刺猬信号通路，并将这些化合物用于治疗高增殖性疾病和血管生成介导的疾病。
• Cyclic sulfonamide containing derivatives as inhibitors of hedgehog signaling pathway
  申请人：NantBioScience, Inc.

  公开号：US10183013B2

  公开（公告）日：2019-01-22

  The invention relates generally to the creation and use of cyclic sulfonamide containing derivatives to inhibit the hedgehog signaling pathway and to the use of those compounds for the treatment of hyperproliferative diseases and angiogenesis mediated diseases.

  本发明一般涉及含有环磺酰胺的衍生物的创制和使用，以抑制刺猬信号通路，并将这些化合物用于治疗过度增殖性疾病和血管生成介导的疾病。
• US9499539B2
  申请人：——

  公开号：US9499539B2

  公开（公告）日：2016-11-22
• Efficient Discovery of Potent Anti-HIV Agents Targeting the Tyr181Cys Variant of HIV Reverse Transcriptase
  作者：William L. Jorgensen、Mariela Bollini、Vinay V. Thakur、Robert A. Domaoal、Krasimir A. Spasov、Karen S. Anderson

  DOI：10.1021/ja2058583

  日期：2011.10.5

  Non-nucleoside reverse transcriptase inhibitors (NNRTIs) that interfere with the replication of human immunodeficiency virus (HIV) are being pursued with guidance from molecular modeling including free-energy perturbation (FEP) calculations for protein inhibitor binding affinities. The previously reported pyrimidinylphenylamine 1 and its chloro analogue 2 are potent anti-HIV agents; they inhibit replication of wild-type HIV-1 in infected human T-cells with EC50 values of 2 and 10 nM, respectively. However, they show no activity against viral strains containing the Tyr181Cys (Y181C) mutation in HIV-RT. Modeling indicates that the problem is likely associated with extensive interaction between the dimethylallyloxy substituent and Tyr181. As an alternative, a phenoxy group is computed to be oriented in a manner diminishing the contact with Tyr181. However, this replacement leads to a roughly 1000-fold loss of activity for 3 (2.5 mu M). The present report details the efficient, computationally driven evolution of 3 to novel NNRTIs with sub-10 nM potency toward both wild-type HIV-1 and Y181C-containing variants. The critical contributors were FEP substituent scans for the phenoxy and pyrimidine rings and recognition of potential benefits of addition of a cyanovinyl group to the phenoxy ring.