4-chloro-N-(4′-fluorobiphenyl-4-ylcarbonyl)-3-nitrobenzenesulfonamide | 406232-64-2

• 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-N-(4′-fluorobiphenyl-4-ylcarbonyl)-3-nitrobenzenesulfonamide
• 英文别名: 4-chloro-N-(4'-fluorobiphenyl-4-carbonyl)-3-nitrobenzenesulfonamide；4-chloro-N-((4'-fluoro(1,1'-biphenyl)-4-yl)carbonyl)-3-nitrobenzenesulfonamide；N-(4-chloro-3-nitrophenyl)sulfonyl-4-(4-fluorophenyl)benzamide
• CAS: 406232-64-2
• 化学式: C₁₉H₁₂ClFN₂O₅S
• 分子量: 434.832
• InChiKey: HRKZUDVMGTWWLZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-chloro-N-(4′-fluorobiphenyl-4-ylcarbonyl)-3-nitrobenzenesulfonamide 在 氨 作用下， 以 甲醇 为溶剂， 生成 4-amino-N-((4'-fluoro-1,1'-biphenyl-4-yl)carbonyl)-3-nitrobenzenesulfonamide
  参考文献：
  名称：

  N-Acylsulfonamide apoptosis promoters

  摘要：

  N-苯甲酰芳基磺胺酰胺具有以下化学式，是BCL-X1抑制剂，有助于促进细胞凋亡。还公开了BCL-X1抑制组合物和在哺乳动物中促进细胞凋亡的方法。

  公开号：

  US20020086887A1
• 作为产物：
  描述：

  4-溴苯甲酸乙酯 在 4-二甲氨基吡啶 、 sodium hydroxide 、 四(三苯基膦)钯 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 乙醇 、 二氯甲烷 为溶剂， 反应 24.25h， 生成 4-chloro-N-(4′-fluorobiphenyl-4-ylcarbonyl)-3-nitrobenzenesulfonamide
  参考文献：
  名称：

  Discovery of a Potent Inhibitor of the Antiapoptotic Protein Bcl-x_L from NMR and Parallel Synthesis

  摘要：

  The antiapoptotic proteins Bcl-x(L) and Bcl-2 play key roles in the maintenance of normal cellular homeostasis. However, their overexpression can lead to oncogenic transformation and is responsible for drug resistance in certain types of cancer. This makes Bcl-x(L) and Bcl-2 attractive targets for the development of potential anticancer agents. Here we describe the structure-based discovery of a potent Bcl-x(L) inhibitor directed at a hydrophobic groove on the surface of the protein. This groove represents the binding site for BH3 peptides from proapoptotic Bcl-2 family members such as Bak and Bad. Application of NMR-based screening yielded an initial biaryl acid with an affinity (K-d) of similar to 300 mu M for the protein. Following the classical "SAR by NMR" approach, a second-site ligand was identified that bound proximal to the first-site ligand in the hydrophobic groove. From NMR-based structural studies and parallel synthesis, a potent ligand was obtained, which binds to Bcl-x(L) with an inhibition constant (K-i) of 36 +/- 2 nM.

  DOI：

  10.1021/jm0507532

文献信息

• N-Acylsulfonamide apoptosis promoters
  申请人：——

  公开号：US20020086887A1

  公开（公告）日：2002-07-04

  N-Benzoyl arylsulfonamides having the formula 1 Are BCL-X1 inhibitors and are useful for promoting apoptosis. Also disclosed are BCL-X1 inhibiting compositions and methods of promoting apoptosis in a mammal.

  N-苯甲酰芳基磺胺酰胺具有以下化学式，是BCL-X1抑制剂，有助于促进细胞凋亡。还公开了BCL-X1抑制组合物和在哺乳动物中促进细胞凋亡的方法。
• Gold-Catalyzed Oxidative Biaryl Cross-Coupling of Organometallics
  作者：Kai Liu、Nian Li、Yunyun Ning、Chengjian Zhu、Jin Xie

  DOI：10.1016/j.chempr.2019.07.023

  日期：2019.10

  without an external base for the synthesis, with excellent functional-group tolerance of asymmetric biaryls. Both coupling partners are readily available, bench-stable, and non-toxic. A broad array of (pseudo)halogenated and borylated coupling partners can be successfully applied to this site-specific biaryl coupling with unprecedented versatility. Its synthetic value has been substantiated by concise preparation

  联芳基亲核试剂之间的偶联（AR δ-：arylboronates或芳基硅烷）和亲电（AR δ+：芳基卤化物）代表了碳-碳键形成的最新技术。这些反应中固有的官能团限制源于钯和镍催化剂对卤素，硼酸酯和碱敏感取代基的高催化反应性。在这里，我们报告了一般的二聚体金催化的芳基硼酸酯和芳基硅烷的氧化交叉偶联反应，而没有用于合成的外部碱，具有不对称联芳基的优异的官能团耐受性。两种偶合剂均易于获得，稳定且无毒。各种各样的（假）卤代和硼化偶合剂可以成功地应用于这种位点特定的联芳基偶合剂，具有前所未有的多功能性。简明地制备几种π共轭有机材料和药效基团已证实了其合成价值。
• N-ACYLSULFONAMIDE APOPTOSIS PROMOTERS
  申请人：Augeri David J.

  公开号：US20090137585A1

  公开（公告）日：2009-05-28

  N-Benzoyl arylsulfonamides having the formula are BCL-Xl inhibitors and are useful for promoting apoptosis. Also disclosed are BCL-Xl inhibiting compositions and methods of promoting apoptosis in a mammal.

  具有以下式子的N-苯甲酰基芳基磺酰胺是BCL-Xl抑制剂，有助于促进细胞凋亡。本文还披露了BCL-Xl抑制剂组合物和在哺乳动物中促进细胞凋亡的方法。
• Discovery and Structure−Activity Relationship of Antagonists of B-Cell Lymphoma 2 Family Proteins with Chemopotentiation Activity in Vitro and in Vivo
  作者：Michael D. Wendt、Wang Shen、Aaron Kunzer、William J. McClellan、Milan Bruncko、Thorsten K. Oost、Hong Ding、Mary K. Joseph、Haichao Zhang、Paul M. Nimmer、Shi-Chung Ng、Alexander R. Shoemaker、Andrew M. Petros、Anatol Oleksijew、Kennan Marsh、Joy Bauch、Tilman Oltersdorf、Barbara A. Belli、Darlene Martineau、Stephen W. Fesik、Saul H. Rosenberg、Steven W. Elmore

  DOI：10.1021/jm050754u

  日期：2006.2.1

  Development of a rationally designed potentiator of cancer chemotherapy, via inhibition of Bcl-X-L function, is described. Lead compounds generated by NMR screening and directed parallel synthesis displayed sub mu M binding but were strongly deactivated in the presence of serum. The dominant component of serum deactivation was identified as domain III of human serum albumin (HSA); NMR solution structures of inhibitors bound to both Bcl-X-L and HSA domain III indicated two potential optimization sites for separation of affinities. Modifications at both sites resulted in compounds with improved Bcl-X-L binding and greatly increased activity in the presence of human serum, culminating in 73R, which bound to Bcl-X-L with a K-i of 0.8 nM. In a cellular assay 73R reversed the protection afforded by Bcl-X-L overexpression against cytokine deprivation in FL5.12 cells with an EC50 of 0.47 mu M. 73R showed little effect on the viability of the human non small cell lung cancer cell line A549. However, consistent with the proposed mechanism, 73R potentiated the activity of paclitaxel and UV irradiation in vitro and potentiated the antitumor efficacy of paclitaxel in a mouse xenograft model.
• US6720338B2
  申请人：——

  公开号：US6720338B2

  公开（公告）日：2004-04-13