N-((4-(benzyloxy)phenyl)sulfonyl)-3',5'-dichloro-[1,1'-biphenyl]-4-carboxamide | 1326777-32-5

• 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: N-((4-(benzyloxy)phenyl)sulfonyl)-3',5'-dichloro-[1,1'-biphenyl]-4-carboxamide
• 英文别名: 4-(3,5-dichlorophenyl)-N-(4-phenylmethoxyphenyl)sulfonylbenzamide
• CAS: 1326777-32-5
• 化学式: C₂₆H₁₉Cl₂NO₄S
• 分子量: 512.413
• InChiKey: RLLAFSQEXHJADT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  80.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-(benzyloxy)benzenesulfonamide 、 3,5-二氯联苯-4-羧酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 N-((4-(benzyloxy)phenyl)sulfonyl)-3',5'-dichloro-[1,1'-biphenyl]-4-carboxamide
  参考文献：
  名称：

  SAR by Interligand Nuclear Overhauser Effects (ILOEs) Based Discovery of Acylsulfonamide Compounds Active against Bcl-x_Land Mcl-1

  摘要：

  Overexpression of antiapoptotic members of the Bcl-2 family proteins, such as Bcl-x(L), and Mfl-1, has been shown to be involved in resistance to chemotherapeutic drugs in many forms of cancers. Recent efforts from the Abbott Laboratories resulted in the development of the acylsulfonamide compound and clinical candidate that targets selectively Bcl-2, Bcl-x(L), and Bcl-w while it is not active against Mcl-1 and Bfl-1. However, early clinical and preclinical studies suggest that pan-Bcl-2 antagonists, targeting simultaneously Mcl-1, Bcl-x(L), and possibly all other four antiapoptotic Bcl-2 proteins, may result in more efficacious drugs. Here, following an NMR fragment-based approach, SAR by ILOEs, we report on compounds that exhibit nanomolar affinities for both Bcl-x(L) and Mcl-1 in vitro. We believe that these molecules can be used as useful starting point for the development of novel Bcl-2 antagonists, in particular targeting Mcl-1.

  DOI：

  10.1021/jm200826s

文献信息

• SAR by Interligand Nuclear Overhauser Effects (ILOEs) Based Discovery of Acylsulfonamide Compounds Active against Bcl-x_Land Mcl-1
  作者：Michele F. Rega、Bainan Wu、Jun Wei、Ziming Zhang、Jason F. Cellitti、Maurizio Pellecchia

  DOI：10.1021/jm200826s

  日期：2011.9.8

  Overexpression of antiapoptotic members of the Bcl-2 family proteins, such as Bcl-x(L), and Mfl-1, has been shown to be involved in resistance to chemotherapeutic drugs in many forms of cancers. Recent efforts from the Abbott Laboratories resulted in the development of the acylsulfonamide compound and clinical candidate that targets selectively Bcl-2, Bcl-x(L), and Bcl-w while it is not active against Mcl-1 and Bfl-1. However, early clinical and preclinical studies suggest that pan-Bcl-2 antagonists, targeting simultaneously Mcl-1, Bcl-x(L), and possibly all other four antiapoptotic Bcl-2 proteins, may result in more efficacious drugs. Here, following an NMR fragment-based approach, SAR by ILOEs, we report on compounds that exhibit nanomolar affinities for both Bcl-x(L) and Mcl-1 in vitro. We believe that these molecules can be used as useful starting point for the development of novel Bcl-2 antagonists, in particular targeting Mcl-1.