2',4'-二氯-3-联苯基羧酸 | 380228-58-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2',4'-二氯-3-联苯基羧酸
• 中文别名: 2',4'-二氯-3-联苯甲酸
• 英文名称: 2',4'-dichloro[1,1'-biphenyl]-3-carboxylic acid
• 英文别名: 2',4'-Dichlorobiphenyl-3-carboxylic acid；3-(2,4-dichlorophenyl)benzoic acid
• CAS: 380228-58-0
• 化学式: C₁₃H₈Cl₂O₂
• 分子量: 267.111
• InChiKey: WUBAPTMRZKVPLO-UHFFFAOYSA-N

物化性质

• 沸点：
  424.5±35.0 °C(Predicted)
• 密度：
  1.397±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  17
• 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：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-苯氧基苯磺酰胺 、 2',4'-二氯-3-联苯基羧酸 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 2',4'-dichloro-N-((4-phenoxyphenyl)sulfonyl)[1,1'-biphenyl]-3-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

• METHODS FOR TREATING TRANSTHYRETIN AMYLOID DISEASES
  申请人：KELLY Jeffery W.

  公开号：US20120065237A1

  公开（公告）日：2012-03-15

  Kinetic stabilization of the native state of transthyretin is an effective mechanism for preventing protein misfolding. Because transthyretin misfolding plays an important role in transthyretin amyloid diseases, inhibiting such misfolding can be used as an effective treatment or prophylaxis for such diseases. Treatment methods are disclosed.

  动力学稳定化甲状腺素转运蛋白的天然状态是防止蛋白质错误折叠的有效机制。因为甲状腺素转运蛋白的错误折叠在甲状腺素转运蛋白淀粉样疾病中扮演重要角色，抑制这种错误折叠可以用作有效的治疗或预防这种疾病的方法。本文公开了治疗方法。
• Methods for treating transthyretin amyloid diseases
  申请人：Kelly W. Jeffery

  公开号：US20070078186A1

  公开（公告）日：2007-04-05

  Kinetic stabilization of the native state of transthyretin is an effective mechanism for preventing protein misfolding. Because transthyretin misfolding plays an important role in transthyretin amyloid diseases, inhibiting such misfolding can be used as an effective treatment or prophylaxis for such diseases. Treatment methods are disclosed.

  转甲状腺素原生态稳定化是预防蛋白质错构的有效机制，因为转甲状腺素的错构在转甲状腺素淀粉样病中扮演着重要角色，抑制此类错构可用作该类疾病的有效治疗或预防。披露了治疗方法。
• Retinol binding protein and transthyretin modulators for treating diabetes
  申请人：Sirion Therapeutics, Inc.

  公开号：EP1930046A1

  公开（公告）日：2008-06-11

  Described herein are methods and compositions for treating certain retionol-related diseases and conditions by modulation of transthyretin (TTR) and retinol binding protein (RBP) availability in the subject. For example, the methods and compositions provide for therapeutic agents for the treatment and/or prevention of age-related macular degeneration and/or dystrophies, metabolic disorders, idiopathic intracranial hypertension, hyperostosis, and protein misfolding and aggregation diseases. The compositions disclosed may be used as single agent therapy or in combination with other agents or therapies. In addition, described herein are methods and assays for selecting appropriate agents that can modulate the TTR and RBP availability in a subject.

  本文描述了通过调节受试者体内转甲状腺素（TTR）和视黄醇结合蛋白（RBP）的可用性来治疗某些视黄醇相关疾病和病症的方法和组合物。例如，这些方法和组合物提供了治疗和/或预防老年性黄斑变性和/或营养不良、代谢紊乱、特发性颅内高压、骨质疏松症以及蛋白质错误折叠和聚集疾病的治疗剂。所公开的组合物可用作单剂疗法，也可与其他制剂或疗法联合使用。此外，本文还描述了用于选择可调节受试者体内 TTR 和 RBP 可用性的适当制剂的方法和检测方法。
• Compositions and method for stabilizing transthyretin and inhibiting transthyretin misfolding
  申请人：The Scripps Research Institute

  公开号：EP1988397A1

  公开（公告）日：2008-11-05

  Kinetic stabilization of the native state of transthyretin is an effective mechanism for preventing protein misfolding. Because transthyretin misfolding plays an important role in transthyretin amyloid diseases, inhibiting such misfolding can be used as an effective treatment or prophylaxis for such diseases. Treatment methods, screening methods, as well as specific transthyretin stabilizing compounds are disclosed.

  转甲状腺素原生态的动力学稳定是防止蛋白质错误折叠的有效机制。由于转甲状腺素错误折叠在转甲状腺素淀粉样变性疾病中起着重要作用，因此抑制这种错误折叠可作为治疗或预防此类疾病的有效方法。本文公开了治疗方法、筛选方法以及特异性转甲状腺素稳定化合物。
• Retinol binding protein and transthyretin modulators for treating hypertosis, Alzheimer's disease or idiopathic intracranial hypertension
  申请人：ReVision Therapeutics, Inc.

  公开号：EP2289500A1

  公开（公告）日：2011-03-02

  Described herein are methods and compositions for treating certain retinol-related diseases and conditions by modulation of transthyretin (TTR) and retinol binding protein (RBP) availability in the subject. For example, the methods and compositions provide for therapeutic agents for the treatment and/or prevention of age-related macular degeneration and/or dystrophies, metabolic disorders, idiopathic intracranial hypertension, hyperostosis, and protein misfolding and aggregation diseases. The compositions disclosed may be used as single agent therapy or in combination with other agents or therapies. In addition, described herein are methods and assays for selecting appropriate agents that can modulate the TTR and RBP availability in a subject.

  本文描述了通过调节受试者体内转甲状腺素（TTR）和视黄醇结合蛋白（RBP）的可用性来治疗某些视黄醇相关疾病和病症的方法和组合物。例如，这些方法和组合物提供了治疗和/或预防老年性黄斑变性和/或营养不良、代谢紊乱、特发性颅内高压、骨质疏松症以及蛋白质错误折叠和聚集疾病的治疗剂。所公开的组合物可用作单剂疗法，也可与其他制剂或疗法联合使用。此外，本文还描述了用于选择可调节受试者体内 TTR 和 RBP 可用性的适当制剂的方法和检测方法。