N-(4-(4-(2-(cyclohexylamino)benzyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-(4-(4-(2-(cyclohexylamino)benzyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide
• 英文别名: N-Benylpiperazine derivative, 23f；4-[4-[[2-(cyclohexylamino)phenyl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylbenzamide
• 化学式: C₄₂H₅₃N₇O₅S₂
• 分子量: 800.059
• InChiKey: YLMURQOFHMQRRU-PGUFJCEWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.6
• 重原子数：
  56
• 可旋转键数：
  16
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  177
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2-氟苯腈 在 三乙酰氧基硼氢化钠 、 二异丁基氢化铝 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 二甲基亚砜 、 甲苯 为溶剂， 反应 19.25h， 生成 N-(4-(4-(2-(cyclohexylamino)benzyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide
  参考文献：
  名称：

  Studies Leading to Potent, Dual Inhibitors of Bcl-2 and Bcl-xL

  摘要：

  Overexpression of the antiapototic proteins Bcl-2 and Bcl-xL provides a common mechanism through which cancer cells gain a survival advantage and become resistant to conventional chemotherapy. Inhibition of these prosurvival proteins is an attractive strategy for cancer therapy. We recently described the discovery of a selective Bcl-xL antagonist that potentiates the antitumor activity of chemotherapy and radiation. Here we describe the use of structure-guided design to exploit a deep hydrophobic binding pocket on the surface of these proteins to develop the first dual, subnanomolar inhibitors of Bcl-xL and Bcl-2. This study culminated in the identification of 2, which exhibited EC50 values of 8 nM and 30 nM in Bcl-2 and Bcl-xL dependent cells, respectively. Compound 2 demonstrated single agent efficacy against human follicular lymphoma cell lines that overexpress Bcl-2, and efficacy in a murine xenograft model of lymphoma when given both as a single agent and in combination with etoposide.

  DOI：

  10.1021/jm061152t

文献信息

• N-acylsulfonamide apoptosis promoters
  申请人：Abbott Laboratories

  公开号：EP2308812A2

  公开（公告）日：2011-04-13

  Disclosed are N-acylsulfonamide compounds which inhibit the activity of anti-apoptotic protein family members, compositions containing the compounds and uses of the compounds for preparing medicaments for treating diseases during which occurs expression of one or more than one anti-apoptotic protein family member.

  本发明公开了抑制抗细胞凋亡蛋白家族成员活性的 N-酰基磺酰胺化合物、含有该化合物的组合物以及该化合物用于制备治疗一种或多种抗细胞凋亡蛋白家族成员表达的疾病的药物的用途。
• Chemical entities that kill senescent cells for use in treating age-related disease
  申请人：Unity Biotechnology, Inc.

  公开号：US10195213B2

  公开（公告）日：2019-02-05

  Disclosed herein are compounds that are effective for treatment of various disease states associated with senescence. The disclosed compounds can be used to eliminate senescent cells for disease treatment. The dosing of the compounds includes both single administration and regimens of cycling dosages.

  本文公开的化合物可有效治疗与衰老有关的各种疾病状态。所公开的化合物可用于消除衰老细胞以治疗疾病。化合物的给药方式包括单次给药和循环给药。
• Apoptosis promoters
  申请人：Bruncko Milan

  公开号：US20060128706A1

  公开（公告）日：2006-06-15

  Disclosed are compounds which inhibit the activity of anti-apoptotic protein family members, compositions containing the compounds and uses of the compounds for preparing medicaments for treating diseases during which occurs expression one or more than one of an anti-apoptotic protein family member.

  本发明公开了抑制抗凋亡蛋白家族成员活性的化合物、含有这些化合物的组合物以及这些化合物用于制备治疗疾病的药物的用途，在这些疾病中，一种或一种以上的抗凋亡蛋白家族成员发生表达。
• N-ACYLSULFONAMIDE APOPTOSIS PROMOTERS
  申请人：AbbVie Bahamas Ltd.

  公开号：EP1685119B1

  公开（公告）日：2016-03-09
• TREATMENT OF MYEOPROLIFERATIVE DISEASES
  申请人：Elmore W. Steven

  公开号：US20080076779A1

  公开（公告）日：2008-03-27

  Methods of reducing the number of platelets in mammals and preventing or treating pro-thrombotic conditions and diseases that are characterized by an excess of, or undesired activation of, platelets using inhibitors of anti-apoptotic Bcl-2 family protein members is disclosed.