4-(4-(2-bromobenzyl)piperazin-1-yl)-2-nitrobenzonitrile | 1027345-29-4

• 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: 4-(4-(2-bromobenzyl)piperazin-1-yl)-2-nitrobenzonitrile
• 英文别名: 4-[4-[(2-Bromophenyl)methyl]piperazin-1-yl]-2-nitrobenzonitrile
• CAS: 1027345-29-4
• 化学式: C₁₈H₁₇BrN₄O₂
• 分子量: 401.263
• InChiKey: KXUXVPCZTXREGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  76.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(4-(2-bromobenzyl)piperazin-1-yl)-2-nitrobenzonitrile 在 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 、 水 、 铁粉 、 sodium carbonate 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 以 乙二醇二甲醚 、 乙醇 、 甲乙醚 、 水 、 1,2-二氯乙烷 为溶剂， 反应 37.42h， 生成 4-chloro-7-(4-((4'-chloro-(1,1'-biphenyl)-2-yl)methyl)piperazin-1-yl)quinazoline
  参考文献：
  名称：

  Quinazoline Sulfonamides as Dual Binders of the Proteins B-Cell Lymphoma 2 and B-Cell Lymphoma Extra Long with Potent Proapoptotic Cell-Based Activity

  摘要：

  ABT-737 and ABT-263 are potent inhibitors of the BH3 antiapoptotic proteins, Bcl-x(L) and Bcl-2. This class of putative anticancer agents invariantly contains an acylsulfonamide core. We have designed and synthesized a series of novel quinazoline-based inhibitors of Bcl-2 and Bcl-xL that contain a heterocyclic alternative to the acylsulfonamide. These compounds exhibit submicromolar, mechanism-based activity in human small-cell lung carcinoma cell lines in the presence of 10% human serum. This comprises the first successful demonstration of a quinazoline sulfonamide core serving as an effective benzoylsulfonamide bioisostere. Additionally, these novel quinazolines comprise only the second known class of Bcl-2 family protein inhibitors to induce mechanism-based cell death.

  DOI：

  10.1021/jm101596e
• 作为产物：
  描述：

  2,4-二硝基苯甲腈 在 三乙胺 作用下， 以 二甲基亚砜 、 异丙醇 、 乙腈 为溶剂， 反应 77.0h， 生成 4-(4-(2-bromobenzyl)piperazin-1-yl)-2-nitrobenzonitrile
  参考文献：
  名称：

  [EN] ARYLSULFONAMIDE COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  [FR] COMPOSÉS ARYLSULFONAMIDES, COMPOSITIONS ET PROCÉDÉS D'UTILISATION

  摘要：

  公开号：

  WO2009143246A3

文献信息

• ARYLSULFONAMIDE COMPOUNDS
  申请人：Baell Jonathan Bayldon

  公开号：US20100056517A1

  公开（公告）日：2010-03-04

  The invention relates generally to small molecules that mimic the biological activity of certain peptides and proteins, to compositions containing them and to their use. In particular, the invention relates to compounds of the general formula (I) that mimic the biological activity of BH3-only proteins and are capable of binding to and neutralizing pro-survival Bcl-2 proteins: wherein A 1 , A 2 , B 1 , B 2 , B 3 , X, Z, R 1 , R 2 , R 3 and t are as described herein. The invention also relates to processes of preparing the benzenesulfonamide compounds that mimic portions of peptides and proteins, and to the use of such compounds in the regulation of cell death and the treatment and/or prophylaxis of diseases or conditions associated with the deregulation of cell death.

  本发明涉及一般性地模拟某些肽和蛋白质的生物活性的小分子，包括含有它们的组合物以及它们的用途。特别地，本发明涉及一般式（I）的化合物，它们模拟BH3-仅有蛋白质的生物活性，并且能够结合和中和前生存的Bcl-2蛋白质：其中A1、A2、B1、B2、B3、X、Z、R1、R2、R3和t如本文所述。本发明还涉及制备模拟肽和蛋白质部分的苯磺酰胺化合物的过程，以及在调节细胞死亡和治疗和/或预防与细胞死亡失调相关的疾病或状况中使用这些化合物的用途。
• WO2008/61208
  申请人：——

  公开号：——

  公开（公告）日：——
• ARYLSULFONAMIDE COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  申请人：Genentech, Inc.

  公开号：EP2279174A2

  公开（公告）日：2011-02-02
• US8168645B2
  申请人：——

  公开号：US8168645B2

  公开（公告）日：2012-05-01
• Quinazoline Sulfonamides as Dual Binders of the Proteins B-Cell Lymphoma 2 and B-Cell Lymphoma Extra Long with Potent Proapoptotic Cell-Based Activity
  作者：Brad E. Sleebs、Peter E. Czabotar、Wayne J. Fairbrother、W. Douglas Fairlie、John A. Flygare、David C. S. Huang、Wilhelmus J. A. Kersten、Michael F. T. Koehler、Guillaume Lessene、Kym Lowes、John P. Parisot、Brian J. Smith、Morey L. Smith、Andrew J. Souers、Ian P. Street、Hong Yang、Jonathan B. Baell

  DOI：10.1021/jm101596e

  日期：2011.3.24

  ABT-737 and ABT-263 are potent inhibitors of the BH3 antiapoptotic proteins, Bcl-x(L) and Bcl-2. This class of putative anticancer agents invariantly contains an acylsulfonamide core. We have designed and synthesized a series of novel quinazoline-based inhibitors of Bcl-2 and Bcl-xL that contain a heterocyclic alternative to the acylsulfonamide. These compounds exhibit submicromolar, mechanism-based activity in human small-cell lung carcinoma cell lines in the presence of 10% human serum. This comprises the first successful demonstration of a quinazoline sulfonamide core serving as an effective benzoylsulfonamide bioisostere. Additionally, these novel quinazolines comprise only the second known class of Bcl-2 family protein inhibitors to induce mechanism-based cell death.