4-[2-(dibutylamino)pyrimidin-4-yl]-N-[[1-[(3,4-dichlorophenyl)methyl]-2,3-dihydroindol-5-yl]sulfonyl]-3-(3,4-dihydro-1H-isoquinoline-2-carbonyl)benzamide | 1383737-95-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 4-[2-(dibutylamino)pyrimidin-4-yl]-N-[[1-[(3,4-dichlorophenyl)methyl]-2,3-dihydroindol-5-yl]sulfonyl]-3-(3,4-dihydro-1H-isoquinoline-2-carbonyl)benzamide
• CAS: 1383737-95-8
• 化学式: C₄₄H₄₆Cl₂N₆O₄S
• 分子量: 825.859
• InChiKey: MNQSMBOLASGXHW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.1
• 重原子数：
  57
• 可旋转键数：
  14
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  在 4-二甲氨基吡啶 、 水 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 4-[2-(dibutylamino)pyrimidin-4-yl]-N-[[1-[(3,4-dichlorophenyl)methyl]-2,3-dihydroindol-5-yl]sulfonyl]-3-(3,4-dihydro-1H-isoquinoline-2-carbonyl)benzamide
  参考文献：
  名称：

  Pyrazole and pyrimidine phenylacylsulfonamides as dual Bcl-2/Bcl-xL antagonists

  摘要：

  5-Butyl-1,4-diphenyl pyrazole and 2-amino-5-chloro pyrimidine acylsulfonamides were developed as potent dual antagonists of Bcl-2 and Bcl-xL. Compounds were optimized for binding to the I88, L92, I95, and F99 pockets normally occupied by pro-apoptotic protein Bim. An X-ray crystal structure confirmed the proposed binding mode. Observation of cytochrome c release from isolated mitochondria in MV-411 cells provides further evidence of target inhibition. Compounds demonstrated submicromolar antiproliferative activity in Bcl-2/Bcl-xL dependent cell lines. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.106

文献信息

• Pyrazole and pyrimidine phenylacylsulfonamides as dual Bcl-2/Bcl-xL antagonists
  作者：Gretchen M. Schroeder、Donna Wei、Patrizia Banfi、Zhen-Wei Cai、Jonathan Lippy、Maria Menichincheri、Michele Modugno、Joseph Naglich、Becky Penhallow、Heidi L. Perez、John Sack、Robert J. Schmidt、Andrew Tebben、Chunhong Yan、Liping Zhang、Arturo Galvani、Louis J. Lombardo、Robert M. Borzilleri

  DOI：10.1016/j.bmcl.2012.04.106

  日期：2012.6

  5-Butyl-1,4-diphenyl pyrazole and 2-amino-5-chloro pyrimidine acylsulfonamides were developed as potent dual antagonists of Bcl-2 and Bcl-xL. Compounds were optimized for binding to the I88, L92, I95, and F99 pockets normally occupied by pro-apoptotic protein Bim. An X-ray crystal structure confirmed the proposed binding mode. Observation of cytochrome c release from isolated mitochondria in MV-411 cells provides further evidence of target inhibition. Compounds demonstrated submicromolar antiproliferative activity in Bcl-2/Bcl-xL dependent cell lines. (C) 2012 Elsevier Ltd. All rights reserved.