4-(5-butyl-3-(ethoxycarbonyl)-1-(4-phenoxyphenyl)-1H-pyrazole-4-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoic acid | 1383737-91-4

• 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: 4-(5-butyl-3-(ethoxycarbonyl)-1-(4-phenoxyphenyl)-1H-pyrazole-4-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoic acid
• 英文别名: 4-(5-butyl-3-(ethoxycarbonyl)-1-(4-phenoxyphenyl)-1H-pyrazol-4-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoic acid；4-[5-butyl-3-ethoxycarbonyl-1-(4-phenoxyphenyl)pyrazol-4-yl]-3-(3,4-dihydro-1H-isoquinoline-2-carbonyl)benzoic acid
• CAS: 1383737-91-4
• 化学式: C₃₉H₃₇N₃O₆
• 分子量: 643.739
• InChiKey: JKAQRPUXVPSBKG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  48
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(5-butyl-3-(ethoxycarbonyl)-1-(4-phenoxyphenyl)-1H-pyrazole-4-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoic acid 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 N,N-二甲基甲酰胺 为溶剂， 生成 4-(5-butyl-3-(hydroxymethyl)-1-(4-phenoxyphenyl)-1H-pyrazole-4-yl)-N-(naphthalen-2-ylsulfonyl)-3-(1,2,3,4-tetrahydroisoquinoline-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
• 作为产物：
  描述：

  1-硝基戊烷 在 4-二甲氨基吡啶 、 potassium tert-butylate 、 乙酸酐 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 22.5h， 生成 4-(5-butyl-3-(ethoxycarbonyl)-1-(4-phenoxyphenyl)-1H-pyrazole-4-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoic acid
  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

• [EN] SUBSTITUTED SULFONAMIDES USEFUL AS ANTIAPOPTOTIC BCL INHIBITORS<br/>[FR] SULFONAMIDES SUBSTITUÉS UTILES COMME INHIBITEURS DE BCL ANTI-APOPTOTIQUES
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2012162365A1

  公开（公告）日：2012-11-29

  Disclosed are compounds of Formula (I), or a pharmaceutically acceptable salt thereof, wherein: W and Q and G are defined herein. Also disclosed are methods of using such compounds as inhibitors of Bcl-2 family antiapoptotic proteins for the treatment of cancer; and pharmaceutical compositions comprising such compounds.

  揭示了式（I）的化合物或其药学上可接受的盐，其中：W、Q和G在此处被定义。还揭示了将这些化合物用作Bcl-2家族抗凋亡蛋白的抑制剂以治疗癌症的方法；以及包含这些化合物的药物组合物。
• SUBSTITUTED SULFONAMIDES USEFUL AS ANTIAPOPTOTIC BCL INHIBITORS
  申请人：Borzilleri Robert M.

  公开号：US20140135318A1

  公开（公告）日：2014-05-15

  Disclosed are compounds of Formula (I), or a pharmaceutically acceptable salt thereof, wherein: W and Q and G are defined herein. Also disclosed are methods of using such compounds as inhibitors of Bcl-2 family antiapoptotic proteins for the treatment of cancer; and pharmaceutical compositions comprising such compounds.

  本发明涉及式（I）的化合物或其药学上可接受的盐，其中：W、Q和G的定义如下。还公开了使用这些化合物作为Bcl-2家族抗凋亡蛋白的抑制剂用于治疗癌症的方法；以及包含这些化合物的药物组合物。
• US9346795B2
  申请人：——

  公开号：US9346795B2

  公开（公告）日：2016-05-24