2-(4-Amino-phenyl)-7-((R)-sec-butoxy)-1-(4-chloro-phenyl)-6-methoxy-1,4-dihydro-2H-isoquinolin-3-one | 1313365-34-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 2-(4-Amino-phenyl)-7-((R)-sec-butoxy)-1-(4-chloro-phenyl)-6-methoxy-1,4-dihydro-2H-isoquinolin-3-one
• 英文别名: 2-(4-aminophenyl)-7-[(2R)-butan-2-yl]oxy-1-(4-chlorophenyl)-6-methoxy-1,4-dihydroisoquinolin-3-one
• CAS: 1313365-34-2
• 化学式: C₂₆H₂₇ClN₂O₃
• 分子量: 450.965
• InChiKey: GVGKZFVOBWIRLH-DIERRCTGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  64.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-Amino-phenyl)-7-((R)-sec-butoxy)-1-(4-chloro-phenyl)-6-methoxy-1,4-dihydro-2H-isoquinolin-3-one 在 三乙酰氧基硼氢化钠 、 溶剂黄146 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 16.5h， 生成 7-((R)-sec-butoxy)-1-(4-chloro-phenyl)-2-{4-[(trans-4-ethylamino-cyclohexylmethyl)-methyl-amino]-phenyl}-6-methoxy-1,4-dihydro-2H-isoquinolin-3-one
  参考文献：
  名称：

  Substituted Isoquinolinones and Quinazolinones

  摘要：

  这项发明涉及公式（I）中的取代氮含有的双环杂环化合物，其中Z为CH2或N—R4，X、R1、R2、R4、R6、R7和n的定义如描述中所述。这类化合物适用于治疗由MDM2和/或MDM4的活性介导的疾病或疾病变体。

  公开号：

  US20110230457A1
• 作为产物：
  描述：

  在 草酰氯 、 水 、 铁粉 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 lithium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 5.25h， 生成 2-(4-Amino-phenyl)-7-((R)-sec-butoxy)-1-(4-chloro-phenyl)-6-methoxy-1,4-dihydro-2H-isoquinolin-3-one
  参考文献：
  名称：

  Discovery of dihydroisoquinolinone derivatives as novel inhibitors of the p53–MDM2 interaction with a distinct binding mode

  摘要：

  Blocking the interaction between the p53 tumor suppressor and its regulatory protein MDM2 is a promising therapeutic concept under current investigation in oncology drug research. We report here the discovery of the first representatives of a new class of small molecule inhibitors of this protein-protein interaction: the dihydroisoquinolinones. Starting from an initial hit identified by virtual screening, a derivatization program has resulted in compound 11, a low nanomolar inhibitor of the p53-MDM2 interaction showing significant cellular activity. Initially based on a binding mode hypothesis, this effort was then guided by a X-ray co-crystal structure of MDM2 in complex with one of the synthesized analogs. The X-ray structure revealed an unprecedented binding mode for p53-MDM2 inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.06.058

文献信息

• SUBSTITUTED ISOQUINOLINONES AND QUINAZOLINONES
  申请人：Novartis AG

  公开号：US20130281473A1

  公开（公告）日：2013-10-24

  The invention relates to substituted nitrogen containing bicyclic heterocycles of the formula (I) wherein Z is CH 2 or N—R 4 and X, R 1 , R 2 , R 4 , R 6 , R 7 and n are as defined in the description. Such compounds are suitable for the treatment of a disorder or disease which is mediated by the activity of MDM2 and/or MDM4, or variants thereof.

  本发明涉及式(I)的取代氮含杂环的双环杂环化合物，其中Z是CH2或N-R4，X，R1，R2，R4，R6，R7和n的定义如说明书中所定义。这类化合物适用于治疗由MDM2和/或MDM4的活性或其变异体介导的疾病或疾病。
• US8440693B2
  申请人：——

  公开号：US8440693B2

  公开（公告）日：2013-05-14
• US9051279B2
  申请人：——

  公开号：US9051279B2

  公开（公告）日：2015-06-09
• Substituted Isoquinolinones and Quinazolinones
  申请人：BERGHAUSEN Joerg

  公开号：US20110230457A1

  公开（公告）日：2011-09-22

  The invention relates to substituted nitrogen containing bicyclic heterocycles of the formula (I) wherein Z is CH 2 or N—R 4 and X, R 1 , R 2 , R 4 , R 6 , R 7 and n are as defined in the description. Such compounds are suitable for the treatment of a disorder or disease which is mediated by the activity of MDM2 and/or MDM4, or variants thereof.

  这项发明涉及公式（I）中的取代氮含有的双环杂环化合物，其中Z为CH2或N—R4，X、R1、R2、R4、R6、R7和n的定义如描述中所述。这类化合物适用于治疗由MDM2和/或MDM4的活性介导的疾病或疾病变体。
• Discovery of dihydroisoquinolinone derivatives as novel inhibitors of the p53–MDM2 interaction with a distinct binding mode
  作者：François Gessier、Joerg Kallen、Edgar Jacoby、Patrick Chène、Thérèse Stachyra-Valat、Stephan Ruetz、Sébastien Jeay、Philipp Holzer、Keiichi Masuya、Pascal Furet

  DOI：10.1016/j.bmcl.2015.06.058

  日期：2015.9

  Blocking the interaction between the p53 tumor suppressor and its regulatory protein MDM2 is a promising therapeutic concept under current investigation in oncology drug research. We report here the discovery of the first representatives of a new class of small molecule inhibitors of this protein-protein interaction: the dihydroisoquinolinones. Starting from an initial hit identified by virtual screening, a derivatization program has resulted in compound 11, a low nanomolar inhibitor of the p53-MDM2 interaction showing significant cellular activity. Initially based on a binding mode hypothesis, this effort was then guided by a X-ray co-crystal structure of MDM2 in complex with one of the synthesized analogs. The X-ray structure revealed an unprecedented binding mode for p53-MDM2 inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.