(R,Z)-2-(5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-5-(2-hydroxy-3-morpholin-4-ylpropyl)-3-methyl-5,6,7,8-tetrahydro-1H-pyrrolo[3,2-c]azepin-4-one L-malate | 1256377-64-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - Pyrroloazepines
• 英文名称: (R,Z)-2-(5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-5-(2-hydroxy-3-morpholin-4-ylpropyl)-3-methyl-5,6,7,8-tetrahydro-1H-pyrrolo[3,2-c]azepin-4-one L-malate
• 英文别名: (R,Z)-2-(5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-5-(2-hydroxy-3-morpholin-4-ylpropyl)-3-methyl-5,6,7,8-tetrahydro-1H-pyrrolo[3,2-c]azepin-4-one L-malic acid；2-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-5-[(2R)-2-hydroxy-3-morpholin-4-ylpropyl]-3-methyl-1,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4-one;(2S)-2-hydroxybutanedioic acid
• CAS: 1256377-64-6
• 化学式: C₄H₆O₅*C₂₅H₂₉FN₄O₄
• 分子量: 602.617
• InChiKey: YKHOVYHVWNMDHQ-NIJADAHPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.94
• 重原子数：
  43
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  193
• 氢给体数：
  6
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  3,5-二甲基-1-氢-吡咯-2-羧酸叔丁酯-4-羧酸乙酯 在 palladium 10% on activated carbon 、 三甲基铝 哌啶 、 ammonium cerium (IV) nitrate 、 硼烷 、 水 、 氢气 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 溶剂黄146 、 甲苯 为溶剂， 反应 82.66h， 生成 (R,Z)-2-(5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-5-(2-hydroxy-3-morpholin-4-ylpropyl)-3-methyl-5,6,7,8-tetrahydro-1H-pyrrolo[3,2-c]azepin-4-one L-malate
  参考文献：
  名称：

  PHARMACEUTICALLY ACCEPTABLE SALTS OF PYRROLO-NITROGENOUS HETEROCYCLIC DERIVATIVES, PREPARATION METHOD AND MEDICAL USE THEREOF

  摘要：

  本文披露了吡咯基氮杂环衍生物的药用可接受盐、制备方法及其医药用途。更具体地，公开了(R,Z)-2-(5-氟-2-氧代-1,2-二氢吲哚-3-亚甲基)-5-(2-羟基-3-吗啉基-4-基丙基)-3-甲基-5,6,7,8-四氢-1H-吡咯[3,2-c]螂啉-4-酮的药用可接受盐，其化学式为(I)，以及其作为治疗剂的制备方法和用途，特别是作为蛋白激酶抑制剂。

  公开号：

  US20120295887A1

文献信息

• Novel Potent Orally Active Multitargeted Receptor Tyrosine Kinase Inhibitors: Synthesis, Structure−Activity Relationships, and Antitumor Activities of 2-Indolinone Derivatives
  作者：Peng Cho Tang、Yi Dong Su、Jun Feng、Jian Hong Fu、Jiang Liang Yang、Lu Xiao、Jiang Hua Peng、Ya Li Li、Lei Zhang、Bing Hu、Ying Zhou、Fang Qiong Li、Bei Bei Fu、Li Guang Lou、Ai Shen Gong、Gao Hong She、Wei Hong Sun、Xian Tai Mong

  DOI：10.1021/jm101036c

  日期：2010.11.25

  The inhibition of receptor tyrosine kinases (RTKs) has become a successful approach in the development of anticancer agents. Many potent small-molecule kinase inhibitors have been discovered. We report herein a series of pyrrolo-fused-heterocycle-2-indolinone analogues as inhibitors of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR). and c-Kit. Among them, some pyrrolo-fused six- and seven-membered-heterocycle derivatives such as 9, 15, 23, and 25 are potent inhibitors of VEGFR, PDGFR, and c-Kit both enzymatically ( < 50 nM) and cellularly, ( < 50 nM). Furthermore, compounds 9 and 25 possess favorable pharmacokinetic profiles and demonstrate good efficacies against human HT-29 cell colon tumor xenografts in nude mice. Further evaluations are in progress.
• PHARMACEUTICALLY ACCEPTABLE SALTS OF PYRROLO-NITROGENOUS HETEROCYCLIC DERIVATIVES, PREPARATION METHOD AND MEDICAL USE THEREOF
  申请人：Tang Peng Cho

  公开号：US20120295887A1

  公开（公告）日：2012-11-22

  Pharmaceutically acceptable salts of pyrrolo-nitrogenous heterocyclic derivatives, preparation method and medical use thereof are disclosed. More specifically, pharmaceutically acceptable salts of (R,Z)-2-(5-fluoro-2-oxo-1,2-dihydro-indol-3-methylene)-5-(2-hydroxy-3-morpholinyl-4-yl-propyl)-3-methyl-5,6,7,8-tetrahydro-1H-pyrrolo[3,2-c]azepin-4-one presented by formula (I), the preparation method and the use thereof as therapeutic agents, especially as protein kinase inhibitors, are disclosed.

  本文披露了吡咯基氮杂环衍生物的药用可接受盐、制备方法及其医药用途。更具体地，公开了(R,Z)-2-(5-氟-2-氧代-1,2-二氢吲哚-3-亚甲基)-5-(2-羟基-3-吗啉基-4-基丙基)-3-甲基-5,6,7,8-四氢-1H-吡咯[3,2-c]螂啉-4-酮的药用可接受盐，其化学式为(I)，以及其作为治疗剂的制备方法和用途，特别是作为蛋白激酶抑制剂。