6-acetylindolin-2-one | 893399-25-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 6-acetylindolin-2-one
• 英文别名: 6-acetyl-1,3-dihydroindol-2-one
• CAS: 893399-25-2
• 化学式: C₁₀H₉NO₂
• 分子量: 175.187
• InChiKey: HCQVZFJJGMUCLV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-acetylindolin-2-one 、 乙酸酐 反应 7.0h， 生成 1,6-diacetylindolin-2-one
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Indolinones as Triple Angiokinase Inhibitors and the Discovery of a Highly Specific 6-Methoxycarbonyl-Substituted Indolinone (BIBF 1120)

  摘要：

  Inhibition of tumor angiogenesis through blockade of the vascular endothelial growth factor (VEGF) signaling pathway is a new treatment modality in oncology. Preclinical findings suggest that blockade of additional pro-angiogenic kinases, such as Fibroblast and platelet-derived growth factor receptors (FGFR and PDGFR), may improve the efficacy of pharmacological cancer treatment. Indolinones substituted in position 6 were identified as selective inhibitors of VEGF-, PDGF-, and FGF-receptor kinases. In particular, 6-methoxycarbonyl-substituted indolinones showed a highly favorable selectivity profile. Optimization identified potent inhibitors of VEGF-related endothelial cell proliferation with additional efficacy on pericyctes and smooth muscle cells. In contrast, no direct inhibition of tumor cell proliferation was observed. Compounds 2 (BIBF 1000) and 3 (BIBF 1120) are orally available and display encouraging efficacy in in vivo tumor models while being well tolerated. The triple angiokinase inhibitor 3 is currently in phase III clinical trials for the treatment of nonsmall cell lung cancer.

  DOI：

  10.1021/jm900431g
• 作为产物：
  描述：

  [2-amino-4-(2-methyl-[1,3]dioxolan-2-yl)phenyl]acetic acid tert-butyl ester 在 盐酸 、 水 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以84%的产率得到6-acetylindolin-2-one
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Indolinones as Triple Angiokinase Inhibitors and the Discovery of a Highly Specific 6-Methoxycarbonyl-Substituted Indolinone (BIBF 1120)

  摘要：

  Inhibition of tumor angiogenesis through blockade of the vascular endothelial growth factor (VEGF) signaling pathway is a new treatment modality in oncology. Preclinical findings suggest that blockade of additional pro-angiogenic kinases, such as Fibroblast and platelet-derived growth factor receptors (FGFR and PDGFR), may improve the efficacy of pharmacological cancer treatment. Indolinones substituted in position 6 were identified as selective inhibitors of VEGF-, PDGF-, and FGF-receptor kinases. In particular, 6-methoxycarbonyl-substituted indolinones showed a highly favorable selectivity profile. Optimization identified potent inhibitors of VEGF-related endothelial cell proliferation with additional efficacy on pericyctes and smooth muscle cells. In contrast, no direct inhibition of tumor cell proliferation was observed. Compounds 2 (BIBF 1000) and 3 (BIBF 1120) are orally available and display encouraging efficacy in in vivo tumor models while being well tolerated. The triple angiokinase inhibitor 3 is currently in phase III clinical trials for the treatment of nonsmall cell lung cancer.

  DOI：

  10.1021/jm900431g

文献信息

• WO2006/64044
  申请人：——

  公开号：——

  公开（公告）日：——
• INDOLINONES AND THEIR USE AS ANTIPROLIFERATIVE AGENTS
  申请人：McConnell Darryl

  公开号：US20070088051A1

  公开（公告）日：2007-04-19

  The invention relates to indolinone compounds of formula (I), wherein Y and R 1 to R 8 are defined as in claim 1, which are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation and the use thereof for preparing a pharmaceutical composition.
• Design, Synthesis, and Evaluation of Indolinones as Triple Angiokinase Inhibitors and the Discovery of a Highly Specific 6-Methoxycarbonyl-Substituted Indolinone (BIBF 1120)
  作者：Gerald J. Roth、Armin Heckel、Florian Colbatzky、Sandra Handschuh、Jörg Kley、Thorsten Lehmann-Lintz、Ralf Lotz、Ulrike Tontsch-Grunt、Rainer Walter、Frank Hilberg

  DOI：10.1021/jm900431g

  日期：2009.7.23

  Inhibition of tumor angiogenesis through blockade of the vascular endothelial growth factor (VEGF) signaling pathway is a new treatment modality in oncology. Preclinical findings suggest that blockade of additional pro-angiogenic kinases, such as Fibroblast and platelet-derived growth factor receptors (FGFR and PDGFR), may improve the efficacy of pharmacological cancer treatment. Indolinones substituted in position 6 were identified as selective inhibitors of VEGF-, PDGF-, and FGF-receptor kinases. In particular, 6-methoxycarbonyl-substituted indolinones showed a highly favorable selectivity profile. Optimization identified potent inhibitors of VEGF-related endothelial cell proliferation with additional efficacy on pericyctes and smooth muscle cells. In contrast, no direct inhibition of tumor cell proliferation was observed. Compounds 2 (BIBF 1000) and 3 (BIBF 1120) are orally available and display encouraging efficacy in in vivo tumor models while being well tolerated. The triple angiokinase inhibitor 3 is currently in phase III clinical trials for the treatment of nonsmall cell lung cancer.