[4-(2-methyl-[1,3]dioxolan-2-yl)-2-nitrophenyl]acetic acid tert-butyl ester | 893399-11-6

• 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-(2-methyl-[1,3]dioxolan-2-yl)-2-nitrophenyl]acetic acid tert-butyl ester
• 英文别名: Tert-butyl 2-[4-(2-methyl-1,3-dioxolan-2-yl)-2-nitrophenyl]acetate
• CAS: 893399-11-6
• 化学式: C₁₆H₂₁NO₆
• 分子量: 323.346
• InChiKey: ZMGFVHASRJOCCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  90.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [4-(2-methyl-[1,3]dioxolan-2-yl)-2-nitrophenyl]acetic acid tert-butyl ester 在 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、344.75 kPa 条件下， 反应 4.5h， 以92%的产率得到[2-amino-4-(2-methyl-[1,3]dioxolan-2-yl)phenyl]acetic acid tert-butyl ester
  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-甲基-2-(3-硝基苯基)-1,3-二噁戊环 、 氯乙酸叔丁酯 在 potassium tert-butylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成 [4-(2-methyl-[1,3]dioxolan-2-yl)-2-nitrophenyl]acetic acid tert-butyl ester
  参考文献：
  名称：

  WO2006/64044

  摘要：

  公开号：

文献信息

• WO2006/64044
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.