(Z)-3-(phenyl(4-(piperidin-1-ylmethyl)phenylamino)methylene)-indolin-2-one | 263337-30-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (Z)-3-(phenyl(4-(piperidin-1-ylmethyl)phenylamino)methylene)-indolin-2-one
• 英文别名: (Z)-3-{phenyl[(4-(piperidin-1-ylmethyl)phenyl)amino]-methylidene}-1,3-dihydro-2H-indolin-2-one；(Z)-3-[phenyl-(4-(piperidin-1-ylmethyl)phenylamino)methylene]-2-oxo-2,3-dihydro-1H-indole；(3Z)-3-[phenyl-[4-(piperidin-1-ylmethyl)anilino]methylidene]-1H-indol-2-one
• CAS: 263337-30-0
• 化学式: C₂₇H₂₇N₃O
• 分子量: 409.531
• InChiKey: VBVJQGOFYMMHKC-QPLCGJKRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.61
• 重原子数：
  31.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  44.37
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  4-(1-哌啶基甲基)苯胺 在 盐酸 、 P4S10-pyridine complex 、 三乙胺 作用下， 以 吡啶 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.67h， 生成 (Z)-3-(phenyl(4-(piperidin-1-ylmethyl)phenylamino)methylene)-indolin-2-one
  参考文献：
  名称：

  使用 Eschenmoser 偶联反应合成激酶抑制剂尼达尼布、橙皮苷及其类似物

  摘要：

  一种新的合成方法，包括取代的 3-溴代吲哚（H, 6-Cl, 6-COOMe, 5-NO 2）与两个取代的硫代苯甲酰胺在二甲基甲酰胺或乙腈中的 Eschenmoser 偶联反应，用于合成八种激酶抑制剂，包括尼达尼布和橙皮苷的产率超过 76%。用于合成的起始化合物也很容易以良好的收率获得。3-溴吲哚是通过三步合成法从相应的靛红制备的，平均总产率为 65%，或者通过羟吲哚的直接溴化（产率为 65-86%）。起始N- (4-哌啶-1-基甲基-苯基)-硫代苯甲酰胺通过相应的苯甲酰苯胺以 86% 的收率和N-甲基-N-(4-硫代苯甲酰氨基苯基)-2-(4-甲基哌嗪-1-基)乙酰胺通过相应苯胺与二硫代苯甲酸甲酯的硫代酰化以86%的产率制备。

  DOI：

  10.1021/acs.joc.1c01269

文献信息

• Repurposing human Aurora kinase inhibitors as leads for anti-protozoan drug discovery
  作者：Gautam Patel、Norma E. Roncal、Patricia J. Lee、Susan E. Leed、Jessey Erath、Ana Rodriguez、Richard J. Sciotti、Michael P. Pollastri

  DOI：10.1039/c4md00045e

  日期：——

  Hesperadin, an established human Aurora B inhibitor, was tested against cultures of Trypanosoma brucei, Leishmania major, and Plasmodium falciparum, and was identified to be a potent proliferation inhibitor.

  Hesperadin，一种已知的人类极光B抑制剂，被测试用于Trypanosoma brucei、Leishmania major和Plasmodium falciparum的培养物中，被确认为一种有效的增殖抑制剂。
• Novel substituted indolines with an inhibitory effect on various kinases and complexes of CDKs
  申请人：Boehringer Ingelheim Pharma KG

  公开号：US20040058978A1

  公开（公告）日：2004-03-25

  The present invention relates to new substituted indolinones of general formula 1 wherein X and R 1 to R 5 are defined as in claim 1, the isomers and the salts thereof which have valuable properties. The above compounds of general formula I wherein R 1 denotes a hydrogen atom, a C 1-3 -alkyl group or a prodrug group have valuable pharmacological properties, particularly an inhibiting effect on various kinases, on viral cyclin and on receptor tyrosine kinases, and the other compounds of the above general formula I wherein R 1 does not represent a hydrogen atom, a C 1-3 -alkyl group or a prodrug group are valuable intermediate products for the preparation of the abovementioned compounds.

  本发明涉及一种新的通式1的取代吲哚酮，其中X和R1至R5的定义如权利要求书1中所述，其异构体和盐具有有价值的性质。通式I中的上述化合物，其中R1表示氢原子，C1-3-烷基或前药基，具有有价值的药理学性质，特别是对多种激酶、病毒细胞周期蛋白和受体酪氨酸激酶具有抑制作用，上述通式I中R1不表示氢原子、C1-3-烷基或前药基的其他化合物是制备上述化合物的有价值中间体。
• 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.
• NEUE SUBSTITUIERTE INDOLINONE MIT EINER INHIBIERENDEN WIRKUNG AUF VERSCHIEDENE KINASEN UND CYCLIN/CDK-KOMPLEXE
  申请人：Boehringer Ingelheim Pharma GmbH & Co.KG

  公开号：EP1115704B1

  公开（公告）日：2003-06-18
• US6855710B2
  申请人：——

  公开号：US6855710B2

  公开（公告）日：2005-02-15