N-methyl-3-chloroindole-5-carboxaldehyde | 1245716-24-8

• 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: N-methyl-3-chloroindole-5-carboxaldehyde
• 英文别名: N-methyl-3-chloroindole-5-carbaldehyde；N-methyl-3-chloroindol-5-carbaldehyde；N-Methyl-3-chloroindol-5-carbaldehyde；3-chloro-1-methylindole-5-carbaldehyde
• CAS: 1245716-24-8
• 化学式: C₁₀H₈ClNO
• 分子量: 193.633
• InChiKey: JNRPUPDHCVYDML-UHFFFAOYSA-N

物化性质

• 沸点：
  353.2±22.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  22
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-methyl-3-chloroindole-5-carboxaldehyde 在 potassium carbonate 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 5.17h， 生成 3-Chloro-1-methyl-5-[3-methyl-5-(3,4,5-trimethoxyphenyl)imidazol-4-yl]indole;hydrochloride
  参考文献：
  名称：

  Combretastatin A-4 derived 5-(1-methyl-4-phenyl-imidazol-5-yl)indoles with superior cytotoxic and anti-vascular effects on chemoresistant cancer cells and tumors

  摘要：

  5-(1-Methyl-4-phenyl-imidazol-5-yl)indoles 5 were prepared and tested as analogs of the natural vascular-disrupting agent combretastatin A-4 (CA-4). The 3-bromo-4,5-dimethoxyphenyl derivative 5c was far more active than CA-4 with low nanomolar IC50 concentrations against multidrug-resistant KB-V1/Vb1 cervix and MCF-7/Topo mamma carcinoma cells, and also against CA-4-resistant HT-29 colon carcinoma cells. While not interfering markedly with the polymerization of tubulin in vitro, indole 5c completely disrupted the microtubule cytoskeleton of cancer cells at low concentrations. It also destroyed real blood vessels, both in the chorioallantoic membrane (CAM) of fertilized chicken eggs and within tumor xenografts in mice, without harming embryo or mouse, respectively. Indole 5c was less toxic than CA-4 to endothelial cells, fibroblasts, and cardiomyocytes. In highly vascularized xenograft tumors 5c induced distinct discolorations and histological features typical of vascular-disrupting agents, such as disrupted vessel structures, hemorrhages, and extensive necrosis. In a first preliminary therapy trial, indole 5c retarded the growth of resistant xenograft tumors in mice. (C) 2016 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.04.045
• 作为产物：
  描述：

  1-甲基-1H-吲哚-5-甲醛 在 N-氯代丁二酰亚胺 作用下， 以 乙腈 为溶剂， 反应 20.0h， 以62%的产率得到N-methyl-3-chloroindole-5-carboxaldehyde
  参考文献：
  名称：

  [EN] COMBRETASTATIN ANALOGS FOR USE IN THE TREATMENT OF CANCER
  [FR] ANALOGUES DE LA COMBRÉTASTATINE POUR UTILISATION DANS LE TRAITEMENT DU CANCER

  摘要：

  本发明涉及康柏替斯汀的特定类似物，特别是本文所描述和定义的式(I)化合物，以及包含这些化合物的药物组合物，以及它们的医疗用途，特别是在治疗或预防癌症，包括多药耐药癌症方面。

  公开号：

  WO2011138409A1

文献信息

• [EN] COMBRETASTATIN ANALOGS FOR USE IN THE TREATMENT OF CANCER<br/>[FR] ANALOGUES DE LA COMBRÉTASTATINE POUR UTILISATION DANS LE TRAITEMENT DU CANCER
  申请人：UNIV BAYREUTH

  公开号：WO2011138409A1

  公开（公告）日：2011-11-10

  The present invention relates to specific analogs of combretastatin, in particular the compounds of formula (I) as described and defined herein, and pharmaceutical compositions comprising the compounds, as well as their medical use, in particular in the treatment or prevention of cancer, including multidrug-resistant cancer.

  本发明涉及康柏替斯汀的特定类似物，特别是本文所描述和定义的式(I)化合物，以及包含这些化合物的药物组合物，以及它们的医疗用途，特别是在治疗或预防癌症，包括多药耐药癌症方面。
• COMBRETASTATIN ANALOGS FOR USE IN THE TREATMENT OF CANCER
  申请人：Schobert Rainer

  公开号：US20130137740A1

  公开（公告）日：2013-05-30

  The present invention relates to specific analogs of combretastatin, in particular the compounds of formula (I) as described and defined herein, and pharmaceutical compositions comprising the compounds, as well as their medical use, in particular in the treatment or prevention of cancer, including multidrug-resistant cancer.

  本发明涉及康布雷塔斯汀的特定类似物，特别是公式（I）中所描述和定义的化合物，以及包含这些化合物的药物组成物，以及它们的医疗用途，特别是在治疗或预防癌症，包括多药耐药性癌症方面的应用。
• Combretastatin analogs for use in the treatment of cancer
  申请人：Schobert Rainer

  公开号：US08980933B2

  公开（公告）日：2015-03-17

  The present invention relates to specific analogs of combretastatin, in particular the compounds of formula (I) as described and defined herein, and pharmaceutical compositions comprising the compounds, as well as their medical use, in particular in the treatment or prevention of cancer, including multidrug-resistant cancer.

  本发明涉及柯布雷他汀的特定类似物，特别是公式(I)中所描述和定义的化合物，以及包含这些化合物的药物组合物，以及它们的医疗用途，特别是在治疗或预防癌症，包括多药耐药癌症方面的应用。
• US8980933B2
  申请人：——

  公开号：US8980933B2

  公开（公告）日：2015-03-17
• 4-(3-Halo/amino-4,5-dimethoxyphenyl)-5-aryloxazoles and -<i>N</i>-methylimidazoles That Are Cytotoxic against Combretastatin A Resistant Tumor Cells and Vascular Disrupting in a Cisplatin Resistant Germ Cell Tumor Model
  作者：Rainer Schobert、Bernhard Biersack、Andrea Dietrich、Katharina Effenberger、Sebastian Knauer、Thomas Mueller

  DOI：10.1021/jm100345r

  日期：2010.9.23

  New combretastatin A analogues featuring oxazole or N-methylimidazole bridged Z-alkenes and haloor amino-substituted A-rings were tested against various cancer cell lines and in testicular germ cell tumor xenografts in mice. Imidazoles with 3-halo-4,5-dimethoxy substituted A-rings and 3-amino-4-methoxy substituted B-rings (7b and 8b) were efficacious at nanomolar concentrations against cells of combretastatin A refractory HT-29 colon carcinoma, multidrug-resistant MCF-7/Topo breast carcinoma, and cisplatin-resistant 1411 HP testicular germ cell tumor. They induced apoptosis and inhibited tubulin polymerization. While well tolerated by mice at high doses, these imidazoles initiated extensive intratumoral hemorrhage and regressions of highly vascularized 1411 HP xenografts.