(6-methoxy-1H-indazol-3-yl)-(3,4,5-trimethoxyphenyl)methanone | 889134-30-9

• 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: (6-methoxy-1H-indazol-3-yl)-(3,4,5-trimethoxyphenyl)methanone
• 英文别名: (6-methoxy-1H-indazol-3-yl)-(3,4,5-trimethoxy-phenyl)-methanone；(6-methoxy-1H-indazol-3-yl)(3,4,5-trimethoxyphenyl)methanone
• CAS: 889134-30-9
• 化学式: C₁₈H₁₈N₂O₅
• 分子量: 342.351
• InChiKey: MJBZIPZVQFVULA-UHFFFAOYSA-N

物化性质

• 熔点：
  188.3-188.5 °C
• 沸点：
  564.9±50.0 °C(Predicted)
• 密度：
  1.271±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  82.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (6-methoxy-1H-indazol-3-yl)-(3,4,5-trimethoxyphenyl)methanone 在 N-碘代丁二酰亚胺 、 溶剂黄146 作用下， 反应 2.0h， 以85%的产率得到(7-iodo-6-methoxy-1H-indazol-3-yl)(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  Potent Antitubulin Tumor Cell Cytotoxins Based on 3-Aroyl Indazoles

  摘要：

  A series of 3-aroyl indazoles was synthesized. Modification of the C-7 position resulted in a significant structure-activity relationship (SAR) with acetylene modifications conferring unusual potency in a tumor cell cytotoxicity assay. The most potent compounds exceeded the activity of combretastatin A4 (CA-4), showing single digit nM IC50 values against all cell lines tested including those with known efflux resistance pumps. The inhibition of in vitro tubulin polymerization was comparable to CA-4, consistent with tubulin being the target for these compounds. Competition binding experiments employing [H-3]colchicine and purified tubulins demonstrated that the compound specifically binds to the colchicine site.

  DOI：

  10.1021/jm061348t
• 作为产物：
  描述：

  4-碘基-3-硝基苯甲醚 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 盐酸 、 铁粉 、 三乙胺 、 sodium nitrite 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 5.5h， 生成 (6-methoxy-1H-indazol-3-yl)-(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  Potent Antitubulin Tumor Cell Cytotoxins Based on 3-Aroyl Indazoles

  摘要：

  A series of 3-aroyl indazoles was synthesized. Modification of the C-7 position resulted in a significant structure-activity relationship (SAR) with acetylene modifications conferring unusual potency in a tumor cell cytotoxicity assay. The most potent compounds exceeded the activity of combretastatin A4 (CA-4), showing single digit nM IC50 values against all cell lines tested including those with known efflux resistance pumps. The inhibition of in vitro tubulin polymerization was comparable to CA-4, consistent with tubulin being the target for these compounds. Competition binding experiments employing [H-3]colchicine and purified tubulins demonstrated that the compound specifically binds to the colchicine site.

  DOI：

  10.1021/jm061348t

文献信息

• Scaffold-Hopping Strategy: Synthesis and Biological Evaluation of 5,6-Fused Bicyclic Heteroaromatics To Identify Orally Bioavailable Anticancer Agents
  作者：Yen-Shih Tung、Mohane Selvaraj Coumar、Yu-Shan Wu、Hui-Yi Shiao、Jang-Yang Chang、Jing-Ping Liou、Paritosh Shukla、Chun-Wei Chang、Chi-Yen Chang、Ching-Chuan Kuo、Teng-Kuang Yeh、Chin-Yu Lin、Jian-Sung Wu、Su-Ying Wu、Chun-Chen Liao、Hsing-Pang Hsieh

  DOI：10.1021/jm101027s

  日期：2011.4.28

  Utilizing scaffold-hopping drug-design strategy, we sought to identify a backup drug candidate for BPR0L075 (1), an indole-based anticancer agent. For this purpose, 5,6-fused bicyclic heteroaromatic scaffolds were designed and synthesized through shuffling of the nitrogen from the N-1 position or by insertion of one or two nitrogen atoms into the indole core of 1. Among these, 7-azaindole core 12 showed potent in vitro anticancer activity and improved oral bioavailability (F = 35%) compared with 1 (F < 10%).
• WO2006/57946
  申请人：——

  公开号：——

  公开（公告）日：——
• Tubulin Binding Anti Cancer Agents And Prodrugs Thereof
  申请人：Matteucci Mark

  公开号：US20090042820A1

  公开（公告）日：2009-02-12

  Novel tubulin binding compounds and hypoxia activated prodrugs of novel and known tubulin binding compounds useful for treating cancer and other hyperproliferative diseases are disclosed.
• US7456289B2
  申请人：——

  公开号：US7456289B2

  公开（公告）日：2008-11-25
• [EN] TUBULIN BINDING ANTI CANCER COMPOUNDS AND PRODRUGS THEREOF<br/>[FR] COMPOSÉS ANTI-CANCÉREUX DE LIAISON À LA TUBULINE ET PROMÉDICAMENTS À BASE DE TELS COMPOSÉS
  申请人：THRESHOLD PHARMACEUTICALS INC

  公开号：WO2007137196A2

  公开（公告）日：2007-11-29

  [EN] Novel tublin binding compuunds and hypoxia activated prodrugs of novel and known tubulin binding compounds are useful for treating cancer and other hyperproliferative diseases.
  [FR] La présente invention concerne de nouveaux composés de liaison à la tubuline et de promédicaments activés par l'hypoxie de composés à base de nouveaux et connus de liaison à la tubuline utiles pour traiter le cancer et d'autres maladies hyperproliférantes.