N,N-Diethyl-9-methoxy-2H-[1]benzothiopyrano[4,3,2-cd]indazole-2-ethanamine | 179632-46-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 硫色烯
• 英文名称: N,N-Diethyl-9-methoxy-2H-[1]benzothiopyrano[4,3,2-cd]indazole-2-ethanamine
• 英文别名: N,N-diethyl-2-(4-methoxy-8-thia-14,15-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-1(15),2(7),3,5,9,11,13(16)-heptaen-14-yl)ethanamine
• CAS: 179632-46-3
• 化学式: C₂₀H₂₃N₃OS
• 分子量: 353.488
• InChiKey: VMMWNGXJXOPHJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  55.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N,N-Diethyl-9-methoxy-2H-[1]benzothiopyrano[4,3,2-cd]indazole-2-ethanamine 在 sodium hydroxide 、 甲酸 、 三乙胺 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 28.0h， 生成 methyl N-[[14-[2-(diethylamino)ethyl]-4-methoxy-8-thia-14,15-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-1(15),2(7),3,5,9,11,13(16)-heptaen-10-yl]methyl]carbamate
  参考文献：
  名称：

  Synthesis and Antitumor Activity of 4-Aminomethylthioxanthenone and 5-Aminomethylbenzothiopyranoindazole Derivatives

  摘要：

  Two new series of antitumor agents, 4-aminomethylthioxanthenones (6-50) and 5-aminomethylbenzothiopyranoindazoles (51-61), are described and compared. Nearly all members of both series display excellent in vivo activity versus murine pancreatic adenocarcinoma 03 (Panc03) although there is little to distinguish the two series from each other. In both series there is no discernible relationship between structure and in vivo efficacy. Selected analogues were evaluated in vitro; all were observed to have moderate to strong DNA binding via intercalation. However, varying degrees of in vitro P388 cytotoxicity and topoisomerase II inhibition were seen. In general, those molecules which exhibited strong topoisomerase II inhibition were significantly more cytotoxic than those which did not. In both series, those derivatives (48-50, 60, and 61) having a phenolic hydroxy substitution exhibited the most potent P388 cytotoxicity and topoisomerase II inhibition.

  DOI：

  10.1021/jm9708083
• 作为产物：
  描述：

  3-chloro-7-methoxy-thioxanthen-9-one 以39%的产率得到N,N-Diethyl-9-methoxy-2H-[1]benzothiopyrano[4,3,2-cd]indazole-2-ethanamine
  参考文献：
  名称：

  Benzothiopyranoindazole antitumor agents

  摘要：

  揭示了作为抗肿瘤剂的新型2H-[1]苯并硫杂吡喃并[4,3,2-cd]吲哚酮。还揭示了含有苯并硫杂吡喃并吲哚酮的组合物以及使用苯并硫杂吡喃并吲哚酮治疗哺乳动物肿瘤和癌症的方法。

  公开号：

  US05532263A1

文献信息

• Cyclic variations of SR 233377 (WIN 33377) and effects on antitumor activity
  作者：Mark P. Wentland、Robert B. Perni、Jianhua I. Huang、Ronald G. Powles、Suzanne C. Aldous、Kristina M. Klingbeil、A. Danielle Peverly、Ronald G. Robinson、Thomas H. Corbett、Julie L. Jones、James B. Rake、Susan A. Coughlin

  DOI：10.1016/0960-894x(96)00230-2

  日期：1996.6

  Novel derivatives of SR 233377 (1, WIN 33377) where a pyrazolo ring fusion has been incorporated at the 1- and 9-positions of the thioxanthone ring displayed outstanding in vivo efficacy against the murine solid tumor Pane 03 (T/C values of 0% with log cell kill greater than or equal to 2.0). No relationship between structure and Pane 03 activity was observed because all analogues studied were highly active. Copyright (C) 1996 Elsevier Science Ltd
• BENZOTHIOPYRANOINDAZOLES ANTITUMOR AGENTS
  申请人：SANOFI WINTHROP, INC.

  公开号：EP0812192A1

  公开（公告）日：1997-12-17
• EP0812192A4
  申请人：——

  公开号：EP0812192A4

  公开（公告）日：2000-03-08
• US5532263A
  申请人：——

  公开号：US5532263A

  公开（公告）日：1996-07-02
• [EN] BENZOTHIOPYRANOINDAZOLES ANTITUMOR AGENTS<br/>[FR] BENZOTHIOPYRANOINDAZOLES COMME AGENTS ANTITUMEUR
  申请人：SANOFI WINTHROP, INC.

  公开号：WO1996026723A1

  公开（公告）日：1996-09-06

  (EN) Novel 2H-[1]benzothiopyrano[4,3,2-cd]indazoles are disclosed as antitumor agents. Compositions containing the benzothiopyranoindazoles and methods of treating tumors and cancer in mammals with benzothiopyranoindazoles are also disclosed.(FR) L'invention concerne de nouveaux 2H-[1]benzothiopyrano[4,3,2-cd]indazoles comme agents antitumeur, ainsi que des compositions contenant ces benzothiopyranoindazoles et des procédés pour traiter des tumeurs et des cancers chez des animaux avec ces benzothiopyranoindazoles.