3-para-methoxyphenyl-8H-thieno<2,3-b>pyrrolizin-8-one | 156274-19-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-para-methoxyphenyl-8H-thieno<2,3-b>pyrrolizin-8-one
• 英文别名: 3-(4-methoxyphenyl)thieno[2,3-b]pyrrolizin-8-one；NSC 676693；3-(4-Methoxyphenyl)-8H-thieno[2,3-b]pyrrolizin-8-one
• CAS: 156274-19-0
• 化学式: C₁₆H₁₁NO₂S
• 分子量: 281.335
• InChiKey: STBQKICVQXGVLM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  59.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-para-methoxyphenyl-8H-thieno<2,3-b>pyrrolizin-8-one 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以88%的产率得到3-(4-Hydroxyphenyl)thieno[2,3-b]pyrrolizin-8-one
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Novel Thienopyrrolizinones as Antitubulin Agents

  摘要：

  Herein, we describe the structure-activity relationship study of a new 3-aryl-8H-thieno[2,3-b]pyrrolizin-8-one series of antitubulin agents. The pharmacological results from the National Cancer Institute in vitro human disease oriented tumor cell line screening allowed us to identify compound 1d (NSC 676693) as a very efficient antitumoral drug in all cancer cell lines tested. This prompted us to define the structural requirements essential for this antiproliferative activity. Among all analogues synthesized in this study, compound 1o was the most promising, being 10-fold more potent than compound 1d. Its activity over a panel of nine tumoral cell lines was in the nanomolar range for all of the histological types tested, and surprisingly, the resistant KB-A1 cell line was also sensitive to this compound. Moreover, a flow cytometric study showed that L1210 cells treated by the most potent compounds were arrested in the G(2)/M phases of the cell cycle with a significant percentage of cells having reinitiated a cycle of DNA synthesis without cell division. This interesting pharmacological profile, resulting from inhibition of tubulin polymerization, encouraged us to perform preliminary in vivo studies that led to a new prodrug chemical approach.

  DOI：

  10.1021/jm030961z
• 作为产物：
  描述：

  对甲氧基苯乙腈 在 4-氯吡啶盐酸盐 、 sodium hydride 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-para-methoxyphenyl-8H-thieno<2,3-b>pyrrolizin-8-one
  参考文献：
  名称：

  Design, synthesis and antiproliferative activity of tripentones: A new series of antitubulin agents

  摘要：

  Structure-activity relationship studies of a new series of tripentones (thieno[2.3-h]pyrrolizin-8-ones), led us to prepare several derivatives with antiproliferative activities. The most promising 3-(3-hydroxy-4-methoxyphenyl)thieno[2.3-b]pyrrolizin-8-one 20 (leukemia L1210. IC50= 15 nM) was shown to be a potent inhibitor of tubulin polymerization. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00403-6

文献信息

• 8H-thieno-[2,3-b]pyrrolizin-8-one compounds
  申请人：Adir et Compagnie

  公开号：US06071945A1

  公开（公告）日：2000-06-06

  A compound selected from those of formula (I): ##STR1## wherein: R.sub.1 represents hydrogen, halogen, alkyl, nitro, hydroxy, alkoxy, trihaloalkyl, trihaloalkoxy or optionally substituted amino, R.sub.2 represents optionally substituted aryl or heteroaryl, R.sub.3 represents hydrogen, halogen, alkyl, nitro, hydroxy, alkoxy, trihaloalkyl, trihaloalkoxy or optionally substituted amino, their isomers and addition pharmaceutically-acceptable acid or base salts thereof and medicinal products containing the same are useful in the treatment of cancer.

  从公式（I）中选择的化合物：##STR1## 其中： R.sub.1代表氢，卤素，烷基，硝基，羟基，烷氧基，三卤代烷基，三卤代烷氧基或可选择取代的氨基，R.sub.2代表可选择取代的芳基或杂环基，R.sub.3代表氢，卤素，烷基，硝基，羟基，烷氧基，三卤代烷基，三卤代烷氧基或可选择取代的氨基，它们的异构体和相应的药学上可接受的酸或碱盐以及含有它们的药物制剂在癌症治疗中有用。
• Hydrogenative desulphurization of thienopyrrolizinones: An easy and selective access to (Z)-phenethylidenepyrrolizinones with in vitro cytotoxic activity
  作者：Vittoria Perri、Christophe Rochais、Jana Sopkova-de Oliveira Santos、Rémi Legay、Thierry Cresteil、Patrick Dallemagne、Sylvain Rault

  DOI：10.1016/j.ejmech.2009.12.021

  日期：2010.3

  Attempts in view to dearomatize some previously reported tripentones with potent antineoplastic activities led in thiophene series to an unexpected hydrogenative desulphurization reaction. The resulting (Z)-phenethylidenepyrrolizinones were tested in vitro over human epidermoid carcinoma KB cell line. The results of this biological evaluation indicated that the tricyclic core of our model can be cleaved with a partial respect of the activity. (C) 2009 Published by Elsevier Masson SAS.
• Lancelot, Jean-Charles; Letois, Bertrand; Rault, Sylvain, Journal of Heterocyclic Chemistry, 1994, vol. 31, # 2, p. 501 - 504
  作者：Lancelot, Jean-Charles、Letois, Bertrand、Rault, Sylvain、Robba, Max、Rogosca, Maria

  DOI：——

  日期：——
• Dérivés de 8H-(2,3-b)-pyrrolizine-8-one, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent
  申请人：LES LABORATOIRES SERVIER

  公开号：EP0982308B1

  公开（公告）日：2003-02-26
• ANTIANGIOGENIC SMALL MOLECULES AND METHODS OF USE
  申请人：Zudaire Enrique

  公开号：US20120129775A1

  公开（公告）日：2012-05-24

  Methods of inhibiting undesired angiogenesis are provided, which methods include administering to a subject a therapeutically effective amount of at least one of the compounds described herein, or a pharmaceutically acceptable salt thereof.