1-cyclopropyl-6,8-dimethyl-7-methoxy-4-oxo-1,5-dihydro-4H-pyrido[3',2':4,5]thieno[3,2-b]indole-3-carboxylic acid | 1307863-58-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡啶类
• 英文名称: 1-cyclopropyl-6,8-dimethyl-7-methoxy-4-oxo-1,5-dihydro-4H-pyrido[3',2':4,5]thieno[3,2-b]indole-3-carboxylic acid
• 英文别名: 6-Cyclopropyl-13-methoxy-12,14-dimethyl-3-oxo-8-thia-6,16-diazatetracyclo[7.7.0.02,7.010,15]hexadeca-1(9),2(7),4,10(15),11,13-hexaene-4-carboxylic acid
• CAS: 1307863-58-6
• 化学式: C₂₀H₁₈N₂O₄S
• 分子量: 382.44
• InChiKey: LMSWOQIBAAPWOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  ethyl 2-chloro-7-cyclopropyl-3-nitro-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylate 在 盐酸 、 水 、 palladium diacetate 、 cesium fluoride 、 亚磷酸三乙酯 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.75h， 生成 1-cyclopropyl-6,8-dimethyl-7-methoxy-4-oxo-1,5-dihydro-4H-pyrido[3',2':4,5]thieno[3,2-b]indole-3-carboxylic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of tetracyclic thienopyridones as antibacterial and antitumor agents

  摘要：

  A facile synthesis of model 4-oxopyrido[3',2':4,5]thieno[3,2-b]indole-3-carboxylic acids 9a-e was achieved via Stille arylation of 2-chloro-3-nitro-4-oxothieno[2,3-b]pyridine-5-carboxylate and a subsequent microwave-assisted phosphite-mediated Cadogan reaction. The new compounds were tested for their in vitro antimicrobial and antiproliferative activity. Compounds 9a-c and 9e exhibited very high potency against Gram positive Bacillus subtilis and Bacillus megaterium at concentrations 0.000015-0.007 mu g/mL. They also displayed excellent activity towards other Gram positive bacilli and staphylococci and Gram negative Haemophilus influenzae, being in most cases superior or equal to commercial fluoroquinolones. Both 9a and 9c were inhibitors of the DNA gyrase activity. As concerns antitumor properties, compounds 9b-e showed growth inhibition of MCF-7 breast tumor and A549 non-small cell lung cancer cells with IC50 1.6-2.8 mu M and 2.6-6.9 mu M, respectively, coupled with absence of cytotoxicity towards normal cells. These compounds are promising as dual acting chemotherapeutics. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.03.018

文献信息

• Synthesis and biological evaluation of tetracyclic thienopyridones as antibacterial and antitumor agents
  作者：Salah A. Al-Trawneh、Mustafa M. El-Abadelah、Jalal A. Zahra、Samir A. Al-Taweel、Franca Zani、Matteo Incerti、Andrea Cavazzoni、Paola Vicini

  DOI：10.1016/j.bmc.2011.03.018

  日期：2011.4

  A facile synthesis of model 4-oxopyrido[3',2':4,5]thieno[3,2-b]indole-3-carboxylic acids 9a-e was achieved via Stille arylation of 2-chloro-3-nitro-4-oxothieno[2,3-b]pyridine-5-carboxylate and a subsequent microwave-assisted phosphite-mediated Cadogan reaction. The new compounds were tested for their in vitro antimicrobial and antiproliferative activity. Compounds 9a-c and 9e exhibited very high potency against Gram positive Bacillus subtilis and Bacillus megaterium at concentrations 0.000015-0.007 mu g/mL. They also displayed excellent activity towards other Gram positive bacilli and staphylococci and Gram negative Haemophilus influenzae, being in most cases superior or equal to commercial fluoroquinolones. Both 9a and 9c were inhibitors of the DNA gyrase activity. As concerns antitumor properties, compounds 9b-e showed growth inhibition of MCF-7 breast tumor and A549 non-small cell lung cancer cells with IC50 1.6-2.8 mu M and 2.6-6.9 mu M, respectively, coupled with absence of cytotoxicity towards normal cells. These compounds are promising as dual acting chemotherapeutics. (C) 2011 Elsevier Ltd. All rights reserved.