1-(8-chloro-10,11-dihydrodibenzo[b,f]thiepin-10-yl)piperazine | 23048-89-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫平类
• 英文名称: 1-(8-chloro-10,11-dihydrodibenzo[b,f]thiepin-10-yl)piperazine
• 英文别名: 1-(8-chloro-10,11-dihydro-dibenzo[b,f]thiepin-10-yl)-piperazine；Noroctoclothepin；1-(3-chloro-5,6-dihydrobenzo[b][1]benzothiepin-5-yl)piperazine
• CAS: 23048-89-7
• 化学式: C₁₈H₁₉ClN₂S
• 分子量: 330.881
• InChiKey: YITAORWEHMMACD-UHFFFAOYSA-N

物化性质

• 沸点：
  441.4±45.0 °C(Predicted)
• 密度：
  1.260±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  40.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(8-chloro-10,11-dihydrodibenzo[b,f]thiepin-10-yl)piperazine 在 盐酸 、 lithium aluminium tetrahydride 、 sodium nitrite 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 0.25h， 生成 2-[4-[[4-(3-chloro-5,6-dihydrobenzo[b][1]benzothiepin-5-yl)piperazin-1-yl]iminomethyl]-2-ethoxyphenoxy]-N,N-dimethylethanamine
  参考文献：
  名称：

  Potential anticonvulsants: Substituted N-benzylidene derivatives of 10-(4-aminopiperazino)-10,11-dihydrodibenzo[b,f]thiepins

  摘要：

  10-(4-氨基哌嗪基)-10,11-二氢二苯并[b,f]噻吩 XIVa-XIVd 与苯甲醛、3,4-二甲氧基苯甲醛、4-二甲基氨基苯甲醛、水杨醛、3-乙氧基-4-羟基苯甲醛、2-(2-二甲基氨基乙氧基)苯甲醛、3-(2-二甲基氨基乙氧基)苯甲醛和3-乙氧基-4-(2-二甲基氨基乙氧基)苯甲醛的反应得到一系列19种缩酮 IIIa-Xc。其中一些显示出预期的抗惊厥效果，但仅对戊四氮唑有效；未观察到最大电击惊厥的拮抗作用。总体上，这些产物具有镇静剂的特性：在较高剂量下，它们产生中枢抑制作用，增强硫喷妥睡眠时间，具有降温作用；在个别情况下观察到抗苯丙胺、抗利血平、抗组胺和猝固效应。经肌肉注射的这些碱性缩酮的水溶性盐 VIIIa, VIIIc, IXc 和 Xc 显示出相当高的急性毒性，并且还显示出肾上腺抑制和降压活性。

  DOI：

  10.1135/cccc19831173
• 作为产物：
  描述：

  2(4-氯苯硫基)苯乙酸 在 titanium(IV) isopropylate 、 sodium tetrahydroborate 、 四磷十氧化物 、 三氟乙酸 作用下， 以 二氯甲烷 、 溶剂黄146 、 甲苯 为溶剂， 反应 48.0h， 生成 1-(8-chloro-10,11-dihydrodibenzo[b,f]thiepin-10-yl)piperazine
  参考文献：
  名称：

  Overcoming chloroquine resistance in malaria: Design, synthesis and structure–activity relationships of novel chemoreversal agents

  摘要：

  Malaria remains a significant infectious disease with even artemisinin-based therapies now facing resistance in the field. Development of new therapies is urgently needed, either by finding new compounds with unique modes of action, or by reversing resistance towards known drugs with 'chemosensitizers' or 'chemoreversal' agents (CRA). Concerning the latter, we have focused on the resistance mechanisms developed against chloroquine (CQ). We have synthesized a series of compounds related to previously identified CRAs, and found promising novel compounds. These compounds show encouraging results in a coumarin labeled chloroquine uptake assay, exhibiting a dose response in resensitising parasites to the antimalarial effects of chloroquine. Selected compounds show consistent potency across a panel of chloroquine and artemisinin sensitive and resistant parasites, and a wide therapeutic window. This data supports further study of CRAs in the treatment of malaria and, ultimately, their use in chloroquine-based combination therapies. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.04.058

文献信息

• Overcoming Chloroquine Resistance in Malaria: Design, Synthesis, and Structure-Activity Relationships of Novel Hybrid Compounds
  作者：Aicha Boudhar、Xiao Wei Ng、Chiew Yee Loh、Wan Ni Chia、Zhi Ming Tan、Francois Nosten、Brian W. Dymock、Kevin S. W. Tan

  DOI：10.1128/aac.02476-15

  日期：2016.5

  Resistance to antimalarial therapies, including artemisinin, has emerged as a significant challenge. Reversal of acquired resistance can be achieved using agents that resensitize resistant parasites to a previously efficacious therapy. Building on our initial work describing novel chemoreversal agents (CRAs) that resensitize resistant parasites to chloroquine (CQ), we herein report new hybrid single agents as an innovative strategy in the battle against resistant malaria. Synthetically linking a CRA scaffold to chloroquine produces hybrid compounds with restored potency toward a range of resistant malaria parasites. A preferred compound, compound 35, showed broad activity and good potency against seven strains resistant to chloroquine and artemisinin. Assessment of aqueous solubility, membrane permeability, and in vitro toxicity in a hepatocyte line and a cardiomyocyte line indicates that compound 35 has a good therapeutic window and favorable drug-like properties. This study provides initial support for CQ-CRA hybrid compounds as a potential treatment for resistant malaria.

  摘要 青蒿素等抗疟药物的抗药性已成为一项重大挑战。使用能使耐药寄生虫对以前有效的疗法重新敏感的制剂可以逆转获得性耐药性。我们最初研究的新型化学逆转剂（CRAs）能使抗药性寄生虫对氯喹（CQ）重新敏感，在此基础上，我们报告了新型混合单药，作为抗击抗药性疟疾的一种创新策略。将 CRA 支架与氯喹合成连接，可产生对一系列抗药性疟疾寄生虫具有恢复效力的混合化合物。优选化合物 35 对七种对氯喹和青蒿素有抗药性的菌株显示出广泛的活性和良好的效力。评估水溶性、膜渗透性和 体外 在肝细胞系和心肌细胞系中的毒性评估表明，化合物 35 具有良好的治疗窗口和类似药物的特性。这项研究为 CQ-CRA 混合化合物作为抗药性疟疾的潜在治疗方法提供了初步支持。
• Jilek, Jiri; Holubek, Jiri; Svatek, Emil, Collection of Czechoslovak Chemical Communications, 1988, vol. 53, # 4, p. 870 - 883
  作者：Jilek, Jiri、Holubek, Jiri、Svatek, Emil、Metys, Jan、Frycova, Hana、et al.

  DOI：——

  日期：——
• Jilek,Jiri; Pomykacek, Josef; Prosek, Zdenek, Collection of Czechoslovak Chemical Communications, 1983, vol. 48, # 3, p. 906 - 927
  作者：Jilek,Jiri、Pomykacek, Josef、Prosek, Zdenek、Holubek, Jiri、Svatek, Emil、et al

  DOI：——

  日期：——
• JILEK, J.;POMYKACEK, J.;PROSEK, Z.;HOLUBEK, J.;SVATEK, E.;METYSOVA, J.;DL+, COLLECT. CZECH. CHEM. COMMUN., 1983, 48, N 3, 906-927
  作者：JILEK, J.、POMYKACEK, J.、PROSEK, Z.、HOLUBEK, J.、SVATEK, E.、METYSOVA, J.、DL+

  DOI：——

  日期：——
• BARTL, V.;HOLUBEK, J.;SVATEK, E.;BARTOSOVA, M.;PROTIVA, M., COLLECT. CZECH. CHEM. COMMUN., 1983, 48, N 4, 1173-1186
  作者：BARTL, V.、HOLUBEK, J.、SVATEK, E.、BARTOSOVA, M.、PROTIVA, M.

  DOI：——

  日期：——