10-Piperazino-10,11-dihydro-dibenzothiepin | 4774-29-2

• 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: 10-Piperazino-10,11-dihydro-dibenzothiepin
• 英文别名: 1-(10,11-dihydrodibenzo[b,f]thiepin-10-yl)piperazine；10-Piperazino-10,11-dihydrodibenzo-[b,f]thiepin；1-(5,6-dihydrobenzo[b][1]benzothiepin-5-yl)piperazine
• CAS: 4774-29-2
• 化学式: C₁₈H₂₀N₂S
• 分子量: 296.436
• InChiKey: LWBLYEUAPNUGIP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 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：

  10-Piperazino-10,11-dihydro-dibenzothiepin 、 1-(3-氯丙基)-1,3-二氢-2H-苯并咪唑-2-酮 在 三乙胺 、 potassium iodide 作用下， 以 甲苯 为溶剂， 以65%的产率得到1-(3-(4-(10,11-dihydrodibenzothiepin-10-yl)-1-piperazinyl)propyl)-1,3-dihydro-2H-benzimidazol-2-one
  参考文献：
  名称：

  Jilek, Jiri; Holubek, Jiri; Svatek, Emil, Collection of Czechoslovak Chemical Communications, 1988, vol. 53, # 4, p. 870 - 883

  摘要：

  DOI：
• 作为产物：
  描述：

  2-碘苯乙酸 在 titanium(IV) isopropylate 、 sodium tetrahydroborate 、 四磷十氧化物 、 铜 、 三氟乙酸 、 potassium hydroxide 作用下， 以 二氯甲烷 、 水 、 溶剂黄146 、 甲苯 为溶剂， 反应 74.0h， 生成 10-Piperazino-10,11-dihydro-dibenzothiepin
  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。
• Modulators of US 28
  申请人：ChemoCentryx

  公开号：US20020127544A1

  公开（公告）日：2002-09-12

  Assays, compositions and methods of treatment are provided for modulating the binding of chemokines to US28 on the surface of cells.

  提供了调节趋化因子与细胞表面 US28 结合的检测方法、组合物和治疗方法。
• Chemomagnetic retrieval of CMV and CMV infected cells
  申请人：ChemoCentryx

  公开号：US20020182594A1

  公开（公告）日：2002-12-05

  Methods and apparatus are provided herein for collecting CMV and/or CMV infected cells from a host infected with CMV. Such methods and apparatus have utility in tracking the dissemination or infection of the host, use as an in vivo or ex vivo collection mechanism to measure mutation rates and selective pressures after in vivo passage, and in therapeutic treatments in which CMV and/or CMV infected cells are removed from a host.

  本文提供了从感染 CMV 的宿主体内收集 CMV 和/或 CMV 感染细胞的方法和装置。这些方法和装置可用于跟踪宿主的传播或感染情况，用作体内或体外收集机制以测量体内通过后的突变率和选择压力，以及用于从宿主体内清除 CMV 和/或 CMV 感染细胞的治疗方法。
• JILEK, JIRI;HOLUBEK, JIRI;SVATEK, EMIL;METYS, JAN;FRYCOVA, HANA;POMYKACEK+, COLLECT. CZECHOSL. CHEM. COMMUN., 53,(1988) N 4, 870-883
  作者：JILEK, JIRI、HOLUBEK, JIRI、SVATEK, EMIL、METYS, JAN、FRYCOVA, HANA、POMYKACEK+

  DOI：——

  日期：——
• US3811026A
  申请人：——

  公开号：US3811026A

  公开（公告）日：1974-05-14