8-methylthiodibenzothiepin-10(11H)-one | 16219-08-2

• 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: 8-methylthiodibenzothiepin-10(11H)-one
• 英文别名: 3-methylsulfanyl-6H-benzo[b][1]benzothiepin-5-one；8-(methylthio)dibenzo[b,f]thiepin-10(11H)-one；8-methylsulfanyl-11H-dibenzo[b,f]thiepin-10-one
• CAS: 16219-08-2
• 化学式: C₁₅H₁₂OS₂
• 分子量: 272.392
• InChiKey: HMKRTOHEGDSUDE-UHFFFAOYSA-N

物化性质

• 熔点：
  88-90 °C(Solv: benzene (71-43-2); ligroine (8032-32-4))
• 沸点：
  450.3±45.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  67.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-methylthiodibenzothiepin-10(11H)-one 在 对甲苯磺酸 、 锌 作用下， 以 溶剂黄146 为溶剂， 反应 6.0h， 生成 甲替平
  参考文献：
  名称：

  Neuroleptics of the 8-methylthio-10-piperazino-10,11-dihydrodibenzo[b,f]thiepin series: New compounds and new procedures

  摘要：

  将8-甲硫基二苯并[b,f]噻吩-10(11H)-酮与1-甲基哌嗪和哌嗪的单-p-甲苯磺酸酯在真空中加热，产率良好地得到烯胺IX-XI，其中第一个被还原为基本物质I（甲硫噻吩）的烯胺被锌和乙酸处理。通过氨基醇II（氧丙硫噻吩）与癸酸在N,N'-碳酰二咪唑存在下反应，并通过用1-(3-癸酰氧丙基)哌嗪替代10-氯-8-甲硫基-10,11-二氢二苯并[b,f]噻吩制得酯III（氧丙硫噻吩癸酸酯）。同一氯化合物与哌嗪的取代反应得到两个立体异构体的1,4-二取代哌嗪V。氨基醇II与辛基异氰酸酯反应得到氨基甲酸酯VI，是氧丙硫噻吩癸酸酯（III）的同分异构体。该物质在狗的抗阿波吗啡活性测试中表现出长效抗恶心的特性。合成了化合物I-III的两种新潜在代谢物（XII, XIII），并为氧丙硫噻吩（II）的另外两种潜在代谢物（XIV, XV）提供了新的药理数据。

  DOI：

  10.1135/cccc19800504
• 作为产物：
  描述：

  2-<2-(4-methylthiophenylthio)phenyl>acetic acid 在 polyphosphoric acid (PPA) 作用下， 以 甲苯 为溶剂， 反应 18.0h， 以77%的产率得到8-methylthiodibenzothiepin-10(11H)-one
  参考文献：
  名称：

  Identification of novel allosteric nonpeptidergic inhibitors of the human cytomegalovirus-encoded chemokine receptor US28

  摘要：

  Human cytomegalovirus ( HCMV) is a widespread human pathogen, possessing onco-modulatory properties. Constitutive signaling of the HCMV-encoded chemokine receptor US28 and its ability to bind a broad spectrum of chemokines might facilitate HCMV-associated tumor progression. Novel nonpeptidergic chemotypes were identified as neutral antagonists or inverse agonists on US28, that allosterically inhibit chemokine binding to US28. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.11.060

文献信息

• [EN] DIHYDROBENZO[B][1]BENZOTHIEPIN COMPOUNDS USEFUL IN THERAPY<br/>[FR] COMPOSÉS DE DIHYDROBENZO[B][1]BENZOTHIÉPINE UTILES EN THÉRAPIE
  申请人：CENTRE NAT RECH SCIENT

  公开号：WO2019092044A1

  公开（公告）日：2019-05-16

  The present invention relates to the use of a compound of formula (I), to decrease or inhibit, in vitro or ex vivo, the Patched receptor drug efflux activity, in particular the chemotherapeutic drug efflux activity and chemotherapy resistance. The present disclosure further relates to uses of such compounds, in particular to prepare a pharmaceutical composition to allow or improve the efficiency of a therapy of cancer in a subject in need thereof. The compound of the invention can indeed be advantageously used, in combination with at least one chemotherapeutic drug, for treating cancer, for preventing cancer metastasis and/or for preventing cancer recurrence in a subject.

  本发明涉及使用式(I)的化合物，以减少或抑制体外或体外Patched受体药物外流活性，特别是化疗药物外流活性和化疗耐药性。本公开还涉及这类化合物的用途，特别是制备药物组合以允许或改善患有癌症的受试者的治疗效果。本发明的化合物确实可以有利地与至少一种化疗药物结合，用于治疗癌症，预防癌症转移和/或预防患者癌症复发。
• Overcoming chloroquine resistance in malaria: Design, synthesis and structure–activity relationships of novel chemoreversal agents
  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：10.1016/j.ejmech.2016.04.058

  日期：2016.8

  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.
• JILEK J.; POMYKACEK J.; DLABAC A.; BARTOSOVA M., COLLECT. CZECH. CHEM. COMMUN., 1980, 45, NO 2, 504-516
  作者：JILEK J.、 POMYKACEK J.、 DLABAC A.、 BARTOSOVA M.

  DOI：——

  日期：——
• ——
  作者：JILEK J.、 PROTIVA M.、 POMYKACEK J.

  DOI：——

  日期：——
• JILEK J. O.; CERVENA I.; KOPICOVA Z.; SINDELAR K.; SVATEK E.; METYSOVA J.+, COLLECT. CZECH. CHEM. COMMUNS <CCCC-AK>, 1976, 41, NO 2, 443-458
  作者：JILEK J. O.、 CERVENA I.、 KOPICOVA Z.、 SINDELAR K.、 SVATEK E.、 METYSOVA J.+

  DOI：——

  日期：——