二苯并[B,F]硫杂卓-10(11H)-酮 | 1898-85-7

• 物质功能分类: 有机原料 - 酮类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫平类
• 中文名称: 二苯并[B,F]硫杂卓-10(11H)-酮
• 英文名称: dibenzo[b,f]thiepin-10(11H)-one
• 英文别名: Dibenzothiepin-10(11H)-on；10,11-Dihydrodibenzothiepin-10-one；10,11-Dihydro-dibenzothiepin-10-on；6H-benzo[b][1]benzothiepin-5-one
• CAS: 1898-85-7
• 化学式: C₁₄H₁₀OS
• 分子量: 226.299
• InChiKey: IEIUIKHMVGQHBH-UHFFFAOYSA-N

物化性质

• 密度：
  1.258

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  二苯并[B,F]硫杂卓-10(11H)-酮 在 selenium(IV) oxide 、 溶剂黄146 作用下， 生成 10,11-dihydrodibenzothiepin-10,11-dione
  参考文献：
  名称：

  二苯并[b，f] oxepin-10（11H）-one和二苯并[b，f] thiepin-10（11H）-one可作为合成各种二苯并[e，h] azulenes的合成子

  摘要：

  本综述着重于二苯并[ b，f ] oxepin-10（11 H）-one（I，X = O）和二苯并[ b，f ] thiepin-10（11 H）-one（I，X = S）作为有效合成各种二苯并噻吩并[4,5]和二苯并噻吩并[4,5]稠合的五元杂环的常用合成子：[2,3]稠合噻吩（II），[3,4]稠合噻吩（III） ，呋喃（IV），吡咯（V），咪唑（VI），吡唑（VII），恶唑（VIII）和噻唑（IX）。我的潜力通过适当的双亲核剂与环缩合反应转变成易于发生杂芳族环化反应的反应性中间体，可以形成一系列列举的官能化二苯并[ e，h ] azulene [4]结构（II，III，IV，V，VI，VII，VIII，IX）。可以进一步修饰二苯并[ e，h ] azulenes作为杂环四环骨架，以获得具有改变的理化和生物学特性的化合物。J.杂环化​​学。（2012）。

  DOI：

  10.1002/jhet.753
• 作为产物：
  描述：

  2-(2-碘苯基)乙酸甲酯 在 copper(l) iodide 、 草酰氯 、 新铜试剂 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 11.5h， 生成 二苯并[B,F]硫杂卓-10(11H)-酮
  参考文献：
  名称：

  Synthesis of targeted dibenzo[b,f]thiepines and dibenzo[b,f]oxepines as potential lead molecules with promising anti-breast cancer activity

  摘要：

  A targeted library of substituted dibenzo[b,f]thiepines and dibenzo[b,f]oxepines (prototypes I, II and III), and structurally analogous to tamoxifen have been synthesized as a new class of anti-breast cancer agents. All the prototype molecules exhibited potential antiproliferative activity against ER + ve and ER-ye breast cancer cell lines. Dibenzo[b,f]thiepine prototypes were found to be more active. Of all the compound tested, 14b exhibited potent in-vitro antiproliferative activity at 133 mu M and 5 mu M concentration in MCF-7 and MDA-MB-231 cell lines and was devoid of any cytotoxicity in normal HEK cells even at 50 mu M. Cell cycle analysis showed that the compound 14b inhibited cell proliferation due to G0/G1 arrest in MCF-7 cells. Annexin-V FITC and PI staining experiments confirmed that the cell inhibition was primarily due to apoptosis and not by necrosis, which was also supported by LDH release assay experiment. Molecular docking studies showed better binding interaction of the new dibenzo[b,f]thiepine analogue 14b with the estrogen receptor (ER) as compared to 4-hydroxy-tamoxifen and this enhanced binding might be responsible for its estrogen antagonistic activity that induces cell cycle arrest, apoptosis and inhibition of breast cancer cells. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.05.035

文献信息

• Sequential One-Pot Synthesis of Tri- and Tetrasubstituted Thiophenes and Fluorescent Push–Pull Thiophene Acrylates Involving (Het)aryl Dithioesters as Thiocarbonyl Precursors
  作者：Anand Acharya、G. Parameshwarappa、B. Saraiah、H. Ila

  DOI：10.1021/jo502429c

  日期：2015.1.2

  An efficient, one-pot three component synthesis of highly functionalized tri- and tetrasubstituted thiophenes has been reported involving (het)aryl dithioesters as thiocarbonyl precursors. Thus, sequential base mediated condensation of readily available (het)aryl active methylene ketones with (het)aryl dithioesters followed by S-alkylation of the resulting enethiolate salts with activated halomethylene

  已经报道了一种高效，一锅三组分的高度官能化的三和四取代噻吩的合成方法，其中涉及（杂）芳基二硫代酯作为硫代羰基前体。因此，容易获得的（杂）芳基活性亚甲基酮与（杂）芳基二硫代酯的顺序碱介导的缩合，然后用活化的卤代亚甲基化合物对所得的烯硫醇盐进行S-烷基化，同时S-烷基化的化合物的分子内醇醛缩合型提供了取代基。噻吩的收率极高。通过使用溴巴豆酸酯作为活化的亚甲基烷基化剂，该方法也已扩展到合成高荧光推挽式取代的噻吩-5-丙烯酸酯。
• Synthesis and Biological Activity of 11-(4-(Cinnamyl)-1-piperazinyl)-6,11-dihydrodibenz(b,e)oxepin Derivatives, Potential Agents for the Treatment of Cerebrovascular Disorders.
  作者：Mikio KUROKAWA、Fuminori SATO、Yoshinobu MASUDA、Takayuki YOSHIDA、Yuko OCHI、Kayoko ZUSHI、Iwao FUJIWARA、Shunsuke NARUTO、Hitoshi UNO、Jun-ichi MATSUMOTO

  DOI：10.1248/cpb.39.2564

  日期：——

  A series of 11-[4-(cinnamyl)-1-piperazinyl]-6, 11-dihydrodibenz[b, e]oxepins and related compounds were synthesized and evaluated for their protective activities against complete ischemia, normobaric hypoxia, lipidperoxidation and convulsion. Structure-activity relationship studies of this series led to the finding of (E)-1-(3-fluoro-6, 11-dihydrodibenz[b, e]oxepin-11-yl)-4-(3-phenyl-2-propenyl)piperazine dimaleate (50), AJ-3941 with the most appropriate property for combined pharmacological activities.

  合成了一系列11-[4-（肉桂基）-1-哌嗪基]-6，11-二氢二苯并[b，e]氧芴及其相关化合物，并评价了它们对完全缺血、常压缺氧、脂质过氧化和惊厥的保护活性。通过对这一系列化合物的构效关系研究，发现了（E）-1-（3-氟-6，11-二氢二苯并[b，e]氧芑-11-基）-4-（3-苯基-2-丙烯基）哌嗪二马来酸盐（50），AJ-3941，它具有最适合的联合药理活性。
• [EN] SPIRO COMPOUNDS USEFUL AS ANTAGONISTS OF THE H1 RECEPTOR<br/>[FR] NOUVEAUX COMPOSÉS
  申请人：GLAXO GROUP LTD

  公开号：WO2009016085A1

  公开（公告）日：2009-02-05

  The invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, for treating diseases and conditions of the central nervous system (CNS), in particular sleep disorders.

  该发明提供了化合物的公式(I)或其药学上可接受的盐，用于治疗中枢神经系统（CNS）疾病和症状，特别是睡眠障碍。
• Dibenzo[b,f]thiepin-10-carbonitrile, its 10,11-dihydro derivative, some transformation products and related compounds
  作者：Karel Šindelář、Jiří Holubek、Miroslav Ryska、Emil Svátek、Jiří Urban、Jaroslava Grimová、Irena Červená、Marta Hrubantová、Miroslav Protiva

  DOI：10.1135/cccc19831187

  日期：——

  Reactions of 10-bromodibenzo[b,f]thiepin (IIIa), its 2-chloro derivative IIIb and 2,8-dichloro derivative IIIc with cuprous cyanide in boiling dimethylformamide gave the carbonitriles Iabc out of which the first two were reduced with sodium borohydride to the 10,11-dihydro derivatives IVab; the amides VIIab were obtained as by-products. Alkaline hydrolysis of the nitriles IVab or their mixtures with the amides VIIab afforded the acids VIIIab. By the addition of 3-dimethylaminopropylmagnesium chloride to the nitrile Ia cis and trans-11-(3-dimethylaminopropyl)-10,11-dihydrodibenzo[b,f]thiepin-10-carbonitriles (XVIII) were obtained. Alkylation of the nitrile IVa with 2-dimethylaminoethyl chloride and 3-dimethylaminopropyl chloride resulted in the 10-(dimethylaminoalkyl) derivatives XX and XXI. A reaction of the crude cyano alcohol XXIII with phosphorus tribromide afforded the 2-bromoethyl derivative XXIV as a by-product only. The main product was the hydrobromide of the spirocyclic imidate XXX which affords by acid hydrolysis the spirocyclic lactone XXXI. An analogous sequence proceeding via the ether XXVI and the alcohol XXVII leads to the 10-(3-bromopropyl) derivative XXVIII as the main product. An attempt at preparing the same substance by alkylation of the nitrile IVa with 1,3-dibromopropane gave stereoisomeric dinitriles XXXII. At high doses the amides VIIab reveal an anticonvulsant effect, the acids VIIIab antiinflammatory actions, the basic nitrile cis-XVIII antireserpine activity and the basic nitriles XX and XXI a central depressant and pseudo-analgesic activity in addition to further peripheral and cardiovascular effects.

  10-溴代二苯并[b,f]噻吩（IIIa）及其2-氯衍生物IIIb和2,8-二氯衍生物IIIc与在沸腾的二甲基甲酰胺中的亚铜氰化物反应，形成碳腈类物质Iabc，其中前两者经过钠硼氢化物还原成为10,11-二氢衍生物IVab；酰胺VIIab作为副产物被获得。对碳腈类物质IVab或其与酰胺VIIab的混合物进行碱性水解，形成酸类物质VIIIab。通过向碳腈类物质Ia cis和trans-11-(3-二甲基氨基丙基)-10,11-二氢二苯并[b,f]噻吩-10-碳腈类物质（XVIII）中加入3-二甲基氨基丙基氯化镁，得到了相应产物。将碳腈类物质IVa与2-二甲基氨基乙基氯化物和3-二甲基氨基丙基氯化物烷基化，形成10-(二甲基氨基烷基)衍生物XX和XXI。将粗制的氰醇XXIII与三溴化磷反应，只得到了2-溴乙基衍生物XXIV作为副产物。主要产物是螺环亚胺酯的氢溴酸盐XXX，经过酸水解得到螺环内酯XXXI。类似的过程通过醚XXVI和醇XXVII导致10-(3-溴丙基)衍生物XXVIII作为主要产物。尝试通过将碳腈类物质IVa与1,3-二溴丙烷烷基化来制备相同物质，得到了立体异构的双碳腈物质XXXII。高剂量下，酰胺VIIab显示出抗惊厥作用，酸类物质VIIIab具有抗炎作用，基础性碳腈物质cis-XVIII具有抗利血平活性，而基础性碳腈物质XX和XXI除了具有中枢抑制和伪镇痛作用外，还具有进一步的外周和心血管作用。
• Expedient Pd-Catalyzed α-Arylation towards Dibenzoxepinones: Pivotal Manske's Ketone for the Formal Synthesis of Cularine Alkaloids
  作者：Julie A. Deichert、Hideya Mizufune、Jignesh J. Patel、Timothy E. Hurst、Ashish Maheta、Matthew O. Kitching、Avena C. Ross、Victor Snieckus

  DOI：10.1002/ejoc.202000424

  日期：2020.8.16

  Patel, J.J., Hurst, T.E., Maheta, A., Kitching, M.O., Ross, A.C. and Snieckus, V. (2020), Expedient Pd‐Catalyzed α‐Arylation towards Dibenzoxepinones: Pivotal Manske's Ketone for the Formal Synthesis of Cularine Alkaloids. Eur. J. Org. Chem.. doi:10.1002/ejoc.202000424, which has been published in final form at https://doi.org/10.1002/ejoc.202000424. This article may be used for non-commercial purposes

  这是以下文章的同行评审版本：Deichert, JA, Mizufune, H., Patel, JJ, Hurst, TE, Maheta, A., Kitching, MO, Ross, AC 和 Snieckus, V. (2020)，权宜之计Pd 催化的 α-芳基化对二苯并氧杂环酮：用于 Cularine 生物碱形式合成的关键曼斯克酮。欧元。J. 组织 Chem.. doi:10.1002/ejoc.202000424，已在 https://doi.org/10.1002/ejoc.202000424 上以最终形式发表。根据 Wiley 使用自存档版本的条款和条件，本文可用于非商业目的。