dibenzo-1,4-thiazepin-11(10H)-thione | 30690-43-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫氮卓类
• 英文名称: dibenzo-1,4-thiazepin-11(10H)-thione
• 英文别名: dibenzo[b,f]-1,4-thiazepin-11(10H)-thione；10H-dibenzo[b,f][1,4]thiazepine-11-thione；10,11-Dihydrodibenzo[b,f][1,4]thiazepin-11-thione；Dibenzo<1,4>thiazepin-11(10H)-thion；Dibenzo[b,f][1,4]thiazepine-11(10H)-thione；5H-benzo[b][1,4]benzothiazepine-6-thione
• CAS: 30690-43-8
• 化学式: C₁₃H₉NS₂
• 分子量: 243.353
• InChiKey: JDGIOVSBPLDWSM-UHFFFAOYSA-N

物化性质

• 溶解度：
  1 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  69.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  dibenzo-1,4-thiazepin-11(10H)-thione 在 一水合肼 作用下， 以 正丁醇 为溶剂， 反应 0.5h， 以65%的产率得到6-[(4-氯苯基)甲硫基]-2H-1,2,4-三嗪-3,5-二酮
  参考文献：
  名称：

  3-(4-Methylpiperazino)dibenzo[b,f]-1,2,4-triazolo[4,3-d]-1,4-thiazepine and its 6-chloro and 12-chloro derivatives; Synthesis and pharmacology

  摘要：

  Dibenzo[b,f]-1,4-thiazepin-11(10H)-ones IIa-IIc 在吡啶中与五硫化磷反应，形成了硫代酮IIIa-IIIc，随后在1-丁醇中用肼水合物处理，转化为肼衍生物IVa-IVc。在乙醇中存在硫酸的情况下，与三乙基正甲酸酯反应，发生环化反应生成了dibenzo[b,f]-1,2,4-三唑并[4,3-d]-1,4-噻吩（Va）及其氯衍生物Vb、Vc，随后用溴在氯仿和吡啶的沸腾混合物中处理，得到3-溴衍生物VIa-VIc。通过过量沸腾的1-甲基哌嗪进行置换反应，得到了标题化合物Ia-Ic。试图制备类似的14H-dibenzo[b,g]-1,2,4-三唑并[4,3-d]-1,4-噻吩环衍生物的尝试在硫代酮X与肼水合物反应阶段中中止，结果形成了偶氮化合物XI。化合物Ia-Ic在静脉注射后具有高毒性，并且在中枢神经系统效应测试中无活性；化合物Ic显示出明显的抗胆碱能活性。

  DOI：

  10.1135/cccc19831465
• 作为产物：
  描述：

  二苯并[b,f][1,4]硫氮杂卓-11-[10H]酮 在 tetraphosphorus decasulfide 作用下， 以 吡啶 为溶剂， 反应 6.5h， 以65%的产率得到dibenzo-1,4-thiazepin-11(10H)-thione
  参考文献：
  名称：

  3-(4-Methylpiperazino)dibenzo[b,f]-1,2,4-triazolo[4,3-d]-1,4-thiazepine and its 6-chloro and 12-chloro derivatives; Synthesis and pharmacology

  摘要：

  Dibenzo[b,f]-1,4-thiazepin-11(10H)-ones IIa-IIc 在吡啶中与五硫化磷反应，形成了硫代酮IIIa-IIIc，随后在1-丁醇中用肼水合物处理，转化为肼衍生物IVa-IVc。在乙醇中存在硫酸的情况下，与三乙基正甲酸酯反应，发生环化反应生成了dibenzo[b,f]-1,2,4-三唑并[4,3-d]-1,4-噻吩（Va）及其氯衍生物Vb、Vc，随后用溴在氯仿和吡啶的沸腾混合物中处理，得到3-溴衍生物VIa-VIc。通过过量沸腾的1-甲基哌嗪进行置换反应，得到了标题化合物Ia-Ic。试图制备类似的14H-dibenzo[b,g]-1,2,4-三唑并[4,3-d]-1,4-噻吩环衍生物的尝试在硫代酮X与肼水合物反应阶段中中止，结果形成了偶氮化合物XI。化合物Ia-Ic在静脉注射后具有高毒性，并且在中枢神经系统效应测试中无活性；化合物Ic显示出明显的抗胆碱能活性。

  DOI：

  10.1135/cccc19831465

文献信息

• PROCESS FOR PREPARING QUETIAPINE AND QUETIAPINE FUMARATE
  申请人：Bosch I Llado Jordi

  公开号：US20090076262A1

  公开（公告）日：2009-03-19

  The invention comprises a process for preparing quetiapine and/or its salts, including, quetiapine fumarate. The process generally comprises reacting dibenzothiazepinone (dibenzo[bf][1,4]thiazepin-11(10H)-one) with phosphorous oxychloride in the presence of triethylamine in an aromatic organic solvent such as toluene or, preferably, xylene at reflux temperature to obtain an aromatic hydrocarbon solution of 11-chloro-dibenzo[bf][1,4]thiazepine. Thereafter, the 11-chloro-dibenzo[bf][1,4]thiazepine is reacted with 2-(2-piperazin-1-ylethoxy)-ethanol to yield, following several processing steps, quetiapine. Compound I can then be further reacted with fumaric acid at elevated temperature to yield quetiapine fumarate. The resulting quetiapine fumarate obtained is suitable for use in pharmaceutical preparations.

  该发明涉及一种制备喹硫平及/或其盐的过程，包括喹硫平富马酸盐。该过程通常包括在芳香有机溶剂（如甲苯或更好的二甲苯）中，在回流温度下，将二苯并噻吩酮（二苯并[bf][1,4]噻吩-11(10H)-酮）与三乙胺的存在下与氯化亚磷酸酯反应，以获得11-氯二苯并[bf][1,4]噻吩的芳香烃溶液。随后，将11-氯二苯并[bf][1,4]噻吩与2-(2-哌嗪-1-基乙氧基)-乙醇反应，经过几个处理步骤，得到喹硫平。化合物I随后可以在高温下与富马酸反应，生成喹硫平富马酸盐。获得的喹硫平富马酸盐适用于制药制剂中的使用。
• Dibenzothiazepinthione as antiviral agents
  申请人：Glaxo Wellcome Inc.

  公开号：US05589474A1

  公开（公告）日：1996-12-31

  Compounds of formula (I) wherein n is 0, 1 or 2; and R.sup.1 and R.sup.2, which may be the same or different, each represent one or more ring substituent(s) selected from: hydroxy, halogen, cyano, nitro, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl or C.sub.1-6 alkoxy (where the alkyl or cycloalkyl moiety may be optionally substituted by one or more substituents selected from halogen atoms and hydroxyl groups); --NR.sup.4 R.sup.5 where R.sup.4 and R.sup.5 which may be the same or different, each represent hydrogen or C.sub.1-6 are each as defined above; phenyl, phenyl C.sub.1-3 alkoxy or phenyl C.sub.1-3 alkyl where the phenyl group may be optionally substituted by one or more substituents independently selected from C.sub.1-6 alkyl, C.sub.1-6 alkoxy, hydroxy, nitro, halogen and amino; and --CO.sub.2 H or --COR.sup.7 where R.sup.7 is C.sub.1-6 alkyl or C.sub.3-6 cycloalkyl; R.sup.3 is hydrogen or C.sub.1-4 alkyl: and esters, salts and other physiologically functional derivatives thereof, show activity as antiviral agents, for example against HIV. The majority of the compounds are novel.

  式(I)的化合物中，其中n为0、1或2；R.sup.1和R.sup.2，可能相同也可能不同，分别代表一个或多个环取代基，可选自：羟基、卤素、氰基、硝基、C.sub.1-6烷基、C.sub.3-6环烷基或C.sub.1-6烷氧基（其中烷基或环烷基基团可能可选择地被一个或多个取代基取代，取代基可选自卤素原子和羟基）；--NR.sup.4 R.sup.5，其中R.sup.4和R.sup.5可能相同也可能不同，分别代表氢或C.sub.1-6如上所定义的烷基；苯基、苯基C.sub.1-3烷氧基或苯基C.sub.1-3烷基，其中苯基可能可选择地被一个或多个取代基独立选择自C.sub.1-6烷基、C.sub.1-6烷氧基、羟基、硝基、卤素和氨基取代；和--CO.sub.2 H或--COR.sup.7，其中R.sup.7为C.sub.1-6烷基或C.sub.3-6环烷基；R.sup.3为氢或C.sub.1-4烷基；以及它们的酯、盐和其他生理功能衍生物，显示出抗病毒药物活性，例如对抗HIV。大多数化合物都是新颖的。
• Compounds, their preparation and use
  申请人：Novo Nordisk A/S

  公开号：US06214820B1

  公开（公告）日：2001-04-10

  The present invention relates to compounds of formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8, A, X, T, Q, Z, U, Y, Ar, p and n are as defined in the specification. These compounds are useful in the treatment and/or prevention of conditions mediated by nuclear receptors, in particular the Peroxisome Proliferator-Activated Receptors (PPAR).

  本发明涉及式(I)中的化合物，其中R1、R2、R3、R4、R5、R6、R7、R8、A、X、T、Q、Z、U、Y、Ar、p和n如规范中所定义。这些化合物在治疗和/或预防核受体介导的疾病方面具有用途，特别是过氧化物酶体增殖物激活受体（PPAR）。
• Process For The Preparation Of An 11-(4-Substituted-I- Piperazinyl)Dibenzo[B,F][1,4:rsqb; Thiazepine Derivative
  申请人：Comely Alexander Christian

  公开号：US20080171869A1

  公开（公告）日：2008-07-17

  A process for the preparation of an 11-(4-substituted-1-piperazinyl)dibenzo[b,f][1,4]thiazepine derivative, of general Formula (I), where A is hydrogen or a —(CH 2 ) 2 —OH group or a —(CH 2 ) 2 -0-(CH 2 ) 2 —OH group, or of a salt thereof, comprises a step in which 10H-dibenzo[b,f][1,4]thiazepin-11-one is reacted with a piperazine derivative in the presence of a titanium alkoxide of general formula Ti(OR) 4 , where R is a straight or branched alkyl group, having from one to eight carbon atoms to obtain said Formula I derivative or a salt thereof. Where A is —CH 2 ) 2 -0-(CH 2 ) 2 —OH, then the piperazine derivative is 1-(2-(2-hydroxyethoxy)ethyl)piperazine and the 11-(4-substituted-1-piperazinyl)dibenzo[b,f][1,4]thiazepine is quetiapine, (11-(4-(2-(2-hydroxyethoxy)ethyl)-1-piperazinyl)dibenzo[b,f][1,4]thiazepine). The process may comprise an additional step of reacting the quetiapine with fumaric acid to obtain quetiapine hemifumarate.

  一种制备通式（I）的11-（4-取代-1-哌嗪基）二苯并[b，f][1,4]噻唑啉衍生物的方法，其中A是氢或—（CH2）2—OH基或—（CH2）2-0-（CH2）2—OH基，或其盐之一，包括一步，在钛醇的存在下，将10H-二苯并[b，f][1,4]噻唑啉-11-酮与哌嗪衍生物反应，其中钛醇的通式为Ti（OR）4，其中R是一种直链或支链烷基，具有从一到八个碳原子，以获得所述的通式I衍生物或其盐。当A是—（CH2）2-0-（CH2）2—OH时，哌嗪衍生物是1-（2-（2-羟乙氧基）乙基）哌嗪，而11-（4-取代-1-哌嗪基）二苯并[b，f][1,4]噻唑啉是喹硫平（11-（4-（2-（2-羟乙氧基）乙基）-1-哌嗪基）二苯并[b，f][1,4]噻唑啉）。该过程还可以包括将喹硫平与富马酸反应以获得喹硫平半富马酸盐的附加步骤。
• Novel Tricyclic-α-alkyloxyphenylpropionic Acids:  Dual PPARα/γ Agonists with Hypolipidemic and Antidiabetic Activity
  作者：Per Sauerberg、Ingrid Pettersson、Lone Jeppesen、Paul S. Bury、John P. Mogensen、Karsten Wassermann、Christian L. Brand、Jeppe Sturis、Helle F. Wöldike、Jan Fleckner、Anne-Sofie T. Andersen、Steen B. Mortensen、L. Anders Svensson、Hanne B. Rasmussen、Søren V. Lehmann、Zdenek Polivka、Karel Sindelar、Vladimira Panajotova、Lars Ynddal、Erik M. Wulff

  DOI：10.1021/jm010964g

  日期：2002.2.1

  Synthesis and structure-activity relationships of tricyclic alpha-ethoxy-phenylpropionic acid derivatives guided by in vitro PPARalpha and PPARgamma transactivation data and computer modeling led to the identification of the novel carbazole analogue, 3q, with dual PPARalpha (EC50 = 0.36 muM) and PPARgamma (EC50 = 0.17 muM) activity in vitro. Ten days treatment of db/db mice with 3q improved the insulin sensitivity, as measured by OGTT, better than that seen with both pioglitazone and rosiglitazone treatment, suggesting in vivo PPARgamma activity. Likewise, 3q lowered plasma triglycerides and cholesterol in high cholesterol fed rats after 4 days treatment, indicating in vivo PPARalpha activity. Investigations of the pharmacokinetics of selected compounds suggested that extended drug exposure improved the in vivo activity of in vitro active compounds.