3,11-二氯-6,11-二氢-6-甲基-二苯并[c,f][1,2]硫氮杂卓 5,5-二氧化物 | 26638-66-4

• 物质功能分类: 医药中间体
• 分子结构分类: 有机化合物 - 有机卤素化合物 - 芳基卤化物
• 中文名称: 3,11-二氯-6,11-二氢-6-甲基-二苯并[c,f][1,2]硫氮杂卓 5,5-二氧化物
• 中文别名: 噻萘中间体B；3,11-二氯-6,11-二氢-6-甲基-二苯并[c,f][1,2]硫氮杂卓5,5-二氧化物；3,11-二氯-6,11-二氢-6-甲基-二苯并[C,F][1,2]硫氮杂卓5,5-二氧化物(噻萘中间体B)
• 英文名称: 3,11-dichloro-6-methyl-6,11-dihydrodibenzo[c,f][1,2]thiazepine 5,5-dioxide
• 英文别名: 3,11-dichloro-6,11-dihydro-6-methyl-dibenzo[c,f][1,2]thiazepine-5,5-dioxide；3,11-Dichloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepine 5,5-dioxide；3,11-dichloro-6-methyl-11H-benzo[c][2,1]benzothiazepine 5,5-dioxide
• CAS: 26638-66-4
• 化学式: C₁₄H₁₁Cl₂NO₂S
• 分子量: 328.219
• InChiKey: FHICZIHQHGRZLE-UHFFFAOYSA-N

物化性质

• 熔点：
  >233oC (dec.)
• 沸点：
  445.3±55.0 °C(Predicted)
• 密度：
  1.54±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  45.8
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090
• 包装等级：
  III
• 危险类别：
  8
• 危险性防范说明：
  P260,P264,P270,P280,P301+P330+P331,P303+P361+P353,P304+P340,P305+P351+P338,P310,P363,P405,P501
• 危险品运输编号：
  1759
• 危险性描述：
  H302,H314
• 储存条件：
  2-8°C

反应信息

• 作为反应物：
  描述：

  3,11-二氯-6,11-二氢-6-甲基-二苯并[c,f][1,2]硫氮杂卓 5,5-二氧化物 在 氨 、 氢气 、 镍 作用下， 以 乙醇 、 乙腈 为溶剂， 60.0~80.0 ℃ 、6.08 MPa 条件下， 反应 6.5h， 生成 (8-chloro-10,10-dioxo-11-methyl-5,11-dihydrodibenzo<1,2>thiazepin-5-yl)methylamine
  参考文献：
  名称：

  New triazine derivatives as potent modulators of multidrug resistance

  摘要：

  A series of 70 triazine derivatives have been synthesized and tested for their capacity to modulate multidrug resistance (MDR) in DC-3F/AD and KB-A1 tumor cells in vitro, in comparison with verapamil (VRP), a calcium channel antagonist currently used in therapy as an antihypertensive drug, which also shows MDR modulating activity. Among the 12 selected compounds, 16 (S9788) showed high MDR reversing properties in vitro (300- and 6-fold VRP at 5-mu-M in DC-3F/AD and KB-A1 cells, respectively) and induced a strong accumulation of adriamycin. The relationship between the increase of ADR accumulation and the fold reversal induced by these compounds and their lack of effects on the sensitive DC-3F cells suggest that they act mainly by inhibiting the P-glycoprotein (Pgp) catalyzed efflux of cytotoxic agents, as already described for a majority of MDR modulators. In vivo, in association with the antitumor drug vincristine (0.25 mg/kg), 16 (100 mg/kg) increased the TIC by 39% in mice bearing the resistant tumor cell line P388/VCR. According to these interesting properties, 16 was selected for a clinical development because it was more bioavailable than 34, even though it was less active.

  DOI：

  10.1021/jm00091a017
• 作为产物：
  描述：

  3-氯-6-甲基二苯并[c,f][1,2]硫氮杂卓-11(6H)-酮 5,5-二氧化物 在 盐酸 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 3,11-二氯-6,11-二氢-6-甲基-二苯并[c,f][1,2]硫氮杂卓 5,5-二氧化物
  参考文献：
  名称：

  New triazine derivatives as potent modulators of multidrug resistance

  摘要：

  A series of 70 triazine derivatives have been synthesized and tested for their capacity to modulate multidrug resistance (MDR) in DC-3F/AD and KB-A1 tumor cells in vitro, in comparison with verapamil (VRP), a calcium channel antagonist currently used in therapy as an antihypertensive drug, which also shows MDR modulating activity. Among the 12 selected compounds, 16 (S9788) showed high MDR reversing properties in vitro (300- and 6-fold VRP at 5-mu-M in DC-3F/AD and KB-A1 cells, respectively) and induced a strong accumulation of adriamycin. The relationship between the increase of ADR accumulation and the fold reversal induced by these compounds and their lack of effects on the sensitive DC-3F cells suggest that they act mainly by inhibiting the P-glycoprotein (Pgp) catalyzed efflux of cytotoxic agents, as already described for a majority of MDR modulators. In vivo, in association with the antitumor drug vincristine (0.25 mg/kg), 16 (100 mg/kg) increased the TIC by 39% in mice bearing the resistant tumor cell line P388/VCR. According to these interesting properties, 16 was selected for a clinical development because it was more bioavailable than 34, even though it was less active.

  DOI：

  10.1021/jm00091a017

文献信息

• [EN] A NEW CLASS OF MU-OPIOID RECEPTOR AGONISTS<br/>[FR] NOUVELLE CLASSE D'AGONISTES DU RÉCEPTEUR MU-OPIOÏDE
  申请人：UNIV COLUMBIA

  公开号：WO2015138791A1

  公开（公告）日：2015-09-17

  The present invention provides a compound having the structure (I) or a pharmaceutically acceptable salt or ester thereof.

  本发明提供了一种具有结构（I）的化合物或其药用可接受的盐或酯。
• [EN] DIBENZOTHIAZEPINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF CNS DISORDERS<br/>[FR] DÉRIVÉS DE DIBENZOTHIAZÉPINE ET LEUR UTILISATION DANS LE TRAITEMENT DE TROUBLES DU SNC
  申请人：NUMEDICUS LTD

  公开号：WO2012143703A1

  公开（公告）日：2012-10-26

  A compound of formula (I): or a pharmaceutically or veterinarily acceptable salt thereof, or a pharmaceutically or veterinarily acceptable solvate of either entity, wherein: R1, R2, R3, R4, R5, R6, X and m are as defined herein.

  化合物的化学式（I）：或其药用或兽医学上可接受的盐，或者任一实体的药用或兽医学上可接受的溶剂，其中：R1、R2、R3、R4、R5、R6、X和m如本文所定义。
• 3,11-디클로로-6-메틸-6,11-디하이드로디벤조[c,f][1,2]티아제핀 5,5-디옥시드의 제조방법
  申请人：HANSEO CHEMICAL CO., LTD. 주식회사 한서켐(120020331393) Corp. No ▼ 115611-0009306

  公开号：KR20200077733A

  公开（公告）日：2020-07-01

  본 발명은 3,11-디클로로-6-메틸-6,11-디하이드로디벤조[c,f][1,2]티아제핀 5,5-디옥시드의 제조방법에 관한 것으로서, 좀 더 상세하게 설명하자면 염화아세틸과 동일 당량의 알코올 환경 하에서 in situ로 생성된 염화수소 기체를 사용하여 출발물질인 3-클로로-6-메틸-6,11-디히드로디벤조[c,f][1,2]티아제핀-11-올 5,5-디옥시드의 히드록시기를 염소기로 치환시킴으로서, 외부에서 과량의 염화수소 기체를 투입하지 않는 정량적 반응으로 안전한 분위기에서 고순도의 3,11-디클로로-6-메틸-6,11-디하이드로디벤조[c,f][1,2]티아제핀 5, 5-디옥시드를 고수율로 제조하는 방법에 관한 것이다.

  这项发明涉及制备3,11-二氯-6-甲基-6,11-二氢二苯并[c,f][1,2]噻唑啉-11-醇5,5-二氧化物的方法。更具体地说，本发明使用在乙醇环境下与乙酰氯等当量的原料一起生成的氢氯酸气体，通过用氯基取代羟基来取代3-氯-6-甲基-6,11-二氢二苯并[c,f][1,2]噻唑啉-11-醇5,5-二氧化物的羟基。本发明通过定量反应而无需从外部加入过量氢氯酸气体，在安全环境中高产率地制备高纯度的3,11-二氯-6-甲基-6,11-二氢二苯并[c,f][1,2]噻唑啉-5,5-二氧化物的方法。
• The Behavioral Effects of the Antidepressant Tianeptine Require the Mu-Opioid Receptor
  作者：Benjamin Adam Samuels、Katherine M Nautiyal、Andrew C Kruegel、Marjorie R Levinstein、Valerie M Magalong、Madalee M Gassaway、Steven G Grinnell、Jaena Han、Michael A Ansonoff、John E Pintar、Jonathan A Javitch、Dalibor Sames、René Hen

  DOI：10.1038/npp.2017.60

  日期：2017.9

  Depression is a debilitating chronic illness that affects around 350 million people worldwide. Current treatments, such as selective serotonin reuptake inhibitors, are not ideal because only a fraction of patients achieve remission. Tianeptine is an effective antidepressant with a previously unknown mechanism of action. We recently reported that tianeptine is a full agonist at the mu opioid receptor (MOR). Here we demonstrate that the acute and chronic antidepressant-like behavioral effects of tianeptine in mice require MOR. Interestingly, while tianeptine also produces many opiate-like behavioral effects such as analgesia and reward, it does not lead to tolerance or withdrawal. Furthermore, the primary metabolite of tianeptine (MC5), which has a longer half-life, mimics the behavioral effects of tianeptine in a MOR-dependent fashion. These results point to the possibility that MOR and its downstream signaling cascades may be novel targets for antidepressant drug development.

  抑郁症是一种使人衰弱的慢性疾病，全球约有3.5亿人受其困扰。目前的治疗方法，如选择性血清素再摄取抑制剂，效果并不理想，因为只有一小部分患者病情得到缓解。天尼汀是一种有效的抗抑郁药，其作用机制此前尚不为人所知。我们最近报告了天尼汀是μ阿片受体（MOR）的全效激动剂。在这里，我们证明了天尼汀对小鼠的急性和慢性抗抑郁样行为效应需要MOR。有趣的是，虽然天尼汀也会产生许多阿片样行为效应，如镇痛和奖励，但它不会导致耐受性或戒断。此外，天尼汀的主要代谢产物（MC5）具有更长的半衰期，以依赖MOR的方式模仿天尼汀的行为效应。这些结果表明，MOR及其下游信号级联可能是抗抑郁药物开发的新靶点。
• [EN] NOVEL PROCESS FOR THE PREPARATION OF 7-((3-CHLORO-6-METHYL-5,5-DIOXO-6,11-DIHYDRODIBENZO(C,F)(1,2) THIAZEPIN-11-YL)AMINO)HEPTANOATE<br/>[FR] NOUVEAU PROCÉDÉ POUR LA PRÉPARATION DE 7-((3-CHLORO-6-MÉTHYL-5,5-DIOXO-6,11-DIHYDRODIBENZO(C,F)(1,2)THIAZÉPIN-11-YL)AMINO)HEPTANOATE
  申请人：BIOPHORE INDIA PHARMACEUTICALS

  公开号：WO2010070667A2

  公开（公告）日：2010-06-24

  The present invention relates to a novel process for the preparation of sodium 7-((3-Chloro-6-methyl-5,5-dioxo-6,11-dihydrodibenzo(c,f)(1,2)thiazepin-11-yl)amino)heptanoate and intermediates. The invention also encompasses isolation of an essentially non-hygroscopic compound which is substantially pure.

  本发明涉及一种制备7-((3-氯-6-甲基-5,5-二氧化-6,11-二氢二苯并(c,f)(1,2)噻唑-11-基)氨基)庚酸钠及其中间体的新工艺。本发明还包括分离一种基本上不吸湿的、基本上纯的化合物。