2,3,5,6-tetrahydropyrrolo<1,2,3-de>-1,2,4-benzothiadiazin-3-one 1,1-dioxide | 113162-39-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻二嗪
• 英文名称: 2,3,5,6-tetrahydropyrrolo<1,2,3-de>-1,2,4-benzothiadiazin-3-one 1,1-dioxide
• 英文别名: 5,6-dihydro-[1,2,4]thiadiazino[6,5,4-hi]indol-3(2H)-one1,1-dioxide；9,9-Dioxo-9lambda6-thia-1,10-diazatricyclo[6.3.1.04,12]dodeca-4(12),5,7-trien-11-one；9,9-dioxo-9λ6-thia-1,10-diazatricyclo[6.3.1.04,12]dodeca-4(12),5,7-trien-11-one
• CAS: 113162-39-3
• 化学式: C₉H₈N₂O₃S
• 分子量: 224.24
• InChiKey: MIKKSTQXSZURNV-UHFFFAOYSA-N

物化性质

• 熔点：
  255-260 °C
• 密度：
  1.69±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,3,5,6-tetrahydropyrrolo<1,2,3-de>-1,2,4-benzothiadiazin-3-one 1,1-dioxide 在 硫酸 作用下， 以 水 为溶剂， 反应 2.0h， 生成 7-吲哚啉磺酰胺
  参考文献：
  名称：

  [EN] INDOLINE AND TETRAHYDROQUINOLINE SULFONYL INHIBITORS OF DIMETALLOENZYMES AND USE OF THE SAME
  [FR] INHIBITEURS DE TYPE INDOLINE ET TÉTRAHYDROQUINOLINE SULFONYLE DES DIMÉTALLO-ENZYMES ET LEUR UTILISATION

  摘要：

  揭示了可以抑制DapE和/或细菌金属β-内酰胺酶（“MBLs”）如NDM-1的吲哚啉和四氢喹啉磺酰化合物。还公开了使用此处披露的化合物治疗患有细菌感染的个体的方法。

  公开号：

  WO2017011408A1
• 作为产物：
  描述：

  吲哚啉 在 aluminum (III) chloride 作用下， 反应 2.25h， 生成 2,3,5,6-tetrahydropyrrolo<1,2,3-de>-1,2,4-benzothiadiazin-3-one 1,1-dioxide
  参考文献：
  名称：

  [EN] INDOLINE AND TETRAHYDROQUINOLINE SULFONYL INHIBITORS OF DIMETALLOENZYMES AND USE OF THE SAME
  [FR] INHIBITEURS DE TYPE INDOLINE ET TÉTRAHYDROQUINOLINE SULFONYLE DES DIMÉTALLO-ENZYMES ET LEUR UTILISATION

  摘要：

  揭示了可以抑制DapE和/或细菌金属β-内酰胺酶（“MBLs”）如NDM-1的吲哚啉和四氢喹啉磺酰化合物。还公开了使用此处披露的化合物治疗患有细菌感染的个体的方法。

  公开号：

  WO2017011408A1

文献信息

• [EN] INDOLINE SULFONAMIDE INHIBITORS OF DAPE AND NDM-1 AND USE OF THE SAME<br/>[FR] INHIBITEURS INDOLINE-SULFONAMIDE DE DAPE ET NDM-1 ET UTILISATION DE CEUX-CI
  申请人：UNIV LOYOLA CHICAGO

  公开号：WO2016025637A1

  公开（公告）日：2016-02-18

  Indoline sulfonamide compounds that can inhibit DapE and/or bacterial metallo-β- lactamases (MBLs), such as NDM-1, are disclosed. Also disclosed are methods of treating an individual suffering from a bacterial infection using the indoline sulfonamide compounds disclosed herein.

  揭示了可以抑制DapE和/或细菌金属β-内酰胺酶（MBLs），如NDM-1的吲哚磺胺类化合物。还揭示了使用这些吲哚磺胺类化合物治疗患有细菌感染的个体的方法。
• Indoline sulfonamide inhibitors of DapE and NDM-1 and use of the same
  申请人：LOYOLA UNIVERSITY OF CHICAGO

  公开号：US10385040B2

  公开（公告）日：2019-08-20

  Indoline sulfonamide compounds that can inhibit DapE and/or bacterial metallo-β-lactamases (MBLs), such as NDM-1, are disclosed. Also disclosed are methods of treating an individual suffering from a bacterial infection using the indoline sulfonamide compounds disclosed herein.

  本发明公开了可抑制 DapE 和/或细菌金属-β-内酰胺酶（MBL）（如 NDM-1）的吲哚啉磺酰胺化合物。 还公开了使用本文公开的吲哚啉磺酰胺化合物治疗细菌感染患者的方法。
• Regioselectivity of electrophilic aromatic substitution: syntheses of 6- and 7-sulfamoylindolines and -indoles
  作者：Alan L. Borror、Efthimios Chinoporos、Michael P. Filosa、Stephen R. Herchen、Cheryl Pizzo Petersen、Carol A. Stern、Kay D. Onan

  DOI：10.1021/jo00244a036

  日期：1988.4
• 5′-Alkyl-benzothiadiazides: A New Subgroup of AMPA Receptor Modulators with Improved Affinity
  作者：Dean Phillips、Jennifer Sonnenberg、Amy C Arai、Rishi Vaswani、Peter O Krutzik、Thomas Kleisli、Markus Kessler、Richard Granger、Gary Lynch、A Richard Chamberlin

  DOI：10.1016/s0968-0896(01)00405-9

  日期：2002.5

  AMPA receptors form a major subdivision of the glutamate receptor family that mediates excitatory synaptic transmission in the brain, Currents through AMPA receptors can be up- or down-regulated by compounds that allosterically modulate receptor kinetics through binding sites distinct from that for glutamate. One of those modulators is the benzothiadiazide IDRA-21 which has been reported to enhance synaptic transmission and be effective in behavioral tests, but typically requires threshold concentrations of at least 100 muM to be active in vitro. In this study, new benzothiadiazides were developed with IDRA-21 as lead compound and examined for their potency in modulating AMPA receptor kinetics. A significant increase in drug affinity was obtained by alkyl substitution at the 5'-position of IDRA-21; substitutions at other positions of the benzothiadiazide core generally did not yield a further gain in affinity and in some cases abolished drug binding. The 5'-ethyl derivative exhibited an EC50 value in the order of 22 muM which represents about a 30-fold gain in affinity over that of IDRA-21. The EC50 value is comparable to that of cyclothiazide, the most potent benzothiadiazide drug, but the effects on AMPA receptors differed substantially between these two compounds in that the 5'-ethyl derivative of IDRA-21 greatly increased the binding affinity for receptor agonists whereas cyclothiazide is known to reduce agonist binding. The structure-activity relationships reported here thus offer to provide new insights how receptor kinetics is linked to particular aspects of receptor-drug interactions. (C) 2002 Published by Elsevier Science Ltd.
• “A Sweet Combination”: Developing Saccharin and Acesulfame K Structures for Selectively Targeting the Tumor-Associated Carbonic Anhydrases IX and XII
  作者：Silvia Bua、Carrie Lomelino、Akilah B. Murray、Sameh M. Osman、Zeid A. ALOthman、Murat Bozdag、Hatem A. Abdel-Aziz、Wagdy M. Eldehna、Robert McKenna、Alessio Nocentini、Claudiu T. Supuran

  DOI：10.1021/acs.jmedchem.9b01669

  日期：2020.1.9

  The sweeteners saccharin (SAC) and acesulfame K (ACE) recently entered the topic of anticancer human carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, as they showed to selectively inhibit the tumor-associated CAs IX/XII over ubiquitous CAs. A drug design strategy is here reported, which took SAC and ACE as leads and produced a series of 2H-benzo [e][1,2,4]thiadiazin-3(4H)-one-1,1-dioxides (BTD). Many derivatives showed greater potency (K(I)s-CA IX 19.1-408.5 nM) and selectivity (II/IX SI 2-76) than the leads (K(I)s-CA IX 103, 2400 nM; II/IX-SI 56, >4) against CA IX/XII over off-target isoforms. A thorough X-ray crystallographic study depicted their binding mode to both CA II and IX-mimic. The most representative BTDs were characterized in vitro for their antitumor activity against A549, PC-3, and HCT-116 cancer cell lines both in normoxia and hypoxia. The two most effective compounds were assayed for their effect on several apoptosis markers, identifying promising leads for the development of new anticancer drugs.