5-chloro-2H-benzo[e][1,2,4]thiadiazin-3(4H)-one 1,1-dioxide | 159190-01-9

• 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: 5-chloro-2H-benzo[e][1,2,4]thiadiazin-3(4H)-one 1,1-dioxide
• 英文别名: 5-chloro-3-oxo-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide；5-chloro-1lambda~6~,2,4-benzothiadiazine-1,1,3(2H,4H)-trione；5-chloro-1,1-dioxo-4H-1λ6,2,4-benzothiadiazin-3-one
• CAS: 159190-01-9
• 化学式: C₇H₅ClN₂O₃S
• 分子量: 232.647
• InChiKey: LHWAXFMPTHUVQY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-chloro-2H-benzo[e][1,2,4]thiadiazin-3(4H)-one 1,1-dioxide 在 吡啶 、 tetraphosphorus decasulfide 作用下， 反应 3.0h， 生成 5-chloro-3-thioxo-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide
  参考文献：
  名称：

  氯取代的3-烷基氨基-4 H -1,2,4-苯并噻二嗪1,1-二氧化物作为ATP敏感的钾通道活化剂：氯原子在芳环上的位置对活性和组织选择性的影响

  摘要：

  描述了5-氯-，6-氯-和8-氯取代的3-烷基氨基/环烷基氨基-4 H -1,2,4-苯并噻二嗪1,1-二氧化物的合成。将它们对胰岛素释放过程的抑制作用及其血管舒张活性与先前报道的7-氯-3-烷基氨基/环烷基氨基-4 H -1,2,4-苯并噻二嗪1,1-二氧化物进行了比较。发现“ 5-氯”化合物对胰岛素分泌和平滑肌细胞均基本无活性。相反，发现“ 8-氯”和“ 6-氯”化合物在分泌胰岛素的细胞上具有活性，其中“ 6-氯”衍生物是最有效的药物。此外，“ 6-氯”类似物比“ 7-氯”对应物表现出更少的髓鞘松弛活性。8-氯-3-异丙基氨基-4 H-1,2,4-苯并噻二嗪1,1-二氧化物（25b）和6-氯-3-环丁基氨基-4 H -1,2,4-苯并噻二嗪1,1-二氧化物（19e）被进一步确定为K ATP通道通过对胰岛素分泌细胞进行放射性同位素测量的开环剂。同样，目前在表达人SUR1 / Kir6.2

  DOI：

  10.1021/jm9010093
• 作为产物：
  描述：

  邻氯苯胺 在 aluminum (III) chloride 作用下， 反应 1.0h， 生成 5-chloro-2H-benzo[e][1,2,4]thiadiazin-3(4H)-one 1,1-dioxide
  参考文献：
  名称：

  “A Sweet Combination”: Developing Saccharin and Acesulfame K Structures for Selectively Targeting the Tumor-Associated Carbonic Anhydrases IX and XII

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.9b01669

文献信息

• Benzothiadiazinone-1,1-Dioxide Carbonic Anhydrase Inhibitors Suppress the Growth of Drug-Resistant Mycobacterium tuberculosis Strains
  作者：Silvia Bua、Alessandro Bonardi、Georgiana Ramona Mük、Alessio Nocentini、Paola Gratteri、Claudiu T. Supuran

  DOI：10.3390/ijms25052584

  日期：——

  chemical features of BTD derivatives meet the criteria for a potent inhibition of β-class CA isozymes. BTD derivatives show chemical features meeting the criteria for a potent inhibition of β-class CA isozymes. Specifically, three β-CAs (MtCA1, MtCA2, and MtCA3) were identified in Mycobacterium tuberculosis and their inhibition was shown to exert an antitubercular action. BTDs derivatives 2a-q effectively

  本文探索基于 2H-苯并[e][1,2,4]噻二嗪-3(4H)-酮 1,1-二氧化物 (BTD) 的碳酸酐酶 (CA) 抑制剂作为新型抗分枝杆菌药物。 BTD衍生物的化学特性符合有效抑制β-类CA同工酶的标准。 BTD 衍生物的化学特征符合有效抑制 β 类 CA 同工酶的标准。具体而言，在结核分枝杆菌中鉴定出三种 β-CA（MtCA1、MtCA2 和 MtCA3），并且对它们的抑制显示出抗结核作用。 BTD 衍生物 2a-q 有效抑制分枝杆菌 CA，尤其是 MtCA2 和 MtCA3，Ki 值高达低纳摩尔范围（MtCA3，Ki = 15.1–2250 nM；MtCA2，Ki = 38.1–4480 nM），并且具有显着的选择性比超过脱靶人类 CA I 和 II。进行了计算研究以阐明化合物的结构-活性关系。重要的是，最有效的 MtCA 抑制剂能够有效抑制对利福平和异烟肼（结核病治疗的标准参考药物）耐药的结核分枝杆菌菌株的生长。
• APPLICATION DE DERIVES DE 2H-1,2,4-BENZOTHIADIAZINE-3(4H)-ONE-1,1-DIOXYDE COMME ANTAGONISTES NON COMPETITIFS DU RECEPTEUR NMDA
  申请人：RHONE-POULENC RORER S.A.

  公开号：EP0687178A1

  公开（公告）日：1995-12-20
• [EN] USE OF 2H-1,2,4-BENZOTHIADIAZINE 3(4H)-ONE 1,1 DIOXIDE DERIVATIVES AS NON-COMPETITIVE NMDA RECEPTOR ANTAGONISTS<br/>[FR] APPLICATION DE DERIVES DE 2H-1,2,4-BENZOTHIADIAZINE-3(4H)-ONE-1,1-DIOXYDE COMME ANTAGONISTES NON COMPETITIFS DU RECEPTEUR NMDA
  申请人：RHONE-POULENC RORER S.A.

  公开号：WO1994020109A1

  公开（公告）日：1994-09-15

  (EN) The use of compounds of formula (I) or salts thereof for preparing non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists is disclosed.(FR) Application des composés de formule (I) ou leurs sels, à la préparation de médicaments antagonistes non compétitifs du récepteur N-méthyl-D-aspartate (NMDA).
• Chloro-Substituted 3-Alkylamino-4<i>H</i>-1,2,4-benzothiadiazine 1,1-Dioxides as ATP-Sensitive Potassium Channel Activators: Impact of the Position of the Chlorine Atom on the Aromatic Ring on Activity and Tissue Selectivity
  作者：Bernard Pirotte、Pascal de Tullio、Quynh-Anh Nguyen、Fabian Somers、Pierre Fraikin、Xavier Florence、Philip Wahl、John Bondo Hansen、Philippe Lebrun

  DOI：10.1021/jm9010093

  日期：2010.1.14

  8-chloro-substituted 3-alkylamino/cycloalkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxides is described. Their inhibitory effect on the insulin releasing process and their vasorelaxant activity was compared to that of previously reported 7-chloro-3-alkylamino/cycloalkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxides. “5-Chloro” compounds were found to be essentially inactive on both the insulin-secreting and

  描述了5-氯-，6-氯-和8-氯取代的3-烷基氨基/环烷基氨基-4 H -1,2,4-苯并噻二嗪1,1-二氧化物的合成。将它们对胰岛素释放过程的抑制作用及其血管舒张活性与先前报道的7-氯-3-烷基氨基/环烷基氨基-4 H -1,2,4-苯并噻二嗪1,1-二氧化物进行了比较。发现“ 5-氯”化合物对胰岛素分泌和平滑肌细胞均基本无活性。相反，发现“ 8-氯”和“ 6-氯”化合物在分泌胰岛素的细胞上具有活性，其中“ 6-氯”衍生物是最有效的药物。此外，“ 6-氯”类似物比“ 7-氯”对应物表现出更少的髓鞘松弛活性。8-氯-3-异丙基氨基-4 H-1,2,4-苯并噻二嗪1,1-二氧化物（25b）和6-氯-3-环丁基氨基-4 H -1,2,4-苯并噻二嗪1,1-二氧化物（19e）被进一步确定为K ATP通道通过对胰岛素分泌细胞进行放射性同位素测量的开环剂。同样，目前在表达人SUR1 / Kir6.2
• “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.