7-氯-4H-苯并[e][1,2,4]噻二嗪1,1-二氧化物 | 19477-12-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻二嗪
• 中文名称: 7-氯-4H-苯并[e][1,2,4]噻二嗪1,1-二氧化物
• 英文名称: 7-chloro-4H-1,2,4-benzothiadiazine 1,1-dioxide
• 英文别名: 7-Chlor-1,2,4-benzothiadiazin-1,1-dioxid；7-Chloro-4H-benzo[e][1,2,4]thiadiazine 1,1-dioxide；7-chloro-4H-1λ6,2,4-benzothiadiazine 1,1-dioxide
• CAS: 19477-12-4
• 化学式: C₇H₅ClN₂O₂S
• 分子量: 216.648
• InChiKey: YFIQALNGUVTNHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  13
• 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：
  66.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-氯-4H-苯并[e][1,2,4]噻二嗪1,1-二氧化物 在 sodium tetrahydroborate 、 potassium carbonate 作用下， 以 异丙醇 、 乙腈 为溶剂， 反应 3.75h， 生成 7-Chloro-4-ethyl-2,3-dihydro-1lambda6,2,4-benzothiadiazine 1,1-dioxide
  参考文献：
  名称：

  Design, Synthesis, and Pharmacology of Novel 7-Substituted 3,4-Dihydro-2H-1,2,4-benzothiadiazine 1,1-Dioxides as Positive Allosteric Modulators of AMPA Receptors

  摘要：

  A series of 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides have been synthesized and evaluated as potentiators of AMPA receptors. Attention was paid to the impact of the substituent introduced at the 7-position of the heterocycle. The biological evaluation was achieved by measuring the AMPA current in rat cortex mRNA-injected Xenopus oocytes. The most potent compound, 4-ethyl-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide (12a) was found to be active in an object recognition test in rats demonstrating cognition enhancing effects in vivo after oral administration.

  DOI：

  10.1021/jm070120i
• 作为产物：
  描述：

  7-chloro-2,3-dihydro-3-oxo-4H-1,2,4-benzothiadiazine 在 硫酸 、 水 作用下， 反应 10.0h， 生成 7-氯-4H-苯并[e][1,2,4]噻二嗪1,1-二氧化物
  参考文献：
  名称：

  10.1111/cbdd.14556

  摘要：

  AbstractHistone deacetylase 6 (HDAC6), as the key regulatory enzyme, plays an important role in the development of the nervous system. More and more studies indicate that HDAC6 has become a promising therapeutic target for CNS diseases. Herein we designed and synthesized a series of novel HDAC6 inhibitors with benzothiadiazinyl systems as cap groups and evaluated their activity in vitro and in vivo. Among them, compound 3 exhibited superior selective inhibitory activity against HDAC6 (IC50 = 5.1 nM, about 30‐fold selectivity over HDAC1). The results of docking showed that compound 3 can interact well with the key amino acid residues of HDAC6. Compound 3 showed lower cytotoxicity (20 μM to SH‐SY5Y cells, inhibition rate = 25.75%) and better neuroprotective activity against L‐glutamate‐induced SH‐SY5Y cell injury model in vitro. Meanwhile, compound 3 exhibited weak cardiotoxicity (10 μM hERG inhibition rate = 17.35%) and possess good druggability properties. Especially, compound 3 could significantly reduce cerebral infarction from 49.87% to 32.18%, and similar with butylphthalide in MCAO model, indicating potential clinical application prospects for alleviating ischemic stroke‐induced brain infarction.

  DOI：

  10.1111/cbdd.14556

文献信息

• COMPOUND, COMPOSITION, AND METHOD FOR PROTECTING SKIN FROM HIGH ENERGY VISIBLE LIGHT
  申请人：PHOTOPROTECTIVE TECHNOLOGIES, INC.

  公开号：US20160317425A1

  公开（公告）日：2016-11-03

  A compound, composition, and method for the protection of skin from the harmful effects of radiation, and particularly the harmful effects of high energy visible (HEV) radiation, are disclosed. The compound is a melanin derivative that can be formulated into compositions containing the melanin derivative and a suitable carrier. The composition is topically applied to the skin to reduce the risk of photoaging and improve skin repair due to damage from radiation.

  揭示了一种用于保护皮肤免受辐射有害影响的化合物、组合物和方法，特别是高能可见光（HEV）辐射的有害影响。该化合物是一种黑色素衍生物，可配制成含有该黑色素衍生物和适当载体的组合物。该组合物局部应用于皮肤，以减少光老化的风险并改善由辐射造成的皮肤修复。
• Fluorinated benzothiadiazine compounds
  申请人：Francotte Pierre

  公开号：US20050165008A1

  公开（公告）日：2005-07-28

  Compounds of formula (I): wherein: R F represents monofluoro- or polyfluoro-alkyl or monofluoro- or polyfluoro-cycloalkylalkyl, R 1 represents hydrogen or a group selected from alkylaminocarbonyl and optionally substituted alkyl, R 2 represents hydrogen, halogen or a group selected from cycloalkyl and optionally substituted alkyl, R 3 to R 6 , which may be the same or different, each represent an atom or group selected from hydrogen, halogen, nitro, cyano, alkylsulphonyl, hydroxy, alkoxy, optionally substituted alkyl and optionally substituted amino, its optical isomers when they exist, and also their addition salts with a pharmaceutically acceptable acid or base. Medicinal products containing the same which are useful as AMPA modulators.

  公式（I）的化合物：其中：RF代表单氟或多氟烷基或单氟或多氟环烷基烷基，R1代表氢或从烷基氨基甲酰基和可选择地取代的烷基中选择的基团，R2代表氢，卤素或从环烷基和可选择地取代的烷基中选择的基团，R3到R6，可以相同也可以不同，每个代表从氢，卤素，硝基，氰基，烷基磺酰基，羟基，烷氧基，可选择地取代的烷基和可选择地取代的氨基中选择的原子或基团，当它们存在时，其光学异构体，以及其与药学上可接受的酸或碱形成的盐。含有这些化合物的药物产品，可用作AMPA调节剂。
• Cycloalkylated benzothiadiazines, a process for their preparation and pharmaceutical compostions containing them
  申请人：FRANCOTTE Pierre

  公开号：US20100009974A1

  公开（公告）日：2010-01-14

  Compounds of formula (I): wherein: R Cy represents an unsubstituted or substituted cycloalkyl group or cycloalkylalkyl group, R 1 , R 2 , R 3 and R 4 , which may be the same or different, each represent a hydrogen or halogen atom or a nitro group; a cyano group; a hydroxy group; an alkoxy group; an alkyl group; an unsubstituted or substituted amino group; a carboxy group; an alkoxycarbonyl group; an aryloxycarbonyl group; an unsubstituted or substituted aminocarbonyl group. Medicinal products containing the same which are useful in treating or preventing conditions treatable by an AMPA receptor modulator.

  式（I）的化合物：其中：RCy表示未取代或取代的环烷基或环烷基烷基，R1、R2、R3和R4，可以相同也可以不同，每个代表氢或卤素原子或硝基团；氰基；羟基；烷氧基；烷基；未取代或取代的氨基团；羧基；烷氧羰基；芳基氧羰基；未取代或取代的氨基羰基。含有这些化合物的药物产品，可用于治疗或预防通过AMPA受体调节剂可治疗的疾病。
• Synthesis and Pharmacology of Mono-, Di-, and Trialkyl-Substituted 7-Chloro-3,4-dihydro-2<i>H</i>-1,2,4-benzothiadiazine 1,1-Dioxides Combined with X-ray Structure Analysis to Understand the Unexpected Structure–Activity Relationship at AMPA Receptors
  作者：Anja Probst Larsen、Pierre Francotte、Karla Frydenvang、Daniel Tapken、Eric Goffin、Pierre Fraikin、Daniel-Henri Caignard、Pierre Lestage、Laurence Danober、Bernard Pirotte、Jette Sandholm Kastrup

  DOI：10.1021/acschemneuro.5b00318

  日期：2016.3.16

  4-monoalkyl-substituted benzothiadiazine dioxides for which the cyclopropyl group constitutes the best choice of substituent. 7b was subjected to X-ray structural analysis in complex with the GluA2 ligand-binding domain. We propose an explanation of the unexpected structure–activity relationship of this new series of mono-, di-, and trialkyl-substituted 1,2,4-benzothiadiazine 1,1-dioxide compounds. The

  2-氨基-3-（3-羟基-5-甲基异恶唑-4-基）丙酸（AMPA）型离子型谷氨酸受体的正构构调节剂是用于治疗神经系统疾病（例如阿尔茨海默氏病）的有前途的化合物。在这里，我们报告一系列单，二或三烷基取代的7-氯-3,4-二氢-2 H -1,2,4-苯并噻二嗪1,1-二氧化物的合成和药理学评估，其中包括总共16个新的调制器。三取代的化合物7b，7d和7e表现出有效的活性（EC 2x= 2.7–4.3μM；在体外细胞荧光测定（FLIPR）中作为AMPA受体增强剂的，负责AMPA介导的应答增加2倍的化合物的浓度。与先前描述的4-单烷基取代的苯并噻二二嗪二氧化物相反，4-环丙基化合物7f的效力明显较低（EC 2x = 60μM），其中环丙基是取代基的最佳选择。7b将其与GluA2配体结合结构域一起进行X射线结构分析。我们提出了这种新的单，二和三烷基取代的1,2,4-苯并噻二嗪1,1-二氧化物化合物系
• Fully Automated Synthesis and Evaluation of [ ¹⁸ F]BPAM121: Potential of an AMPA Receptor Positive Allosteric Modulator as PET Radiotracer
  作者：Alexandra Manos‐Turvey、Guillaume Becker、Pierre Francotte、Maria Elisa Serrano、André Luxen、Bernard Pirotte、Alain Plenevaux、Christian Lemaire

  DOI：10.1002/cmdc.201800816

  日期：2019.4.3

  significant burden on society. In the search for new AD drugs, modulators of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are of particular interest, as loss of synaptic AMPARs has been linked to AD learning and memory deficits. Previously reported fluorine-containing BPAM121, an AMPA positive allosteric modulator (pam) with high activity, low toxicity, and slow metabolism,

  阿尔茨海默氏病（AD）仍然是社会的重大负担。在寻找新的AD药物时，α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）的调节剂特别令人关注，因为突触AMPAR的丢失与AD学习和记忆缺陷有关。先前报道的含氟BPAM121是AMPA阳性变构调节剂（pam），具有高活性，低毒性和缓慢的代谢，被认为是正电子发射断层扫描（PET）AD诊断研究的理想18 F标记候选物。为了在临床上使用该化合物，开发了一种自动合成技术，避免了人体辐射暴露。本文介绍了使用GE Healthcare提供的商用FASTlab合成仪以及全套质量控制方法，以较高的量详细生产[18 F] BPAM121的方法，以及甲苯磺酸化前体和氟化参考物的合成方法。为了评估[18 F] BPAM121作为潜在AD诊断的临床实用性，随后在小鼠中进行了一些体内研究，同时进行了阻断和竞争研究。