4-cyclopropyl-3,4-dihydro-7-hydroxy-2H-1,2,4-benzothiadiazine 1,1-dioxide | 1204575-09-6

• 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: 4-cyclopropyl-3,4-dihydro-7-hydroxy-2H-1,2,4-benzothiadiazine 1,1-dioxide
• 英文别名: 4-cyclopropyl-7-hydroxy-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide；4-cyclopropyl-7-hydroxy-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine-1,1-dioxide；BPAM521；4-cyclopropyl-1,1-dioxo-2,3-dihydro-1λ6,2,4-benzothiadiazin-7-ol
• CAS: 1204575-09-6
• 化学式: C₁₀H₁₂N₂O₃S
• 分子量: 240.283
• InChiKey: OMEAYSCNDLQLNC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  78
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-cyclopropyl-3,4-dihydro-7-hydroxy-2H-1,2,4-benzothiadiazine 1,1-dioxide 、 3-甲氧基苯硼酸 在 吡啶 、 copper diacetate 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以31%的产率得到4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide
  参考文献：
  名称：

  7-苯氧基取代的3,4-二氢-2 H -1,2,4-苯并噻二嗪1,1-二氧化物作为α-氨基-3-羟基-5-羟基-4-甲基-4-异恶唑丙酸（AMPA）的正变构调节剂具有纳摩尔效价的受体

  摘要：

  我们在这里报告7-苯氧基取代的3,4-二氢-2 H -1,2,4-苯并噻二嗪1,1-二氧化物的合成及其作为AMPA受体阳性变构调节剂（AMPApams）的评估。考察了取代对苯氧基和4-位氮原子的影响。在HEK293细胞中表达的GluA2（Q）处（钙通量实验），最有效的化合物是11m（4-环丙基-7-（3-甲氧基苯氧基）-3,4-二氢-2 H -1,2,4-苯并噻二嗪1,1-二氧化物，EC 50= 2.0 nM）。使用隔离的GluA2配体结合结构域（GluA2-LBD）进行的小角X射线散射（SAXS）实验中的筛选中的Hill系数和二聚化曲线的形状与每个二聚体界面结合一个11m的分子是一致的，与迄今为止开发的大多数苯并噻二嗪二氧化物相反。通过与GluA2-LBD结合的11m的X射线结构和NMR证实了该观察结果。这是第一个达到纳摩尔范围的二氧化苯并噻二嗪二甲酰胺。

  DOI：

  10.1021/acs.jmedchem.7b01323
• 作为产物：
  描述：

  2-氨基-5-甲氧基-苯磺酰胺 在 sodium tetrahydroborate 、 三氟化硼乙醚 、 三溴化硼 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 、 异丙醇 为溶剂， 反应 62.0h， 生成 4-cyclopropyl-3,4-dihydro-7-hydroxy-2H-1,2,4-benzothiadiazine 1,1-dioxide
  参考文献：
  名称：

  调节剂在离子型谷氨酸受体 GluA2 结合中的焓-熵补偿

  摘要：

  离子型谷氨酸受体 A2 (GluA2) 的 1,2,4-苯并噻二嗪 1,1-二氧化物类型的正变构调节剂是治疗认知障碍（例如阿尔茨海默病）的有前景的先导化合物。调节剂在由两个相邻配体结合域的界面形成的裂缝中结合，并通过稳定激动剂结合的开放通道构象而起作用。这些调节剂结合背后的驱动力可以显着改变，只需对母体分子进行少量替换。在这项研究中，我们表明将调节剂 BPAM97 (2) 和 BPAM344 (3) 的 7-氟取代基改变为羟基（分别为 BPAM557 (4) 和 BPAM521 (5)），会导致更有利的结合焓。 ΔH，kcal/mol) 从 -4.9 (2) 和 -7.5 (3) 到 -6.2 (4) 和 -14.5 (5)，但也有一个不太有利的结合熵 (-TΔS, kcal/mol)，从 -2.3 (2) 和 -1.3 (3) 到 -0.5 (4) 和 4.8 (5)。因此，4 (11.2)

  DOI：

  10.1016/j.bpj.2016.04.032

文献信息

• 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。
• Cycloalkylated benzothiadiazines, a process for their preparation and pharmaceutical compositions containing them
  申请人：Les Laboratoires Servier

  公开号：US07741320B2

  公开（公告）日：2010-06-22

  Compounds of formula (I): wherein: RCy represents an unsubstituted or substituted cycloalkyl group or cycloalkylalkyl group, R1, R2, R3 and R4, 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.

  化合物的公式（I）： 其中： RCy代表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，分别代表氢原子或卤素原子或硝基基团；氰基；羟基；烷氧基；烷基；未取代或取代的氨基基团；羧基；烷氧羰基基团；芳基氧羰基基团；未取代或取代的氨基羰基基团。 含有上述化合物的药物可用于治疗或预防可通过AMPA受体调节剂治疗的疾病。
• Radiosynthesis of a carbon-11-labeled AMPAR allosteric modulator as a new PET radioligand candidate for imaging of Alzheimer’s disease
  作者：Caihong Miao、Fugui Dong、Limeng Jia、Wei Li、Min Wang、Qi-Huang Zheng、Zhidong Xu

  DOI：10.1016/j.bmcl.2019.03.027

  日期：2019.5

  To develop PET tracers for imaging of Alzheimer's disease, a new carbon-11-labeled AMPAR allosteric modulator 4-cyclopropyl-7-(3-[C-11] methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4] thiadiazine 1,1-dioxide ([C-11] 8) has been synthesized. The reference standard 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4] thiadiazine 1,1-dioxide (8) and its corresponding desmethylated precursor 4-cyclopropyl-7-(3-hydroxyphenoxy)3,4- dihydro-2H-benzo[e][1,2,4] thiadiazine 1,1-dioxide (9) were synthesized from 4-methoxyabiline and chlorosulfonyl isocyanate in eight and nine steps with 3% and 1% overall chemical yield, respectively. The target tracer [C-11] 8 was prepared from the precursor 9 with [C-11] CH3OTf through O-[C-11] methylation and isolated by HPLC combined with SPE in 10-15% radiochemical yield, based on [C-11] CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was> 99%, and the molar activity (AM) at EOB was 370-740 GBq/mu mol with a total synthesis time of 35-40-minutes from EOB.
• Nouveaux dérivés de benzothiadiazines cycloalkylées, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent
  申请人：Les Laboratoires Servier

  公开号：EP2147915B1

  公开（公告）日：2010-09-15
• Modulation of AMPA/kainate Receptors for the Treatment of Hypoglycemia
  申请人：Vanderklish Peter

  公开号：US20200397751A1

  公开（公告）日：2020-12-24

  Methods for modulating the levels of glucagon and blood glucose of a mammal are provided. In the subject methods, a positive allosteric modulator of AMPA/kainate receptors is administered to a host. The subject methods find use in applications where it is desired to increase one or both of the glucagon and blood glucose levels in a mammalian host. The subject methods find use in applications where it is desired to decrease the size, or breadth, of the circadian range of blood glucose levels in a mammalian host. The subject methods also find use in applications where it is desired to decrease the frequency, severity, or occurrence of hypoglycemia in a mammalian host. Finally, the subject method finds use in applications where it is desired to decrease the frequency, severity, or occurrence of nocturnal hypoglycemia in a mammalian host, particularly that which occurs in diabetics as a result of therapy with insulins or insulin analogs or other glucose lowering agents, or combinations of such agents.