4-cyclopropyl-3,4-dihydro-7-nitro-2H-1,2,4-benzothiadiazine 1,1-dioxide | 1204573-81-8

• 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-nitro-2H-1,2,4-benzothiadiazine 1,1-dioxide
• 英文别名: 4-Cyclopropyl-7-nitro-2,3-dihydro-1lambda6,2,4-benzothiadiazine 1,1-dioxide；4-cyclopropyl-7-nitro-2,3-dihydro-1λ6,2,4-benzothiadiazine 1,1-dioxide
• CAS: 1204573-81-8
• 化学式: C₁₀H₁₁N₃O₄S
• 分子量: 269.281
• InChiKey: HHEDIWRTQHXSNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 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：
  104
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  7-chloro-4-cyclopropyl-4H-1,2,4-benzothiadiazine-1,1-dioxide 在 sodium tetrahydroborate 作用下， 以 异丙醇 为溶剂， 以60%的产率得到4-cyclopropyl-3,4-dihydro-7-nitro-2H-1,2,4-benzothiadiazine 1,1-dioxide
  参考文献：
  名称：

  Synthesis, Pharmacological and Structural Characterization, and Thermodynamic Aspects of GluA2-Positive Allosteric Modulators with a 3,4-Dihydro-2H-1,2,4-benzothiadiazine 1,1-Dioxide Scaffold

  摘要：

  Positive allosteric modulators of ionotropic glutamate receptors are potential compounds for treatment of cognitive disorders, e.g., Alzheimer's disease. The modulators bind within the dimer interface of the ligand-binding domain (LBD) and stabilize the agonist-bound conformation, thereby slowing receptor desensitization and/or deactivation. Here we describe the synthesis and pharmacological testing at GluA2 of a new generation of 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides. The most potent modulator 3 in complex with GluA2-LBD-L483Y-N754S was subjected to structural analysis by X-ray crystallography, and the thermodynamics of binding was studied by isothermal titration calorimetry. Compound 3 binds to GluA2-LBD-L483Y-N754S with a K-d of 0.35 mu M (Delta H = -7.5 kcal/mol and -T Delta S = -1.3 kcal/mol). This is the first time that submicromolar binding affinity has been achieved for this type of positive allosteric modulator. The major structural factor increasing the binding affinity of 3 seems to be interactions between the cyclopropyl group of 3 and the backbone of Phe495 and Met496.

  DOI：

  10.1021/jm4012092

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。
• 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
• US7741320B2
  申请人：——

  公开号：US7741320B2

  公开（公告）日：2010-06-22
• [EN] NEW CYCLOALKYLATED BENZOTHIADIAZINE DERIVATIVES, METHOD FOR PREPARING THEM AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM<br/>[FR] NOUVEAUX DERIVES DE BENZOTHIADIAZINES CYCLOALKYLEES, LEUR PROCEDE DE PREPARATION ET LES COMPOSITIONS PHARMACEUTIQUES QUI LES CONTIENNENT
  申请人：SERVIER LAB

  公开号：WO2010004139A1

  公开（公告）日：2010-01-14

  Composés de formule (I) dans laquelle Rcy représente un groupement cycloalkyle ou un groupement cycloalkylalkyle non- substitué ou substitué, R1, R2, R3 et R4, identiques ou différents, représentent chacun un atome d'hydrogène ou d'halogène ou un groupement nitro; cyano; hydroxy; alkoxy; alkyle; amino non-substitué ou substitué; carboxy; alkoxycarbonyle; loxycarbonyle; aminocarbonyle non-substitué ou substitué.
• Synthesis, Pharmacological and Structural Characterization, and Thermodynamic Aspects of GluA2-Positive Allosteric Modulators with a 3,4-Dihydro-2<i>H</i>-1,2,4-benzothiadiazine 1,1-Dioxide Scaffold
  作者：Ann-Beth Nørholm、Pierre Francotte、Lars Olsen、Christian Krintel、Karla Frydenvang、Eric Goffin、Sylvie Challal、Laurence Danober、Iuliana Botez-Pop、Pierre Lestage、Bernard Pirotte、Jette S. Kastrup

  DOI：10.1021/jm4012092

  日期：2013.11.14

  Positive allosteric modulators of ionotropic glutamate receptors are potential compounds for treatment of cognitive disorders, e.g., Alzheimer's disease. The modulators bind within the dimer interface of the ligand-binding domain (LBD) and stabilize the agonist-bound conformation, thereby slowing receptor desensitization and/or deactivation. Here we describe the synthesis and pharmacological testing at GluA2 of a new generation of 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides. The most potent modulator 3 in complex with GluA2-LBD-L483Y-N754S was subjected to structural analysis by X-ray crystallography, and the thermodynamics of binding was studied by isothermal titration calorimetry. Compound 3 binds to GluA2-LBD-L483Y-N754S with a K-d of 0.35 mu M (Delta H = -7.5 kcal/mol and -T Delta S = -1.3 kcal/mol). This is the first time that submicromolar binding affinity has been achieved for this type of positive allosteric modulator. The major structural factor increasing the binding affinity of 3 seems to be interactions between the cyclopropyl group of 3 and the backbone of Phe495 and Met496.