7-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide | 37162-49-5

• 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: 7-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide
• 英文别名: 7-methyl-4H-benzo[e][1,2,4]thiadiazine-1,1-dioxide；7-methyl-4H-1lambda6,2,4-benzothiadiazine 1,1-dioxide；7-methyl-4H-1λ6,2,4-benzothiadiazine 1,1-dioxide
• CAS: 37162-49-5
• 化学式: C₈H₈N₂O₂S
• 分子量: 196.23
• InChiKey: DQTWWADBZWIDRU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 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-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide 在 sodium tetrahydroborate 、 potassium carbonate 作用下， 以 异丙醇 、 乙腈 为溶剂， 反应 3.75h， 生成 4,7-dimethyl-2,3-dihydro-4H-1,2,4-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-甲基-1,1-二氧代-1,4-二氢-2H-1 lambda*6*-苯并[1,2,4]噻二嗪-3- 酮 在 硫酸 作用下， 以 水 为溶剂， 反应 8.5h， 生成 7-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide
  参考文献：
  名称：

  C7修饰对苯并噻二嗪-1,1-二氧化物衍生物的抑制活性和对醛糖还原酶选择性的影响

  摘要：

  糖尿病患者慢性并发症的发展和进展，例如视网膜病，肾病，神经病，白内障和中风，与醛糖还原酶（ALR2）的激活和/或过表达有关，醛糖还原酶是醛糖-酮基还原酶的成员超家族。进行结构-活性关系研究，重点研究1,2,4-苯并噻二嗪-1,1-二氧化物衍生物的C7位置，试图发现具有增强的效能和选择性的ALR2抑制剂。这些研究导致了一系列新的C7取代的化合物，这些化合物被评估了对ALR2的抑制活性。他们表现出的IC 50值在2.80–45.13 n M的范围内。发现分别具有C7-二甲基氨基甲酰基和C7-二乙基氨基甲酰基取代基的两种化合物最具活性，并且相对于醛还原酶（ALR1）具有极好的ALR2选择性。本文介绍的结构-活性关系分析和分子建模研究突显了C7位置疏水和庞大基团对于抑制ALR2的活性和选择性的重要性。

  DOI：

  10.1002/cmdc.201200386

文献信息

• Effect of C7 Modifications on Benzothiadiazine-1,1-dioxide Derivatives on Their Inhibitory Activity and Selectivity toward Aldose Reductase
  作者：Shuzhen Zhang、Xin Chen、Shagufta Parveen、Saghir Hussain、Yanchun Yang、Chaojun Jing、Changjin Zhu

  DOI：10.1002/cmdc.201200386

  日期：2013.4

  activation and/or overexpression of aldose reductase (ALR2), which is a member of the aldo–keto reductase superfamily. A structure–activity relationship study focused on the C7 position of 1,2,4‐benzothiadiazine‐1,1‐dioxide derivatives was pursued in an attempt to discover ALR2 inhibitors with enhanced potency and selectivity. These studies led to a series of new C7‐substituted compounds, which were

  糖尿病患者慢性并发症的发展和进展，例如视网膜病，肾病，神经病，白内障和中风，与醛糖还原酶（ALR2）的激活和/或过表达有关，醛糖还原酶是醛糖-酮基还原酶的成员超家族。进行结构-活性关系研究，重点研究1,2,4-苯并噻二嗪-1,1-二氧化物衍生物的C7位置，试图发现具有增强的效能和选择性的ALR2抑制剂。这些研究导致了一系列新的C7取代的化合物，这些化合物被评估了对ALR2的抑制活性。他们表现出的IC 50值在2.80–45.13 n M的范围内。发现分别具有C7-二甲基氨基甲酰基和C7-二乙基氨基甲酰基取代基的两种化合物最具活性，并且相对于醛还原酶（ALR1）具有极好的ALR2选择性。本文介绍的结构-活性关系分析和分子建模研究突显了C7位置疏水和庞大基团对于抑制ALR2的活性和选择性的重要性。
• BICYCLIC LACTAM FACTOR VIIA INHIBITORS USEFUL AS ANTICOAGULANTS
  申请人：Wurtz Nicholas Ronald

  公开号：US20100041664A1

  公开（公告）日：2010-02-18

  The present invention provides novel bicyclic lactams derivatives, and analogues thereof, of Formula (I): or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein the variables A, B, C, W, Y, Z 1 , Z 2 , Z 3 , Z 4 , R 8 , and R 9 are as defined herein. These compounds are selective inhibitors of factor VIIa which can be used as medicaments.

  本发明提供了新型双环内酰胺衍生物及其类似物，其化学式为(I)：或其立体异构体、互变异构体、药学上可接受的盐、溶剂化物或前药。其中，变量A、B、C、W、Y、Z1、Z2、Z3、Z4、R8和R9的定义如本文所述。这些化合物是选择性因子VIIa抑制剂，可用作药物。
• New Fluorinated 1,2,4-Benzothiadiazine 1,1-Dioxides: Discovery of an Orally Active Cognitive Enhancer Acting through Potentiation of the 2-Amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic Acid Receptors
  作者：Pierre Francotte、Eric Goffin、Pierre Fraikin、Pierre Lestage、Jean-Claude Van Heugen、Florian Gillotin、Laurence Danober、Jean-Yves Thomas、Patrice Chiap、Daniel-Henri Caignard、Bernard Pirotte、Pascal de Tullio

  DOI：10.1021/jm901495t

  日期：2010.2.25

  In the search of a potent cognitive enhancer, a series of 3,4-dihydro-2H-1,2,4-benzothiadiazine 1, 1-dioxides have been synthesized and evaluated its positive allosteric modulators of the AMPA receptors. In the present work, we focused our efforts on the insertion of mono- or polyfluoro-substituted alkyl chains at the 4-position of the thiadiazine ring In all attempt to enhance the pharmacokinetic behavior of previously described compounds. Among all the described compounds, 7-chloro-4-(2-fluoroethyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine 1, 1-dioxide, 12b, was shown to exert a strong activity on AMPA receptors in vitro and it marked cognitive-enhancing effect in vivo after oral administration to Wistar rats. Considering its in vivo activity, the metabolic degradation of 12b was studied and compared to that of its nonfluorinated analogue 9b. Taken together, results of this study clearly validated the positive impact of the fluorine atom on the alkyl chain at file 4-position of benzothiadiazine dioxides oil activity and metabolic stability.
• NOUVEAUX DERIVES DE BENZOTHIADIAZINES, LEUR PROCEDE DE PREPARATION ET LES COMPOSITIONS PHARMACEUTIQUES QUI LES CONTIENNENT
  申请人：Les Laboratoires Servier

  公开号：EP1233953B1

  公开（公告）日：2003-05-14
• MACROCYCLIC FACTOR VIIA INHIBITORS USEFUL AS ANTICOAGULANTS
  申请人：Wurtz Nicholas Ronald

  公开号：US20100113488A1

  公开（公告）日：2010-05-06

  The present invention relates generally to novel macrocycles of Formula (I): or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein the variables A, B, C, D, L, M, W, Z 1 , Z 2 , Z 3 , Z 4 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 are as defined herein. These compounds are selective inhibitors of factor VIIa which can be used as medicaments.