6-Chloro-4-ethyl-3,4-dihydro-2H-thieno[3,2-e][1,2,4]thiadiazine 1,1-dioxide

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 6-Chloro-4-ethyl-3,4-dihydro-2H-thieno[3,2-e][1,2,4]thiadiazine 1,1-dioxide
• 英文别名: 6-chloro-4-ethyl-3,4-dihydro-2H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide；6-chloro-4-ethyl-2,3-dihydrothieno[3,2-e][1,2,4]thiadiazine 1,1-dioxide
• 化学式: C₇H₉ClN₂O₂S₂
• 分子量: 252.746
• InChiKey: RUADYIPVGGYJMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  86
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-Chloro-4-ethyl-3,4-dihydro-2H-thieno[3,2-e][1,2,4]thiadiazine 1,1-dioxide 、 异氰酸乙酯 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 6-Chloro-N-ethyl-4-ethyl-3,4-dihydro-2H-thieno[3,2-e][1,2,4]thiadiazine-2-carboxamide 1,1-dioxide
  参考文献：
  名称：

  Thiadiazine derivatives and use thereof as positive ampa receptor modulators

  摘要：

  化合物的式子（I）： 其中： A代表噻吩基、呋喃基、吡咯基、氧硫杂环基、噻唑基、异噻唑基、噁唑基或咪唑基； 代表单键或双键； R1代表氢、线性或支链（C1-C6）烷基，可选地被卤素或（C1-C6）烷氧基-(C1-C6)烷基中的一种或多种基团取代； R2代表氢或线性或支链（C1-C6）烷基，可选地被一种或多种卤素取代； R3代表氢或从线性或支链（C1-C6）烷基、CONHR′和SO2NHR′中选出的一种基团，其中R′代表线性或支链（C1-C6）烷基。这些化合物的对映体和二对映异构体，以及与药学上可接受的酸或碱形成的加合物都包括在内。含有这些化合物的药物，可用作AMPA抑制剂。

  公开号：

  US20070004709A1
• 作为产物：
  描述：

  6-chloro-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide 在 sodium tetrahydroborate 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 异丙醇 、 乙腈 为溶剂， 反应 7.08h， 生成 6-Chloro-4-ethyl-3,4-dihydro-2H-thieno[3,2-e][1,2,4]thiadiazine 1,1-dioxide
  参考文献：
  名称：

  Development of Thiophenic Analogues of Benzothiadiazine Dioxides as New Powerful Potentiators of 2-Amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic Acid (AMPA) Receptors

  摘要：

  On the basis of the results obtained in previous series of AMPA potentiators belonging to 3,4-dihydro-2H-benzo- and 3,4-dihydro-2H-pyrido-1,2,4-thiadiazine 1,1-dioxides, the present work focuses on the design of original isosteric 3,4-dihydro-2H-thieno-1,2,4-thiadiazine 1,1-dioxides. Owing to the sulfur position, three series of compounds were developed and their activity as AMPA potentiators was characterized. In each of the developed series, potent compounds were discovered. After screening the selected active compounds on a safety in vivo test, 6-chloro-4-ethyl-3,4-dihydro-2H-thieno[2,3-e]-1,2,4-thiadiazine 1,1-dioxide (24) appeared as the most promising compound and was further evaluated. Its effects on long-term potentiation in vivo and on AMPA-mediated noradrenaline release were measured to predict its potential cognitive enhancing properties. Finally, an object recognition test performed in mice revealed that 24 was able to significantly enhance cognition, after oral administration, at doses as low as 0.3 mg/kg. This study validates the interest of the isosteric replacement of the benzene or pyridine nuclei by the thiophene nucleus in the ring-fused thiadiazine dioxides class of AMPA potentiators.

  DOI：

  10.1021/jm400676g

文献信息

• Thiadiazine derivatives and use thereof as positive AMPA receptor modulators
  申请人：Les Laboratoires Servier

  公开号：US07476668B2

  公开（公告）日：2009-01-13

  Compounds of formula (I): wherein: A represents thienyl, furyl, pyrrolyl, oxathiol, thiazole, isothiazole, oxazole or imidazole, represents a single bond or a double bond, R1 represents hydrogen, linear or branched (C1-C6)alkyl optionally substituted by one or more groups selected from halogen or (C1-C6)alkoxy-(C1-C6)alkyl, R2 represents hydrogen or linear or branched (C1-C6)alkyl group optionally substituted by one or more halogen, R3 represents hydrogen or a group selected from linear or branched (C1-C6)alkyl, CONHR′ and SO2NHR′ wherein R′ represents linear or branched (C1-C6)alkyl, its enantiomers and diastereoisomers, and addition salts thereof with a pharmaceutically acceptable acid or base. Medicinal products containing the same, which are useful as AMPA inhibitors.

  化合物的式子（I）： 其中： A代表噻吩基、呋喃基、吡咯基、氧硫杂环基、噻唑基、异噻唑基、噁唑基或咪唑基，表示单键或双键， R1代表氢、线性或支链（C1-C6）烷基，可选地被卤素或（C1-C6）烷氧基-(C1-C6）烷基中的一个或多个基团取代， R2代表氢或线性或支链（C1-C6）烷基，可选地被一个或多个卤素取代， R3代表氢或从线性或支链（C1-C6）烷基、CONHR′和SO2NHR′中选择的一个基团，其中R′代表线性或支链（C1-C6）烷基，以及其对映体和非对映异构体，以及与药学上可接受的酸或碱形成的加合物。 含有上述化合物的药物，其作为AMPA抑制剂是有用的。
• DERIVES DE THIADIAZINE ET LEUR UTILISATION COMME MODULATEURS POSITIFS DES RECEPTEURS AMPA
  申请人：Les Laboratoires Servier

  公开号：EP1620441A1

  公开（公告）日：2006-02-01
• US7476668B2
  申请人：——

  公开号：US7476668B2

  公开（公告）日：2009-01-13
• [EN] THIADIAZINE DERIVATIVES AND USE THEREOF AS POSITIVE AMPA RECEPTOR MODULATORS<br/>[FR] DERIVES DE THIADIAZINE ET LEUR UTILISATION COMME MODULATEURS POSITIFS DES RECEPTEURS AMPA
  申请人：SERVIER LAB

  公开号：WO2004099217A1

  公开（公告）日：2004-11-18

  Composés de formule (I) dans laquelle A représente un groupement thiényle, furyle, pyrrolyle, oxathiole, thiazole, isothiazole, oxazole ou imidazole, • ç représente une liaison simple ou une liaison double, R1 représente un atome d'hydrogène, un groupement alkyle (C1-C6) linéaire ou ramifié, éventuellement substitué par un ou plusieurs atomes d'halogène, ou un groupement alkoxy (C1-C6) alkyle (C1-C6), R2 représente un atome d'hydrogène ou un groupement alkyle (C1-C6) linéaire ou ramifié, éventuellement substitué par un ou plusieurs atomes d'halogène, R3 représente un atome d'hydrogène ou un groupement choisi parmi alkyle (C1-C6) linéaire ou ramifié, CONHR' ou SO2NHR' dans lesquels R' représente un groupement alkyle (C1-C6) linéaire ou ramifié, leurs énantiomères, diastéréoisomères ainsi que leurs sels d'addition à un acide ou à une base pharmaceutiquement acceptable. Médicaments.
• Development of Thiophenic Analogues of Benzothiadiazine Dioxides as New Powerful Potentiators of 2-Amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic Acid (AMPA) Receptors
  作者：Pierre Francotte、Eric Goffin、Pierre Fraikin、E. Graindorge、Pierre Lestage、Laurence Danober、Sylvie Challal、Nathalie Rogez、Olivier Nosjean、Daniel-Henri Caignard、Bernard Pirotte、Pascal de Tullio

  DOI：10.1021/jm400676g

  日期：2013.10.24

  On the basis of the results obtained in previous series of AMPA potentiators belonging to 3,4-dihydro-2H-benzo- and 3,4-dihydro-2H-pyrido-1,2,4-thiadiazine 1,1-dioxides, the present work focuses on the design of original isosteric 3,4-dihydro-2H-thieno-1,2,4-thiadiazine 1,1-dioxides. Owing to the sulfur position, three series of compounds were developed and their activity as AMPA potentiators was characterized. In each of the developed series, potent compounds were discovered. After screening the selected active compounds on a safety in vivo test, 6-chloro-4-ethyl-3,4-dihydro-2H-thieno[2,3-e]-1,2,4-thiadiazine 1,1-dioxide (24) appeared as the most promising compound and was further evaluated. Its effects on long-term potentiation in vivo and on AMPA-mediated noradrenaline release were measured to predict its potential cognitive enhancing properties. Finally, an object recognition test performed in mice revealed that 24 was able to significantly enhance cognition, after oral administration, at doses as low as 0.3 mg/kg. This study validates the interest of the isosteric replacement of the benzene or pyridine nuclei by the thiophene nucleus in the ring-fused thiadiazine dioxides class of AMPA potentiators.