3-Cyclohexyl-1,3-dihydro-5-(3,6-dihydro-2-oxo-2H-1,3,4-thiadiazin-5-yl)-2H-indol-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 3-Cyclohexyl-1,3-dihydro-5-(3,6-dihydro-2-oxo-2H-1,3,4-thiadiazin-5-yl)-2H-indol-2-one
• 英文别名: 5-(3-Cyclohexyl-2-oxo-1,3-dihydroindol-5-yl)-3,6-dihydro-1,3,4-thiadiazin-2-one
• 化学式: C₁₇H₁₉N₃O₂S
• 分子量: 329.423
• InChiKey: ZJXYMFDESVJZQB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-环己基-1,3-二氢吲哚-2-酮 在 三氯化铝 、 N,N-二甲基甲酰胺 、 三氟乙酸 作用下， 以 乙腈 为溶剂， 反应 5.0h， 生成 3-Cyclohexyl-1,3-dihydro-5-(3,6-dihydro-2-oxo-2H-1,3,4-thiadiazin-5-yl)-2H-indol-2-one
  参考文献：
  名称：

  Stereospecificity of myofibrillar calcium sensitivity and PDE inhibition in cardiotonic thiadiazinones

  摘要：

  In pyridazinone or thiadiazinone cardiotonic agents with one chiral centre, the PDE inhibitory action resides mainly in one enantiomer and the myofibrillar calcium sensitization mainly in the other. This phenomenon is observed when the chiral centre is located on the pyridazinone or thiadiazinone heterocycle, but cannot be extended to structures where the chiral centre is elsewhere on the molecule. For the first time a stereoselective synthesis of a 5-substituted 3,6-dihydro-6-methyl-2H-1,3,4-thiadiazine-2-one has been achieved and an absolute configuration is proposed.

  DOI：

  10.1016/0223-5234(96)83974-2

文献信息

• Phosphodiesterase inhibitors
  申请人：LES LABORATOIRES BEECHAM S.A.

  公开号：EP0381374A1

  公开（公告）日：1990-08-08

  A compound of formula (I), or a pharmaceutically acceptable salt thereof: in which, R₁ is hydrogen, C₁₋₆ alkyl or CH₂OR₆; R₂ is hydrogen or C₁₋₆ alkyl; R₃ is hydrogen or C₁₋₆ alkyl; each of W and Z, which are different, represents -CR₄R₅- or -(CRxRy)n-, in which, R₄ is hydrogen, C₁₋₃ alkyl, C₁₋₃ alkylthio, C₁₋₃ alkoxy or C₁₋₆ alkyl phenyl; R₅ is C₁₋₃ alkyl, C₁₋₃ alkylthio, C₁₋₃ alkoxy, phenyl, substituted phenyl, C₃₋₆ cycloalkyl, phenylthio, C₁₋₆ alkyl phenyl, halo-substituted benzyl, or heteroaryl; or together R₄ and R₅ form a 3 to 6 membered carbocyclic ring, or a heterocyclic ring containing one or two ring oxygen, nitrogen or sulphur atoms, or R₄ and R₅ together form an oxo or methylene group; each of Rx and Ry is hydrogen or C₁₋₃ alkyl; n is zero or 1; R₆ is phenyl substituted aminocarbonyl, C₁₋₆ alkoxy carbonyl-C₁₋₆ alkyl, phenyl-C₁₋₆ alkyl, phenyl, C₃₋₆ cycloalkylcarbonyl, C₃₋₆ cycloalkylcarbonyl-C₁₋₆ alkyl, C₃₋₆ cycloalkyl C₁₋₆ alkyl; C₁₋₆ alkylthiocarbonyl; halo-substituted C₁₋₆ alkoxycarbonyl; C₁₋₆ alkoxy C₁₋₆ alkyleneoxycarbonyl; C₁₋₆ alkylthio C₁₋₆ alkyleneoxycarbonyl; C₁₋₆ alkoxythiocarbonyl; C₃₋₆ cycloalkyloxycarbonyl; cyano substituted C₁₋₆ alkoxycarbonyl; di-C₁₋₆ alkylphosphonate; C₁₋₆ alkenyloxycarbonyl; or R₆ is hydrogen when R₅ is phenyl, C₃₋₆ cycloalkyl, phenylthio, C₁₋₆ alkylphenyl or halo-substituted benzyl; R₆ is benzoyl or aminobenzoyl when R₄ and R₅ form a C₃₋₆ cycloalkyl ring; R₇ is hydrogen, C₁₋₆ alkyl or halogen; X is oxygen or sulphur; and A is sulphur, oxygen or -NH-, is useful for the treatment of heart disease.

  式（I）的化合物，或其药学上可接受的盐：其中，R₁为氢，C₁₋₆烷基或CH₂OR₆；R₂为氢或C₁₋₆烷基；R₃为氢或C₁₋₆烷基；W和Z中的每一个，它们不同，代表-CR₄R₅-或-(CRxRy)n-，其中，R₄为氢，C₁₋₃烷基，C₁₋₃烷基硫，C₁₋₃烷氧基或C₁₋₆烷基苯基；R₅为C₁₋₃烷基，C₁₋₃烷基硫，C₁₋₃烷氧基，苯基，取代苯基，C₃₋₆环烷基，苯硫基，C₁₋₆烷基苯基，卤代苄基或杂环烷基；或者R₄和R₅一起形成3到6成员的碳环，或者含有一个或两个环氧原子、氮原子或硫原子的杂环；或者R₄和R₅一起形成氧或亚甲基基团；Rx和Ry中的每一个为氢或C₁₋₃烷基；n为零或1；R₆为苯基取代氨基甲酰基，C₁₋₆烷氧基甲酰基-C₁₋₆烷基，苯基-C₁₋₆烷基，苯基，C₃₋₆环烷基甲酰基，C₃₋₆环烷基甲酰基-C₁₋₆烷基，C₃₋₆环烷基C₁₋₆烷基；C₁₋₆烷基硫代甲酰基；卤代C₁₋₆烷氧基甲酰基；C₁₋₆烷氧基-C₁₋₆烷基氧基甲酰基；C₁₋₆烷基硫基-C₁₋₆烷基氧基甲酰基；C₁₋₆烷氧基硫代甲酰基；C₃₋₆环烷氧基甲酰基；氰基取代C₁₋₆烷氧基甲酰基；二C₁₋₆烷基膦酸酯；C₁₋₆烯氧基甲酰基；或者当R₅为苯基，C₃₋₆环烷基，苯硫基，C₁₋₆烷基苯基或卤代苄基时，R₆为氢；当R₄和R₅形成C₃₋₆环烷基环时，R₆为苯甲酰基或氨基苯甲酰基；R₇为氢，C₁₋₆烷基或卤素；X为氧或硫；A为硫，氧或-NH-，用于治疗心脏病。
• Stereospecificity of myofibrillar calcium sensitivity and PDE inhibition in cardiotonic thiadiazinones
  作者：G Nadler、I Delimoge、P Lahouratate、I Leger、M Morvan、RG Zimmermann

  DOI：10.1016/0223-5234(96)83974-2

  日期：1996.1

  In pyridazinone or thiadiazinone cardiotonic agents with one chiral centre, the PDE inhibitory action resides mainly in one enantiomer and the myofibrillar calcium sensitization mainly in the other. This phenomenon is observed when the chiral centre is located on the pyridazinone or thiadiazinone heterocycle, but cannot be extended to structures where the chiral centre is elsewhere on the molecule. For the first time a stereoselective synthesis of a 5-substituted 3,6-dihydro-6-methyl-2H-1,3,4-thiadiazine-2-one has been achieved and an absolute configuration is proposed.