(4S)-4-{4-cyano-2-(methylsulfinyl)phenyl}-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile | 1164201-95-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4S)-4-{4-cyano-2-(methylsulfinyl)phenyl}-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile
• 英文别名: (4S)-4-{4-Cyano-2-[methylsulfinyl]phenyl}-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile；(6S)-6-(4-cyano-2-methylsulfinylphenyl)-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-1,6-dihydropyrimidine-5-carbonitrile
• CAS: 1164201-95-9
• 化学式: C₂₁H₁₅F₃N₄O₂S
• 分子量: 444.437
• InChiKey: JUJDKQGAENKARI-MFUYNUFSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (4S)-4-{4-cyano-2-(methylsulfinyl)phenyl}-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 在 dirhodium tetraacetate 、 碘苯二乙酸 、 magnesium oxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran 为溶剂， 反应 56.0h， 生成 (R_S)-N-[(5-Cyano-2-{(4S)-5-cyano-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidin-4-yl}phenyl)(methyl)oxido-λ⁶-sulfanylidene]-2,2,2-trifluoroacetamide
  参考文献：
  名称：

  冻结生物活性构象以增强效能：BAY 85-8501的鉴定，BAY 85-8501是人类中性粒细胞弹性蛋白酶对肺部疾病的选择性和强效抑制剂

  摘要：

  Human neutrophil elastase (HNE) is a key protease for matrix degradation. High HNE activity is observed in inflammatory diseases. Accordingly, HNE is a potential target for the treatment of pulmonary diseases such as chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), bronchiectasis (BE), and pulmonary hypertension (PH). HNE inhibitors

  DOI：

  10.1002/cmdc.201500131
• 作为产物：
  描述：

  4-氰基-2-氟苯甲醛 在 吗啉 、 sodium periodate 、 四(三苯基膦)钯 、 伯吉斯试剂 、 磷酸三乙酯 、 四磷十氧化物 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氯化铵 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 甲基叔丁基醚 、 水 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 反应 24.25h， 生成 (4S)-4-{4-cyano-2-(methylsulfinyl)phenyl}-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile
  参考文献：
  名称：

  冻结生物活性构象以增强效能：BAY 85-8501的鉴定，BAY 85-8501是人类中性粒细胞弹性蛋白酶对肺部疾病的选择性和强效抑制剂

  摘要：

  Human neutrophil elastase (HNE) is a key protease for matrix degradation. High HNE activity is observed in inflammatory diseases. Accordingly, HNE is a potential target for the treatment of pulmonary diseases such as chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), bronchiectasis (BE), and pulmonary hypertension (PH). HNE inhibitors

  DOI：

  10.1002/cmdc.201500131

文献信息

• 4-(4-CYANO-2-THIOARYL)DIHYDROPYRIMIDINONES AND THEIR USE
  申请人：Von Nussbaum Franz

  公开号：US20110034433A1

  公开（公告）日：2011-02-10

  The present invention relates to novel 4-(4-cyano-2-thioaryl)dihydropyrimidin-2-one derivatives, to processes for their preparation, to their use alone or in combination for the treatment and/or prevention of diseases and also to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of disorders of the lung and the cardiovascular system.

  本发明涉及新颖的4-(4-氰基-2-硫代芳基)二氢嘧啶-2-酮衍生物，涉及它们的制备方法，以及它们单独或与其他药物结合用于治疗和/或预防疾病，还涉及它们用于制备用于治疗和/或预防疾病的药物，特别是用于治疗和/或预防肺部和心血管系统疾病的用途。
• 4-(4-cyano-2-thioaryl)dihydropyrimidinones and their use
  申请人：Bayer Intellectual Property GmbH

  公开号：US08288402B2

  公开（公告）日：2012-10-16

  The present invention relates to novel 4-(4-cyano-2-thioaryl)dihydropyrimidin-2-one derivatives, to processes for their preparation, to their use alone or in combination for the treatment and/or prevention of diseases and also to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of disorders of the lung and the cardiovascular system.

  本发明涉及新颖的4-(4-氰基-2-硫基芳基)二氢嘧啶-2-酮衍生物，其制备方法，其单独或联合用于治疗和/或预防疾病，以及其用于制备用于治疗和/或预防疾病的药物，尤其是用于治疗和/或预防肺部和心血管系统疾病的药物。
• SULFONIC AMIDE AND SULFOXIMINE-SUBSTTTUTED DIARYL-DIHYDROPYRIMIDINONES AND USAGE THEREOF
  申请人：Von Nussbaum Franz

  公开号：US20120094968A1

  公开（公告）日：2012-04-19

  The present application relates to novel sulfonamidw- or sulfoximine-substituted 1,4-diaryldihydropyrimidin-2-one derivatives, to processes for their preparation, to their use alone or in combination for the treatment and/or prevention of diseases and also to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of disorders of the lung and the cardiovascular system.

  本申请涉及新型磺酰胺或亚砜取代的1,4-二芳基二氢嘧啶-2-酮衍生物，其制备方法，其单独或联合用于治疗和/或预防疾病以及用于制备治疗和/或预防疾病的药物，特别是用于治疗和/或预防肺和心血管系统疾病的药物。
• Sulfonic amide and sulfoximine-substituted diaryl-dihydropyrimidinones and usage thereof
  申请人：Von Nussbaum Franz

  公开号：US08691817B2

  公开（公告）日：2014-04-08

  The present application relates to novel sulfonamide- or sulfoximine-substituted 1,4-diaryldihydropyrimidin-2-one derivatives, to processes for their preparation, to their use alone or in combination for the treatment and/or prevention of diseases and also to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of disorders of the lung and the cardiovascular system.

  本申请涉及新型磺酰胺或亚磺酰胺取代的1,4-二芳基二氢嘧啶-2-酮衍生物，其制备过程，它们单独或组合用于治疗和/或预防疾病，以及它们用于制备治疗和/或预防疾病的药物，特别是用于治疗和/或预防肺和心血管系统疾病。
• 4-(4-CYANO-2-THIOARYL)DIHYDROPYRIMIDINONES AND USE THEREOF
  申请人：Bayer Intellectual Property GmbH

  公开号：US20150045344A1

  公开（公告）日：2015-02-12

  The present invention relates to novel 4-(4-cyano-2-thioaryl)dihydropyrimidin-2-one derivatives, to processes for their preparation, to their use alone or in combination for the treatment and/or prevention of diseases and also to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of disorders of the lung and the cardiovascular system.

  本发明涉及新型4-(4-氰基-2-硫基芳基)二氢嘧啶-2-酮衍生物，其制备方法，其单独或联合用于治疗和/或预防疾病以及用于制备治疗和/或预防疾病的药物，特别是用于治疗和/或预防肺和心血管系统疾病的药物。