tert-butyl {(6R)-5-cyano-6-(4-cyanophenyl)-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-3,6-dihydropyrimidin-1(2H)-yl}acetate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl {(6R)-5-cyano-6-(4-cyanophenyl)-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-3,6-dihydropyrimidin-1(2H)-yl}acetate
• 英文别名: tert-butyl[(6R)-5-cyano-6-(4-cyanophenyl)-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-3,6-dihydropyrimidin-1(2H)-yl]acetate；tert-butyl 2-[(4R)-5-cyano-4-(4-cyanophenyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4H-pyrimidin-3-yl]acetate
• 化学式: C₂₆H₂₃F₃N₄O₃
• 分子量: 496.489
• InChiKey: YRMPYUPRZKGJRU-HSZRJFAPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  97.4
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl {(6R)-5-cyano-6-(4-cyanophenyl)-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-3,6-dihydropyrimidin-1(2H)-yl}acetate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以58%的产率得到{(6R)-5-cyano-6-(4-cyanophenyl)-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-3,6-dihydropyrimidin-1(2H)-yl}acetic acid
  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：

  3-(三氟甲基)苯硫脲 在 4-二甲氨基吡啶 、 methyl N-(triethylammoniosulfonyl) carbamate 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 potassium carbonate 、 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.25h， 生成 tert-butyl {(6R)-5-cyano-6-(4-cyanophenyl)-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-3,6-dihydropyrimidin-1(2H)-yl}acetate
  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

• USE OF1,4-DIARYL-DIHYDROPYRIMIDINE-2-ON DERIVATIVES FOR TREATING PULMONARY ARTERIAL HYPERTENSION
  申请人：Von Nussbaum Franz

  公开号：US20100010024A1

  公开（公告）日：2010-01-14

  The present application relates to the use of 1,4-diaryldihydropyrimidin-2-one derivatives of the formula (I) for the treatment and/or prophylaxis of pulmonary arterial hypertension and other types of pulmonary hypertension, and to the use thereof for the manufacture of medicaments for the treatment and/or prophylaxis of pulmonary arterial hypertension and other types of pulmonary hypertension.

  本申请涉及使用式(I)的1,4-二芳基二氢嘧啶-2-酮衍生物用于治疗和/或预防肺动脉高压和其他类型的肺动脉高压，以及用于制造用于治疗和/或预防肺动脉高压和其他类型的肺动脉高压的药物。
• Freezing the Bioactive Conformation to Boost Potency: The Identification of BAY 85-8501, a Selective and Potent Inhibitor of Human Neutrophil Elastase for Pulmonary Diseases
  作者：Franz von Nussbaum、Volkhart M.-J. Li、Swen Allerheiligen、Sonja Anlauf、Lars Bärfacker、Martin Bechem、Martina Delbeck、Mary F. Fitzgerald、Michael Gerisch、Heike Gielen-Haertwig、Helmut Haning、Dagmar Karthaus、Dieter Lang、Klemens Lustig、Daniel Meibom、Joachim Mittendorf、Ulrich Rosentreter、Martina Schäfer、Stefan Schäfer、Jens Schamberger、Leila A. Telan、Adrian Tersteegen

  DOI：10.1002/cmdc.201500131

  日期：2015.7

  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

  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