(2S)-2-{[(4S,5S)-3-(tert-butoxycarbonyl)-4-{[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]methyl}-2,2-dimethyl-1,3-oxazolidin-5-yl]methyl}-3-methylbutanoic acid | 1436430-30-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (2S)-2-{[(4S,5S)-3-(tert-butoxycarbonyl)-4-{[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]methyl}-2,2-dimethyl-1,3-oxazolidin-5-yl]methyl}-3-methylbutanoic acid
• CAS: 1436430-30-6
• 化学式: C₂₉H₄₄ClN₃O₆
• 分子量: 566.138
• InChiKey: GBAADCKAZLHAOQ-VJBMBRPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.25
• 重原子数：
  39.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  99.62
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (2S)-2-{[(4S,5S)-3-(tert-butoxycarbonyl)-4-{[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]methyl}-2,2-dimethyl-1,3-oxazolidin-5-yl]methyl}-3-methylbutanoic acid 在 盐酸 、 甲醇 、 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.08h， 生成 (2S,4S,5S)-5-amino-6-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-4-hydroxy-N-(3-hydroxyadamantan-1-yl)-2-isopropylhexanamide fumarate
  参考文献：
  名称：

  Lead optimization of 5-amino-6-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)-4-hydroxyhexanamides to reduce a cardiac safety issue: Discovery of DS-8108b, an orally active renin inhibitor

  摘要：

  With the aim to address an undesired cardiac issue observed with our related compound in the recently disclosed novel series of renin inhibitors, further chemical modifications of this series were performed. Extensive structure-activity relationships studies as well as in vivo cardiac studies using the electrophysiology rat model led to the discovery of clinical candidate trans-adamantan-1-ol analogue 56 (DS-8108b) as a potent renin inhibitor with reduced potential cardiac risk. Oral administration of single doses of 3 and 10 mg/kg of 56 in cynomolgus monkeys pre-treated with furosemide led to significant reduction of mean arterial blood pressure for more than 12 h. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.022
• 作为产物：
  描述：

  在 水 、 4-甲基苯磺酸吡啶 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 13.0h， 生成 (2S)-2-{[(4S,5S)-3-(tert-butoxycarbonyl)-4-{[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]methyl}-2,2-dimethyl-1,3-oxazolidin-5-yl]methyl}-3-methylbutanoic acid
  参考文献：
  名称：

  Lead optimization of 5-amino-6-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)-4-hydroxyhexanamides to reduce a cardiac safety issue: Discovery of DS-8108b, an orally active renin inhibitor

  摘要：

  With the aim to address an undesired cardiac issue observed with our related compound in the recently disclosed novel series of renin inhibitors, further chemical modifications of this series were performed. Extensive structure-activity relationships studies as well as in vivo cardiac studies using the electrophysiology rat model led to the discovery of clinical candidate trans-adamantan-1-ol analogue 56 (DS-8108b) as a potent renin inhibitor with reduced potential cardiac risk. Oral administration of single doses of 3 and 10 mg/kg of 56 in cynomolgus monkeys pre-treated with furosemide led to significant reduction of mean arterial blood pressure for more than 12 h. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.022