(S)-tert-butyl 1-(N-methyl-2-(trimethylsilyl)ethoxycarbonylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamate | 942144-46-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧烷类
• 英文名称: (S)-tert-butyl 1-(N-methyl-2-(trimethylsilyl)ethoxycarbonylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamate
• 英文别名: 2-trimethylsilylethyl N-methyl-N-[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-[(3R)-oxan-3-yl]propyl]carbamate
• CAS: 942144-46-9
• 化学式: C₂₀H₄₀N₂O₅Si
• 分子量: 416.634
• InChiKey: HKOPZDFLHTXNIQ-SJORKVTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  77.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl 1-(N-methyl-2-(trimethylsilyl)ethoxycarbonylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamate 在 四乙基氟化铵水合物 、 对甲苯磺酸 、 N,N-二异丙基乙胺 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 19.33h， 生成 methyl 2-((R)-(3-chlorophenyl)((R)-1-((S)-1-(methylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamate trifluoroacetate
  参考文献：
  名称：

  Discovery of VTP-27999, an Alkyl Amine Renin Inhibitor with Potential for Clinical Utility

  摘要：

  Structure guided optimization of a series of nonpeptidic alkyl amine renin inhibitors allowed the rational incorporation of additional polar functionality. Replacement of the c-yclohexylmethyl group occupying the SI pocket with a (R)-(tetrahydropyran-3-yl)methyl group and utilization of a different attachment point led to the identification of clinical candidate 9. This compound demonstrated excellent selectivity over related and unrelated off-targets, >15% oral bioavailability in three species, oral efficacy in a double transgenic rat model of hypertension, and good exposure in humans.

  DOI：

  10.1021/ml200137x
• 作为产物：
  描述：

  (S)-2-(tert-butoxycarbonylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propyl methanesulfonate 在 potassium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 18.0h， 生成 (S)-tert-butyl 1-(N-methyl-2-(trimethylsilyl)ethoxycarbonylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamate
  参考文献：
  名称：

  Discovery of VTP-27999, an Alkyl Amine Renin Inhibitor with Potential for Clinical Utility

  摘要：

  Structure guided optimization of a series of nonpeptidic alkyl amine renin inhibitors allowed the rational incorporation of additional polar functionality. Replacement of the c-yclohexylmethyl group occupying the SI pocket with a (R)-(tetrahydropyran-3-yl)methyl group and utilization of a different attachment point led to the identification of clinical candidate 9. This compound demonstrated excellent selectivity over related and unrelated off-targets, >15% oral bioavailability in three species, oral efficacy in a double transgenic rat model of hypertension, and good exposure in humans.

  DOI：

  10.1021/ml200137x