(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

文献信息

• Discovery of VTP-27999, an Alkyl Amine Renin Inhibitor with Potential for Clinical Utility
  作者：Lanqi Jia、Robert D. Simpson、Jing Yuan、Zhenrong Xu、Wei Zhao、Salvacion Cacatian、Colin M. Tice、Joan Guo、Alexey Ishchenko、Suresh B. Singh、Zhongren Wu、Brian M. McKeever、Yuri Bukhtiyarov、Judith A. Johnson、Christopher P. Doe、Richard K. Harrison、Gerard M. McGeehan、Lawrence W. Dillard、John J. Baldwin、David A. Claremon

  DOI：10.1021/ml200137x

  日期：2011.10.13

  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.