tert-butyl (S)-1-(methylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamate | 942144-45-8

• 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: tert-butyl (S)-1-(methylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamate
• 英文别名: tert-butyl N-[(2S)-1-(methylamino)-3-[(3R)-oxan-3-yl]propan-2-yl]carbamate
• CAS: 942144-45-8
• 化学式: C₁₄H₂₈N₂O₃
• 分子量: 272.388
• InChiKey: SGLXBTCVSYLULG-NEPJUHHUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  59.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-1-(methylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamate 在 potassium carbonate 、 对甲苯磺酸 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 4.0h， 生成 2-(trimethylsilyl)ethyl (S)-2-amino-3-((R)-tetrahydro-2H-pyran-3-yl)propyl(methyl)carbamate
  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)-tert-butyl 4-((R)-2-((tert-butyldimethylsilyloxy)methyl)-5-(methylsulfonyloxy)pentyl)-2,2-dimethyloxazolidine-3-carboxylate 在 水 、 四乙基氟化铵水合物 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 33.5h， 生成 tert-butyl (S)-1-(methylamino)-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

• Piperidine derivatives as renin inhibitors
  申请人：Baldwin John J.

  公开号：US20090318501A1

  公开（公告）日：2009-12-24

  The present invention is directed to aspartic protease inhibitors represented by the following structural formula; or a pharmaceutically acceptable salt thereof. The present invention is also directed to pharmaceutical compositions comprising the aspartic protease inhibitors of Structural Formula (I). Methods of antagonizing one or more aspartic proteases in a subject in need thereof, and methods for treating an aspartic protease mediated disorder in a subject using these aspartic protease inhibitors are also disclosed.

  本发明涉及以下结构式所表示的天冬氨酸蛋白酶抑制剂; 或其药学上可接受的盐。本发明还涉及包括结构式（I）的天冬氨酸蛋白酶抑制剂的制药组合物。本发明还揭示了在需要拮抗一种或多种天冬氨酸蛋白酶的主体中拮抗一种或多种天冬氨酸蛋白酶的方法，以及使用这些天冬氨酸蛋白酶抑制剂治疗天冬氨酸蛋白酶介导的疾病的方法。
• Aspartic Protease Inhibitors
  申请人：Baldwin John J.

  公开号：US20100048636A1

  公开（公告）日：2010-02-25

  The present invention is directed to aspartic protease inhibitors. Certain aspartic protease inhibitors of the invention can be represented by the following structural formula or a pharmaceutically acceptable salt thereof. The present invention is also directed to pharmaceutical compositions comprising the disclosed aspartic protease inhibitors. The present invention is further directed to methods of antagonizing one or more aspartic proteases in a subject in need thereof, and methods for treating an aspartic protease mediated disorder in a subject using the disclosed aspartic protease inhibitors.

  本发明涉及天冬氨酸蛋白酶抑制剂。本发明所述的某些天冬氨酸蛋白酶抑制剂可以用以下结构式或其药学上可接受的盐来表示。本发明还涉及包括所述天冬氨酸蛋白酶抑制剂的药物组合物。本发明还涉及在需要拮抗一种或多种天冬氨酸蛋白酶的主体中的方法，以及使用所述天冬氨酸蛋白酶抑制剂治疗天冬氨酸蛋白酶介导的疾病的方法。
• ASPARTIC PROTEASE INHIBITORS
  申请人：Vitae Pharmaceuticals, Inc.

  公开号：EP1966139B1

  公开（公告）日：2011-12-21
• PIPERIDINE DERIVATIVES AS RENIN INHIBITORS
  申请人：Vitae Pharmaceuticals, Inc.

  公开号：EP2081927B1

  公开（公告）日：2011-08-17
• US8487108B2
  申请人：——

  公开号：US8487108B2

  公开（公告）日：2013-07-16