(3R)-3-((S)-1-(3-chlorophenyl)-1-hydroxy-5-methoxypentyl)-N-((S)-3-cyclohexyl-1-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)-amino)propan-2-yl)piperidine-1-carboxamide | 884513-99-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (3R)-3-((S)-1-(3-chlorophenyl)-1-hydroxy-5-methoxypentyl)-N-((S)-3-cyclohexyl-1-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)-amino)propan-2-yl)piperidine-1-carboxamide
• 英文别名: 2-trimethylsilylethyl N-[(2S)-2-[[(3R)-3-[(1S)-1-(3-chlorophenyl)-1-hydroxy-5-methoxypentyl]piperidine-1-carbonyl]amino]-3-cyclohexylpropyl]-N-methylcarbamate
• CAS: 884513-99-9
• 化学式: C₃₄H₅₈ClN₃O₅Si
• 分子量: 652.39
• InChiKey: JATOCJNWAULADJ-YHDFVFTKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.51
• 重原子数：
  44
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  91.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3R)-3-((S)-1-(3-chlorophenyl)-1-hydroxy-5-methoxypentyl)-N-((S)-3-cyclohexyl-1-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)-amino)propan-2-yl)piperidine-1-carboxamide 在 aluminum (III) chloride 、 四丁基碘化铵 作用下， 以 乙腈 为溶剂， 反应 4.0h， 生成 Piperidine-1-carboxamide, 21c
  参考文献：
  名称：

  Optimization of orally bioavailable alkyl amine renin inhibitors

  摘要：

  Structure-guided drug design led to new alkylamine renin inhibitors with improved in vitro and in vivo potency. Lead compound 21a, has an IC50 of 0.83 nM for the inhibition of human renin in plasma (PRA). Oral administration of 21a at 10 mg/kg resulted in >20 h reduction of blood pressure in a double transgenic rat model of hypertension. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.066
• 作为产物：
  描述：

  (S)-(1-(3-chlorophenyl)-5-methoxy-1(R)-piperidin-3-yl)pentan-1-ol 、 4-nitrophenyl (S)-(3-cyclohexyl-1-((2-(trimethylsilyl)ethylcarbamate)methylamino)propan-2-yl)carbamate 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 (3R)-3-((S)-1-(3-chlorophenyl)-1-hydroxy-5-methoxypentyl)-N-((S)-3-cyclohexyl-1-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)-amino)propan-2-yl)piperidine-1-carboxamide
  参考文献：
  名称：

  Design and optimization of renin inhibitors: Orally bioavailable alkyl amines

  摘要：

  Structure-based drug design led to the identification of a novel class of potent, low MW alkylamine renin inhibitors. Oral administration of lead compound 21l, with MW of 508 and IC(50) of 0.47 nM, caused a sustained reduction in mean arterial blood pressure in a double transgenic rat model of hypertension. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.04.140

文献信息

• Diaminoalkane Aspartic Protease Inhibitors
  申请人：Baldwin John J.

  公开号：US20090018103A1

  公开（公告）日：2009-01-15

  Diaminoalkanes of Formula I have now been found which are orally active and bind to aspartic proteases to inhibit their activity. They are useful in the treatment or amelioration of diseases associated with elevated levels of aspartic protease activity. The invention also relates to a method for the use of the compounds of Formula I in ameliorating or treating aspartic protease related disorders in a subject in need thereof comprising administering to said subject an effective amount of a compound of Formula I.

  公式I的Diaminoalkanes现已被发现，它们具有口服活性并结合到天冬氨酸蛋白酶以抑制其活性。它们在治疗或改善与天冬氨酸蛋白酶活性升高相关的疾病方面非常有用。本发明还涉及使用公式I化合物治疗或改善需要的天冬氨酸蛋白酶相关疾病的方法，包括向该受体施用公式I化合物的有效量。
• Diaminoalkane aspartic protease inhibitors
  申请人：Vitae Pharmaceuticals, Inc.

  公开号：US07754737B2

  公开（公告）日：2010-07-13

  Diaminoalkanes of Formula I have now been found which are orally active and bind to aspartic proteases to inhibit their activity. They are useful in the treatment or amelioration of diseases associated with elevated levels of aspartic protease activity. The invention also relates to a method for the use of the compounds of Formula I in ameliorating or treating aspartic protease related disorders in a subject in need thereof comprising administering to said subject an effective amount of a compound of Formula I.

  已经发现了具有公式I的二氨基烷，其口服活性并结合天冬氨酸蛋白酶以抑制其活性。它们在治疗或改善与天冬氨酸蛋白酶活性升高相关的疾病方面是有用的。本发明还涉及一种使用公式I的化合物改善或治疗需要该方案的主体中的天冬氨酸蛋白酶相关疾病的方法，包括向该主体施用公式I的化合物的有效量。
• Optimization of orally bioavailable alkyl amine renin inhibitors
  作者：Zhenrong Xu、Salvacion Cacatian、Jing Yuan、Robert D. Simpson、Lanqi Jia、Wei Zhao、Colin M. Tice、Patrick T. Flaherty、Joan Guo、Alexey Ishchenko、Suresh B. Singh、Zhongren Wu、Brian M. McKeever、Boyd B. Scott、Yuri Bukhtiyarov、Jennifer Berbaum、Jennifer Mason、Reshma Panemangalore、Maria Grazia Cappiello、Ross Bentley、Christopher P. Doe、Richard K. Harrison、Gerard M. McGeehan、Lawrence W. Dillard、John J. Baldwin、David A. Claremon

  DOI：10.1016/j.bmcl.2009.11.066

  日期：2010.1

  Structure-guided drug design led to new alkylamine renin inhibitors with improved in vitro and in vivo potency. Lead compound 21a, has an IC50 of 0.83 nM for the inhibition of human renin in plasma (PRA). Oral administration of 21a at 10 mg/kg resulted in >20 h reduction of blood pressure in a double transgenic rat model of hypertension. (C) 2009 Elsevier Ltd. All rights reserved.
• Design and optimization of renin inhibitors: Orally bioavailable alkyl amines
  作者：Colin M. Tice、Zhenrong Xu、Jing Yuan、Robert D. Simpson、Salvacion T. Cacatian、Patrick T. Flaherty、Wei Zhao、Joan Guo、Alexey Ishchenko、Suresh B. Singh、Zhongren Wu、Boyd B. Scott、Yuri Bukhtiyarov、Jennifer Berbaum、Jennifer Mason、Reshma Panemangalore、Maria Grazia Cappiello、Dominik Müller、Richard K. Harrison、Gerard M. McGeehan、Lawrence W. Dillard、John J. Baldwin、David A. Claremon

  DOI：10.1016/j.bmcl.2009.04.140

  日期：2009.7

  Structure-based drug design led to the identification of a novel class of potent, low MW alkylamine renin inhibitors. Oral administration of lead compound 21l, with MW of 508 and IC(50) of 0.47 nM, caused a sustained reduction in mean arterial blood pressure in a double transgenic rat model of hypertension. (C) 2009 Elsevier Ltd. All rights reserved.