4-nitrophenyl (S)-(3-cyclohexyl-1-((2-(trimethylsilyl)ethylcarbamate)methylamino)propan-2-yl)carbamate | 884511-70-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-nitrophenyl (S)-(3-cyclohexyl-1-((2-(trimethylsilyl)ethylcarbamate)methylamino)propan-2-yl)carbamate
• 英文别名: (S)-4-nitrophenyl 1-cyclohexyl-3-(methyl((2-(trimethylsilyl)ethoxy)carbonyl)amino)propan-2-ylcarbamate；2-trimethylsilylethyl N-[(2S)-3-cyclohexyl-2-[(4-nitrophenoxy)carbonylamino]propyl]-N-methylcarbamate
• CAS: 884511-70-0
• 化学式: C₂₃H₃₇N₃O₆Si
• 分子量: 479.649
• InChiKey: RMBXBKVCRIBLND-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.43
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  114
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 2-((R)-1-(3-chlorophenyl)-1-((R)-piperidin-3-yl)ethoxy)acetate 、 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 为溶剂， 反应 24.0h， 生成 ethyl 2-((R)-1-(3-chlorophenyl)-1-((R)-1-((S)-1-cyclohexyl-3-(methyl((2-(trimethylsilyl)ethoxy)carbonyl)amino)propan-2-ylcarbamoyl)piperidin-3-yl)ethoxy)acetate
  参考文献：
  名称：

  WO2007/70201

  摘要：

  公开号：
• 作为产物：
  描述：

  N-[2-(三甲基硅基)乙氧羰氧基]琥珀酰亚胺 在 吡啶 、 potassium carbonate 、 对甲苯磺酸 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 2.08h， 生成 4-nitrophenyl (S)-(3-cyclohexyl-1-((2-(trimethylsilyl)ethylcarbamate)methylamino)propan-2-yl)carbamate
  参考文献：
  名称：

  Biphenyl/diphenyl ether renin inhibitors: Filling the S1 pocket of renin via the S3 pocket

  摘要：

  Structure-based design led to the discovery of a novel class of renin inhibitors in which an unprecedented phenyl ring filling the S1 site is attached to the phenyl ring filling the S3 pocket. Optimization for several parameters including potency in the presence of human plasma, selectivity against CYP3A4 inhibition and improved rat oral bioavailability led to the identification of 8d which demonstrated antihypertensive efficacy in a transgenic rat model of human hypertension. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.043

文献信息

• 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。
• Piperidinyl carbamate intermediates for the synthesis of aspartic protease inhibitors
  申请人：Baldwin John J.

  公开号：US08487108B2

  公开（公告）日：2013-07-16

  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。本发明还涉及包含所述天冬氨酸蛋白酶抑制剂的制药组合物。本发明还涉及在需要拮抗一种或多种天冬氨酸蛋白酶的受体的主体中的方法，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。
• 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.
• WO2007/70201
  申请人：——

  公开号：——

  公开（公告）日：——