1,1-dimethylethyl [(1S,2R)-2-hydroxy-3-(methylamino)-1-(phenylmethyl)propyl]carbamate | 160232-54-2

• 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: 1,1-dimethylethyl [(1S,2R)-2-hydroxy-3-(methylamino)-1-(phenylmethyl)propyl]carbamate
• 英文别名: tert-butyl (2S,3R)-3-hydroxy-4-(methylamino)-1-phenylbutan-2-yl-carbamate；1,1-dimethylethyl [(1S,2R)-2-hydroxy-3-(methylamino)-1-(phenylmethyl)propyl]-carbamate；tert-butyl N-[(2S,3R)-3-hydroxy-4-(methylamino)-1-phenylbutan-2-yl]carbamate
• CAS: 160232-54-2
• 化学式: C₁₆H₂₆N₂O₃
• 分子量: 294.394
• InChiKey: WROXBXSKMFXBTD-UONOGXRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  70.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,1-dimethylethyl [(1S,2R)-2-hydroxy-3-(methylamino)-1-(phenylmethyl)propyl]carbamate 在 sodium tetrahydroborate 、 碳酸氢钠 、 sodium iodide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 <(S)-3-<<(R,S)-3-<<(1,1-dimethylethoxy)carbonyl>amino>-2-hydroxy-4-phenylbutyl>methylamino>-2-hydroxy-1-(phenylmethyl)propyl>carbamic acid, 1,1-dimethylethyl ester
  参考文献：
  名称：

  Amino Diol HIV Protease Inhibitors. 1. Design, Synthesis, and Preliminary SAR

  摘要：

  A series of HIV protease inhibitors containing a novel C-2 symmetrical ''aminodiol'' core structure were prepared from amino acid starting materials. The ability of the aminodiols to inhibit HIV replication in cell culture is comparable to their ability to inhibit the isolated enzyme, a result compatible with good cell membrane penetration by this class of compounds. Optimization of the structure-activity in this series led to aminodiol 9a (K-i = 100 nM; ED(50) (HIV-1) = 80 nM) containing P-1/P-1', benzyl and P-2/P-2' Boc substituents. Compound 9a is a selective inhibitor of HIV protease versus other aspartyl proteases such as human renin, human cathepsin D, and porcine pepsin. In addition, 9a is equipotent against HIV-1 and HIV-2 in cell culture and demonstrates similar activity in infected T-lymphocytes and PBMCs. After iv and oral administration in rats, 9a displayed significant oral bioavailability (ca. 40%) and a promising plasma elimination half-life (4 h).

  DOI：

  10.1021/jm00038a005
• 作为产物：
  描述：

  (1S,2S)-(1-苄基-3-氯-2-羟基丙基)氨基甲酸叔丁酯 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 19.5h， 生成 1,1-dimethylethyl [(1S,2R)-2-hydroxy-3-(methylamino)-1-(phenylmethyl)propyl]carbamate
  参考文献：
  名称：

  Amino Diol HIV Protease Inhibitors. 1. Design, Synthesis, and Preliminary SAR

  摘要：

  A series of HIV protease inhibitors containing a novel C-2 symmetrical ''aminodiol'' core structure were prepared from amino acid starting materials. The ability of the aminodiols to inhibit HIV replication in cell culture is comparable to their ability to inhibit the isolated enzyme, a result compatible with good cell membrane penetration by this class of compounds. Optimization of the structure-activity in this series led to aminodiol 9a (K-i = 100 nM; ED(50) (HIV-1) = 80 nM) containing P-1/P-1', benzyl and P-2/P-2' Boc substituents. Compound 9a is a selective inhibitor of HIV protease versus other aspartyl proteases such as human renin, human cathepsin D, and porcine pepsin. In addition, 9a is equipotent against HIV-1 and HIV-2 in cell culture and demonstrates similar activity in infected T-lymphocytes and PBMCs. After iv and oral administration in rats, 9a displayed significant oral bioavailability (ca. 40%) and a promising plasma elimination half-life (4 h).

  DOI：

  10.1021/jm00038a005

文献信息

• Sulfonamide inhibitors of aspartyl protease
  申请人：Vertex Pharmaceuticals, Incorporated

  公开号：US06372778B1

  公开（公告）日：2002-04-16

  The present invention relates to a novel class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of HIV aspartyl protease inhibitors characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting HIV-1 and HIV-2 protease activity and consequently, may be advantageously used as anti-viral agents against the HIV-1 and HIV-2 viruses. This invention also relates to methods for inhibiting the activity of HIV aspartyl protease using the compounds of this invention and methods for screening compounds for anti-HIV activity.

  本发明涉及一种新型磺胺类化合物，其为天冬氨酸蛋白酶抑制剂。在一个实施例中，本发明涉及一种新型HIV天冬氨酸蛋白酶抑制剂，其具有特定的结构和理化特征。本发明还涉及包含这些化合物的药物组合物。本发明的化合物和药物组合物特别适用于抑制HIV-1和HIV-2蛋白酶活性，因此，可以有利地用作抗HIV-1和HIV-2病毒的抗病毒剂。本发明还涉及使用本发明的化合物抑制HIV天冬氨酸蛋白酶活性的方法，以及筛选具有抗HIV活性的化合物的方法。
• Synthesis and In Vivo Antimalarial Evaluation of Novel Hydroxyethylamine Derivatives
  作者：Mariana Conceicao de Souza、Triciana Goncalves-Silva、Marcele Moreth、Claudia R.B. Gomes

  DOI：10.2174/157340612800493638

  日期：2012.4.26

  A series of hydroxyethylamines has been synthesized from the reaction of (2S,3S )Boc-phenylalanine epoxide with alkyl amines in good yields and evaluated for their in vivo antimalarial activity in mice. Compound 4g presented better activity then the reference artesunate in percentage of inhibition of parasitemia in treated P. berghei-infected mice and compare to the activity of artesunate in the survival

  从（2S，3S）Boc-苯丙氨酸环氧化物与烷基胺的反应中，以高收率合成了一系列羟乙胺，并对其在小鼠体内的抗疟活性进行了评估。在治疗的伯氏疟原虫感染的小鼠中，化合物4g表现出比参比青蒿琥酯更好的活​​性，其抑制寄生虫病的百分比，并且与感染后14天青蒿琥酯在小鼠存活中的活性相比。在成瘾中，未发现溶血活性，这表明对寄生虫病的抑制归因于抗疟疾活性。化合物4g抑制了向裂殖体的分化，表明寄生虫代谢可能是4g的靶标。这些结果表明，这类化合物对于新抗疟药的开发具有广阔的前景。
• Hydroxyethylamine derivatives for the treatment of alzheimer's disease
  申请人：Demont H Emmanuel

  公开号：US20060025459A1

  公开（公告）日：2006-02-02

  The present invention relates to novel hydroxyethylamine compounds having Asp2 (β-secretase, BACE1 or Memapsin) inhibitory activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by elevated β-amyloid levels or β-amyloid deposits, particularly Alzheimer's disease.

  本发明涉及具有Asp2（β-秘鲁酶、BACE1或Memapsin）抑制活性的新型羟乙基胺化合物，其制备方法，包含它们的组合物以及它们在治疗由高β-淀粉样蛋白水平或β-淀粉样蛋白沉积物所特征的疾病，特别是阿尔茨海默病中的应用。
• Probing pockets S2–S4′ of the γ-secretase active site with (hydroxyethyl)urea peptidomimetics
  作者：William P Esler、Chittaranjan Das、Michael S Wolfe

  DOI：10.1016/j.bmcl.2004.01.077

  日期：2004.4

  (Hydroxyethyl)urea peptidomimetics are potent inhibitors of gamma-secretase that are accessible in a few synthetic steps. Systematic alteration of P2-P4' revealed that the corresponding S2-S4' active site pockets accommodate a variety of substituents, consistent with the fact that this protease cleaves a variety of single-pass membrane proteins; however, phenylalanine is not well tolerated at P2'. A compound spanning P2-P3' was identified as a low nM inhibitor of gamma-secretase activity both in cells and under cell-free conditions. (C) 2004 Published by Elsevier Ltd.
• Second Generation of Hydroxyethylamine BACE-1 Inhibitors: Optimizing Potency and Oral Bioavailability
  作者：Nicolas Charrier、Brian Clarke、Leanne Cutler、Emmanuel Demont、Colin Dingwall、Rachel Dunsdon、Philip East、Julie Hawkins、Colin Howes、Ishrut Hussain、Phil Jeffrey、Graham Maile、Rosalie Matico、Julie Mosley、Alan Naylor、Alistair O’Brien、Sally Redshaw、Paul Rowland、Virginie Soleil、Kathrine J. Smith、Sharon Sweitzer、Pam Theobald、David Vesey、Daryl S. Walter、Gareth Wayne

  DOI：10.1021/jm800138h

  日期：2008.6.1

  BACE-1 inhibition has the potential to provide a disease-modifying therapy for the treatment of Alzheimer's disease. Optimization of a first generation of BACE-1 inhibitors led to the discovery of novel hydroxyethylamines (HEAs) bearing a tricyclic nonprime side. These derivatives have nanomolar cell potency and are orally bioavailable.