(S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-6-(4-nitrophenylsulfonylamido)hexanoic acid | 120402-59-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-6-(4-nitrophenylsulfonylamido)hexanoic acid
• 英文别名: Fmoc-Lys(Nosyl)-OH；Nε-(4-Nitrobenzenesulfonyl)-Nα-(9-fluorenylmethoxycarbonyl)-L-lysine；Nepsilon-(4-nitrobenzenesulfonyl)-Nalpha-(9-fluorenylmethoxycarbonyl)-L-lysine；(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-6-[(4-nitrophenyl)sulfonylamino]hexanoic acid
• CAS: 120402-59-7
• 化学式: C₂₇H₂₇N₃O₈S
• 分子量: 553.593
• InChiKey: OVZJYXVJFKPWLN-VWLOTQADSA-N

物化性质

• 熔点：
  67-69 °C
• 密度：
  1.387±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  39
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  176
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-6-(4-nitrophenylsulfonylamido)hexanoic acid 在 钯 作用下， 以 乙酸乙酯 为溶剂， 反应 2.0h， 以to yield the title compound in 95% yield的产率得到Nε-(4-Aminobenzenesulfonyl)-Nα-(9-fluorenylmethoxycarbonyl)-L-lysine
  参考文献：
  名称：

  Amino acid derivatives as HIV aspartyl protease inhibitors

  摘要：

  本发明涉及一类具有HIV天冬氨酸蛋白酶抑制作用的氨基酸衍生物。

  公开号：

  US06455587B1
• 作为产物：
  描述：

  (S)-methyl 2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-6-(4-nitrophenylsulfonylamido)hexanoate 在 水 、 calcium chloride 、 sodium hydroxide 、 溶剂黄146 作用下， 以 异丙醇 、 水 为溶剂， 反应 6.0h， 以0.54 g的产率得到(S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-6-(4-nitrophenylsulfonylamido)hexanoic acid
  参考文献：
  名称：

  Nε-Modified lysine containing inhibitors for SIRT1 and SIRT2

  摘要：

  Sirtuins catalyze the NAD(+) dependent deacetylation of N-epsilon-acetyl lysine residues to nicotinamide, O '-acetyl- ADP-ribose (OAADPR) and N-epsilon-deacetylated lysine. Here, an easy-to-synthesize Ac-Ala-Lys-Ala sequence has been used as a probe for the screening of novel N-epsilon-modified lysine containing inhibitors against SIRT1 and SIRT2. N-epsilon-Selenoacetyl and N-epsilon-isothiovaleryl were the most potent moieties found in this study, comparable to the widely studied N-epsilon-thioacetyl group. The N-epsilon-3,3-dimethylacryl and N-epsilon-isovaleryl moieties gave significant inhibition in comparison to the N-epsilon-acetyl group present in the substrates. In addition, the studied N-epsilon-alkanoyl, N-epsilon-alpha,beta-unsaturated carbonyl and N-epsilon-aroyl moieties showed that the acetyl binding pocket can accept rather large groups, but is sensitive to even small changes in electronic and steric properties of the N-epsilon-modification. These results are applicable for further screening of Ne-acetyl analogues. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.035

文献信息

• Amino acid derivatives as HIV aspartyl protease inhibitors
  申请人：Pharmacor Inc.

  公开号：US06455587B1

  公开（公告）日：2002-09-24

  The present invention relates to a class of amino acid derivatives with HIV aspartyl protease inhibitory properties.

  本发明涉及一类具有HIV天冬氨酸蛋白酶抑制性能的氨基酸衍生物。
• A Novel Continuous Assay for the Deacylase Sirtuin 5 and Other Deacetylases
  作者：Claudia Roessler、Christian Tüting、Marat Meleshin、Clemens Steegborn、Mike Schutkowski

  DOI：10.1021/acs.jmedchem.5b00293

  日期：2015.9.24

  concentrations in microtiter plates. Here we describe an improved continuous sirtuin 5 assay based on the coupling of the sirtuin reaction to a proteolytic cleavage using internally fluorescence-quenched substrates. Systematic optimization of a carbamoyl phosphate synthetase 1 derived, glutarylated peptide yielded a Sirt5 substrate with kcat/KM value of 337 000 M–1 s–1, which represents the best sirtuin substrate

  Sirtuins是NAD +依赖性赖氨酸脱酰基酶，参与许多调控过程，例如代谢途径的控制，DNA修复和应激反应。瑟土因活性的调节剂作为揭示这些酶的生物学功能的工具和潜在的治疗剂是需要的。缺乏在微量滴定板中以低瑟土因浓度运行的有效且简单的连续活性测定法，阻碍了此类调节剂的系统性发现。在这里，我们基于使用内部荧光猝灭底物的sirtuin反应与蛋白水解切割的偶联，描述了一种改进的连续sirtuin 5分析方法。对氨基甲酰磷酸合成酶1衍生的，戊二酰化肽进行系统优化后，产生的Sirt5底物为k cat /K M值为337 000 M –1 s –1，代表了迄今为止描述的最好的瑟土因底物。这些非凡的底物性质允许在微量滴定板形式中仅存在10 nM沉默调节蛋白的情况下可靠地测定不同抑制剂的K i值。测定条件可有效转移至其他赖氨酸脱乙酰基酶，如sirtuin 2和sirtuin 3，从而使更有效地开发针对sirtuin的药物成为可能。
• KARUP, GUNNAR;MELDAL, MORTEN;NIELSEN, PETER E.;BUCHARDT, OLE, INT. J. PEPTIDE AND PROTEIN RES., 32,(1988) N, C. 331-343
  作者：KARUP, GUNNAR、MELDAL, MORTEN、NIELSEN, PETER E.、BUCHARDT, OLE

  DOI：——

  日期：——
• Nε-Modified lysine containing inhibitors for SIRT1 and SIRT2
  作者：Tero Huhtiniemi、Tiina Suuronen、Maija Lahtela-Kakkonen、Tanja Bruijn、Sanna Jääskeläinen、Antti Poso、Antero Salminen、Jukka Leppänen、Elina Jarho

  DOI：10.1016/j.bmc.2010.06.035

  日期：2010.8

  Sirtuins catalyze the NAD(+) dependent deacetylation of N-epsilon-acetyl lysine residues to nicotinamide, O '-acetyl- ADP-ribose (OAADPR) and N-epsilon-deacetylated lysine. Here, an easy-to-synthesize Ac-Ala-Lys-Ala sequence has been used as a probe for the screening of novel N-epsilon-modified lysine containing inhibitors against SIRT1 and SIRT2. N-epsilon-Selenoacetyl and N-epsilon-isothiovaleryl were the most potent moieties found in this study, comparable to the widely studied N-epsilon-thioacetyl group. The N-epsilon-3,3-dimethylacryl and N-epsilon-isovaleryl moieties gave significant inhibition in comparison to the N-epsilon-acetyl group present in the substrates. In addition, the studied N-epsilon-alkanoyl, N-epsilon-alpha,beta-unsaturated carbonyl and N-epsilon-aroyl moieties showed that the acetyl binding pocket can accept rather large groups, but is sensitive to even small changes in electronic and steric properties of the N-epsilon-modification. These results are applicable for further screening of Ne-acetyl analogues. (C) 2010 Elsevier Ltd. All rights reserved.
• Amino acid derivatives useful for the treatment of alzheimer's disease
  申请人：John Varghese

  公开号：US20060079550A1

  公开（公告）日：2006-04-13

  The present invention is a method of treating Alzheimer's disease, and other diseases, and/or inhibiting beta-secretase enzyme, and/or inhibiting deposition of A beta peptide in a mammal, by use of known compounds of formula (I): wherein R 1 , R 2 , R 3 , R 4 , W and C x are herein defined.

  本发明涉及一种治疗阿尔茨海默病和其他疾病，和/或抑制β-分泌酶酶，和/或抑制哺乳动物体内Aβ肽沉积的方法，使用已知的式(I)化合物，其中R1、R2、R3、R4、W和Cx在此定义。