(S)-phenylalanine N'-(benzyloxy)amide trifluoroacetate | 58207-46-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-phenylalanine N'-(benzyloxy)amide trifluoroacetate
• 英文别名: H-Phe-NHBzl*CF₃COOH；phenylalanine hydroxamic acid benzyl ester mono TFA salt；HPheNHOBzl.CF3COOH；H2N-Phe-NHOBzl.CF3COOH；(2S)-2-amino-3-phenyl-N-phenylmethoxypropanamide;2,2,2-trifluoroacetic acid
• CAS: 58207-46-8
• 化学式: C₂HF₃O₂*C₁₆H₁₈N₂O₂
• 分子量: 384.355
• InChiKey: ZZOLNVCVWGNPHR-RSAXXLAASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.44
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  102
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (S)-phenylalanine N'-(benzyloxy)amide trifluoroacetate 在 sodium hydroxide 、 1-羟基苯并三唑一水物 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 3.25h， 生成 (S)-N-<(R,S)-2-carboxy-1-oxopropyl>phenylalanine N'-(benzyloxy)amide
  参考文献：
  名称：

  Retro-inverso概念适用于脑啡肽降解酶的完全抑制剂。

  摘要：

  另一方面，在第一系列抑制剂中，逆反修饰导致对DAP和APN的抑制作用略有改善，而在第二系列抑制剂中则出现相反的结果。因此，在P'1位置含有α-氨基酸部分的化合物表现为三种酶的弱抑制剂，IC50值在微摩尔范围内，而在相同位置带有β-氨基酸部分的化合物比在P'1位置具有更强特异性。 NEP抑制的母体化合物。

  DOI：

  10.1021/jm00117a025
• 作为产物：
  描述：

  BOC-L-苯丙氨酸 在 1-羟基苯并三唑一水物 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 2.0h， 生成 (S)-phenylalanine N'-(benzyloxy)amide trifluoroacetate
  参考文献：
  名称：

  Retro-inverso概念适用于脑啡肽降解酶的完全抑制剂。

  摘要：

  另一方面，在第一系列抑制剂中，逆反修饰导致对DAP和APN的抑制作用略有改善，而在第二系列抑制剂中则出现相反的结果。因此，在P'1位置含有α-氨基酸部分的化合物表现为三种酶的弱抑制剂，IC50值在微摩尔范围内，而在相同位置带有β-氨基酸部分的化合物比在P'1位置具有更强特异性。 NEP抑制的母体化合物。

  DOI：

  10.1021/jm00117a025

文献信息

• Synthesis, physicochemical characterization and neuroprotective evaluation of novel 1-hydroxypyrazin-2(1<i>H</i>)-one iron chelators in an <i>in vitro</i> cell model of Parkinson's disease
  作者：Frank W. Lewis、Kathleen Bird、Jean-Philippe Navarro、Rawa El Fallah、Jeremy Brandel、Véronique Hubscher-Bruder、Andrew Tsatsanis、James A. Duce、David Tétard、Samuel Bourne、Mahmoud Maina、Ilse S. Pienaar

  DOI：10.1039/d1dt02604f

  日期：——

  Iron dysregulation, dopamine depletion, cellular oxidative stress and α-synuclein protein mis-folding are key neuronal pathological features seen in the progression of Parkinson's disease. Iron chelators endowed with one or more therapeutic modes of action have long been suggested as disease modifying therapies for its treatment. In this study, novel 1-hydroxypyrazin-2(1H)-one iron chelators were synthesized

  铁失调、多巴胺耗竭、细胞氧化应激和 α-突触核蛋白错误折叠是帕金森病进展中的关键神经元病理特征。具有一种或多种治疗作用模式的铁螯合剂长期以来一直被建议作为其治疗的疾病修饰疗法。本研究合成了新型1-羟基吡嗪-2( 1H )-酮铁螯合剂，并评估了其理化性质、铁螯合能力、抗氧化能力以及在帕金森病细胞培养模型中的神经保护作用。物理化学性质（log β 、log D 7.4 、pL 0.5 ）表明这些配体穿透细胞膜并形成较弱铁络合物的能力比密切相关的 1-羟基吡啶-2(1 H )-one 更差。尽管如此，我们表明这些配体在体外针对儿茶酚胺能神经毒素 6-羟基多巴胺提供的神经保护水平与之前使用 1-羟基吡啶-2(1 H )-one 和临床使用的铁螯合剂去铁酮所观察到的神经保护水平相当。与对照相比，其中两种配体将细胞活力恢复至 ≥89%。其中两个配体被赋予了额外的酚部分，试图衍生出具有双重铁螯合/抗氧化活性的多功能螯合剂。
• Novel dipeptidyl hydroxamic acids that inhibit human and bacterial dipeptidyl peptidase III
  作者：Ana Cvitešić、Igor Sabljić、Janja Makarević、Marija Abramić

  DOI：10.1080/14756366.2016.1186021

  日期：2016.11.2

  Human dipeptidyl peptidase III (hDPP III), a zinc-metallopeptidase of the family M49, is an activator of the Keap1-Nrf2 cytoprotective pathway involved in defense against oxidative stress. Pathophysiological roles of DPP III have not been elucidated yet, partly due to the lack of specific inhibitors. We showed that substrate analog H-Tyr-Phe-NHOH is a strong competitive inhibitor of hDPP III, while

  人二肽基肽酶III（hDPP III）是M49家族的锌金属肽酶，是Keap1-Nrf2细胞保护途径的激活物，参与抗氧化应激的防御。DPP III的病理生理作用尚未阐明，部分原因是缺乏特异性抑制剂。我们表明，底物类似物H-Tyr-Phe-NHOH是hDPP III的强竞争性抑制剂，而H-Tyr-Gly-NHOH则表现出弱得多的抑制作用。为了研究氨基酸取代在抑制剂P1位置上的作用，我们合成了三种新的二肽基异羟肟酸酯，并研究了它们对人肠道共生菌拟杆菌（theactotaides thetaiotaomicron）的hDPP III和DPP III活性的影响。hDPP III的抑制程度而不是细菌酶的抑制程度取决于P1中的氨基酸。
• 10.1002/1099-0690(20022)2002:3<428::aid-ejoc428<3.0.co;2-j
  作者：Volonterio, Alessandro、Bellosta, Stefano、Bravo, Pierfrancesco、Canavesi, Monica、Corradi, Eleonora、Meille, Stefano V.、Monetti, Mara、Moussier, Nathalie、Zanda, Matteo

  DOI：10.1002/1099-0690(20022)2002:3<428::aid-ejoc428<3.0.co;2-j

  日期：——
• Solution/solid-phase synthesis of partially modified retro- ψ [NHCH(CF 3 )]-peptidyl hydroxamates
  作者：Alessandro Volonterio、Pierfrancesco Bravo、Matteo Zanda

  DOI：10.1016/s0040-4039(01)00375-6

  日期：2001.4

  The synthesis of a novel family of partially-modified (PM) retropeptidyl hydroxamates incorporating a [CH(CF3)CH2CO] unit as a surrogate of the conventional malonyl group, has been accomplished both in solution and in solid-phase. The key step is the Michael-type N-addition of free or polymer bound alpha -amino hydroxamates to 3-(E-enoyl)-1,3-oxazolidin-2-ones, which takes place very effectively, although with low stereocontrol. A number of tri- and tetra-peptidyl hydroxamates were obtained either in diastereomerically pure form (by solution-phase synthesist after chromatographic purification), or as mixtures of two epimers in very good chemical purity (by solid-phase, after release from the resin), demonstrating that this method is suitable for preparing combinatorial libraries of PM retro-psi [NHCH(CF3)]-peptidyl hydroxamates for screening as metalloprotease inhibitors. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Absolutely conserved tryptophan in M49 family of peptidases contributes to catalysis and binding of competitive inhibitors
  作者：Jasminka Špoljarić、Branka Salopek-Sondi、Janja Makarević、Bojana Vukelić、Dejan Agić、Šumski Šimaga、Nina Jajčanin-Jozić、Marija Abramić

  DOI：10.1016/j.bioorg.2009.03.002

  日期：2009.6

  The role of the unique fully conserved tryptophan in metallopeptidase family M49 (dipeptidyl peptidase III family) was investigated by site-directed mutagenesis on human dipeptidyl peptidase III (DPP III) where Trp300 was subjected to two substitutions (W300F and W300L). The mutant enzymes showed thermal stability equal to the wild-type DPP III. Conservative substitution of the Trp300 with phenylalanine decreased enzyme activity 2-4 fold, but did not significantly change the K-m values for two dipeptidyl 2-naphthylamide substrates. However, the K-m for the W300L mutant was elevated 5-fold and the k(cat) value was reduced 16-fold with Arg-Arg-2-naphthylamide. Both substitutions had a negative effect on the binding of two competitive inhibitors designed to interact with S1 and S2 subsites.These results indicate the importance of the aromatic nature of W300 in DPP III ligand binding and catalysis, and contribution of this residue in maintaining the functional integrity of this enzyme's S2 subsite. (C) 2009 Elsevier Inc. All rights reserved.