N-isovaleryl-L-valyl-L-valine | 59452-57-2

• 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: N-isovaleryl-L-valyl-L-valine
• 英文别名: Iva-Val-Val-OH；Iva-Val-Val；N-(3-Methylbutanoyl)-L-valyl-L-valine；(2S)-3-methyl-2-[[(2S)-3-methyl-2-(3-methylbutanoylamino)butanoyl]amino]butanoic acid
• CAS: 59452-57-2
• 化学式: C₁₅H₂₈N₂O₄
• 分子量: 300.398
• InChiKey: AEUGESYRZDPJLS-STQMWFEESA-N

物化性质

• 沸点：
  541.6±35.0 °C(Predicted)
• 密度：
  1.055±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  95.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-isovaleryl-L-valyl-L-valine 在 N-甲基吗啉 、 lithium hydroxide 、 氯甲酸异丁酯 作用下， 以 水 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 反应 102.08h， 生成 5,5,5-Trifluoro-3-hydroxy-4-[2-(5,5,5-trifluoro-3-hydroxy-4-{3-methyl-2-[3-methyl-2-(3-methyl-butyrylamino)-butyrylamino]-butyrylamino}-pentanoylamino)-propionylamino]-pentanoic acid
  参考文献：
  名称：

  包含两个三氟甲基羟亚甲基等排体（Tfm-GABOB）的胃抑素类似物的全合成和含Tfm-GABOB的肽作为HIV-1蛋白酶和MMP-9抑制剂的评估

  摘要：

  我们描述了天冬氨酸蛋白酶抑制剂胃抑素的三氟甲基（Tfm）类似物的不对称总合成，该蛋白结合了两个γ-Tfm-γ-氨基-β-羟基丁酸（γ-Tfm-GABOB）单元而不是天然他汀类单元。测试了标题化合物以及几种Tfm取代的前体作为HIV-1蛋白酶和明胶酶B（MMP-9）的抑制剂

  DOI：

  10.1016/s0040-4020(01)00543-9
• 作为产物：
  描述：

  L-缬氨酸乙酯盐酸盐 在 sodium hydroxide 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 生成 N-isovaleryl-L-valyl-L-valine
  参考文献：
  名称：

  Affinity chromatography of pepsin using pepstatin fragments as ligands of specific sorbents

  摘要：

  DOI：

  10.1007/bf00573554

文献信息

• BIOLOGICAL ACTIVITY OF PEPSTATINS, PEPSTANONE A AND PARTIAL PEPTIDES ON PEPSIN, CATHEPSIN D AND RENIN
  作者：TAKAAKI AOYAGI、HAJIME MORISHIMA、RINZO NISHIZAWA、SETSUKO KUNIMOTO、TOMIO TAKEUCHI、HAMAO UMEZAWA、HIROH IKEZAWA

  DOI：10.7164/antibiotics.25.689

  日期：——

  The inhibition of pepsin, cathepsin D and renin by pepstatins, pepstanone A and their partial peptides is described. A new method using a nonapeptide containing 3H-Val as the substrate was devised for determination of renin activity. The pepstatin partial peptides valyl-valyl-4-amino-3-hydroxy-6-methylheptanoic acid (Val-Val-AHMHA), isovaleryl-valyl-valyl-4-amino-3-hydroxy-6-methylheptanoic acid (IVA-Val-Val-AHMHA) and carbobenzoxyvalyl-valyl-4-amino-3-hydroxy-6-methylheptanoic acid (Z-Val-Val-AHMHA) weakly inhibited proteolysis by pepsin and did not inhibit renin. Pepstatins B, C, E and G were as active as pepstatin A against pepsin and were slightly more active against renin than pepstatin A. Pepstanone A was as active as pepstatin A against pepsin but slightly less active against renin.

  本文介绍了胃蛋白酶、胰蛋白酶 D 和肾素对epstatins、pepstanone A 及其部分肽的抑制作用。还设计了一种使用含有 3H-Val 的非肽作为底物来测定肾素活性的新方法。表司他丁部分肽缬氨酰-缬氨酰-4-氨基-3-羟基-6-甲基庚酸（Val-Val-AHMHA）、异戊基-缬氨酰-缬氨酰-4-氨基-3-羟基-6-甲基庚酸（IVA-Val-Val-AHMHA）和羧基苄氧基缬氨酰-缬氨酰-4-氨基-3-羟基-6-甲基庚酸（Z-Val-Val-AHMHA）可弱化胃蛋白酶的蛋白水解作用，但对肾素没有抑制作用。抑肽酶 B、C、E 和 G 对胃蛋白酶的活性与抑肽酶 A 相当，但对肾素的活性略高于抑肽酶 A；抑肽酶 A 对胃蛋白酶的活性与抑肽酶 A 相当，但对肾素的活性略低于抑肽酶 A。
• Synthesis of the novel .pi.-(benzyloxymethyl)-protected histidine analog of statine. Inhibition of penicillopepsin by pepstatin-derived peptides containing different statine side-chain derivatives
  作者：Juergen Maibaum、Daniel H. Rich

  DOI：10.1021/jm00127a028

  日期：1989.7

  inhibitor 3 and 2-3 times more potent than the new (3S,4S)-4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA) analogue 17 (Ki = 1.5 x 10(-8) M). However, compound 16, which has an imidazole residue at the P1 position, is a significantly weaker inhibitor of the enzyme than the corresponding analogues with the lysine (5) and ornithine (6) side chains at P1. Considerations that led to the synthesis of 16 and

  衍生自一种新的他汀（Sta），（3S，4S）-4-氨基-3-羟基-5-（咪唑-4-基）戊酸（HiSta，20）的组氨酸侧链类似物的天冬氨酸蛋白酶抑制剂的合成），被报告。Boc-HiSta（BOM）-OMe（7）以Boc-His（pi-BOM）-OH的总收率为16％的方式制备，方法是形成四酸衍生物11并用NaBH4进行立体选择性顺式还原成4-羟基内酰胺12 ·通过DCC / HOBt预活化方法，从酯7（对映体纯度ee ＝ 88-90％）上除去Boc基团，并偶联至三肽链段Iva-Val-Val-OH（13），然后氢解除去pi-。碳上Pd（OH）2上的BOM组得到Iva-Val-Val-HiSta-OMe（16）。这种新的肽16是真菌天冬氨酸蛋白酶Penicillopsepsin的非常有效的抑制剂（Ki = 4。5 x 10（-9）M），其活性是同类含Sta的抑制剂3的10倍，且效力是新的（3S
• Simplified Pepstatins:  Synthesis and Evaluation of N-Terminally Modified Analogues
  作者：Martin Kratzel、Birgit Schlichtner、Roland Kirchmayer、Andreas Bernkop-Schnürch

  DOI：10.1021/jm9807306

  日期：1999.6.1

  The promising strategy of gastric ulcer healing with perorally administered epidermal growth factor (EGF) is so far strongly limited by the pepsinic degradation of this therapeutic polypeptide in the stomach. The incorporation of EGF in a bioadhesive polymer-pepsin inhibitor conjugate used as drug carrier matrix, however, might provide sufficient protection toward pepsinic degradation. The synthesis of appropriate pepsin inhibitors represents a prerequisite for the development of such polymer-inhibitor conjugates. The presented study demonstrates that modifications at the N-terminus of simplified analogues of pepstatin which can be synthesized in a simple and straight way result only in slight variations of the inhibitory activity. These analogues display only 10-fold reduced-inhibitory activity, compared to pepstatin A, when bearing a greater N-terminal group like isovaleryl, Boc, or Cbz. Compounds which are substituted at the N-terminus by a shorter N-acyl group like propionyl or cyclopropylcarbonyl show further reduced activity (0.01, compared to pepstatin A). The presence of an amide or a urethane moiety at the N-terminus has no considerable effect on enzyme inhibition. Therefore, the N-terminus of these analogues is able to be modified forming a covalent bond to various bioadhesive polymers via a suitable functionality.
• Total synthesis of a Pepstatin analogue incorporating two trifluoromethyl hydroxymethylene isosteres
  作者：Cristina Pesenti、Alberto Arnone、Anne Marie Aubertin、Pierfrancesco Bravo、Massimo Frigerio、Walter Panzeri、Sylvie Schmidt、Fiorenza Viani、Matteo Zanda

  DOI：10.1016/s0040-4039(00)01244-2

  日期：2000.9

  The total synthesis of a trifluoromethyl (Tfm) analogue of the aspartate protease inhibitor Pepstatin has been accomplished via incorporation of two alpha-Tfm-amino beta-hydroxy peptide isosteres instead of the natural statine units. The title compound as well as several Tfm-substituted precursors did not show anti-HIV activity. (C) 2000 Elsevier Science Ltd. All rights reserved.
• MAIBAUM, JUERGEN;RICH, DANIEL H., J. MED. CHEM., 32,(1989) N, C. 1571-1576
  作者：MAIBAUM, JUERGEN、RICH, DANIEL H.

  DOI：——

  日期：——