DL-norleucine amide | 7324-07-4

• 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: DL-norleucine amide
• 英文别名: (S)-2-aminohexanamide；L-norleucine amide；H-Nle-NH2；Nle-NH2；L-norleucinamide；Norleucine amide；(2S)-2-aminohexanamide
• CAS: 7324-07-4
• 化学式: C₆H₁₄N₂O
• 分子量: 130.19
• InChiKey: YTIHIRCOUAPRCS-YFKPBYRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  9
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  69.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  DL-norleucine amide 在 sodium azide 、 copper(ll) sulfate pentahydrate 、 三氟甲磺酸酐 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 16.0h， 生成 (2S)-2-azidohexanamide
  参考文献：
  名称：

  [EN] HETEROARYL NITRILE COMPOUNDS USEFUL AS INHIBITORS OF CATHEPSIN-S
  [FR] COMPOSÉS D'HÉTÉROARYL-NITRILE UTILES COMME INHIBITEURS DE CATHEPSINE-S

  摘要：

  揭示了具有以下化学式（I）的Cathepsin-S可逆抑制剂化合物，可用于治疗自身免疫和其他疾病。还揭示了含有这些化合物的药物组合物，以及制备和使用这些化合物的方法。

  公开号：

  WO2011109470A1
• 作为产物：
  描述：

  L-norleucine methyl ester 在 氨 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以85%的产率得到DL-norleucine amide
  参考文献：
  名称：

  Specificity of Lysine:N6-Hydroxylase: A Hypothesis for a Reactive Substrate Intermediate in the Catalytic Mechanism

  摘要：

  The recombinant cytoplasmic preparation of lysine: N-6-hydroxlase catalyzes the conversion of L-lysine to its N-6-hydroxy derivative when supplemented with the cofactors NADPH and FAD. A number of lysine analogs reflecting minor alterations in the inherent structural features of the amino acid as well compounds with relatively high affinity for lysine binding domains in other proteins were examined for their ability to serve as substrates of lysine: N-6-hydroxylase. These studies have revealed that the enzyme does not tolerate any change in the structural features of L-lysine, its preferred substrate, with the exception of the replacement of the CgammaH2-methylene group by sulfur, as in (S)-2-aminoethyl-L-cysteine. L-Norleucine is a potent inhibitor of the enzyme while L-norvaline and L-alpha-aminobutyric acid do not exhibit such effect, indicating the importance of a C-4 hydrophobic side chain for effective interaction with the enzyme. Among the N-alkyl amides of hydrophobic amino acids, only L-norleucine methylamide and L-alpha-aminobutyric acid ethylamide serve as moderate inhibitors of lysine : N-6-hydroxylase. Based on the enzyme's stringent substrate specificity, a mechanism involving the conversion of L-lysine to 2-aminocaprolactam prior to its oxygenation by the 4a-peroxyflavin intermediate in the catalytic cycle is proposed. (C) 1996 Academic Press, Inc.

  DOI：

  10.1006/bioo.1996.0034

文献信息

• Synthesis and Biological Activity of a Novel Class of Small Molecular Weight Peptidomimetic Competitive Inhibitors of Protein Tyrosine Phosphatase 1B
  作者：Scott D. Larsen、Tjeerd Barf、Charlotta Liljebris、Paul D. May、Derek Ogg、Theresa J. O'Sullivan、Barbara J. Palazuk、Heinrich J. Schostarez、F. Craig Stevens、John E. Bleasdale

  DOI：10.1021/jm010393s

  日期：2002.1.1

  sulfate with other potential phosphate mimics. The most potent analogue arising from this effort was triacid 71, which inhibits PTP1B competitively with a K(i) = 0.22 microM without inhibiting SHP-2 or LAR at concentrations up to 100 microM. Overall, the inhibitors generated in this work showed little or no enhancement of insulin signaling in cellular assays. However, potential prodrug triester 70 did induce

  蛋白质酪氨酸磷酸酶1B（PTP1B）部分地通过使胰岛素受体（IR）的β亚基调节域内的关键酪氨酸残基去磷酸化，从而负调节胰岛素信号传导，从而减弱受体酪氨酸激酶的活性。因此，抑制PTP1B有望改善胰岛素抵抗，并且最近已成为旨在鉴定用于治疗II型糖尿病的新药物的发现工作的重点。我们以前曾报道三肽Ac-Asp-Tyr（SO（3）H）-Nle-NH（2）是PTP1B的令人惊讶的有效抑制剂（K（i）= 5 microM）。为了改善该引线的稳定性和效力以及减弱其肽特性，进行了模拟程序。该程序初始阶段的具体内容包括用非氨基酸成分替换N和C末端，修饰酪氨酸亚基以及用其他潜在的磷酸盐模拟物替换硫酸酪氨酸。从这种努力中产生的最有效的类似物是三酸71，它以K（i）= 0.22 microM竞争性抑制PTP1B，而在浓度高达100 microM的情况下却不抑制SHP-2或LAR。总体而言，这项工作中产生的抑制剂在细
• Inhibitors of protein tyrosine phosphatase
  申请人：Pharmacia & Upjohn Company

  公开号：US06353023B1

  公开（公告）日：2002-03-05

  The present invention comprises small molecular weight, non-peptidic inhibitors of formula I and II of Protein Tyrosine Phosphatase 1 (PTP1) which are useful for the treatment and/or prevention of Non-Insulin Dependent Diabetes Mellitus (NIDDM).

  本发明涉及小分子量、非肽类的蛋白酪氨酸磷酸酶1（PTP1）的化学式I和II的抑制剂，用于治疗和/或预防非胰岛素依赖型糖尿病（NIDDM）。
• Fast Iterative Synthetic Approach toward Identification of Novel Highly Selective p38 MAP Kinase Inhibitors
  作者：Sandra Röhm、Benedict-Tilman Berger、Martin Schröder、Apirat Chaikuad、Rob Winkel、Koen F. W. Hekking、Jorg J. C. Benningshof、Gerhard Müller、Roberta Tesch、Mark Kudolo、Michael Forster、Stefan Laufer、Stefan Knapp

  DOI：10.1021/acs.jmedchem.9b01227

  日期：2019.12.12

  have led to the discovery of several potent inhibitors; however, so far no highly selective type-II inhibitors have been reported. We previously identified VPC-00628 as a potent and selective type-II inhibitor of p38α/β with few off-targets. Here we analyzed the chemical building blocks of VPC-00628 that played a key role in achieving potency and selectivity through targeting an inactive state of the

  p38丝裂原活化的蛋白激酶是环境应激反应的关键介质，并且是治疗炎症性疾病和癌症的有希望的靶标。大量的努力导致发现了几种有效的抑制剂。然而，到目前为止，还没有报道高选择性的II型抑制剂。我们先前将VPC-00628确定为p38α/β的有效且选择性的II型抑制剂，几乎没有脱靶现象。在这里，我们分析了VPC-00628的化学结构单元，这些结构单元通过靶向由独特的折叠P环构象诱导的激酶的非活性状态，在实现效能和选择性方面发挥了关键作用。使用快速，系统的组合合成方法，我们确定了化合物93（SR-318）对p38α/β具有极强的效力和选择性，可有效抑制全血中TNF-α的释放。因此，SR-318提供了一种有效的，选择性的p38α/βII型抑制剂，可用作化学探针，用于靶向这两种p38同工型的特定非活性状态。
• Methods and compounds for inhibiting &bgr;-amyloid peptide release and/or its synthesis
  申请人：Elan Pharmaceuticals, Inc.

  公开号：US06191166B1

  公开（公告）日：2001-02-20

  Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.

  揭示了一种抑制β-淀粉样肽释放和/或合成的化合物，因此在治疗阿尔茨海默病方面具有用途。还揭示了包括抑制β-淀粉样肽释放和/或合成的化合物的药物组合物，以及使用这种药物组合物预防性和治疗性地治疗阿尔茨海默病的方法。
• Compounds for inhibiting &bgr;-amyloid peptide release and/or its synthesis
  申请人：Elan Pharmaceuticals, Inc.

  公开号：US06207710B1

  公开（公告）日：2001-03-27

  Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis.

  揭示了一些抑制β-淀粉样肽释放和/或其合成的化合物，因此在治疗阿尔茨海默病方面具有用途。还揭示了包括抑制β-淀粉样肽释放和/或其合成的化合物的药物组合物。