(2S)-2-氨基-4-[(叔丁氧羰基)氨基]丁酸甲酯 | 125279-44-9

• 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
• 中文名称: (2S)-2-氨基-4-[(叔丁氧羰基)氨基]丁酸甲酯
• 英文名称: (S)-methyl 2-amino-4-((tert-butoxycarbonyl)amino)butanoate
• 英文别名: (S)-methyl-2-amino-4-(tert-butoxycarbonylamino) butanoate；methyl (2S)-2-amino-4-[(tert-butoxymethyl)amino]butanoate；methyl (2S)-2-amino-4-(tert-butoxycarbonylamino)butyrate；L-Dbu(Boc)-OCH3；γ-Boc-L-Dab-OMe；NH2-Dab(Boc)-OMe；methyl (2S)-2-amino-4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate
• CAS: 125279-44-9
• 化学式: C₁₀H₂₀N₂O₄
• 分子量: 232.28
• InChiKey: LWOHDYABQSVXIE-ZETCQYMHSA-N

物化性质

• 沸点：
  342.3±32.0 °C(Predicted)
• 密度：
  1.088±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  90.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S)-2-氨基-4-[(叔丁氧羰基)氨基]丁酸甲酯 在 palladium on activated charcoal 氢气 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 methyl (2S)-2-[[(2S)-1-(benzenesulfonyl)pyrrolidine-2-carbonyl]amino]-4-[[(2S)-2-[methyl-[2-[4-[(2-methylphenyl)carbamoylamino]phenyl]acetyl]amino]-6-[6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoylamino]hexanoyl]amino]butanoate
  参考文献：
  名称：

  An Assessment of the Mechanistic Differences Between Two Integrin α₄β₁Inhibitors, the Monoclonal Antibody TA-2 and the Small Molecule BIO5192, in Rat Experimental Autoimmune Encephalomyelitis

  摘要：

  整合素α4β1通过调节淋巴细胞向炎症组织的迁移，在炎症过程中发挥着重要作用。在这里，我们评估了两种α4β1抑制剂的生化、药理和药效学特性，以及它们在多发性硬化症模型--实验性自身免疫性脑脊髓炎（EAE）中的疗效、抗大鼠 α4 单克隆抗体 TA-2 和小分子抑制剂 BIO5192 [2( S )-{[1-(3,5- 二氯苯磺酰基)-吡咯烷-2( S )- 甲酰基]-氨基}-4-[4-甲基-2( S )-(甲基-{2-[4-(3-邻甲苯基脲基)-苯基]-乙酰基}-氨基)-戊酰氨基]-丁酸]。TA-2 已在大鼠体内进行了广泛研究，为评估功能提供了基准。BIO5192 是一种高选择性、强效（K D <10 pM）的 α4β1 抑制剂。两种抑制剂的给药方案均已确定，可在研究期间提供充分的受体占用。两种抑制剂都能诱导白细胞增多，这种效应被用作活性的药效学标志，而且在EAE模型中都有疗效。用TA-2治疗会导致细胞表面的α4整合素表达减少，这是α4整合素/TA-2复合物内化的结果。相比之下，BIO5192 对细胞表面的 α4β1 没有调节作用。我们对 BIO5192 的研究结果表明，α4β7 在该模型中不起作用，阻断α4β1/配体之间的相互作用而不进行下调足以对大鼠 EAE 产生疗效。BIO5192 具有高度选择性，能与四种受试物种中四种的 α4β1 高度亲和地结合。这些研究表明，BIO5192 是一种新型、强效、选择性的 α4β1 整合素抑制剂，它将成为评估 α4β1 生物学特性的重要试剂，并可能为治疗人类炎症性疾病提供一种新疗法。

  DOI：

  10.1124/jpet.102.047332
• 作为产物：
  描述：

  NAlpha-芴甲氧羰基-Nγ-羰-L-2,4-氨基丁酸 在 氢气 作用下， 以 乙醚 为溶剂， 反应 0.17h， 生成 (2S)-2-氨基-4-[(叔丁氧羰基)氨基]丁酸甲酯
  参考文献：
  名称：

  Synthesis and Evaluation of Peptidomimetics as Selective Inhibitors and Active Site Probes of Nitric Oxide Synthases

  摘要：

  Nitric oxide synthase (NOS) catalyzes the conversion of L-arginine to L-citrilline and nitric oxide (NO). Selective inhibition of the isoforms of NOS could have great therapeutic potential in the treatment of certain disease states arising from pathologically elevated synthesis of NO. Recently, we reported dipeptide amides containing a basic amine side chain as potent and selective inhibitors of neuronal NOS (Huang, H.; Martasek, P.; Roman, L. J.; Masters, B. S. S.; Silverman, R. B. J. Med. Chem. 1999, 42, 3147). The mast potent nNOS inhibitor among these compounds is L-Arg(NO2)-L-Dbu-NH2 (1) (K-i = 130 nM), which also exhibits the highest selectivity over eNOS (>1500-fold) with excellent selectivity over iNOS (190-fold). Here we describe the design and synthesis of a series of peptidomimetic analogues of this dipeptide as potential selective inhibitors of nNOS. The biochemical evaluation of these compounds also revealed the binding requirements of the dipeptide inhibitors with NOS. Incorporation of protecting groups at the N-terminus of the dipeptide amide 1 (compounds 4 and 5) resulted in dramatic decreases in the inhibitory potency of nNOS. Masking the NH group of the peptide bond (peptoids 6-8 and N-methylated compounds 9-11) also gave much poorer nNOS inhibitors than I. Both of the results demonstrate the importance of the cl-amine of the dipeptide and the NH moiety of the peptide bond for binding at the active site. Modifications at the C-terminus of the peptide included converting the amide to the methyl ester (12), tert-butyl ester (13), and carboxylic acid (14) and also descarboxamide analogues (15-17), which revealed less restricted binding requirements for the C-terminus of the dipeptide. Further optimization should be possible when we learn more about the binding requirements at the active sites of NOSs.

  DOI：

  10.1021/jm000127z

文献信息

• [EN] COMPOSITIONS AND METHODS FOR THE TREATMENT OF BACTERIAL INFECTIONS<br/>[FR] COMPOSÉS ET MÉTHODES POUR LE TRAITEMENT D'INFECTIONS BACTÉRIENNES
  申请人：CIDARA THERAPEUTICS INC

  公开号：WO2018006063A1

  公开（公告）日：2018-01-04

  Compositions and methods for the treatment of bacterial infections include compounds containing dimers of cyclic heptapeptides conjugated to one or more monosaccharide or oligosaccharide moieties. In particular, compounds can be used in the treatment of bacterial infections caused by Gram-negative bacteria.

  用于治疗细菌感染的组合物和方法包括含有环七肽二聚体与一个或多个单糖或寡糖基团结合的化合物。特别是，这些化合物可用于治疗由革兰氏阴性细菌引起的细菌感染。
• [EN] MACROCYCLIC BROAD SPECTRUM ANTIBIOTICS<br/>[FR] ANTIBIOTIQUES MACROCYCLIQUES À LARGE SPECTRE
  申请人：RQX PHARMACEUTICALS INC

  公开号：WO2017084630A1

  公开（公告）日：2017-05-26

  Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of bacterial type 1 signal peptidase (SpsB), an essential protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.

  本文提供了抗菌化合物，其中在某些实施例中，这些化合物具有广谱生物活性。在各种实施例中，这些化合物通过抑制细菌类型1信号肽酶（SpsB）发挥作用，这是细菌中的一种必需蛋白质。还提供了使用所述化合物的药物组合物和治疗方法。
• [EN] COMPOUNDS FOR THE TREATMENT OF HEPATITIS C<br/>[FR] COMPOSÉS DESTINÉS AU TRAITEMENT DE L'HÉPATITE C
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2011139513A1

  公开（公告）日：2011-11-10

  The disclosure provides compounds of formula I, including pharmaceutically acceptable salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV. [INSERT CHEMICAL STRUCTURE HERE] I

  该披露提供了公式I的化合物，包括药用可接受的盐，以及使用这些化合物的组合物和方法。这些化合物对丙型肝炎病毒（HCV）具有活性，并可能对感染HCV的人有用。【在此插入化学结构】。
• [EN] LINEAR PEPTIDE ANTIBIOTICS<br/>[FR] ANTIBIOTIQUES À PEPTIDE LINÉAIRE
  申请人：RQX PHARMACEUTICALS INC

  公开号：WO2013123456A1

  公开（公告）日：2013-08-22

  Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. The compounds provided herein can in other embodiments overcome the resistance conferred by single amino acid mutations at defined positions of bacterial Signal Peptidases (SPases) and in other embodiments provide for a broad spectrum of antibiotic bioactivity. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.

  本文提供了抗菌化合物，其中在某些实施例中，这些化合物具有广谱生物活性。本文提供的化合物在其他实施例中可以克服细菌信号肽酶（SPases）特定位置的单个氨基酸突变所带来的耐药性，并在其他实施例中提供广谱抗生素生物活性。还提供了使用所述化合物的药物组合物和治疗方法。
• [EN] INHIBITORS OF CYTOCHROME P450 (CYP3A4)<br/>[FR] INHIBITEURS DE CYTOCHROME P450 (CYP3A4)
  申请人：GILEAD SCIENCES INC

  公开号：WO2012088178A1

  公开（公告）日：2012-06-28

  The present application provides for a compound of formula I, and related compounds, or a pharmaceutically acceptable salt, solvate, and/or ester thereof, compositions containing such compounds, therapeutic methods that include the administration of such compounds, and therapeutic methods that include the administration of such compounds with at least one additional therapeutic agent.

  本申请提供了一种I式化合物，以及相关化合物，或其药学上可接受的盐、溶剂合物和/或酯，含有这种化合物的组合物，包括给予这种化合物的治疗方法，以及包括给予这种化合物和至少一种额外治疗剂的治疗方法。