(methoxysuccinyl)-L-alanyl-L-alanine | 102284-27-5

• 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: (methoxysuccinyl)-L-alanyl-L-alanine
• 英文别名: (2S)-2-[[(2S)-2-[(4-methoxy-4-oxobutanoyl)amino]propanoyl]amino]propanoic acid
• CAS: 102284-27-5
• 化学式: C₁₁H₁₈N₂O₆
• 分子量: 274.274
• InChiKey: RNGVMPRBNWYIGW-BQBZGAKWSA-N

物化性质

• 沸点：
  596.0±45.0 °C(Predicted)
• 密度：
  1.241±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  122
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (methoxysuccinyl)-L-alanyl-L-alanine 在 N-甲基吗啉 、 mercury(II) trifluoroacetate 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 20.17h， 生成 (3S,5S,2'S)-3-isopropyl-5--6-methylene-4-oxatetrahydro-2-pyranone
  参考文献：
  名称：

  Synthesis of proline-valine pseudodipeptide enol lactones, serine protease inhibitors

  摘要：

  Pseudodipeptides of proline-valine that incorporate protio or halo enol lactone moieties have been synthesized from common acetylenic acid precursors; in each case, two diasteromers were prepared in enantiomerically pure form. The preparation began with isomeric propargylic alcohols derived from L-prolinal, which are further elaborated into the methyleneoxy valine pseudodipeptide analogues via an oxalactam intermediate. Stereochemical assignments were made by comparisons of nuclear Overhauser enhancement factors. The pseudodipeptide acetylenic acids could by cyclized to the protio enol lactones by mercuric salts and could be elaborated to tetrapeptide analogues either before or after cyclization. The relative stability of the two diastereomeric enol lactone systems toward intramolecular acyl transfer could be rationalized by molecular mechanics energy calculations on ground-state and tetrahedral intermediates believed to be involved in the reaction. While the halo enol lactones derived from the pseudotetrapeptides proved to be very unstable, they could be prepared from the n-butyl carbamate derivatives of the dipeptide. An evaluation of these protio and halo enol lactone systems as inhibitors of serine proteases will be discussed elsewhere.

  DOI：

  10.1021/jo00008a011
• 作为产物：
  描述：

  methyl (S)-4-((1-(benzyloxy)-1-oxopropan-2-yl)amino)-4-oxobutanoate 在 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 38.25h， 生成 (methoxysuccinyl)-L-alanyl-L-alanine
  参考文献：
  名称：

  弹性蛋白酶活性报告物，用于电子顺磁共振（EPR）和Overhauser增强磁共振成像（OMRI），作为移线型一氧化氮

  摘要：

  肺炎性疾病是全世界的主要负担。他们有大量嗜中性粒细胞流入。中性粒细胞在炎症部位分泌未经检查的蛋白酶，因此导致蛋白酶/抑制剂失衡。在这些蛋白酶中，中性粒细胞弹性蛋白酶通过弹性蛋白片段化负责肺结构的降解。因此，非侵入性地监测肺中蛋白酶/抑制剂的状态将是重要的诊断工具。 在这里，我们介绍MeO-Suc-（Ala）2 -Pro-Val-硝基氧化物的合成，这是一种适用于电子顺磁共振波谱（EPR）和Overhauser增强磁共振成像（OMRI）的线移弹性蛋白酶活性探针。它是一种快速灵敏的嗜中性粒细胞弹性蛋白酶底物，K m = 15±2.9 µM，k cat / K m = 930,000 s -1 M -1和K m = 25±5.4 µM，k cat / K m = 640,000 s -1中号-1为ř和小号异构体。这些特性适合于准确检测低至1 nM的嗜中性粒细胞弹性蛋白酶浓度。用衍生自肺炎假单胞菌小

  DOI：

  10.1016/j.freeradbiomed.2018.08.006

文献信息

• [EN] NITROXIDES FOR USE AS CONTRAST AGENTS FOR OVERHAUSER MAGNETIC RESONANCE IMAGING (OMRI)<br/>[FR] NITROXYDES DESTINÉS À ÊTRE UTILISÉS COMME AGENTS DE CONTRASTE POUR L'IMAGERIE PAR RÉSONANCE MAGNÉTIQUE OVERHAUSER (OMRI)
  申请人：UNIV AIX MARSEILLE

  公开号：WO2017005879A1

  公开（公告）日：2017-01-12

  The present invention relates to an in vitro method for detecting and/ or quantifying the catalytic activity of an enzyme E, said method comprising the steps of: i) Contacting enzyme E with a compound of formula (la), or (lb): ii) Monitoring the conversion of compound (la) or (lb) into compound (IlIa) or (lllb) by Electron Paramagnetic Resonance (EPR) or Overhauser-enhanced Magnetic Resonance Imaging (OMRI), or by Proton Electron Double Resonance Imaging (PEDRI) thereby detecting or quantifying the activity of enzyme E wherein: Y is OC(=O), S(C=O), NR7; X is CH or N; R1, R2, R3, are each independently selected from C1-C6 alkyl optionally substituted by OH, NRe, COOH; R4, R5 are each independently selected from H, C1-C6 alkyl, C1-C6 alkoxy, NR8R9, SR10;R6 is H or C1-C6 alkyl; ==W is =W or is absent; W is O, S, or NR11; R7, R8, R9, R10, R11 are each independently selected from C1-C6 alkyl; n is 0, 1, 2 or 3, Z is a substrate residue of an enzyme E.

  本发明涉及一种体外方法，用于检测和/或定量酶E的催化活性，所述方法包括以下步骤：i) 将酶E与化合物（la）或（lb）的公式接触；ii) 通过电子顺磁共振（EPR）或Overhauser增强磁共振成像（OMRI），或通过质子电子双共振成像（PEDRI）监测化合物（la）或（lb）转化为化合物（IIIa）或（IIIb），从而检测或定量酶E的活性，其中：Y为OC(=O)，S(C=O)，NR7；X为CH或N；R1、R2、R3分别独立选择自C1-C6烷基，可选择性地被OH，NRe，COOH取代；R4、R5分别独立选择自H，C1-C6烷基，C1-C6烷氧基，NR8R9，SR10；R6为H或C1-C6烷基；==W为=W或不存在；W为O，S或NR11；R7、R8、R9、R10、R11分别独立选择自C1-C6烷基；n为0，1，2或3，Z为酶E的底物残基。
• Peptidyl carbamates incorporating amino acid isosteres as novel elastase inhibitors
  作者：George A. Digenis、Bushra J. Agha、Kiyoshi Tsuji、Masayuki Kato、Masaki Shinogi

  DOI：10.1021/jm00158a025

  日期：1986.8

  The design and synthesis of 13 novel peptidyl carbamates are described. When tested for inhibitory activity toward porcine pancreatic elastase, trypsin, and chymotrypsin, six compounds were found to specifically inhibit elastase without affecting the other two serine proteases. All the active inhibitors had an amino acid isostere at the P1 position. Kinetic studies indicated that the inhibition was competitive with Ki values ranging from 4.23 X 10(-5) to 2.4 X 10(-6) M. The degree of inhibition was found to be dependent on the specificity of the peptide chain for the extended subsites on the enzyme as well as on the nature of P1'. Preliminary work on one inhibitor indicates that the inhibition is reversible and proceeds via the rapid formation of a strong enzyme-inhibitor complex, followed by slow acylation of the serine residue on the active site of the enzyme. Peptidyl carbamates represent a novel class of elastase inhibitors.
• OLEKSYSZYN, JOZEF;POWERS, JAMES C., BIOCHEMISTRY, 30,(1991) N, C. 485-493
  作者：OLEKSYSZYN, JOZEF、POWERS, JAMES C.

  DOI：——

  日期：——
• REED, PETER E.;KATZENELLENBOGEN, JOHN A., J. ORG. CHEM., 56,(1991) N, C. 2624-2634
  作者：REED, PETER E.、KATZENELLENBOGEN, JOHN A.

  DOI：——

  日期：——
• ——
  作者：DIGENIS G. A.、 AGHA BUSHRA J.、 TSUJI KIYOSHI

  DOI：——

  日期：——