Mu-Ala-OH

• 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: Mu-Ala-OH
• 英文别名: N-morpholinecarbonyl-L-alanine；N-morpholinocarbonyl-L-alanine；(2S)-2-(morpholine-4-carbonylamino)propanoic acid
• 化学式: C₈H₁₄N₂O₄
• 分子量: 202.21
• InChiKey: AAJCBYFEHKDLCH-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  L-丙氨酸甲酯盐酸盐 、 Mu-Ala-OH 在 N-甲基吗啉 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以60%的产率得到Mu-Ala-Ala-OCH3
  参考文献：
  名称：

  Aza-Peptidyl Michael Acceptor and Epoxide Inhibitors—Potent and Selective Inhibitors of Schistosoma mansoni and Ixodes ricinus Legumains (Asparaginyl Endopeptidases)

  摘要：

  Aza-peptide Michael acceptors and epoxides with the general structure of YCO-Ala-Ala-AAsn-trans-CH=CHCOR and YCO-Ala-Ala-AAsn-EP-COR, respectively, are shown to be potent inhibitors of asparaginyl endopeptidases (legumains) from the bloodfluke, Schistosoma mansoni (SmAE), and the hard tick, Ixodes ricinus (IrAE). Structure-activity relationships (SARs) were determined for a set of 41 aza-peptide Michael acceptors and eight aza-peptide epoxides. Both enzymes prefer disubstituted amides to monosubstituted amides in the P1' position, and potency increased as we increased the hydrophobicity of the inhibitor in this position. Extending the inhibitor to P5 resulted in increased potency, especially against IrAE, and both enzymes prefer small over large hydrophobic residues at P2. Aza-peptide Michael acceptor inhibitors are more potent than aza-peptide epoxide inhibitors, and for some of these compounds, second-order inhibiton rate constants are the fastest yet discovered. Given the central functions of these enzymes in both parasites, the data presented here may facilitate the eventual design of selective antiparasitic drugs.

  DOI：

  10.1021/jm900849h
• 作为产物：
  描述：

  Mu-Ala-OCH3 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以89%的产率得到Mu-Ala-OH
  参考文献：
  名称：

  Aza-Peptidyl Michael Acceptor and Epoxide Inhibitors—Potent and Selective Inhibitors of Schistosoma mansoni and Ixodes ricinus Legumains (Asparaginyl Endopeptidases)

  摘要：

  Aza-peptide Michael acceptors and epoxides with the general structure of YCO-Ala-Ala-AAsn-trans-CH=CHCOR and YCO-Ala-Ala-AAsn-EP-COR, respectively, are shown to be potent inhibitors of asparaginyl endopeptidases (legumains) from the bloodfluke, Schistosoma mansoni (SmAE), and the hard tick, Ixodes ricinus (IrAE). Structure-activity relationships (SARs) were determined for a set of 41 aza-peptide Michael acceptors and eight aza-peptide epoxides. Both enzymes prefer disubstituted amides to monosubstituted amides in the P1' position, and potency increased as we increased the hydrophobicity of the inhibitor in this position. Extending the inhibitor to P5 resulted in increased potency, especially against IrAE, and both enzymes prefer small over large hydrophobic residues at P2. Aza-peptide Michael acceptor inhibitors are more potent than aza-peptide epoxide inhibitors, and for some of these compounds, second-order inhibiton rate constants are the fastest yet discovered. Given the central functions of these enzymes in both parasites, the data presented here may facilitate the eventual design of selective antiparasitic drugs.

  DOI：

  10.1021/jm900849h

文献信息

• Design and Synthesis of Dipeptide Nitriles as Reversible and Potent Cathepsin S Inhibitors
  作者：Yancey D. Ward、David S. Thomson、Leah L. Frye、Charles L. Cywin、Tina Morwick、Michel J. Emmanuel、Renée Zindell、Daniel McNeil、Younes Bekkali、Marc Girardot,、Matt Hrapchak、Molly DeTuri、Kathy Crane、Della White、Susan Pav、Yong Wang、Ming-Hong Hao、Christine A. Grygon、Mark E. Labadia、Dorothy M. Freeman、Walter Davidson、Jerry L. Hopkins、Maryanne L. Brown、Denice M. Spero

  DOI：10.1021/jm020209i

  日期：2002.12.1

  T-cells, should, in theory, modulate the immune response. The cysteine protease Cathepsin S performs a fundamental step in antigen presentation and therefore represents an attractive target for inhibition. Herein, we report a series of potent and reversible Cathepsin S inhibitors based on dipeptide nitriles. These inhibitors show nanomolar inhibition of the target enzyme as well as cellular potency in

  免疫应答的特异性取决于外源蛋白的加工和抗原肽在细胞表面的呈递。从理论上讲，抑制抗原呈递以及随后激活T细胞应能调节免疫反应。半胱氨酸蛋白酶组织蛋白酶S在抗原呈递中执行基本步骤，因此代表了诱人的抑制靶标。本文中，我们报告了一系列基于二肽腈的有效且可逆的组织蛋白酶S抑制剂。这些抑制剂在人B细胞系中显示出对目标酶的纳摩尔抑制作用以及细胞效价。还报道了与组织蛋白酶S共结晶的可逆抑制剂的第一个X射线晶体结构。
• Irreversible HIV protease inhibitors, intermediates, compositions and
  申请人：Lucky Limited.

  公开号：US05744621A1

  公开（公告）日：1998-04-28

  Cis-epoxide compounds of formula (I-1) and pharmaceutically acceptable salts, hydrates and solvates thereof: ##STR1## wherein: R.sup.1 is a cycloalkyl, or aryl-substituted lower alkyl group; A is a functionalized acyl group of the formula ##STR2## wherein R.sup.2 is a C.sub.1-4 alkyl, or amide-substituted C.sub.1-2 alkyl group; R.sup.3 is a C.sub.1-4 alkoxy, aryloxyalkyl or arylalkoxy, or a nitrogen-containing aromatic radical, or a lower alkoxy group substituted with a nitrogen-containing aromatic radical, or a radical having the formula of ##STR3## wherein R.sup.4 is a hydrogen or a methyl group and R.sup.5 is an alkyl group substituted with a nitrogen-containing aromatic radical; and m is 0 or 1; and B is a functionalized amino group of the formula ##STR4## wherein R.sup.8 and R.sup.9 are independently a C.sub.1-4 alkyl group optionally substituted with an aromatic radical, or an aromatic group.

  化合物(I-1)的顺式环氧化合物及其药学上可接受的盐、水合物和溶剂化合物：##STR1## 其中：R.sup.1是环烷基或芳基取代的较低烷基基团；A是式子##STR2##的官能化酰基，其中R.sup.2是C.sub.1-4烷基或酰胺取代的C.sub.1-2烷基基团；R.sup.3是C.sub.1-4烷氧基、芳氧基烷基或芳基烷氧基，或含氮芳基基团，或取代含氮芳基基团的较低烷氧基，或具有式子##STR3##的基团，其中R.sup.4是氢或甲基基团，R.sup.5是取代含氮芳基基团的烷基基团；m为0或1；B是式子##STR4##的官能化氨基基团，其中R.sup.8和R.sup.9分别是C.sub.1-4烷基基团（可选地取代芳基基团）或芳基基团。
• Cis-epoxide derivatives useful as irreversible HIV protease inhibitors and process and intermediates for their preparation
  申请人：LUCKY LTD.

  公开号：EP0601486B1

  公开（公告）日：1997-10-29
• US5587388A
  申请人：——

  公开号：US5587388A

  公开（公告）日：1996-12-24
• US5744621A
  申请人：——

  公开号：US5744621A

  公开（公告）日：1998-04-28