N-(benzyloxycarbonyl)-L-leucyl-L-phenylalanine methylamide | 60079-69-8

• 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-(benzyloxycarbonyl)-L-leucyl-L-phenylalanine methylamide
• 英文别名: Z-leucine-phenylalanine-N-methylamide；N-[(Benzyloxy)carbonyl]-L-leucyl-N-methyl-L-phenylalaninamide；benzyl N-[(2S)-4-methyl-1-[[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopentan-2-yl]carbamate
• CAS: 60079-69-8
• 化学式: C₂₄H₃₁N₃O₄
• 分子量: 425.528
• InChiKey: LUACFVQEOLMFKZ-SFTDATJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  96.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(benzyloxycarbonyl)-L-leucyl-L-phenylalanine methylamide 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 生成 Thioacetic acid S-{[(S)-3-methyl-1-((S)-1-methylcarbamoyl-2-phenyl-ethylcarbamoyl)-butylcarbamoyl]-methyl} ester
  参考文献：
  名称：

  A novel series of matrix metalloproteinase inhibitors for the treatment of inflammatory disorders

  摘要：

  The preparation of a novel series of matrix metalloproteinase inhibitors is described, based on the use of a mercaptoacyl zinc binding moiety. The compounds have been tested in a model of rheumatoid arthritis and show good oral activity. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00125-x
• 作为产物：
  描述：

  (S)-N-Benzyloxycarbonyl-phenylalanine-N'-methylamide 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 生成 N-(benzyloxycarbonyl)-L-leucyl-L-phenylalanine methylamide
  参考文献：
  名称：

  A novel series of matrix metalloproteinase inhibitors for the treatment of inflammatory disorders

  摘要：

  The preparation of a novel series of matrix metalloproteinase inhibitors is described, based on the use of a mercaptoacyl zinc binding moiety. The compounds have been tested in a model of rheumatoid arthritis and show good oral activity. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00125-x

文献信息

• Peptidyl 3-substituted 1-hydroxyureas as isosteric analogues of succinylhydroxamate MMP inhibitors
  作者：Cristina Campestre、Paolo Tortorella、Mariangela Agamennone、Serena Preziuso、Alessandro Biasone、Elisa Nuti、Armando Rossello、Carlo Gallina

  DOI：10.1016/j.ejmech.2007.07.002

  日期：2008.5

  displays IC(50) in the range of nM vs MMP-1, -3, -7 and sub-nM vs MMP-2, -8, and -9. The peptidyl 1-hydroxyurea 1a attained an IC(50) of 20 microM vs MMP-9, and substantially approaches inhibition of known N-hydroxyureas based on aminoacids or peptides against other zinc metalloenzymes and non-peptidic N-hydroxyureas against MMPs. Strong preference of the O-N1-C=O unit for the antiperiplanar amide bond

  为了在MMP抑制剂的设计中评价N-羟基脲作为锌结合基团，通过非对映二肽H-Leu-Phe-NHMe和HD-Leu-Phe-NHMe的N-羟基氨基甲酰化制备了两个肽基1-羟基脲。肽基1-羟基脲比母体肽更有效，但比等排性（R）-琥珀酰异羟肟酸酯类似物弱得多（4-5个数量级），后者在nM对MMP-1范围内显示IC（50），- 3，-7和sub-nM对MMP-2，-8和-9。与MMP-9相比，肽基1-羟基脲1a的IC（50）为20 microM，并且基本上接近基于氨基酸或肽的已知N-羟基脲对其他锌金属酶和非肽N-羟基脲对MMP的抑制作用。O-N1-C = O单元强烈倾向于反周酰胺键构象，这似乎是更有效的锌螯合的主要限制。肽基1-羟基脲在N3处的甲基化，以促进锌螯合所需的上平面O-N1-C = O构象并提高亲和力，导致不希望的分子内反应使甲基咪唑烷-2,4-二酮释放，使人想起埃德曼肽降解。
• The Use of PeptiCLEC-TR in the Preparation of Dipeptides
  作者：Susan J. Faulconbridge、Karen E. Holt、Christopher J. Lock、Stephen J. C. Taylor、Martin Woods

  DOI：10.1021/op0000430

  日期：2000.11.1

  Dipeptides are important intermediates in many pharmaceutical products. To support a research programme on matrix metalloproteinases (MMP) we needed to prepare the dipeptide, Leu-Phe-NHMe (3). Chemical methods provided the material but not to the quality required, and thus an alternative preparation was sought. The use of enzymes in chemical synthesis was a tool that we had used before but not in the preparation of dipeptides, This contribution will show the utility of PeptiCLEC-TR in the preparation of dipeptide (3) and its application to other dipeptides, It will highlight the amenability of PeptiCLEC-TR to scale-up and demonstrate the recycling of this enzyme, which will make this a cost-effective route.
• PEPTIDYL COMPOUNDS AND THEIR THERAPEUTIC USE AS INHIBITORS OF METALLOPROTEINASES
  申请人：Darwin Discovery Limited

  公开号：EP0728144B1

  公开（公告）日：2000-01-19
• US5853623A
  申请人：——

  公开号：US5853623A

  公开（公告）日：1998-12-29