2-(N-benzyloxycarbonyl-L-leucinyl)-2'-(N-benzyloxycarbonyl-L-norvalinyl)carbohydrazide

• 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: 2-(N-benzyloxycarbonyl-L-leucinyl)-2'-(N-benzyloxycarbonyl-L-norvalinyl)carbohydrazide
• 英文别名: benzyl N-[(2S)-4-methyl-1-oxo-1-[2-[[[(2S)-2-(phenylmethoxycarbonylamino)pentanoyl]amino]carbamoyl]hydrazinyl]pentan-2-yl]carbamate
• 化学式: C₂₈H₃₈N₆O₇
• 分子量: 570.646
• InChiKey: OQEAEJGUIOENFU-GOTSBHOMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  41
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  176
• 氢给体数：
  6
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (1S)-1-benzyloxycarbonylamino-3-methyl-1-(1,3,4-oxadiazol-2-on-5-yl)butane 在 1-羟基苯并三唑 、 一水合肼 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 40.0h， 生成 2-(N-benzyloxycarbonyl-L-leucinyl)-2'-(N-benzyloxycarbonyl-L-norvalinyl)carbohydrazide
  参考文献：
  名称：

  Structure-Based Design of Cathepsin K Inhibitors Containing a Benzyloxy-Substituted Benzoyl Peptidomimetic

  摘要：

  Peptidomimetic cathepsin K inhibitors have been designed using binding models which were based on the X-ray crystal structure of an amino acid-based, active site-spanning inhibitor complexed with cathepsin K. These inhibitors, which contain a benzyloxybenzoyl group in place of a Cbz-leucine moiety, maintained good inhibitory potency relative to the amino acid-based inhibitor, and the binding models were found to be very predictive of relative inhibitor potency. The binding mode of one of the inhibitors was confirmed by X-ray crystallography, and the crystallographically determined structure is in close qualitative agreement with the initial binding model. These results strengthen the validity of a strategy involving iterative cycles of structure-based design, inhibitor synthesis and evaluation, and crystallographic structure determination for the discovery of peptidomimetic inhibitors.

  DOI：

  10.1021/jm980474x

文献信息

• Structure-Based Design of Cathepsin K Inhibitors Containing a Benzyloxy-Substituted Benzoyl Peptidomimetic
  作者：Scott K. Thompson、Ward W. Smith、Baoguang Zhao、Stacie M. Halbert、Thaddeus A. Tomaszek、David G. Tew、Mark A. Levy、Cheryl A. Janson、Karla J. D‘Alessio、Michael S. McQueney、Jeff Kurdyla、Christopher S. Jones、Renee L. DesJarlais、Sherin S. Abdel-Meguid、Daniel F. Veber

  DOI：10.1021/jm980474x

  日期：1998.10.1

  Peptidomimetic cathepsin K inhibitors have been designed using binding models which were based on the X-ray crystal structure of an amino acid-based, active site-spanning inhibitor complexed with cathepsin K. These inhibitors, which contain a benzyloxybenzoyl group in place of a Cbz-leucine moiety, maintained good inhibitory potency relative to the amino acid-based inhibitor, and the binding models were found to be very predictive of relative inhibitor potency. The binding mode of one of the inhibitors was confirmed by X-ray crystallography, and the crystallographically determined structure is in close qualitative agreement with the initial binding model. These results strengthen the validity of a strategy involving iterative cycles of structure-based design, inhibitor synthesis and evaluation, and crystallographic structure determination for the discovery of peptidomimetic inhibitors.