benzyl N-[(2S,3S)-1-[[(2S)-3-(1H-indol-3-yl)-1-[methoxy(methyl)amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamate | 182216-59-7

• 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: benzyl N-[(2S,3S)-1-[[(2S)-3-(1H-indol-3-yl)-1-[methoxy(methyl)amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamate
• CAS: 182216-59-7
• 化学式: C₂₇H₃₄N₄O₅
• 分子量: 494.591
• InChiKey: DABHHDAAHKJTII-NWVWQQAFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl N-[(2S,3S)-1-[[(2S)-3-(1H-indol-3-yl)-1-[methoxy(methyl)amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamate 在 palladium on activated charcoal 4-二甲氨基吡啶 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 5.0h， 生成 (2S,3S)-N-[(2S)-3-(1H-indol-3-yl)-1-[methoxy(methyl)amino]-1-oxopropan-2-yl]-3-methyl-2-(naphthalen-1-ylsulfonylamino)pentanamide
  参考文献：
  名称：

  Synthesis of Peptide Aldehyde Derivatives as Selective Inhibitors of Human Cathepsin L and Their Inhibitory Effect on Bone Resorption

  摘要：

  Cathepsin L, a lysosomal cysteine protease, is secreted by osteoclasts and participates in bone collagen degradation. In a search for cathepsin L inhibitors as antiosteoporotic agents, a series of peptide aldehyde derivatives were prepared by two synthetic approaches, DMSO oxidation of the corresponding alcohol derivatives and DIBAL-H reduction of the corresponding N,O-dimethylhydroxylamide derivatives, and evaluated for inhibitory activity against human cathepsin L and for inhibitory effects on bone resorption. Some of the peptide aldehyde derivatives including alpha-acylamino aldehyde derivatives showed potent activities. Among these compounds, N-(1-naphthalenylsulfonyl-L-isoleucyl-L-tryptophanal (12) was selected as a candidate for further investigation. Compound 12, a potent, selective, and reversible inhibitor of human cathepsin L with an IC50 Of 1.9 nM, inhibited the release of Ca2+ and hydroxyproline from bone in in vitro bone culture system and also prevented bone loss in ovariectomized mice at an oral dose of 50 mg/kg.

  DOI：

  10.1021/jm9803065
• 作为产物：
  描述：

  N-苄氧羰基-L-色氨酸 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 32.0h， 生成 benzyl N-[(2S,3S)-1-[[(2S)-3-(1H-indol-3-yl)-1-[methoxy(methyl)amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamate
  参考文献：
  名称：

  Synthesis of Peptide Aldehyde Derivatives as Selective Inhibitors of Human Cathepsin L and Their Inhibitory Effect on Bone Resorption

  摘要：

  Cathepsin L, a lysosomal cysteine protease, is secreted by osteoclasts and participates in bone collagen degradation. In a search for cathepsin L inhibitors as antiosteoporotic agents, a series of peptide aldehyde derivatives were prepared by two synthetic approaches, DMSO oxidation of the corresponding alcohol derivatives and DIBAL-H reduction of the corresponding N,O-dimethylhydroxylamide derivatives, and evaluated for inhibitory activity against human cathepsin L and for inhibitory effects on bone resorption. Some of the peptide aldehyde derivatives including alpha-acylamino aldehyde derivatives showed potent activities. Among these compounds, N-(1-naphthalenylsulfonyl-L-isoleucyl-L-tryptophanal (12) was selected as a candidate for further investigation. Compound 12, a potent, selective, and reversible inhibitor of human cathepsin L with an IC50 Of 1.9 nM, inhibited the release of Ca2+ and hydroxyproline from bone in in vitro bone culture system and also prevented bone loss in ovariectomized mice at an oral dose of 50 mg/kg.

  DOI：

  10.1021/jm9803065

文献信息

• Synthesis of Peptide Aldehyde Derivatives as Selective Inhibitors of Human Cathepsin L and Their Inhibitory Effect on Bone Resorption
  作者：Tsuneo Yasuma、Satoru Oi、Nobuo Choh、Toshiyuki Nomura、Naoki Furuyama、Atsushi Nishimura、Yukio Fujisawa、Takashi Sohda

  DOI：10.1021/jm9803065

  日期：1998.10.1

  Cathepsin L, a lysosomal cysteine protease, is secreted by osteoclasts and participates in bone collagen degradation. In a search for cathepsin L inhibitors as antiosteoporotic agents, a series of peptide aldehyde derivatives were prepared by two synthetic approaches, DMSO oxidation of the corresponding alcohol derivatives and DIBAL-H reduction of the corresponding N,O-dimethylhydroxylamide derivatives, and evaluated for inhibitory activity against human cathepsin L and for inhibitory effects on bone resorption. Some of the peptide aldehyde derivatives including alpha-acylamino aldehyde derivatives showed potent activities. Among these compounds, N-(1-naphthalenylsulfonyl-L-isoleucyl-L-tryptophanal (12) was selected as a candidate for further investigation. Compound 12, a potent, selective, and reversible inhibitor of human cathepsin L with an IC50 Of 1.9 nM, inhibited the release of Ca2+ and hydroxyproline from bone in in vitro bone culture system and also prevented bone loss in ovariectomized mice at an oral dose of 50 mg/kg.