(2S)-N-[(2R,3R)-3-(benzyloxy)-1-(5-fluoro-2,3-dihydro-1H-indol-1-yl)butan-2-yl]-4-cyclohexyl-2-[(3-methoxyphenyl)formamido]butanamide | 769963-66-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S)-N-[(2R,3R)-3-(benzyloxy)-1-(5-fluoro-2,3-dihydro-1H-indol-1-yl)butan-2-yl]-4-cyclohexyl-2-[(3-methoxyphenyl)formamido]butanamide
• 英文别名: N-[(2S)-4-cyclohexyl-1-[[(2R,3R)-1-(5-fluoro-2,3-dihydroindol-1-yl)-3-phenylmethoxybutan-2-yl]amino]-1-oxobutan-2-yl]-3-methoxybenzamide
• CAS: 769963-66-8
• 化学式: C₃₇H₄₆FN₃O₄
• 分子量: 615.788
• InChiKey: CXYMWYIUDRQGTR-VCXVHRGASA-N

物化性质

• 沸点：
  810.2±65.0 °C(Predicted)
• 密度：
  1.156±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  45
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  79.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S)-N-[(2R,3R)-3-(benzyloxy)-1-(5-fluoro-2,3-dihydro-1H-indol-1-yl)butan-2-yl]-4-cyclohexyl-2-[(3-methoxyphenyl)formamido]butanamide 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 生成 N-{(S)-3-Cyclohexyl-1-[(1R,2R)-1-(5-fluoro-2,3-dihydro-indol-1-ylmethyl)-2-hydroxy-propylcarbamoyl]-propyl}-3-methoxy-benzamide
  参考文献：
  名称：

  Arylaminoethyl amides as noncovalent inhibitors of cathepsin S. Part 2: Optimization of P1 and N-aryl

  摘要：

  A systematic study of anilines led to the discovery of a metabolically robust fluoroindoline replacement for the alkoxy aniline toxicophore in 1. Investigations of the PI pocket resulted in the discovery of a wide tolerance of functionality leading to the discovery of 11 as a potent and selective inhibitor of cathepsin S. (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.12.056
• 作为产物：
  描述：

  (2S,3S)-2-(Boc-氨基)-3-苄氧基-1-丁醇 在 sodium cyanoborohydride 、 戴斯-马丁氧化剂 、 溶剂黄146 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2S)-N-[(2R,3R)-3-(benzyloxy)-1-(5-fluoro-2,3-dihydro-1H-indol-1-yl)butan-2-yl]-4-cyclohexyl-2-[(3-methoxyphenyl)formamido]butanamide
  参考文献：
  名称：

  Arylaminoethyl amides as noncovalent inhibitors of cathepsin S. Part 2: Optimization of P1 and N-aryl

  摘要：

  A systematic study of anilines led to the discovery of a metabolically robust fluoroindoline replacement for the alkoxy aniline toxicophore in 1. Investigations of the PI pocket resulted in the discovery of a wide tolerance of functionality leading to the discovery of 11 as a potent and selective inhibitor of cathepsin S. (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.12.056

文献信息

• Inhibitors of cathepsin S
  申请人：IRM LLC

  公开号：US20040248887A1

  公开（公告）日：2004-12-09

  The present invention provides compounds, compositions and methods for the selective inhibition of cathepsin S. In a preferred aspect, cathepsin S is selectively inhibited in the presence of at least one other cathepsin isozyme. The present invention also provides methods for treating a disease state in a subject by selectively inhibiting cathepsin S.

  本发明提供了化合物、组合物和方法，用于选择性抑制蛋白酶S。在首选方面，当存在至少一种其他蛋白酶同工酶时，选择性抑制蛋白酶S。本发明还提供了通过选择性抑制蛋白酶S治疗受试者的疾病状态的方法。
• INHIBITORS OF CATHEPSIN S
  申请人：Liu Hong

  公开号：US20080242671A1

  公开（公告）日：2008-10-02

  The present invention provides compounds, compositions and methods for the selective inhibition of cathepsin S. In a preferred aspect, cathepsin S is selectively inhibited in the presence of at least one other cathepsin isozyme. The present invention also provides methods for treating a disease state in a subject by selectively inhibiting cathepsin S.

  本发明提供了化合物、组合物和方法，用于选择性抑制蛋白酶S。在首选方面，当存在至少一种其他蛋白酶同工酶时，选择性地抑制蛋白酶S。本发明还提供了通过选择性抑制蛋白酶S治疗受试者疾病状态的方法。
• US7384970B2
  申请人：——

  公开号：US7384970B2

  公开（公告）日：2008-06-10
• [EN] INHIBITORS OF CATHEPSIN S<br/>[FR] INHIBITEURS DE LA CATHEPSINE S
  申请人：IRM LLC

  公开号：WO2004084843A2

  公开（公告）日：2004-10-07

  The present invention provides compounds, compositions and methods for the selective inhibition of cathepsin S. In a preferred aspect, cathepsin S is selectively inhibited in the presence of at least one other cathepsin isozyme. The present invention also provides methods for treating a disease state in a subject by selectively inhibiting cathepsin S.
• Arylaminoethyl amides as noncovalent inhibitors of cathepsin S. Part 2: Optimization of P1 and N-aryl
  作者：Phillip B. Alper、Hong Liu、Arnab K. Chatterjee、KhanhLinh T. Nguyen、David C. Tully、Christine Tumanut、Jun Li、Jennifer L. Harris、Tove Tuntland、Jonathan Chang、Perry Gordon、Thomas Hollenbeck、Donald S. Karanewsky

  DOI：10.1016/j.bmcl.2005.12.056

  日期：2006.3

  A systematic study of anilines led to the discovery of a metabolically robust fluoroindoline replacement for the alkoxy aniline toxicophore in 1. Investigations of the PI pocket resulted in the discovery of a wide tolerance of functionality leading to the discovery of 11 as a potent and selective inhibitor of cathepsin S. (C) 2005 Elsevier Ltd. All rights reserved.