3-(s)-Benzyloxycarbonylamino-4-(5-fluoro-2,3-dihydro-indol-1-yl)-butyric acid tert-butyl ester | 819076-55-6

• 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: 3-(s)-Benzyloxycarbonylamino-4-(5-fluoro-2,3-dihydro-indol-1-yl)-butyric acid tert-butyl ester
• 英文别名: tert-butyl (3S)-4-(5-fluoro-2,3-dihydroindol-1-yl)-3-(phenylmethoxycarbonylamino)butanoate
• CAS: 819076-55-6
• 化学式: C₂₄H₂₉FN₂O₄
• 分子量: 428.504
• InChiKey: SNLCANSAKLFRMW-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(s)-Benzyloxycarbonylamino-4-(5-fluoro-2,3-dihydro-indol-1-yl)-butyric acid tert-butyl ester 在 palladium on activated charcoal 氢气 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 tert-butyl (3S)-3-[(2S)-2-[(6-chloro-1,3-benzoxazol-2-yl)amino]-3-cyclohexylpropanamido]-4-(5-fluoro-2,3-dihydro-1H-indol-1-yl)butanoate
  参考文献：
  名称：

  Synthesis and evaluation of arylaminoethyl amides as noncovalent inhibitors of cathepsin S. Part 3: Heterocyclic P3

  摘要：

  A series of N-alpha-2-benzoxazolyl-alpha-amino acid-(arylaminoethyl)amides were identified as potent, selective, and noncovalent inhibitors of cathepsin S. Structure-activity relationships including strategies for modulating the selectivities among cathepsins S, K, and L, and in vivo pharmacokinetics are discussed. A X-ray structure of compound 3 bound to the active site of cathepsin S is also reported. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.12.095
• 作为产物：
  描述：

  N-苄氧羰基-L-天门冬氨酸 4-叔丁酯 在 sodium cyanoborohydride 、 戴斯-马丁氧化剂 、 溶剂黄146 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 3-(s)-Benzyloxycarbonylamino-4-(5-fluoro-2,3-dihydro-indol-1-yl)-butyric acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and evaluation of arylaminoethyl amides as noncovalent inhibitors of cathepsin S. Part 3: Heterocyclic P3

  摘要：

  A series of N-alpha-2-benzoxazolyl-alpha-amino acid-(arylaminoethyl)amides were identified as potent, selective, and noncovalent inhibitors of cathepsin S. Structure-activity relationships including strategies for modulating the selectivities among cathepsins S, K, and L, and in vivo pharmacokinetics are discussed. A X-ray structure of compound 3 bound to the active site of cathepsin S is also reported. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.12.095

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：US20070123523A1

  公开（公告）日：2007-05-31

  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.

  本发明提供了一种选择性抑制蛋白酶S的化合物、组合物和方法。在一种优选方面，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治疗主体的疾病状态的方法。
• 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.
• US7173051B2
  申请人：——

  公开号：US7173051B2

  公开（公告）日：2007-02-06
• US7307095B2
  申请人：——

  公开号：US7307095B2

  公开（公告）日：2007-12-11