{(1S,2R,3R)-1-Benzyl-3-(4-dimethylamino-benzylamino)-2-hydroxy-3-[(S)-1-(2-hydroxy-4-methoxy-benzylcarbamoyl)-2-methyl-propylcarbamoyl]-propyl}-carbamic acid tert-butyl ester | 376644-26-7

• 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: {(1S,2R,3R)-1-Benzyl-3-(4-dimethylamino-benzylamino)-2-hydroxy-3-[(S)-1-(2-hydroxy-4-methoxy-benzylcarbamoyl)-2-methyl-propylcarbamoyl]-propyl}-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(2S,3R,4R)-4-[[4-(dimethylamino)phenyl]methylamino]-3-hydroxy-5-[[(2S)-1-[(2-hydroxy-4-methoxyphenyl)methylamino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxo-1-phenylpentan-2-yl]carbamate
• CAS: 376644-26-7
• 化学式: C₃₈H₅₃N₅O₇
• 分子量: 691.868
• InChiKey: WNIGSMLFPNMARQ-GFOUJFQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  50
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  162
• 氢给体数：
  6
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  {(1S,2R,3R)-1-Benzyl-3-(4-dimethylamino-benzylamino)-2-hydroxy-3-[(S)-1-(2-hydroxy-4-methoxy-benzylcarbamoyl)-2-methyl-propylcarbamoyl]-propyl}-carbamic acid tert-butyl ester 在 盐酸 、 O-(1,2-dihydro-2-oxo-1-pyridyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基乙酰胺 为溶剂， 生成 (2R,3R,4S)-4-((S)-2-Amino-3,3-dimethyl-butyrylamino)-2-(4-dimethylamino-benzylamino)-3-hydroxy-5-phenyl-pentanoic acid [(S)-1-(2-hydroxy-4-methoxy-benzylcarbamoyl)-2-methyl-propyl]-amide
  参考文献：
  名称：

  Structure-Based optimisation of 2-aminobenzylstatine derivatives: potent and selective inhibitors of the chymotrypsin-Like activity of the human 20S proteasome

  摘要：

  We have identified 2-aminobenzylstatine derivatives that inhibit non-covalently the chymotrypsin-like activity of the human 20S proteasome. A structure-based optimisation approach has allowed us to improve the potency of this structural class of proteasome inhibitors from micromolar to nanomolar level. The new derivatives showed good selectivity against the trypsin-like and post-glutamyl-peptide hydrolytic activities of this enzyme. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00178-6
• 作为产物：
  描述：

  N-Boc-L-苯丙氨醇 在 lithium hydroxide 、 草酰氯 、 O-(1,2-dihydro-2-oxo-1-pyridyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 二甲基亚砜 、 三乙胺 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 {(1S,2R,3R)-1-Benzyl-3-(4-dimethylamino-benzylamino)-2-hydroxy-3-[(S)-1-(2-hydroxy-4-methoxy-benzylcarbamoyl)-2-methyl-propylcarbamoyl]-propyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Structure-Based optimisation of 2-aminobenzylstatine derivatives: potent and selective inhibitors of the chymotrypsin-Like activity of the human 20S proteasome

  摘要：

  We have identified 2-aminobenzylstatine derivatives that inhibit non-covalently the chymotrypsin-like activity of the human 20S proteasome. A structure-based optimisation approach has allowed us to improve the potency of this structural class of proteasome inhibitors from micromolar to nanomolar level. The new derivatives showed good selectivity against the trypsin-like and post-glutamyl-peptide hydrolytic activities of this enzyme. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00178-6

文献信息

• 2-Amino-3-hydroxy-4-tert-leucyl-amino-5 phenyl-pentanoic acid amide derivatives
  申请人：——

  公开号：US20030166572A1

  公开（公告）日：2003-09-04

  The invention relates to compounds of formula (I), wherein the substituents and symbols are defined as indicated in the description, to processes for the preparation thereof, to medicaments comprising those compounds, and to the use thereof in the preparation of pharmaceutical compositions for the therapeutic treatment of warm-blooded animals, including humans.

  该发明涉及式（I）的化合物，其中取代基和符号如描述中所示定义，以及其制备方法，包含这些化合物的药物，以及在制备用于治疗温血动物（包括人类）的药物组合物中的应用。
• 2-Amino-3-hydroxy-4-tert-leucyl-amino-5-phenyl-pentanoic acid amide derivatives
  申请人：Furet Pascal

  公开号：US20060205673A1

  公开（公告）日：2006-09-14

  The invention relates to compounds of formula I wherein the substituents and symbols are defined as indicated in the description, to processes for the preparation thereof, to medicaments comprising those compounds, and to the use thereof in the preparation of pharmaceutical compositions for the therapeutic treatment of warm-blooded animals, including humans.

  本发明涉及式I的化合物，其中所述的取代基和符号如描述中所示，以及其制备方法，包括这些化合物的药物和在制备温血动物（包括人类）的治疗药物组合物中使用的方法。
• 2-AMINO-3-HYDROXY-4-TERT-LEUCYL-AMINO-5-PHENYL-PENTANOIC ACID AMIDE DERIVATIVES
  申请人：Novartis AG

  公开号：EP1290012B1

  公开（公告）日：2006-05-10
• [EN] 2-AMINO-3-HYDROXY-4-TERT-LEUCYL-AMINO-5-PHENYL-PENTANOIC ACID AMIDE DERIVATIVES<br/>[FR] DERIVES DE L'AMIDE DE L'ACIDE 2-AMINO-3-HYDROXY-4-TERT-LEUCYL-AMINO-5-PHENYL-PENTANOIQUE
  申请人：NOVARTIS AG

  公开号：WO2001089282A2

  公开（公告）日：2001-11-29

  The invention relates to compounds of formula (I), wherein the substituents and symbols are defined as indicated in the description, to processes for the preparation thereof, to medicaments comprising those compounds, and to the use thereof in the preparation of pharmaceutical compositions for the therapeutic treatment of warm-blooded animals, including humans.
• Structure-Based optimisation of 2-aminobenzylstatine derivatives: potent and selective inhibitors of the chymotrypsin-Like activity of the human 20S proteasome
  作者：Pascal Furet、Patricia Imbach、Peter Fuerst、Marc Lang、Maria Noorani、Johann Zimmermann、Carlos Garcı́a-Echeverrı́a

  DOI：10.1016/s0960-894x(02)00178-6

  日期：2002.5

  We have identified 2-aminobenzylstatine derivatives that inhibit non-covalently the chymotrypsin-like activity of the human 20S proteasome. A structure-based optimisation approach has allowed us to improve the potency of this structural class of proteasome inhibitors from micromolar to nanomolar level. The new derivatives showed good selectivity against the trypsin-like and post-glutamyl-peptide hydrolytic activities of this enzyme. (C) 2002 Elsevier Science Ltd. All rights reserved.