(2R,3S,4S)-4-<<(1,1-dimethylethoxy)carbonyl>amino>-3-hydroxy-2-<(4-methoxybenzyl)amino>-5-phenylpentanoic acid | 164515-11-1

• 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: (2R,3S,4S)-4-<<(1,1-dimethylethoxy)carbonyl>amino>-3-hydroxy-2-<(4-methoxybenzyl)amino>-5-phenylpentanoic acid
• CAS: 164515-11-1
• 化学式: C₂₄H₃₂N₂O₆
• 分子量: 444.528
• InChiKey: IFAIOJRQMDQSDU-PWRODBHTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.73
• 重原子数：
  32.0
• 可旋转键数：
  10.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  117.12
• 氢给体数：
  4.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (2R,3S,4S)-4-<<(1,1-dimethylethoxy)carbonyl>amino>-3-hydroxy-2-<(4-methoxybenzyl)amino>-5-phenylpentanoic acid 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-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  A New Structural Class of Selective and Non-covalent Inhibitors of the Chymotrypsin-like Activity of the 20S Proteasome

  摘要：

  We describe the identification and in vitro characterization of a series of 2-aminobenzylstatine derivatives that inhibit non-covalently the chymotrypsin-like activity of the 20S proteasome. Our initial SAR data demonstrate that the 2-aminobenzylstatine core structure can effectively serve as the basis for designing potent, selective and non-covalent inhibitors of the chymotrypsin-like activity of the 20S proteasome. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00205-0
• 作为产物：
  描述：

  (R)-3-((S)-1-tert-Butoxycarbonylamino-2-phenyl-ethyl)-oxirane-2-carboxylic acid ethyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 (2R,3S,4S)-4-<<(1,1-dimethylethoxy)carbonyl>amino>-3-hydroxy-2-<(4-methoxybenzyl)amino>-5-phenylpentanoic acid
  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

• Inhibitors of Human Immunodeficiency Virus Type 1 Protease Containing 2-Aminobenzyl-Substituted 4-Amino-3-hydroxy-5-phenylpentanoic Acid:  Synthesis, Activity, and Oral Bioavailability
  作者：Philipp Lehr、Andreas Billich、Brigitte Charpiot、Peter Ettmayer、Dieter Scholz、Brigitte Rosenwirth、Hubert Gstach

  DOI：10.1021/jm9508696

  日期：1996.1.1

  Systematic modifications of HIV protease inhibitor (2R,3S,4S)-4-[[(benzyloxycarbonyl)-L-valyl]-amino]-3-hydroxy-2-[(4- methoxybenzyl)amino]-5-phenylpentanoyl)-L-valine 2-(aminomethyl)- benzimidazole amide led to a novel series of inhibitors with shortened, modified carboxy terminus. Their synthesis, in vitro enzyme inhibitory data, and antiviral activities are reported. Of particular interest are derivatives

  HIV蛋白酶抑制剂（2R，3S，4S）-4-[[[（苄氧羰基）-L-戊基]-氨基] -3-羟基-2-[（（4-甲氧苄基）氨基] -5-苯基戊酰基）-的系统修饰L-缬氨酸2-（氨基甲基）-苯并咪唑酰胺产生了一系列具有缩短的，修饰的羧基末端的新型抑制剂。报告了它们的合成，体外酶抑制数据和抗病毒活性。特别令人感兴趣的是在P2′-位具有（1S，2R）-1-氨基-2-羟基茚满部分的衍生物，因为其中一些在小鼠中表现出相当大的口服生物利用度。讨论了水溶性和结构参数对抑制剂口服吸收的影响。在P2位置使用L-叔亮氨酸可以最佳地提高口服生物利用度，从而发现了（2R，3S，
• Inhibitors of HIV-1 Proteinase Containing 2-Heterosubstituted 4-Amino-3-hydroxy-5-phenylpentanoic Acid: Synthesis, Enzyme Inhibition, and Antiviral Activity
  作者：Dieter Scholz、Andreas Billich、Brigitte Charpiot、Peter Ettmayer、Philipp Lehr、Brigitte Rosenwirth、Erwin Schreiner、Hubert Gstach

  DOI：10.1021/jm00045a013

  日期：1994.9

  A convenient procedure for the synthesis of 2-heterosubstituted statine derivatives as novel building blocks in HN-protease inhibitors has been developed. The synthesis starts with protected L-phenylalaninols, which were converted to gamma-amino alpha,beta-unsaturated esters in a one-pot procedure. A highly diastereoseletive epoxidation of the N-protected (E)-enoates, followed by regioselective ring opening of the corresponding 2,3-epoxy esters with a variety of heteronucleophiles, resulted in 2-heterosubstituted statine derivatives. The overall stereochemical outcome of the transformations meets the required configuration of HIV-protease inhibitors. The short, synthetically flexible, and highly diastereoselective synthesis of 2-heterosubstituted statines has enabled a broad derivation, covering the S3, S2, and S1'-S3' sites of the enzyme. In a series of 46 derivatives, several potent inhibitors were obtained with K-i values as low as 3.4 nM and antiviral activity in the lower nanomolar-range. The structural parameters of the compounds which determine the potency of inhibition and selectivity for the viral enzyme are discussed.