benzyl N-[(1S)-1-benzyl-3-[(2S)-2-(tert-butylcarbamoyl)pyrrolidin-1-yl]-2-hydroxy-3-oxo-propyl]carbamate | 227317-36-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: benzyl N-[(1S)-1-benzyl-3-[(2S)-2-(tert-butylcarbamoyl)pyrrolidin-1-yl]-2-hydroxy-3-oxo-propyl]carbamate
• 英文别名: benzyl N-[(2S)-4-[(2S)-2-(tert-butylcarbamoyl)pyrrolidin-1-yl]-3-hydroxy-4-oxo-1-phenylbutan-2-yl]carbamate
• CAS: 227317-36-4
• 化学式: C₂₇H₃₅N₃O₅
• 分子量: 481.592
• InChiKey: FEDKAIMWKYUZDG-OJSMNCEXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl N-[(1S)-1-benzyl-3-[(2S)-2-(tert-butylcarbamoyl)pyrrolidin-1-yl]-2-hydroxy-3-oxo-propyl]carbamate 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 生成 (2S)-1-[(3S)-3-amino-2-hydroxy-4-phenylbutanoyl]-N-tert-butylpyrrolidine-2-carboxamide
  参考文献：
  名称：

  Development of a New Type of Protease Inhibitors, Efficacious against FIV and HIV Variants

  摘要：

  Based on the structural analysis of FIV protease and drug-resistant HIV proteases and molecular modeling, a new type of inhibitors with a small P3 residue has been developed. These inhibitors are effective against HIV and its drug-resistant mutants, as well as SIV and FIV. Modification of existing HIV protease inhibitors by reducing the size of the P3 residue has the same effect. This finding provides a new strategy for the development of HIV protease inhibitors effective against the wild-type and drug-resistant mutants. It further supports the use of FIV protease as a useful model for drug-resistant HIV proteases, which often have a more constricted binding region for the P3 group or the combined P3 and P1 groups.

  DOI：

  10.1021/ja982893p
• 作为产物：
  描述：

  (2RS,3S)-3-(benzyloxycarbonyl)amino-2-hydroxy-4-phenylbutanenitrile 在 盐酸 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 生成 benzyl N-[(1S)-1-benzyl-3-[(2S)-2-(tert-butylcarbamoyl)pyrrolidin-1-yl]-2-hydroxy-3-oxo-propyl]carbamate
  参考文献：
  名称：

  Development of a New Type of Protease Inhibitors, Efficacious against FIV and HIV Variants

  摘要：

  Based on the structural analysis of FIV protease and drug-resistant HIV proteases and molecular modeling, a new type of inhibitors with a small P3 residue has been developed. These inhibitors are effective against HIV and its drug-resistant mutants, as well as SIV and FIV. Modification of existing HIV protease inhibitors by reducing the size of the P3 residue has the same effect. This finding provides a new strategy for the development of HIV protease inhibitors effective against the wild-type and drug-resistant mutants. It further supports the use of FIV protease as a useful model for drug-resistant HIV proteases, which often have a more constricted binding region for the P3 group or the combined P3 and P1 groups.

  DOI：

  10.1021/ja982893p

文献信息

• New beta-amino-alpha-hydroxycarboxylic acids and their use
  申请人：Sankyo Company Limited

  公开号：EP0498680A1

  公开（公告）日：1992-08-12

  The compounds of the invention are β-amino-α-hydroxycarboxylic acid derivatives having the formula (I): wherein: R¹ represents a group of formula R(Z)xA-    wherein R is hydrogen, or a substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl or heterocyclic group or R is a group of formula -NRaRb wherein Ra and Rb are hydrogen atoms, alkyl groups, unsubstituted or substituted cycloalkyl, heterocyclic, aralkenyl or aryl groups,    Z represents oxygen or sulphur;    A represents a group of formula -CO-, -COCO-, -SO-, -SO₂- or -CS-; and    x is the cipher 0 or the integer 1; R² represents a hydrogen atom, or a substituted or unsubstituted alkyl group; R³ is hydrogen, or a substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl or heterocyclic group; R⁴ is a hydrogen atom, a substituted or unsubstituted alkyl, aryl or heterocyclic group;    and R⁵ represents a group of formula -B-(CO)-Y-Rcy , wherein    B represents a heterocyclic group unsubstituted or substituted with at least one alkyl group;    Y represents an oxygen atom, a nitrogen atom or a sulphur atom;    y is the integer 1 when Y represents an oxygen atom or a sulphur atom, and 2 when Y represents a nitrogen atom; and    Rc represents       is hydrogen, or a substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl or heterocyclic group;    and, where there are two groups or atoms represented by Rc, they are the same or different; and and pharmaceutically acceptable salts and esters thereof.

  本发明的化合物是β-氨基-α-羟基羧酸衍生物，具有以下式子（I）：其中：R¹表示以下式子的基团R（Z）xA-，其中R为氢，或取代或未取代的烷基，烯基，炔基，芳基或杂环基，或R为以下式子的基团-NRaRb，其中Ra和Rb为氢原子，烷基，未取代或取代的环烷基，杂环基，芳烯基或芳基；Z表示氧或硫；A表示以下式子的基团-CO-，-COCO-，-SO-，-SO₂-或-CS-；x为0或整数1；R²表示氢原子，或取代或未取代的烷基；R³为氢，或取代或未取代的烷基，烯基，炔基，芳基或杂环基；R⁴为氢原子，取代或未取代的烷基，芳基或杂环基；和R⁵表示以下式子的基团-B-（CO）-Y-Rcy，其中B表示未取代或取代的至少有一个烷基的杂环基；Y表示氧原子，氮原子或硫原子；当Y表示氧原子或硫原子时，y为整数1，当Y表示氮原子时，y为整数2；并且Rc表示氢原子，或取代或未取代的烷基，烯基，炔基，芳基或杂环基；当有两个由Rc表示的基团或原子时，它们是相同的或不同的；以及其药学上可接受的盐和酯。
• Development of a New Type of Protease Inhibitors, Efficacious against FIV and HIV Variants
  作者：Taekyu Lee、Van-Duc Le、Dongyeol Lim、Ying-Chuan Lin、Garrett M. Morris、Andrew L. Wong、Arthur J. Olson、John H. Elder、Chi-Huey Wong

  DOI：10.1021/ja982893p

  日期：1999.2.1

  Based on the structural analysis of FIV protease and drug-resistant HIV proteases and molecular modeling, a new type of inhibitors with a small P3 residue has been developed. These inhibitors are effective against HIV and its drug-resistant mutants, as well as SIV and FIV. Modification of existing HIV protease inhibitors by reducing the size of the P3 residue has the same effect. This finding provides a new strategy for the development of HIV protease inhibitors effective against the wild-type and drug-resistant mutants. It further supports the use of FIV protease as a useful model for drug-resistant HIV proteases, which often have a more constricted binding region for the P3 group or the combined P3 and P1 groups.