L-trans-epoxysuccinyl-L-tyrosylamido(3-methyl)butane ethylester | 154415-60-8

• 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: L-trans-epoxysuccinyl-L-tyrosylamido(3-methyl)butane ethylester
• 英文别名: ethyl (2S,3S)-3-[[(2S)-3-(4-hydroxyphenyl)-1-(3-methylbutylamino)-1-oxopropan-2-yl]carbamoyl]oxirane-2-carboxylate
• CAS: 154415-60-8
• 化学式: C₂₀H₂₈N₂O₆
• 分子量: 392.452
• InChiKey: JTQPNKCWFAMHGY-ULQDDVLXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  117
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  L-trans-epoxysuccinyl-L-tyrosylamido(3-methyl)butane ethylester 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以83%的产率得到L-trans-epoxysuccinyl-L-tyrosylamido(3-methyl)butane
  参考文献：
  名称：

  Iodo and diiodotyrosine epoxysuccinyl derivatives as selective inhibitors of cathepsin B

  摘要：

  Eight new analogs of L-trans-epoxysuccinyl-L-leucylamido(3-methyl)butane (E-64-c) containing Phe, Tyr, Tyr(I) or Tyr(I-2) in place of Leu, were synthesized and tested as inhibitors of papain, bovine spleen cathepsin B, calpain I and II from porcine red cells and porcine kidney, respectively. By use of kinetic methods, the new E-64 analogs proved to irreversibly inactivate both papain and cathepsin B via reversible enzyme-inhibitor intermediates EI. Second-order rate constants for inactivation were in the range 3500-55 100 M(-1)s(-1) for papain and 650-105 000 M(-1)s(-1) for cathepsin B. For the inactivation of calpain I and II they ranged between 250 and 2000 M(-1)s(-1) and were similar to those of the known E-64-c. The effectiveness of the amino acid contained in the inhibitors tested increased in the order Tyr(I) approximate to Tyr(I-2) < Tyr < Phe < Leu for papain and Phe < Tyr < Tyr(I)e Leu < Tyr(I-2) for cathepsin B inactivation. Replacement of the L with the D-trans-epoxysuccinyl unit caused a 10-100-fold decrease in inhibitor potencies.

  DOI：

  10.1016/0223-5234(93)90046-h
• 作为产物：
  描述：

  N-苄氧羰基-L-酪氨酸 在 钯 N-甲基吗啉 、 氢气 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 为溶剂， 反应 8.0h， 生成 L-trans-epoxysuccinyl-L-tyrosylamido(3-methyl)butane ethylester
  参考文献：
  名称：

  Iodo and diiodotyrosine epoxysuccinyl derivatives as selective inhibitors of cathepsin B

  摘要：

  Eight new analogs of L-trans-epoxysuccinyl-L-leucylamido(3-methyl)butane (E-64-c) containing Phe, Tyr, Tyr(I) or Tyr(I-2) in place of Leu, were synthesized and tested as inhibitors of papain, bovine spleen cathepsin B, calpain I and II from porcine red cells and porcine kidney, respectively. By use of kinetic methods, the new E-64 analogs proved to irreversibly inactivate both papain and cathepsin B via reversible enzyme-inhibitor intermediates EI. Second-order rate constants for inactivation were in the range 3500-55 100 M(-1)s(-1) for papain and 650-105 000 M(-1)s(-1) for cathepsin B. For the inactivation of calpain I and II they ranged between 250 and 2000 M(-1)s(-1) and were similar to those of the known E-64-c. The effectiveness of the amino acid contained in the inhibitors tested increased in the order Tyr(I) approximate to Tyr(I-2) < Tyr < Phe < Leu for papain and Phe < Tyr < Tyr(I)e Leu < Tyr(I-2) for cathepsin B inactivation. Replacement of the L with the D-trans-epoxysuccinyl unit caused a 10-100-fold decrease in inhibitor potencies.

  DOI：

  10.1016/0223-5234(93)90046-h

文献信息

• Iodo and diiodotyrosine epoxysuccinyl derivatives as selective inhibitors of cathepsin B
  作者：C Giordano、R Calabretta、C Gallina、V Consalvi、R Scandurra、F Chiaia Noya、C Franchini

  DOI：10.1016/0223-5234(93)90046-h

  日期：1993.1

  Eight new analogs of L-trans-epoxysuccinyl-L-leucylamido(3-methyl)butane (E-64-c) containing Phe, Tyr, Tyr(I) or Tyr(I-2) in place of Leu, were synthesized and tested as inhibitors of papain, bovine spleen cathepsin B, calpain I and II from porcine red cells and porcine kidney, respectively. By use of kinetic methods, the new E-64 analogs proved to irreversibly inactivate both papain and cathepsin B via reversible enzyme-inhibitor intermediates EI. Second-order rate constants for inactivation were in the range 3500-55 100 M(-1)s(-1) for papain and 650-105 000 M(-1)s(-1) for cathepsin B. For the inactivation of calpain I and II they ranged between 250 and 2000 M(-1)s(-1) and were similar to those of the known E-64-c. The effectiveness of the amino acid contained in the inhibitors tested increased in the order Tyr(I) approximate to Tyr(I-2) < Tyr < Phe < Leu for papain and Phe < Tyr < Tyr(I)e Leu < Tyr(I-2) for cathepsin B inactivation. Replacement of the L with the D-trans-epoxysuccinyl unit caused a 10-100-fold decrease in inhibitor potencies.