1-(N-benzyloxycarbonyl-L-tyrosyl)-2-methyl-2-bromoacetyl hydrazine

• 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: 1-(N-benzyloxycarbonyl-L-tyrosyl)-2-methyl-2-bromoacetyl hydrazine
• 英文别名: benzyl N-[(2S)-1-[2-(2-bromoacetyl)-2-methylhydrazinyl]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamate
• 化学式: C₂₀H₂₂BrN₃O₅
• 分子量: 464.316
• InChiKey: QDQTZZHWXYINBX-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-苄氧羰基-L-酪氨酸 在 N-甲基吗啉 、 盐酸 、 碳酸氢钠 作用下， 以 四氢呋喃 、 氯仿 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 反应 8.0h， 生成 1-(N-benzyloxycarbonyl-L-tyrosyl)-2-methyl-2-bromoacetyl hydrazine
  参考文献：
  名称：

  Synthesis and inhibiting activities of 1-peptidyl-2-haloacetyl hydrazines toward cathepsin B and calpains

  摘要：

  Twenty-four 1-peptidyl-2-haloacetyl hydrazines which can be considered azapeptide halomethanes were synthesized and tested as models of cathepsin B, calpain I and calpain II inhibitors. Reagents designed for cathepsin B inactivation include Z-Tyr, Z-Tyr(I) and Z-Leu-Leu attached to an alpha-azaglycine or alpha-azaalanine unit in P1. By use of kinetic analysis, they proved to irreversibly inactivate cathepsin B via a reversible enzyme-inhibitor intermediate. Second-order rate constants in the range 725-306 000 M-1s-1 were found for cathepsin B inactivation, with no more than 7 500 M-1s-1 for calpain II. K(I) for the reversible EI adducts ranged from 11 to 0.06 muM for cathepsin B. Structure of the possible reversible EI complex is proposed and used to discuss the effects of structural variation of the inhibitors on the kinetic parameters of inactivation. I-Peptidyl-2-haloacetyl hydrazines designed for calpain inactivation include Boc-Val-(N(epsilon)-carbomethoxy)Lys-Leu, Boc-Val-Lys(N(epsilon)-Z)-Leu, Boc-Val-Lys(N(epsilon)-Tos)-Leu and Z-Leu-Leu attached to an alpha-azatyrosine unit in P1. They gave poor results. Title compounds proved to be selective for cysteine proteases, since no inhibiting activity could be detected toward trypsin, chymotrypsin and porcine pancreatic elastase at 0.1 mM concentration. Relatively low aspecific alkylating properties were also demonstrated in tests using glutathione as the nucleophile.

  DOI：

  10.1016/0223-5234(93)90147-7

文献信息

• Synthesis and inhibiting activities of 1-peptidyl-2-haloacetyl hydrazines toward cathepsin B and calpains
  作者：C Giordano、R Calabretta、C Gallina、V Consalvi、R Scandurra、F Chiaia Noya、C Franchini

  DOI：10.1016/0223-5234(93)90147-7

  日期：1993.1

  Twenty-four 1-peptidyl-2-haloacetyl hydrazines which can be considered azapeptide halomethanes were synthesized and tested as models of cathepsin B, calpain I and calpain II inhibitors. Reagents designed for cathepsin B inactivation include Z-Tyr, Z-Tyr(I) and Z-Leu-Leu attached to an alpha-azaglycine or alpha-azaalanine unit in P1. By use of kinetic analysis, they proved to irreversibly inactivate cathepsin B via a reversible enzyme-inhibitor intermediate. Second-order rate constants in the range 725-306 000 M-1s-1 were found for cathepsin B inactivation, with no more than 7 500 M-1s-1 for calpain II. K(I) for the reversible EI adducts ranged from 11 to 0.06 muM for cathepsin B. Structure of the possible reversible EI complex is proposed and used to discuss the effects of structural variation of the inhibitors on the kinetic parameters of inactivation. I-Peptidyl-2-haloacetyl hydrazines designed for calpain inactivation include Boc-Val-(N(epsilon)-carbomethoxy)Lys-Leu, Boc-Val-Lys(N(epsilon)-Z)-Leu, Boc-Val-Lys(N(epsilon)-Tos)-Leu and Z-Leu-Leu attached to an alpha-azatyrosine unit in P1. They gave poor results. Title compounds proved to be selective for cysteine proteases, since no inhibiting activity could be detected toward trypsin, chymotrypsin and porcine pancreatic elastase at 0.1 mM concentration. Relatively low aspecific alkylating properties were also demonstrated in tests using glutathione as the nucleophile.