N-benzyloxycarbonyl-S-(4-bromobenzyl)glutatione | 85261-23-0

• 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: N-benzyloxycarbonyl-S-(4-bromobenzyl)glutatione
• 英文别名: N-[(Phenylmethoxy)carbonyl]-L-I(3)-glutamyl-S-[(4-bromophenyl)methyl]-L-cysteinylglycine；(2S)-5-[[(2R)-3-[(4-bromophenyl)methylsulfanyl]-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-5-oxo-2-(phenylmethoxycarbonylamino)pentanoic acid
• CAS: 85261-23-0
• 化学式: C₂₅H₂₈BrN₃O₈S
• 分子量: 610.483
• InChiKey: KLXINTVDASPXAL-PMACEKPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  38
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  196
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-benzyloxycarbonyl-S-(4-bromobenzyl)glutatione 在 氯化亚砜 作用下， 生成 {(S)-3-[(R)-2-(4-Bromo-benzylsulfanyl)-1-(chlorocarbonylmethyl-carbamoyl)-ethylcarbamoyl]-1-chlorocarbonyl-propyl}-carbamic acid benzyl ester
  参考文献：
  名称：

  Structure−Activity Study on the in Vitro Antiprotozoal Activity of Glutathione Derivatives

  摘要：

  A series of N-, S-, and COOH-blocked glutathione derivatives were evaluated against the pathogenic parasites Trypanosoma brucei, Trypanosoma cruzi, and Leishmania donovani in vitro, to identify the determinants necessary for activity and for further development; into an active lead structure. The results show that N,S-blocked glutathione diesters are the most effective inhibitors of T. brucei with structures 14-16 being the most active, 14 having an IG(50) similar to 1.9 mu M. The toxicity effects observed for glutathione derivatives 12, 14, and 16 have been correlated to the K562 antileukemic activity of these compounds and their inhibitory effects on the glyoxalase system of the host. Diester compounds based on S-2,4-dinitrophenyl-glutathione (17-22) were found to be significantly better inhibitors of T. brucei with ED50's in the range 16-0.19 mu M. Compounds 19 and 20 were the two best inhibitors, with an ED50 of similar to 1.07 and 0.19 mu M, respectively; however 20 displayed toxicity in parasitic assays. Monoesters, monoamides, and diamides tested generally exhibited low in vitro activity. The compounds did not inhibit glutathionylspermidine synthetase and trypanothione reductase enzyme targets in:the unique trypanothione pathway of these parasites. Diester compounds per se were considered to he ineffective inhibitors of trypanothione metabolism suggesting that these compounds might act as prodrugs, being hydrolyzed in situ into a variety of glutathione derivatives which include combinations of monoesters, free acids, and amines, some of which are-inhibitors of trypanothione metabolism.

  DOI：

  10.1021/jm990259w