trans-5S-(2'S-benzyloxycarbonylamino-3'phenylpropanamido)-7-(2"-naphthylsulfonyl)hept-6-en-1-tert-butyloxycarbonylamine | 1451454-08-2

• 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: trans-5S-(2'S-benzyloxycarbonylamino-3'phenylpropanamido)-7-(2"-naphthylsulfonyl)hept-6-en-1-tert-butyloxycarbonylamine
• 英文别名: benzyl N-[(2S)-1-[[(E,3S)-7-[(2-methylpropan-2-yl)oxycarbonylamino]-1-naphthalen-2-ylsulfonylhept-1-en-3-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate
• CAS: 1451454-08-2
• 化学式: C₃₉H₄₅N₃O₇S
• 分子量: 699.868
• InChiKey: YNOLGYGWSVUCNJ-AKYHUVEASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  50
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  148
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  N-Boc-L-赖氨酸甲酯盐酸盐 在 sodium tetrahydroborate 、 sodium hydride 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 pyridinium chlorochromate 、 lithium chloride 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 mineral oil 为溶剂， 反应 54.5h， 生成 trans-5S-(2'S-benzyloxycarbonylamino-3'phenylpropanamido)-7-(2"-naphthylsulfonyl)hept-6-en-1-tert-butyloxycarbonylamine
  参考文献：
  名称：

  Vinyl Sulfone-Based Peptidomimetics as Anti-Trypanosomal Agents: Design, Synthesis, Biological and Computational Evaluation

  摘要：

  A series of vinyl sulfone-containing peptidomimetics were rationally designed, synthesized, and evaluated against Trypanosoma brucei brucei. These electrophilic compounds are likely to exert their antitrypanosomal activity via inhibition of trypanosomal cysteine proteases, TbCatB and rhodesain, through alkylation of a key cysteine residue Within the protease active site. The series was designed to present complementary groups to naturally recognized peptide substrates while probing tolerance to a range of substitutions at the PI, P1', and P2 positions. The most potent compound, 29 (EC50 = 70 nM, T. b. brucei whole cell assay), displayed minimal toxicity (>785 times Selectivity) when assayed for cytotoxicity against the human promyelocytic leukemia (HL-60) cell line. Cells treated with compound 29, as with K777 (2), exhibited an increase in both the number of multinucleated cells and cells with swollen flagellar pockets. Computational analysis revealed a strong correlation between the hypothetical binding mode in TbCatB/rhodesain and trypanocidal activity in vitro.

  DOI：

  10.1021/jm400294w

文献信息

• Vinyl Sulfone-Based Peptidomimetics as Anti-Trypanosomal Agents: Design, Synthesis, Biological and Computational Evaluation
  作者：Elizabeth Dunny、William Doherty、Paul Evans、J. Paul G. Malthouse、Derek Nolan、Andrew J. S. Knox

  DOI：10.1021/jm400294w

  日期：2013.9.12

  A series of vinyl sulfone-containing peptidomimetics were rationally designed, synthesized, and evaluated against Trypanosoma brucei brucei. These electrophilic compounds are likely to exert their antitrypanosomal activity via inhibition of trypanosomal cysteine proteases, TbCatB and rhodesain, through alkylation of a key cysteine residue Within the protease active site. The series was designed to present complementary groups to naturally recognized peptide substrates while probing tolerance to a range of substitutions at the PI, P1', and P2 positions. The most potent compound, 29 (EC50 = 70 nM, T. b. brucei whole cell assay), displayed minimal toxicity (>785 times Selectivity) when assayed for cytotoxicity against the human promyelocytic leukemia (HL-60) cell line. Cells treated with compound 29, as with K777 (2), exhibited an increase in both the number of multinucleated cells and cells with swollen flagellar pockets. Computational analysis revealed a strong correlation between the hypothetical binding mode in TbCatB/rhodesain and trypanocidal activity in vitro.