trans-5S-(2'S-benzyloxycarbonylamino-3'phenylpropanamido)-7-(phenylsulfonyl)hept-6-en-1-tert-butyloxycarbonylamine | 1451454-05-9

• 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-(phenylsulfonyl)hept-6-en-1-tert-butyloxycarbonylamine
• 英文别名: trans-3S-(2S-benzyloxycarbonylamino-3-phenylpropanamido)-1-(phenylsulfonyl)hept-1-en-7-tert-butyloxycarbonyl amine；benzyl N-[(2S)-1-[[(E,3S)-1-(benzenesulfonyl)-7-[(2-methylpropan-2-yl)oxycarbonylamino]hept-1-en-3-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate
• CAS: 1451454-05-9
• 化学式: C₃₅H₄₃N₃O₇S
• 分子量: 649.808
• InChiKey: MAROJPPOMVMMHJ-OXLTXWBDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  46
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  148
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  trans-5S-(2'S-benzyloxycarbonylamino-3'phenylpropanamido)-7-(phenylsulfonyl)hept-6-en-1-tert-butyloxycarbonylamine 在 溶剂黄146 、 三乙胺 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 64.0h， 生成 trans-5S-(2'S-benzyloxycarbonylamino-3'phenylpropanamido)-7-(phenylsulfonyl)hept-6-en-1-(4-methylphenyl)sulfonamide
  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
• 作为产物：
  描述：

  二乙基(苯基硫代甲基)磷酸酯 在 双氧水 、 sodium hydride 、 溶剂黄146 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 16.5h， 生成 trans-5S-(2'S-benzyloxycarbonylamino-3'phenylpropanamido)-7-(phenylsulfonyl)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

• Preparation, anti-trypanosomal activity and localisation of a series of dipeptide-based vinyl sulfones
  作者：William Doherty、Jinju James、Paul Evans、Laura Martin、Nikoletta Adler、Derek Nolan、Andrew Knox

  DOI：10.1039/c4ob01412j

  日期：——

  An improved, Weinreb amide-based, synthesis of anti-trypanosomal lysine-containing vinyl sulfones is described incorporating, as a feature, diversity at the ε-lysine amino group. Members of this family demonstrated moderate to good efficacy as anti-trypanosomal agents and a fluorescent dansyl (19) derivative was used to investigate subcellular localisation of the compound class.

  描述了一种改进的基于Weinreb酰胺的抗锥虫含赖氨酸的乙烯基砜的合成，其特征是在ε-赖氨酸氨基上具有多样性。该家族成员作为抗锥虫剂显示出中等至良好的功效，并且使用荧光丹磺酰（19）衍生物研究化合物类别的亚细胞定位。
• 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.