N-α-{3-(2-chloroethyl)-3,4-dihydro-4-oxoimidazo[5,1-d]-1,2,3,5-tetrazin-8-carbonyl}-N-ε-tert-butoxycarbonyl-L-lysine methyl ester

• 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-α-{3-(2-chloroethyl)-3,4-dihydro-4-oxoimidazo[5,1-d]-1,2,3,5-tetrazin-8-carbonyl}-N-ε-tert-butoxycarbonyl-L-lysine methyl ester
• 英文别名: methyl (2S)-2-[[3-(2-chloroethyl)-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-carbonyl]amino]-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoate
• 化学式: C₁₉H₂₈ClN₇O₆
• 分子量: 485.928
• InChiKey: AXJZKGTTXGHUIH-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  33
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  157
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-α-{3-(2-chloroethyl)-3,4-dihydro-4-oxoimidazo[5,1-d]-1,2,3,5-tetrazin-8-carbonyl}-N-ε-tert-butoxycarbonyl-L-lysine methyl ester 在 三乙基硅烷 、 三异丙基硅烷 、 三氟乙酸 作用下， 反应 2.0h， 以50%的产率得到N-α-{3-(2-chloroethyl)-3,4-dihydro-4-oxoimidazo[5,1-d]-1,2,3,5-tetrazin-8-carbonyl}-L-lysine methyl ester
  参考文献：
  名称：

  Antitumor Imidazotetrazines. 41. Conjugation of the Antitumor Agents Mitozolomide and Temozolomide to Peptides and Lexitropsins Bearing DNA Major and Minor Groove-Binding Structural Motifs

  摘要：

  Carboxylic acids derived from the amido groups of the antitumor agents mitozolomide and temozolomide have been conjugated to simple amino acids and peptides by carbodiimide coupling. Solid-state peptide synthesis has been applied to link the acids to DNA major groove-binding peptidic motifs known to adopt alpha-helical conformations. Attachment of the acids to pyrrole and imidazole polyamidic lexitropsins gave a series of potential DNA minor groove- binding ligands. In vitro biological evaluation of a limited number of these novel conjugates failed to demonstrate any enhanced growth-inhibitory activity compared to the unconjugated drugs; sites of alkylation at tracts of multiple guanines were also unaffected. Attachment of additional residues at C-8 of the imidazotetrazines did not perturb the chemistry of activation of the bicyclic nucleus, and biological sequelae can be rationalized by invoking the liberation of a common, diffusible, reactive chemical intermediate, the methanediazonium ion.

  DOI：

  10.1021/jm020936d
• 作为产物：
  描述：

  3-(2-氯乙基)-4-氧代-3H-咪唑并(5,1-d)-1,2,3,5-四嗪-8-羧酸 、 N-Boc-L-赖氨酸甲酯盐酸盐 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以64%的产率得到N-α-{3-(2-chloroethyl)-3,4-dihydro-4-oxoimidazo[5,1-d]-1,2,3,5-tetrazin-8-carbonyl}-N-ε-tert-butoxycarbonyl-L-lysine methyl ester
  参考文献：
  名称：

  Antitumor Imidazotetrazines. 41. Conjugation of the Antitumor Agents Mitozolomide and Temozolomide to Peptides and Lexitropsins Bearing DNA Major and Minor Groove-Binding Structural Motifs

  摘要：

  Carboxylic acids derived from the amido groups of the antitumor agents mitozolomide and temozolomide have been conjugated to simple amino acids and peptides by carbodiimide coupling. Solid-state peptide synthesis has been applied to link the acids to DNA major groove-binding peptidic motifs known to adopt alpha-helical conformations. Attachment of the acids to pyrrole and imidazole polyamidic lexitropsins gave a series of potential DNA minor groove- binding ligands. In vitro biological evaluation of a limited number of these novel conjugates failed to demonstrate any enhanced growth-inhibitory activity compared to the unconjugated drugs; sites of alkylation at tracts of multiple guanines were also unaffected. Attachment of additional residues at C-8 of the imidazotetrazines did not perturb the chemistry of activation of the bicyclic nucleus, and biological sequelae can be rationalized by invoking the liberation of a common, diffusible, reactive chemical intermediate, the methanediazonium ion.

  DOI：

  10.1021/jm020936d

文献信息

• Antitumor Imidazotetrazines. 41. Conjugation of the Antitumor Agents Mitozolomide and Temozolomide to Peptides and Lexitropsins Bearing DNA Major and Minor Groove-Binding Structural Motifs
  作者：Jill Arrowsmith、Sharon A. Jennings、Alan S. Clark、Malcolm F. G. Stevens

  DOI：10.1021/jm020936d

  日期：2002.12.1

  Carboxylic acids derived from the amido groups of the antitumor agents mitozolomide and temozolomide have been conjugated to simple amino acids and peptides by carbodiimide coupling. Solid-state peptide synthesis has been applied to link the acids to DNA major groove-binding peptidic motifs known to adopt alpha-helical conformations. Attachment of the acids to pyrrole and imidazole polyamidic lexitropsins gave a series of potential DNA minor groove- binding ligands. In vitro biological evaluation of a limited number of these novel conjugates failed to demonstrate any enhanced growth-inhibitory activity compared to the unconjugated drugs; sites of alkylation at tracts of multiple guanines were also unaffected. Attachment of additional residues at C-8 of the imidazotetrazines did not perturb the chemistry of activation of the bicyclic nucleus, and biological sequelae can be rationalized by invoking the liberation of a common, diffusible, reactive chemical intermediate, the methanediazonium ion.