4-methyl-trans-(+/-)-1,2-diazidocyclohexane | 1246967-35-0

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 4-methyl-trans-(+/-)-1,2-diazidocyclohexane
• 英文别名: 1,2-Diazido-4-methylcyclohexane
• CAS: 1246967-35-0
• 化学式: C₇H₁₂N₆
• 分子量: 180.212
• InChiKey: PROTXFCZOXOFCI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  28.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-methyl-trans-(+/-)-1,2-diazidocyclohexane 在 氢气 作用下， 以 乙醇 为溶剂， 反应 24.0h， 生成 4-methyl-cyclohexane-1,2-diyldiamine
  参考文献：
  名称：

  {(1R,2R,4R)-4-Methyl-1,2-cyclohexanediamine}oxalatoplatinum(II): A Novel Enantiomerically Pure Oxaliplatin Derivative Showing Improved Anticancer Activity in Vivo

  摘要：

  Novel derivatives of the clinically established anticancer drug oxaliplatin were synthesized. Cytotoxicity of the compounds was studied in six human cancer cell lines by means of the MTT assay. Additionally, most promising complexes were also investigated in cisplatin- and oxaliplatin-resistant human cancer cell models. The therapeutic efficacy in vivo was studied in the murine L1210 leukemia model. Most remarkably, {(1R,2R,4R)-4-methyl-1,2-cyclohexanediamine}oxalatoplatinum(II), comprising an equatorial methyl substituent at position 4 of the cyclohexane ring, was as potent as oxaliplatin in vitro but distinctly more effective in the L1210 model in vivo at the optimal dose. The advantage observed in the in vivo situation was mainly based on a more favorable therapeutic index. The maximum tolerated dose of the novel analogue was higher than that of oxaliplatin and caused a greater increase in life span (>200% versus 152%), with more animals experiencing long-term survival (5/6 versus 2/6). These data support further (pre)clinical development of the methyl-substituted oxaliplatin analogue with improved anticancer activity.

  DOI：

  10.1021/jm100953c
• 作为产物：
  描述：

  4-甲基-1-环己烯 在 sodium azide 、 三氟乙酸 作用下， 以 乙腈 为溶剂， 反应 3.0h， 生成 4-methyl-trans-(+/-)-1,2-diazidocyclohexane
  参考文献：
  名称：

  甲基取代的反式-1,2-环己二胺作为奥沙利铂型配合物的新配体

  摘要：

  提出了三种不同的途径合成取代的反式-（±）-1,2-环己二胺作为奥沙利铂类化合物的新配体。不同的合成路线导致（i）通过取代环己酮的邻溴化合成化合物，然后与羟胺反应并用氢还原，（ii）通过将乙酸锰（III）介导的叠氮化物加到环己烯中并还原通过氢，或（iii）通过环己烯的反二羟基化，然后转化成各自的甲磺酸酯或甲苯磺酸酯，随后被叠氮化物取代，和在4-甲基-反式的情况下还原-（±）-1,2-环己二胺分别优选在赤道上，主要在轴向上或仅在赤道上或轴向上定向的4-甲基。

  DOI：

  10.1016/j.tet.2007.10.069

文献信息

• Methyl-substituted trans-1,2-cyclohexanediamines as new ligands for oxaliplatin-type complexes
  作者：Ladislav Habala、Claudia Dworak、Alexey A. Nazarov、Christian G. Hartinger、Sergey A. Abramkin、Vladimir B. Arion、Wolfgang Lindner、Mathea S. Galanski、Bernhard K. Keppler

  DOI：10.1016/j.tet.2007.10.069

  日期：2008.1

  different synthetic routes lead (i) by the synthesis of the compound via ortho-bromination of a substituted cyclohexanone followed by reaction with hydroxylamine and reduction by hydrogen, (ii) by addition of azide to cyclohexene mediated by manganese(III) acetate and reduction by hydrogen, or (iii) by trans-dihydroxylation of cyclohexene, and subsequent conversion into the respective mesylate or tosylate

  提出了三种不同的途径合成取代的反式-（±）-1,2-环己二胺作为奥沙利铂类化合物的新配体。不同的合成路线导致（i）通过取代环己酮的邻溴化合成化合物，然后与羟胺反应并用氢还原，（ii）通过将乙酸锰（III）介导的叠氮化物加到环己烯中并还原通过氢，或（iii）通过环己烯的反二羟基化，然后转化成各自的甲磺酸酯或甲苯磺酸酯，随后被叠氮化物取代，和在4-甲基-反式的情况下还原-（±）-1,2-环己二胺分别优选在赤道上，主要在轴向上或仅在赤道上或轴向上定向的4-甲基。
• {(1<i>R</i>,2<i>R</i>,4<i>R</i>)-4-Methyl-1,2-cyclohexanediamine}oxalatoplatinum(II): A Novel Enantiomerically Pure Oxaliplatin Derivative Showing Improved Anticancer Activity in Vivo
  作者：Sergey A. Abramkin、Ute Jungwirth、Seied M. Valiahdi、Claudia Dworak、Ladislav Habala、Kristof Meelich、Walter Berger、Michael A. Jakupec、Christian G. Hartinger、Alexey A. Nazarov、Mathea Sophia Galanski、Bernhard K. Keppler

  DOI：10.1021/jm100953c

  日期：2010.10.28

  Novel derivatives of the clinically established anticancer drug oxaliplatin were synthesized. Cytotoxicity of the compounds was studied in six human cancer cell lines by means of the MTT assay. Additionally, most promising complexes were also investigated in cisplatin- and oxaliplatin-resistant human cancer cell models. The therapeutic efficacy in vivo was studied in the murine L1210 leukemia model. Most remarkably, (1R,2R,4R)-4-methyl-1,2-cyclohexanediamine}oxalatoplatinum(II), comprising an equatorial methyl substituent at position 4 of the cyclohexane ring, was as potent as oxaliplatin in vitro but distinctly more effective in the L1210 model in vivo at the optimal dose. The advantage observed in the in vivo situation was mainly based on a more favorable therapeutic index. The maximum tolerated dose of the novel analogue was higher than that of oxaliplatin and caused a greater increase in life span (>200% versus 152%), with more animals experiencing long-term survival (5/6 versus 2/6). These data support further (pre)clinical development of the methyl-substituted oxaliplatin analogue with improved anticancer activity.