ethyl 5-sec-butyl-1H-imidazole-4-carboxylate | 1367701-97-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 5-sec-butyl-1H-imidazole-4-carboxylate
• 英文别名: ethyl 5-butan-2-yl-1H-imidazole-4-carboxylate
• CAS: 1367701-97-0
• 化学式: C₁₀H₁₆N₂O₂
• 分子量: 196.249
• InChiKey: IXMNCKUXVOATHI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  55
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 5-sec-butyl-1H-imidazole-4-carboxylate 在 manganese(IV) oxide 、 lithium aluminium tetrahydride 、 caesium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 19.0h， 生成 (3Z,6Z)-3-benzylidene-6-((5-sec-butyl-1H-imidazol-4-yl)methylene)piperazine-2,5-dione trifluoroacetate
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationship Study of Antimicrotubule Agents Phenylahistin Derivatives with a Didehydropiperazine-2,5-dione Structure

  摘要：

  Plinabulin (11, NPI-2358) is a potent microtubule-targeting agent derived from the natural diketopiperazine "phenylahistin" (1) with a colchicine-like tubulin depolymerization activity. Compound 11 was recently developed as VDA and is now under phase II clinical trials as an anticancer drug. To develop more potent antimicrotubule and cytotoxic derivatives based on the didehydro-DKP skeleton, we performed further modification on the tert-butyl or phenyl groups of 11, and evaluated their cytotoxic and tubulin-binding activities. In the SAR study, we developed more potent derivatives 33 with 2,5-difluorophenyl and 50 with activity of 33 and 50 exhibited a lowest effective concentration The values of 33 and 50 were 5 and 10 times more potent than second-generation derivative with both vascular disrupting and a benzophenone in place of the phenyl group. The anti-HuVEC of 2 and 1 nM for microtubule depolymerization, respectively. that of CA-4, respectively. These derivatives could be a valuable cytotoxic activities.

  DOI：

  10.1021/jm2009088
• 作为产物：
  描述：

  2-甲基丁酸 在 草酰氯 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 ethyl 5-sec-butyl-1H-imidazole-4-carboxylate
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationship Study of Antimicrotubule Agents Phenylahistin Derivatives with a Didehydropiperazine-2,5-dione Structure

  摘要：

  Plinabulin (11, NPI-2358) is a potent microtubule-targeting agent derived from the natural diketopiperazine "phenylahistin" (1) with a colchicine-like tubulin depolymerization activity. Compound 11 was recently developed as VDA and is now under phase II clinical trials as an anticancer drug. To develop more potent antimicrotubule and cytotoxic derivatives based on the didehydro-DKP skeleton, we performed further modification on the tert-butyl or phenyl groups of 11, and evaluated their cytotoxic and tubulin-binding activities. In the SAR study, we developed more potent derivatives 33 with 2,5-difluorophenyl and 50 with activity of 33 and 50 exhibited a lowest effective concentration The values of 33 and 50 were 5 and 10 times more potent than second-generation derivative with both vascular disrupting and a benzophenone in place of the phenyl group. The anti-HuVEC of 2 and 1 nM for microtubule depolymerization, respectively. that of CA-4, respectively. These derivatives could be a valuable cytotoxic activities.

  DOI：

  10.1021/jm2009088

文献信息

• Synthesis and Structure–Activity Relationship Study of Antimicrotubule Agents Phenylahistin Derivatives with a Didehydropiperazine-2,5-dione Structure
  作者：Yuri Yamazaki、Koji Tanaka、Benjamin Nicholson、Gordafaried Deyanat-Yazdi、Barbara Potts、Tomoko Yoshida、Akiko Oda、Takayoshi Kitagawa、Sumie Orikasa、Yoshiaki Kiso、Hiroyuki Yasui、Miki Akamatsu、Takumi Chinen、Takeo Usui、Yuki Shinozaki、Fumika Yakushiji、Brian R. Miller、Saskia Neuteboom、Michael Palladino、Kaneo Kanoh、George Kenneth Lloyd、Yoshio Hayashi

  DOI：10.1021/jm2009088

  日期：2012.2.9

  Plinabulin (11, NPI-2358) is a potent microtubule-targeting agent derived from the natural diketopiperazine "phenylahistin" (1) with a colchicine-like tubulin depolymerization activity. Compound 11 was recently developed as VDA and is now under phase II clinical trials as an anticancer drug. To develop more potent antimicrotubule and cytotoxic derivatives based on the didehydro-DKP skeleton, we performed further modification on the tert-butyl or phenyl groups of 11, and evaluated their cytotoxic and tubulin-binding activities. In the SAR study, we developed more potent derivatives 33 with 2,5-difluorophenyl and 50 with activity of 33 and 50 exhibited a lowest effective concentration The values of 33 and 50 were 5 and 10 times more potent than second-generation derivative with both vascular disrupting and a benzophenone in place of the phenyl group. The anti-HuVEC of 2 and 1 nM for microtubule depolymerization, respectively. that of CA-4, respectively. These derivatives could be a valuable cytotoxic activities.