(3Z,6Z)-3-benzylidene-6-((5-butyl-1H-imidazol-4-yl)methylene)piperazine-2,5-dione | 1056465-60-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (3Z,6Z)-3-benzylidene-6-((5-butyl-1H-imidazol-4-yl)methylene)piperazine-2,5-dione
• 英文别名: (3Z,6Z)-3-benzylidene-6-[(5-butyl-1H-imidazol-4-yl)methylidene]piperazine-2,5-dione
• CAS: 1056465-60-1
• 化学式: C₁₉H₂₀N₄O₂
• 分子量: 336.393
• InChiKey: ATLALIOIRJKBST-APGQMXJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  86.9
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  戊酸酐 在 manganese(IV) oxide 、 lithium aluminium tetrahydride 、 caesium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 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-butyl-1H-imidazol-4-yl)methylene)piperazine-2,5-dione
  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

• ANALOGS OF DEHYDROPHENYLAHISTINS AND THEIR THEAPEUTIC USE
  申请人：Palladino Michael A.

  公开号：US20080221122A1

  公开（公告）日：2008-09-11

  Compounds represented by the following structure (II) are disclosed: as are methods for making such compounds. Compositions and methods for treating various disease conditions including cancer and non-cancer diseases associated with vascular proliferation are also disclosed.

  由以下结构（II）表示的化合物已被披露：制备这种化合物的方法也已被披露。还披露了用于治疗各种疾病条件的组合物和方法，包括与血管增殖相关的癌症和非癌症疾病。
• US8129527B2
  申请人：——

  公开号：US8129527B2

  公开（公告）日：2012-03-06
• 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.