4-(imidazol-1-yl)-3-methyl-1-phenyl-2-phospholene 1-oxide | 1438418-20-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(imidazol-1-yl)-3-methyl-1-phenyl-2-phospholene 1-oxide
• 英文别名: 3-Imidazol-1-yl-4-methyl-1-phenyl-2,3-dihydro-1lambda5-phosphole 1-oxide；3-imidazol-1-yl-4-methyl-1-phenyl-2,3-dihydro-1λ5-phosphole 1-oxide
• CAS: 1438418-20-2
• 化学式: C₁₄H₁₅N₂OP
• 分子量: 258.26
• InChiKey: DFPKQDBTVOKAOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  咪唑 、 4-bromo-3-methyl-1-phenyl-2-phospholene 1-oxide 以 乙腈 为溶剂， 反应 24.0h， 以89%的产率得到4-(imidazol-1-yl)-3-methyl-1-phenyl-2-phospholene 1-oxide
  参考文献：
  名称：

  Research on Phospha Sugar Analogues to Develop Novel Multiple Type Molecular Targeted Antitumor Drugs Against Various Types of Tumor Cells

  摘要：

  The synthesis and antitumor activity evaluation of new branched phospha sugars, especially deoxybromophospha sugar derivatives or bromophospholanes of 2,3-dibromo-3-methyl-1-phenylphospholane 1-oxide (DBMPP: 3) and 2,3,4-tribromo-3-methyl-1- phenylphospholane 1-oxide (TBMPP: 4), against various types of leukemia cell lines as well as the results of the mechanistic studies for characterizing and developing the novel multiple type molecular targeted antitumor agents are reported in this paper. DBMPP and TBMPP were prepared from 1-phenyl-3-methyl-2-phospholene 1-oxide (1). The isomer mixture of phospha sugars prepared were evaluated as novel antitumor agents by MTT in vitro method. DBMPP and TBMPP were characterized by flow cytometry and Western blot analysis and were revealed to be potential antitumor agents against leukemia cell lines of K562 (one type of leukemia cell lines of CML) and U937 (one type of leukemia cell lines of AML) as well as against the various types of leukemia cell lines and also against solid tumor cell lines of stomach, skin, and lung cancers by MTT evaluation and observation by a handstand phase-contrast microscope. The results of the flow cytometry indicated that the mechanism of apoptosis induced by phospha sugar derivatives not only to tumor cells of leukemia cell lines of U937 but also to tumor cells of various kinds of leukemia cell lines selectively to decrease the tumor cell viability of various kinds of leukemia cell lines. The Western blot analyses for phospha sugar DBMPP against U937 leukemia cell lines showed that the phospha sugar affected on the expressions of the factors of cell cycles in the manners of suppressing the expression of the accelerator factors of cell cycles of tumor cells and enhancing the expression of suppressor factors of cell cycles of tumor cells by the medications of phospha sugars. TBMPP enhanced the expression of IER5 and then suppressed the expression of Cdc25B, which is the common factor to accelerate the cell cycles of various kinds of tumor cells. Therefore, suppression of the expression of Cdc25B by TBMPP implies that the branched deoxybromophospha sugar derivatives might be novel and potential multiple type molecular targeted antitumor agents against various kinds of tumor cell lines.

  DOI：

  10.1080/10426507.2012.744016

文献信息

• Research on Phospha Sugar Analogues to Develop Novel Multiple Type Molecular Targeted Antitumor Drugs Against Various Types of Tumor Cells
  作者：Reiko Makita、Mitsuji Yamashita、Michio Fujie、Mayumi Yamaoka、Keita Kiyofuji、Manabu Yamada、Junko Yamashita、Kenji Tsunekawa、Kazuhide Asai、Takuya Suyama、Mitsuo Toda、Yasutaka Tanaka、Haruhiko Sugimura、Yasuhiro Magata、Kazunori Ohnishi、Satoki Nakamura

  DOI：10.1080/10426507.2012.744016

  日期：2013.1.1

  The synthesis and antitumor activity evaluation of new branched phospha sugars, especially deoxybromophospha sugar derivatives or bromophospholanes of 2,3-dibromo-3-methyl-1-phenylphospholane 1-oxide (DBMPP: 3) and 2,3,4-tribromo-3-methyl-1- phenylphospholane 1-oxide (TBMPP: 4), against various types of leukemia cell lines as well as the results of the mechanistic studies for characterizing and developing the novel multiple type molecular targeted antitumor agents are reported in this paper. DBMPP and TBMPP were prepared from 1-phenyl-3-methyl-2-phospholene 1-oxide (1). The isomer mixture of phospha sugars prepared were evaluated as novel antitumor agents by MTT in vitro method. DBMPP and TBMPP were characterized by flow cytometry and Western blot analysis and were revealed to be potential antitumor agents against leukemia cell lines of K562 (one type of leukemia cell lines of CML) and U937 (one type of leukemia cell lines of AML) as well as against the various types of leukemia cell lines and also against solid tumor cell lines of stomach, skin, and lung cancers by MTT evaluation and observation by a handstand phase-contrast microscope. The results of the flow cytometry indicated that the mechanism of apoptosis induced by phospha sugar derivatives not only to tumor cells of leukemia cell lines of U937 but also to tumor cells of various kinds of leukemia cell lines selectively to decrease the tumor cell viability of various kinds of leukemia cell lines. The Western blot analyses for phospha sugar DBMPP against U937 leukemia cell lines showed that the phospha sugar affected on the expressions of the factors of cell cycles in the manners of suppressing the expression of the accelerator factors of cell cycles of tumor cells and enhancing the expression of suppressor factors of cell cycles of tumor cells by the medications of phospha sugars. TBMPP enhanced the expression of IER5 and then suppressed the expression of Cdc25B, which is the common factor to accelerate the cell cycles of various kinds of tumor cells. Therefore, suppression of the expression of Cdc25B by TBMPP implies that the branched deoxybromophospha sugar derivatives might be novel and potential multiple type molecular targeted antitumor agents against various kinds of tumor cell lines.