4-bromo-3-methyl-1-phenyl-2-phospholene 1-oxide | 174078-54-7

• 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-bromo-3-methyl-1-phenyl-2-phospholene 1-oxide
• 英文别名: 3-bromo-4-methyl-1-phenyl-2,3-dihydro-1λ5-phosphole 1-oxide
• CAS: 174078-54-7
• 化学式: C₁₁H₁₂BrOP
• 分子量: 271.093
• InChiKey: FHSPRRPWDHWCFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-bromo-3-methyl-1-phenyl-2-phospholene 1-oxide 在 溴 作用下， 以 四氯化碳 为溶剂， 以50%的产率得到2,3,4-tribromo-3-methyl-1-phenylphospholane 1-oxide
  参考文献：
  名称：

  Research and Development of Phospha Sugar Anti-cancer Agents with Anti-leukemic Activity

  摘要：

  DOI：

  10.1515/hc.2010.16.2-3.89
• 作为产物：
  描述：

  2-甲基-丁烯 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 水 作用下， 生成 4-bromo-3-methyl-1-phenyl-2-phospholene 1-oxide
  参考文献：
  名称：

  Novel Multiple Type Molecular Targeted Antitumor Agents: Preparation and Preclinical Evaluation of Low-Molecular-Weight Phospha Sugar Derivatives

  摘要：

  Phospha sugar derivatives of 2,3-dibromo-3-methyl-1-phenylphospholane 1-oxide and 2,3,4-tribromo-3-methyl-1-phenylphospholane 1-oxide were synthesized from 2-phospholenes and evaluated by in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide method against leukemia cell lines, and then characterized by cell cycle analysis, Western blot analysis, and molecular docking simulation. Phospha sugar derivatives were revealed to be potential antitumor agents against leukemia cell lines such as U937 and K562. Cell cycle analysis indicated that phospha sugar derivatives induced apoptoses. Western blot analyses against U937 showed that phospha sugar derivatives regulate many mitotic regulators in cell cycle. Results of molecular docking simulation suggested that phospha sugar derivatives enter the pockets present in cell cycle and apoptosis-related proteins.

  DOI：

  10.1080/10426507.2014.993758

文献信息

• Preparation and characterization of novel 4-bromo-3,4-dimethyl-1-phenyl-2-phospholene 1-oxide and the analogous phosphorus heterocycles or phospha sugars
  作者：Manabu Yamada、Mitsuji Yamashita、Takuya Suyama、Junko Yamashita、Kazuhide Asai、Taishi Niimi、Nobuhisa Ozaki、Michio Fujie、Kasthuraiah Maddali、Satoki Nakamura、Kazunori Ohnishi

  DOI：10.1016/j.bmcl.2010.01.061

  日期：2010.10

  first synthesized from 3,4-dimethyl-1-phenyl-2-phospholene 1-oxide (2c) by a bromo-radical substitution reaction occurred at C-4 position by N-bromosuccinimide and 2,2′-azobisisobutyronitrile. The novel phospha sugar analogue 3c exerted high anti-proliferative effect on U937 cells evaluated by MTT in vitro methods and was much more efficient than that of Gleevec®, which is known as a molecule targeting

  首先由3,4-二甲基-1-苯基-2-苯酚1氧化物（2c）通过溴代合成4-溴-3,4-二甲基-1-苯基-2-苯酚1-氧化物（3c）。N-溴代琥珀酰亚胺和2,2'-偶氮二异丁腈在C-4位发生自由基取代反应。通过MTT体外方法评估，新型磷酸糖类似物3c对U937细胞具有很高的抗增殖作用，并且比被称为分子靶向化学治疗剂的Gleevec®更有效。C-3和C-4位的2-膦烯基被甲基以及4-溴取代基取代表明具有良好的抗增殖作用。
• 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.
• Preparation of Phospha Sugar Analogues and Their Evaluation as Novel Molecular Targeting Anticancer Agents
  作者：Kenji Tsunekawa、Mitsuji Yamashita、Michio Fujie、Taishi Niimi、Takuya Suyama、Kazuhide Asai、Satoru Ito、Junko Yamashita、Manabu Yamada、Nobuhisa Ozaki、Satoki Nakamura

  DOI：10.1080/10426507.2010.530326

  日期：2011.3.31

  Phospha sugars were prepared by a novel synthetic route starting from phosphorus heterocyclic compounds, 2-phospholenes. The anhydro-and deoxy-phospha sugar derivatives have been revealed to have potential anticancer activities against human leukemia of K562 and U937 cell lines. In this article, deoxybromophospha sugars with different numbers of bromo substituents were prepared, and their anticancer activities were evaluated by MTT method. The order of the activities depending on the number of bromo substituent was first revealed, and trideoxytribromotetrofuranose type phospha sugar [2,3,4-tribromo-3-methyl-1-phenylphospholane 1-oxide (4: TBMPPAO)] was the most active among these phospha sugars prepared. Diasteromers of dideoxydibromotetrofuranose-type phospha sugar [2,3-dibromo-3-methyl-1-phenylphospholane 1-oxide (2: DBMPPAO)] were separated into four components, and the structure as well as the character of each component was assigned by spectral and chromatographic data as well as by MTT method.The deoxybromophospha sugars have higher antileukemia activity than Gleevec against U937 cells.
• Research and Development of Phospha Sugar Anti-cancer Agents with Anti-leukemic Activity
  作者：Junko Yamashita,、Takuya Suyama,、Kazuhide Asai,、Manabu Yamada,、Taishi Niimi,、Michio Fujie,、Satoki Nakamura,、Kazunori Ohnishi,、Mitsuji Yamashita,

  DOI：10.1515/hc.2010.16.2-3.89

  日期：2010.6
• Novel Multiple Type Molecular Targeted Antitumor Agents: Preparation and Preclinical Evaluation of Low-Molecular-Weight Phospha Sugar Derivatives
  作者：Reiko Makita、Mitsuji Yamashita、Mayumi Yamaoka、Michio Fujie、Satoki Nakamura、Tatsuo Oshikawa、Junko Yamashita、Manabu Yamada、Kazuhide Asai、Takuya Suyama、Mitsuru Kondo、Hiroko Hasegawa、Yoshimitsu Okita、Kazutaka Hirakawa、Mitsuo Toda、Kazunori Ohnishi、Haruhiko Sugimura

  DOI：10.1080/10426507.2014.993758

  日期：2015.6.3

  Phospha sugar derivatives of 2,3-dibromo-3-methyl-1-phenylphospholane 1-oxide and 2,3,4-tribromo-3-methyl-1-phenylphospholane 1-oxide were synthesized from 2-phospholenes and evaluated by in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide method against leukemia cell lines, and then characterized by cell cycle analysis, Western blot analysis, and molecular docking simulation. Phospha sugar derivatives were revealed to be potential antitumor agents against leukemia cell lines such as U937 and K562. Cell cycle analysis indicated that phospha sugar derivatives induced apoptoses. Western blot analyses against U937 showed that phospha sugar derivatives regulate many mitotic regulators in cell cycle. Results of molecular docking simulation suggested that phospha sugar derivatives enter the pockets present in cell cycle and apoptosis-related proteins.