methyl 2-((2E,6E)-8-bromo-2,6-dimethylocta-2,6-dienylamino)benzoate | 928267-81-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: methyl 2-((2E,6E)-8-bromo-2,6-dimethylocta-2,6-dienylamino)benzoate
• CAS: 928267-81-6
• 化学式: C₁₈H₂₄BrNO₂
• 分子量: 366.298
• InChiKey: PVIPFWASCXZHPU-GGQZXFEVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.95
• 重原子数：
  22.0
• 可旋转键数：
  8.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  38.33
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  methyl 2-((2E,6E)-8-bromo-2,6-dimethylocta-2,6-dienylamino)benzoate 在 2,4,6-三甲基吡啶 、 15-冠醚-5 、 碘代三甲硅烷 、 sodium hydride 、 溶剂黄146 、 1,2-二溴乙烷 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 、 mineral oil 为溶剂， 反应 30.25h， 生成 2-((2E,6E)-15-carboxy-15,15-difluoro-14-hydroxy-2,6,14-trimethyl-9,9-diphosphonopentadeca-2,6-dienylamino)benzoic acid pentalithium salt
  参考文献：
  名称：

  Multi-target-directed design, syntheses, and characterization of fluorescent bisphosphonate derivatives as multifunctional enzyme inhibitors in mevalonate pathway

  摘要：

  Background: Mevalonate pathway is an important cellular metabolic pathway present in all higher eukaryotes and many bacteria. Four enzymes in mevalonate pathway, including MVK, PMK, MDD, and FPPS, play important regulatory roles in cholesterol biosynthesis and cell proliferation.Methods: The following methods were used: cloning, expression and purification of enzymes in mevalonate pathway, organic syntheses of multifunctional enzyme inhibitors, measurement of their IC50 values for above four enzymes, kinetic studies of enzyme inhibitions, molecular modeling studies, cell viability tests, and fluorescence microscopy.Results and conclusions: We report our multi-target-directed design, syntheses, and characterization of two blue fluorescent bisphosphonate derivatives compounds 15 and 16 as multifunctional enzyme inhibitors in mevalonate pathway. These two compounds had good inhibition to all these four enzymes with their IC50 values at nanomolar to micromolar range. Kinetic and molecular modeling studies showed that these two compounds could bind to the active sites of all these four enzymes. The fluorescence microscopy indicated that these two compounds could easily get into cancer cells.General significance: Multifunctional enzyme inhibitors are generally more effective than single enzyme inhibitors, with fewer side effects. Our results showed that these multifunctional inhibitors could become lead compounds for further development for the treatment of soft-tissue tumors and hypercholesteremia. (C) 2013 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.bbagen.2013.02.011
• 作为产物：
  描述：

  香叶醇 在 selenium(IV) oxide 、 lanthanum(III) nitrate hexahydrate 、 三溴化磷 、 三乙酰氧基硼氢化钠 、 potassium carbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 1,2-二氯乙烷 为溶剂， 反应 28.78h， 生成 methyl 2-((2E,6E)-8-bromo-2,6-dimethylocta-2,6-dienylamino)benzoate
  参考文献：
  名称：

  Multi-target-directed design, syntheses, and characterization of fluorescent bisphosphonate derivatives as multifunctional enzyme inhibitors in mevalonate pathway

  摘要：

  Background: Mevalonate pathway is an important cellular metabolic pathway present in all higher eukaryotes and many bacteria. Four enzymes in mevalonate pathway, including MVK, PMK, MDD, and FPPS, play important regulatory roles in cholesterol biosynthesis and cell proliferation.Methods: The following methods were used: cloning, expression and purification of enzymes in mevalonate pathway, organic syntheses of multifunctional enzyme inhibitors, measurement of their IC50 values for above four enzymes, kinetic studies of enzyme inhibitions, molecular modeling studies, cell viability tests, and fluorescence microscopy.Results and conclusions: We report our multi-target-directed design, syntheses, and characterization of two blue fluorescent bisphosphonate derivatives compounds 15 and 16 as multifunctional enzyme inhibitors in mevalonate pathway. These two compounds had good inhibition to all these four enzymes with their IC50 values at nanomolar to micromolar range. Kinetic and molecular modeling studies showed that these two compounds could bind to the active sites of all these four enzymes. The fluorescence microscopy indicated that these two compounds could easily get into cancer cells.General significance: Multifunctional enzyme inhibitors are generally more effective than single enzyme inhibitors, with fewer side effects. Our results showed that these multifunctional inhibitors could become lead compounds for further development for the treatment of soft-tissue tumors and hypercholesteremia. (C) 2013 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.bbagen.2013.02.011

文献信息

• Synthesis of fluorescently tagged isoprenoid bisphosphonates that inhibit protein geranylgeranylation
  作者：Mona A. Maalouf、Andrew J. Wiemer、Craig H. Kuder、Raymond J. Hohl、David F. Wiemer

  DOI：10.1016/j.bmc.2007.01.002

  日期：2007.3

  Geminal bisphosphonates call be used for a variety of purposes in human disease including reduction of bone resorption in osteoporosis, treatment of fractures associated with malignancies of the prostate, breast, and lung, and direct anticancer activity against bone marrow derived malignancies. Previous research led to identification of some novel isoprenoid bisphosplionates that inhibit geranylgeranyl pyrophosphate (GGPP) synthesis and diminish protein geranylgeranylation. Described here is the synthesis of fluorescent anthranilate analogues of the most active isoprenoid bisphosphonates and examine their ability to impact post-translational processing of the small GTPases Ras, Rap I a, and Rab6. Similar to their non-fluorescent counterparts, some of these fluorescent isoprenoid bisphosphonates diminish protein geranylgeranylation. Their biological activity and fluorescent character suggest that they may be useful in studies of bisphosphonate localization both ill Cultured cells and in whole organisms. (c) 2007 Elsevier Ltd. All rights reserved.