5,5'-dibromo-3,3'-dicarbomethoxy-2,2'-dimethoxydiphenylmethane | 178599-73-0

• 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: 5,5'-dibromo-3,3'-dicarbomethoxy-2,2'-dimethoxydiphenylmethane
• 英文别名: 5,5'-dibromo-2,2'-dimethoxy-3,3'-bis(methoxycarbonyl)diphenylmethane；Methyl 5-bromo-3-[(5-bromo-2-methoxy-3-methoxycarbonylphenyl)methyl]-2-methoxybenzoate
• CAS: 178599-73-0
• 化学式: C₁₉H₁₈Br₂O₆
• 分子量: 502.156
• InChiKey: ZIJSUTQLYZBCOF-UHFFFAOYSA-N

物化性质

• 熔点：
  81 °C
• 沸点：
  558.8±50.0 °C(Predicted)
• 密度：
  1.545±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5,5'-dibromo-3,3'-dicarbomethoxy-2,2'-dimethoxydiphenylmethane 在 chromium(VI) oxide 、 乙酸酐 作用下， 以88%的产率得到5,5'dibromo-2,2'-dimethoxy-3,3'dicarbomethoxybenzophenone
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Certain Alkenyldiarylmethanes as Anti-HIV-1 Agents Which Act as Non-Nucleoside Reverse Transcriptase Inhibitors

  摘要：

  Several novel alkenyldiarylmethane (ADAM) non-nucleoside HIV-1 reverse transcriptase inhibitors were synthesized. The most potent of these proved to be 3',3''-dibromo-4',4 ''-dimethoxy-5',5 ''-bis(methoxycarbonyl)-1,1-diphenyl-1-heptene (8). ADAM 8 inhibited the cytopathic effect of HIV-1 in CEM cell culture with an EC(50) value of 7.1 mu M and was active against an array of laboratory strains of HIV-1 in CEM-SS and MT-4 cells, but was inactive as an inhibitor of HIV-2. In common with the other known non-nucleoside reverse transcriptase inhibitors, ADAM 8 was an effective inhibitor of HIV-1 reverse transcriptase (IC50 1 mu M) with poly(rC). oligo(dG), but not with poly(rA). oligo(dT), as the template/primer. ADAM 8 was inactive against HIV-1 reverse transcriptases containing non-nucleoside reverse transcriptase inhibitor resistance mutations at residues 101, 106, 108, 139, 181, 188, and 236, while it remained active against enzymes with mutations at residues 74, 98, 100, 103, and at 103/181. An AZT-resistant virus having four mutations in reverse transcriptase was more sensitive to inhibition by ADAM 8 than the wild-type HIV-1. In addition, ADAM 8 displayed synergistic activity with AZT, but lacked synergy with ddI. ADAM 8 or a structurally related analog may therefore be useful as an antiviral agent in combination with AZT or with other NNRTIs that are made ineffective by mutations at residues which do not confer resistance to ADAM 8.

  DOI：

  10.1021/jm960082v
• 作为产物：
  描述：

  5-溴水杨酸 在 硫酸 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 53.0h， 生成 5,5'-dibromo-3,3'-dicarbomethoxy-2,2'-dimethoxydiphenylmethane
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Certain Alkenyldiarylmethanes as Anti-HIV-1 Agents Which Act as Non-Nucleoside Reverse Transcriptase Inhibitors

  摘要：

  Several novel alkenyldiarylmethane (ADAM) non-nucleoside HIV-1 reverse transcriptase inhibitors were synthesized. The most potent of these proved to be 3',3''-dibromo-4',4 ''-dimethoxy-5',5 ''-bis(methoxycarbonyl)-1,1-diphenyl-1-heptene (8). ADAM 8 inhibited the cytopathic effect of HIV-1 in CEM cell culture with an EC(50) value of 7.1 mu M and was active against an array of laboratory strains of HIV-1 in CEM-SS and MT-4 cells, but was inactive as an inhibitor of HIV-2. In common with the other known non-nucleoside reverse transcriptase inhibitors, ADAM 8 was an effective inhibitor of HIV-1 reverse transcriptase (IC50 1 mu M) with poly(rC). oligo(dG), but not with poly(rA). oligo(dT), as the template/primer. ADAM 8 was inactive against HIV-1 reverse transcriptases containing non-nucleoside reverse transcriptase inhibitor resistance mutations at residues 101, 106, 108, 139, 181, 188, and 236, while it remained active against enzymes with mutations at residues 74, 98, 100, 103, and at 103/181. An AZT-resistant virus having four mutations in reverse transcriptase was more sensitive to inhibition by ADAM 8 than the wild-type HIV-1. In addition, ADAM 8 displayed synergistic activity with AZT, but lacked synergy with ddI. ADAM 8 or a structurally related analog may therefore be useful as an antiviral agent in combination with AZT or with other NNRTIs that are made ineffective by mutations at residues which do not confer resistance to ADAM 8.

  DOI：

  10.1021/jm960082v

文献信息

• Mono- and disalicylic acid derivatives: PTP1B inhibitors as potential anti-obesity drugs
  作者：Suja Shrestha、Bharat Raj Bhattarai、Keun-Hyeung Lee、Hyeongjin Cho

  DOI：10.1016/j.bmc.2007.07.010

  日期：2007.10

  A series of compounds containing one or two salicylic acid moieties were synthesized, and their efficacy to inhibit the phosphohydrolase activity of PTP1B examined. Some of the methylenedisalicylic acid derivatives were potent inhibitors of PTP1B. Of those derivatives, 3c exhibited about a 14-fold selectivity against TC-PTP, and this compound was tested in a mouse model for its efficacy to prevent

  合成了一系列包含一个或两个水杨酸部分的化合物，并研究了其抑制PTP1B磷酸水解酶活性的功效。一些亚甲基二水杨酸衍生物是PTP1B的有效抑制剂。在这些衍生物中，3c对TC-PTP表现出约14倍的选择性，并在小鼠模型中测试了该化合物预防饮食引起的肥胖的功效。它有效地抑制了体重和脂肪的增加，而没有任何明显的毒性作用。该化合物还可以防止血浆甘油三酸酯，胆固醇和非酯化脂肪酸浓度的增加。因此，将其治疗潜力扩展到其他相关的代谢性疾病，例如高脂血症和高胆固醇血症。
• Synthesis and Biological Evaluation of Certain Alkenyldiarylmethanes as Anti-HIV-1 Agents Which Act as Non-Nucleoside Reverse Transcriptase Inhibitors
  作者：Mark Cushman、W. Marek Golebiewski、Lisa Graham、Jim A. Turpin、William G. Rice、Valerie Fliakas-Boltz、Robert W. Buckheit

  DOI：10.1021/jm960082v

  日期：1996.1.1

  Several novel alkenyldiarylmethane (ADAM) non-nucleoside HIV-1 reverse transcriptase inhibitors were synthesized. The most potent of these proved to be 3',3''-dibromo-4',4 ''-dimethoxy-5',5 ''-bis(methoxycarbonyl)-1,1-diphenyl-1-heptene (8). ADAM 8 inhibited the cytopathic effect of HIV-1 in CEM cell culture with an EC(50) value of 7.1 mu M and was active against an array of laboratory strains of HIV-1 in CEM-SS and MT-4 cells, but was inactive as an inhibitor of HIV-2. In common with the other known non-nucleoside reverse transcriptase inhibitors, ADAM 8 was an effective inhibitor of HIV-1 reverse transcriptase (IC50 1 mu M) with poly(rC). oligo(dG), but not with poly(rA). oligo(dT), as the template/primer. ADAM 8 was inactive against HIV-1 reverse transcriptases containing non-nucleoside reverse transcriptase inhibitor resistance mutations at residues 101, 106, 108, 139, 181, 188, and 236, while it remained active against enzymes with mutations at residues 74, 98, 100, 103, and at 103/181. An AZT-resistant virus having four mutations in reverse transcriptase was more sensitive to inhibition by ADAM 8 than the wild-type HIV-1. In addition, ADAM 8 displayed synergistic activity with AZT, but lacked synergy with ddI. ADAM 8 or a structurally related analog may therefore be useful as an antiviral agent in combination with AZT or with other NNRTIs that are made ineffective by mutations at residues which do not confer resistance to ADAM 8.