1-bromo-4,4-bis[8',8''-dichloro-2',2',2'',2''-tetramethyl-4',4''-dioxo-6',6''-(1,3-benzodioxyl)]-3-butene

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: 1-bromo-4,4-bis[8',8''-dichloro-2',2',2'',2''-tetramethyl-4',4''-dioxo-6',6''-(1,3-benzodioxyl)]-3-butene
• 英文别名: 6-[4-Bromo-1-(8-chloro-2,2-dimethyl-4-oxo-1,3-benzodioxin-6-yl)but-1-enyl]-8-chloro-2,2-dimethyl-1,3-benzodioxin-4-one
• 化学式: C₂₄H₂₁BrCl₂O₆
• 分子量: 556.237
• InChiKey: XJMUIRCKKLBSBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4,4-bis[8',8"-dichloro-2',2',2",2"-tetramethyl-4',4"-dioxo-6',6"-(1,3-benzodioxyl)]-3-buten-1-ol 在 四溴化碳 、 三苯基膦 作用下， 以 乙腈 为溶剂， 反应 20.0h， 以56%的产率得到1-bromo-4,4-bis[8',8''-dichloro-2',2',2'',2''-tetramethyl-4',4''-dioxo-6',6''-(1,3-benzodioxyl)]-3-butene
  参考文献：
  名称：

  New Alkenyldiarylmethanes with Enhanced Potencies as Anti-HIV Agents Which Act as Non-Nucleoside Reverse Transcriptase Inhibitors

  摘要：

  Twenty-two new alkenyldiarylmethanes (ADAMs) were synthesized and evaluated for inhibition of HIV-1 replication. The most potent compound proved to be methyl 3',3 "-dichloro-4',4 "-dimethoxy-5', 5 "-bis(methoxycarbonyl)-6, (ADAM II), which displayed an EC50 of 13 nM for inhibition of the cytopathic effect of HIV-1(RF) in CEM-SS cells. ADAM II inhibited HIV-1 reverse transcriptase with an IC50 of 0.3 mu M but was inactive as an inhibitor of HIV-1 attachment/fusion to cells, protease, integrase, and the nucleocapsid protein. Molecular target-based and cell-based assays revealed that ADAM II acted biologically as a nonnucleoside reverse transcriptase inhibitor (NNRTI). ADAM II inhibited replication of a wide variety of laboratory, clinical, and clade-representative isolates of HIV-1 in T cell lines and cultures of peripheral blood mononuclear cells or monocyte/macrophages. Mutations that conferred resistance to ADAM II clustered at residues 101, 103, 108, 139, 179, 181, and 188, which line the nonnucleoside binding pocket of HIV-1 reverse transcriptase. However, HIV-1 NL4-3 strain expressing a mutation at residue 100 of reverse transcriptase, and an AZT-resistant virus, displayed increased sensitivity to ADAM II. Thus, ADAM II could serve as an adjunct therapy to AZT and NNRTIs that select for L100I resistance mutations.

  DOI：

  10.1021/jm9800595

文献信息

• New Alkenyldiarylmethanes with Enhanced Potencies as Anti-HIV Agents Which Act as Non-Nucleoside Reverse Transcriptase Inhibitors
  作者：Mark Cushman、Agustin Casimiro-Garcia、Elzbieta Hejchman、Jeffrey A. Ruell、Mingjun Huang、Catherine A. Schaeffer、Karen Williamson、William G. Rice、Robert W. Buckheit

  DOI：10.1021/jm9800595

  日期：1998.6.1

  Twenty-two new alkenyldiarylmethanes (ADAMs) were synthesized and evaluated for inhibition of HIV-1 replication. The most potent compound proved to be methyl 3',3 "-dichloro-4',4 "-dimethoxy-5', 5 "-bis(methoxycarbonyl)-6, (ADAM II), which displayed an EC50 of 13 nM for inhibition of the cytopathic effect of HIV-1(RF) in CEM-SS cells. ADAM II inhibited HIV-1 reverse transcriptase with an IC50 of 0.3 mu M but was inactive as an inhibitor of HIV-1 attachment/fusion to cells, protease, integrase, and the nucleocapsid protein. Molecular target-based and cell-based assays revealed that ADAM II acted biologically as a nonnucleoside reverse transcriptase inhibitor (NNRTI). ADAM II inhibited replication of a wide variety of laboratory, clinical, and clade-representative isolates of HIV-1 in T cell lines and cultures of peripheral blood mononuclear cells or monocyte/macrophages. Mutations that conferred resistance to ADAM II clustered at residues 101, 103, 108, 139, 179, 181, and 188, which line the nonnucleoside binding pocket of HIV-1 reverse transcriptase. However, HIV-1 NL4-3 strain expressing a mutation at residue 100 of reverse transcriptase, and an AZT-resistant virus, displayed increased sensitivity to ADAM II. Thus, ADAM II could serve as an adjunct therapy to AZT and NNRTIs that select for L100I resistance mutations.