8,8'-dichloro-2,2,2',2'-tetramethyl-4,4'-dioxo-6,6'-di(1,3-benzodioxyl) ketone | 173173-57-4

• 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: 8,8'-dichloro-2,2,2',2'-tetramethyl-4,4'-dioxo-6,6'-di(1,3-benzodioxyl) ketone
• 英文别名: 4H-1,3-Benzodioxin-4-one, 6,6'-carbonylbis[8-chloro-2,2-dimethyl-；8-chloro-6-(8-chloro-2,2-dimethyl-4-oxo-1,3-benzodioxine-6-carbonyl)-2,2-dimethyl-1,3-benzodioxin-4-one
• CAS: 173173-57-4
• 化学式: C₂₁H₁₆Cl₂O₇
• 分子量: 451.26
• InChiKey: JCOKOOJWIPXXBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  30
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  88.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  8,8'-dichloro-2,2,2',2'-tetramethyl-4,4'-dioxo-6,6'-di(1,3-benzodioxyl) ketone 在 四丁基氟化铵 、 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 52.25h， 生成 4,4-Bis(8-chloro-2,2-dimethyl-4-oxo-1,3-benzodioxin-6-yl)but-3-enyl octadecyl 3-oxobutan-2-yl phosphate
  参考文献：
  名称：

  Correlation of Anti-HIV Potency with Lipophilicity in a Series of Cosalane Analogs Having Normal Alkenyl and Phosphodiester Chains as Cholestane Replacements

  摘要：

  In order to define the role of the cholestane moiety in the anti-HIV agent cosalane, a series of cosalane analogs was synthesized in which the cholestane ring system was replaced by normal alkenyl and phosphodiester substituents having varied chain lengths and lipophilicities. The compounds containing simple alkenyl substituents were found to be more potent as inhibitors of the cytopathic effect of HIV-1 in cell culture than the phosphodiesters. In addition, the potencies of the alkene congeners correlated positively with chain length and lipophilicity of the alkene. The results indicate that the cholestane moiety of cosalane functions as a lipophilic accessory appendage to escort the dichlorodisalicylmethane pharmacophore to a lipid environment.

  DOI：

  10.1021/jm950666h
• 作为产物：
  描述：

  3,3'-dicarboxy-5,5'-dichloro-4,4'-dihydroxydiphenylmethane 在 chromium(VI) oxide 、 硼烷四氢呋喃络合物 、 乙酸酐 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 45.5h， 生成 8,8'-dichloro-2,2,2',2'-tetramethyl-4,4'-dioxo-6,6'-di(1,3-benzodioxyl) ketone
  参考文献：
  名称：

  Correlation of Anti-HIV Potency with Lipophilicity in a Series of Cosalane Analogs Having Normal Alkenyl and Phosphodiester Chains as Cholestane Replacements

  摘要：

  In order to define the role of the cholestane moiety in the anti-HIV agent cosalane, a series of cosalane analogs was synthesized in which the cholestane ring system was replaced by normal alkenyl and phosphodiester substituents having varied chain lengths and lipophilicities. The compounds containing simple alkenyl substituents were found to be more potent as inhibitors of the cytopathic effect of HIV-1 in cell culture than the phosphodiesters. In addition, the potencies of the alkene congeners correlated positively with chain length and lipophilicity of the alkene. The results indicate that the cholestane moiety of cosalane functions as a lipophilic accessory appendage to escort the dichlorodisalicylmethane pharmacophore to a lipid environment.

  DOI：

  10.1021/jm950666h

文献信息

• Synthesis of substituted diarylmethylenepiperidines (DAMPs), a novel class of anti-HIV agents
  作者：Guozhang Xu、Arunachalam Kannan、Tracy L Hartman、Heather Wargo、Karen Watson、Jim A Turpin、Robert W Buckheit、Allison A Johnson、Yves Pommier、Mark Cushman

  DOI：10.1016/s0968-0896(02)00095-0

  日期：2002.8

  Substituted diarymethylenepiperidines (DAMPs) were synthesized as conformationally restricted analogues of the alkenyldiarylmethane (ADAM) class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Although, like the ADAMs, the DAMPs were found to inhibit the cytopathic effect of HIV-1(RF) in CEM-SS cells, they were completely inactive as inhibitors of HIV-1 reverse transcriptase. The DAMPs were assessed for inhibition of HIV attachment and fusion. DAMP 14 was active in both assays with IC50 values of 26.5 muM (TI 3.8) and 12.1 muM (TI: > 8), respectively. DAMP 15 also inhibited HIV fusion with all IC50 12.8 muM (TI: > 6), but not virus attachment. However, attempts to verity inhibition of virus attachment and fusion as antiviral targets using time-of-addition experiments failed to confirm these observations, and instead identified all antiviral target Occurring after completion of reverse transcription. DAMPs 11, 12, 14, and 15 were found to inhibit virus replication if added 8 h post virus exposure, and DAMP 11 was equipotent at inhibition of virus replication if added 24 It after Virus addition. DAMPs 11, 12, and 15 did not inhibit virus replication in TNF-alpha induced latently infected U1 cells, a model for post-integrative antiviral targets. When tested in both 3' end-processing and strand-transfer assays in the presence of HIV-1 integrase. none of the DAMPs showed any inhibitory activity, indicating that HIV-1 integrase is not involved in the mechanism of the antiviral action. Thus, the DAMPs are novel conformationally restricted analogues of the previously published ADAM series with all unidentified antiviral target bounded by the completion of reverse transcription and virus integration. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Synthesis and anti-HIV activity of cosalane analogues incorporating two dichlorodisalicylmethane pharmacophore fragments
  作者：Agustin Casimiro-Garcia、Erik De Clercq、Christophe Pannecouque、Myriam Witvrouw、Tracy L Loftus、Jim A Turpin、Robert W Buckheit、Phillip E Fanwick、Mark Cushman

  DOI：10.1016/s0968-0896(01)00152-3

  日期：2001.11

  A new series of cosalane analogues incorporating two fragments of the dichlorodisalicylmethane pharmacophore has been synthesized. In order to identify the position for the attachment of the pharmacophore fragments to the steroid ring that results in the most potent analogues, two types of compounds were designed. In the first type, the two pharmacophore fragments were attached at C-3 and C-17 of the steroid ring by using appropriate linker units. In the second type, both pharmacophore groups were connected to C-3 of the steroid through an alkenyl chain containing an amide moiety. All of the new compounds displayed antiviral activity versus HIV-1(RF), HIV-1(IIIB), and HIV-2(ROD) in cell culture. The relative potencies of the compounds resulting from the two attachment strategies were found to depend on the viral strain as well as the cell type, Overall, the attachment of the second pharmacophore did not result in either a large gain or a large loss in anti-HIV activity, and the results are therefore consistent with the hypothesis that the two pharmacophores act independently, and one at a time, with positively charged amino acid side chains present on the surface of gp120 and CD4. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Correlation of Anti-HIV Potency with Lipophilicity in a Series of Cosalane Analogs Having Normal Alkenyl and Phosphodiester Chains as Cholestane Replacements
  作者：Robert F. Keyes、W. Marek Golebiewski、Mark Cushman

  DOI：10.1021/jm950666h

  日期：1996.1.1

  In order to define the role of the cholestane moiety in the anti-HIV agent cosalane, a series of cosalane analogs was synthesized in which the cholestane ring system was replaced by normal alkenyl and phosphodiester substituents having varied chain lengths and lipophilicities. The compounds containing simple alkenyl substituents were found to be more potent as inhibitors of the cytopathic effect of HIV-1 in cell culture than the phosphodiesters. In addition, the potencies of the alkene congeners correlated positively with chain length and lipophilicity of the alkene. The results indicate that the cholestane moiety of cosalane functions as a lipophilic accessory appendage to escort the dichlorodisalicylmethane pharmacophore to a lipid environment.