3',3''-dichloro-4',4''-dihydroxy-5',5''-bis(methoxycarbonyl)-1,1-diphenyl-1-heptene | 162547-51-5

• 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: 3',3''-dichloro-4',4''-dihydroxy-5',5''-bis(methoxycarbonyl)-1,1-diphenyl-1-heptene
• 英文别名: 1,1-bis<5'-chloro-4'-hydroxy-3'-(methoxycarbonyl)phenyl>-1-heptene；Methyl 3-chloro-5-[1-(3-chloro-4-hydroxy-5-methoxycarbonylphenyl)hept-1-enyl]-2-hydroxybenzoate
• CAS: 162547-51-5
• 化学式: C₂₃H₂₄Cl₂O₆
• 分子量: 467.346
• InChiKey: OBFKUPOQRWRNCR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3',3''-dichloro-4',4''-dihydroxy-5',5''-bis(methoxycarbonyl)-1,1-diphenyl-1-heptene 在 sodium hydroxide 、 盐酸羟胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 20.0h， 以90%的产率得到1,1-bis<5'-chloro-4'-hydroxy-3'-(N-hydroxycarbamoyl)phenyl>-1-heptene
  参考文献：
  名称：

  Cosalane Analogs with Enhanced Potencies as Inhibitors of HIV-1 Protease and Integrase

  摘要：

  Several new analogues of the novel anti-HIV agent cosalane have been synthesized and evaluated as inhibitors of HIV-1 integrase and protease, HIV-1 replication, HIV-1 and HIV-2 cytopathicity, HIV-1- and HIV-2-mediated syncytium formation, and cytopathicity of a variety of human pathogenic viruses. The congeners displayed enhanced potencies relative to cosalane itself as inhibitors of HIV-1 integrase and protease. The two most potent analogues against HIV-1 integrase displayed IC50 values of 2.2 mu M, while the three most potent compounds against HIV-1 protease had IC50 values in the 0.35-0.39 mu M range. In addition to its activity against HIV-1 and HIV-2 cytopathicity, cosalane inhibited the cytopathic effects of herpes simplex virus-1, herpes simplex virus-2, and human cytomegalovirus at concentrations that were well below the cytotoxic concentrations. Potentially useful antiviral activities were also revealed for some of the new cosalane congeners against influenza virus, Junin virus, and Tacaribe virus.

  DOI：

  10.1021/jm00003a007
• 作为产物：
  描述：

  n-溴代已基三苯基膦 在 硫酸 、 三溴化硼 、 sodium hydride 、 二甲基亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 195.25h， 生成 3',3''-dichloro-4',4''-dihydroxy-5',5''-bis(methoxycarbonyl)-1,1-diphenyl-1-heptene
  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

• Cosalane Analogs with Enhanced Potencies as Inhibitors of HIV-1 Protease and Integrase
  作者：Mark Cushman、W. Marek Golebiewski、Yves Pommier、Abhijit Mazunder、Diane Reymen、Erik De Clercq、Lisa Grahm、William G. Rice

  DOI：10.1021/jm00003a007

  日期：1995.2

  Several new analogues of the novel anti-HIV agent cosalane have been synthesized and evaluated as inhibitors of HIV-1 integrase and protease, HIV-1 replication, HIV-1 and HIV-2 cytopathicity, HIV-1- and HIV-2-mediated syncytium formation, and cytopathicity of a variety of human pathogenic viruses. The congeners displayed enhanced potencies relative to cosalane itself as inhibitors of HIV-1 integrase and protease. The two most potent analogues against HIV-1 integrase displayed IC50 values of 2.2 mu M, while the three most potent compounds against HIV-1 protease had IC50 values in the 0.35-0.39 mu M range. In addition to its activity against HIV-1 and HIV-2 cytopathicity, cosalane inhibited the cytopathic effects of herpes simplex virus-1, herpes simplex virus-2, and human cytomegalovirus at concentrations that were well below the cytotoxic concentrations. Potentially useful antiviral activities were also revealed for some of the new cosalane congeners against influenza virus, Junin virus, and Tacaribe virus.
• 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.