Methyl 3-chloro-5-[1-(3-chloro-4-methoxy-5-methoxycarbonyl-phenyl)-6-(ethylcarbamoyloxy)hex-1-enyl]-2-methoxy-benzoate

• 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: Methyl 3-chloro-5-[1-(3-chloro-4-methoxy-5-methoxycarbonyl-phenyl)-6-(ethylcarbamoyloxy)hex-1-enyl]-2-methoxy-benzoate
• 英文别名: methyl 3-chloro-5-[1-(3-chloro-4-methoxy-5-methoxycarbonylphenyl)-6-(ethylcarbamoyloxy)hex-1-enyl]-2-methoxybenzoate
• 化学式: C₂₇H₃₁Cl₂NO₈
• 分子量: 568.451
• InChiKey: RWJOMNAWFJRJBM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  38
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  异氰酸乙酯 、 3',3''-dichloro-4',4''-dimethoxy-5',5''-bis(methoxycarbonyl)-1,1-diphenyl-1-hexen-6-ol 在 4-二甲氨基吡啶 、 三乙胺 作用下， 反应 48.0h， 以98%的产率得到Methyl 3-chloro-5-[1-(3-chloro-4-methoxy-5-methoxycarbonyl-phenyl)-6-(ethylcarbamoyloxy)hex-1-enyl]-2-methoxy-benzoate
  参考文献：
  名称：

  Novel Modifications in the Alkenyldiarylmethane (ADAM) Series of Non-Nucleoside Reverse Transcriptase Inhibitors

  摘要：

  In an effort to obtain more insight into the interaction between HIV-1 reverse transcriptase and the alkenyldiarylmethanes (ADAMs), a new series of compounds has been synthesized and evaluated for inhibition of HIV-1 replication. The modifications reported in this new series include primarily changes to the alkenyl chain. The most potent compound proved to be methyl 3', 3 "-dibromo-4',4 "-dimethoxy-5',5 "-bis(methoxycarbonyl)-6,6-diphenyl-5-hexanoate (28), which displayed an EC50 of 1.3 nM for inhibition of the cytopathic effect of HIV-1(RF) in CEM-SS cells. ADAM 28 inhibited HIV-1 reverse transcriptase with an IC50 of 0.3 mu M. Mutations that conferred greater than 10-fold resistance to ADAM 28 clustered at residues Val 106, Val 179, Tyr 181, and Tyr 188. Results derived from this series indicate that ADAMs containing chlorines in the aromatic rings might bind to HIV-1 reverse transcriptase in a slightly different mode when compared with those analogues incorporating bromine in the aromatic rings.

  DOI：

  10.1021/jm990343b

文献信息

• Novel Modifications in the Alkenyldiarylmethane (ADAM) Series of Non-Nucleoside Reverse Transcriptase Inhibitors
  作者：Agustin Casimiro-Garcia、Mark Micklatcher、Jim A. Turpin、Tracy L. Stup、Karen Watson、Robert W. Buckheit、Mark Cushman

  DOI：10.1021/jm990343b

  日期：1999.11.1

  In an effort to obtain more insight into the interaction between HIV-1 reverse transcriptase and the alkenyldiarylmethanes (ADAMs), a new series of compounds has been synthesized and evaluated for inhibition of HIV-1 replication. The modifications reported in this new series include primarily changes to the alkenyl chain. The most potent compound proved to be methyl 3', 3 "-dibromo-4',4 "-dimethoxy-5',5 "-bis(methoxycarbonyl)-6,6-diphenyl-5-hexanoate (28), which displayed an EC50 of 1.3 nM for inhibition of the cytopathic effect of HIV-1(RF) in CEM-SS cells. ADAM 28 inhibited HIV-1 reverse transcriptase with an IC50 of 0.3 mu M. Mutations that conferred greater than 10-fold resistance to ADAM 28 clustered at residues Val 106, Val 179, Tyr 181, and Tyr 188. Results derived from this series indicate that ADAMs containing chlorines in the aromatic rings might bind to HIV-1 reverse transcriptase in a slightly different mode when compared with those analogues incorporating bromine in the aromatic rings.