6,6-Bis-(3-chloro-5-hydroxymethyl-4-methoxy-phenyl)-hex-5-en-1-ol

• 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: 6,6-Bis-(3-chloro-5-hydroxymethyl-4-methoxy-phenyl)-hex-5-en-1-ol
• 英文别名: 6,6-Bis[3-chloro-5-(hydroxymethyl)-4-methoxyphenyl]hex-5-en-1-ol
• 化学式: C₂₂H₂₆Cl₂O₅
• 分子量: 441.351
• InChiKey: PXZHTCYJOQKMEH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  79.2
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  碘甲烷 、 6,6-Bis-(3-chloro-5-hydroxymethyl-4-methoxy-phenyl)-hex-5-en-1-ol 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以41%的产率得到1-Chloro-5-{1-[3-chloro-4-methoxy-5-(methoxymethyl)phenyl]-6-methoxyhex-1-enyl}-2-methoxy-3-(methoxymethyl)benzene
  参考文献：
  名称：

  Design, Synthesis, Anti-HIV Activities, and Metabolic Stabilities of Alkenyldiarylmethane (ADAM) Non-nucleoside Reverse Transcriptase Inhibitors

  摘要：

  The alkenyldiarylmethane (ADAM) HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) are effective anti-HIV agents in cell culture. However, the potential clinical utility of the ADAMs is expected to be limited by the presence of methyl ester moieties that are likely to be metabolized by nonspecific esterases in blood plasma to biologically inactive carboxylic acid derivatives. The present investigation was therefore undertaken to investigate the anti-HIV activities of the ADAMs versus HIV-1(IIIB) and HIV-2(ROD) in MT-4 cells and the stabilities of the biologically active ADAMs in rat plasma. The ADAMs displayed a wide range of metabolic stabilities in rat plasma, with half-lives ranging from 0.9 to 76.6 min. A wide assortment of structural modifications was tolerated, with 18 of the 32 compounds tested displaying EC50 values between 0.3 and 3.7 muM versus HIV-1(IIIB) in MT-4 cells, 3 compounds in the EC50 = 13.2-35.4 muM range, and the remaining compounds inactive. Consistent with the mechanism of action of the ADAMs as NNRTIs, they were inactive or displayed comparatively low activity versus HIV-2ROD. The replacement of the two aromatic methyl ester substituents in one of the most active ADAMs (EC50 = 0.6 muM) with two methyl thioester groups resulted in an increase in plasma half-life from 5.8 to 55.3 min, while maintaining the antiviral potency at the EC50 = 1.8 muM level. At the same time, the bis(thioester) modification was less cytotoxic to uninfected MT-4 cells, with a CC50 of >224 muM versus 160 muM for the parent compound.

  DOI：

  10.1021/jm049916x
• 作为产物：
  描述：

  methyl-3',3-dichloro-4',4-dimethoxy-5',5-bis(methoxycarbonyl)-6,6-diphenylhexenoate 在 二异丁基氢化铝 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以74%的产率得到6,6-Bis-(3-chloro-5-hydroxymethyl-4-methoxy-phenyl)-hex-5-en-1-ol
  参考文献：
  名称：

  Design, Synthesis, Anti-HIV Activities, and Metabolic Stabilities of Alkenyldiarylmethane (ADAM) Non-nucleoside Reverse Transcriptase Inhibitors

  摘要：

  The alkenyldiarylmethane (ADAM) HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) are effective anti-HIV agents in cell culture. However, the potential clinical utility of the ADAMs is expected to be limited by the presence of methyl ester moieties that are likely to be metabolized by nonspecific esterases in blood plasma to biologically inactive carboxylic acid derivatives. The present investigation was therefore undertaken to investigate the anti-HIV activities of the ADAMs versus HIV-1(IIIB) and HIV-2(ROD) in MT-4 cells and the stabilities of the biologically active ADAMs in rat plasma. The ADAMs displayed a wide range of metabolic stabilities in rat plasma, with half-lives ranging from 0.9 to 76.6 min. A wide assortment of structural modifications was tolerated, with 18 of the 32 compounds tested displaying EC50 values between 0.3 and 3.7 muM versus HIV-1(IIIB) in MT-4 cells, 3 compounds in the EC50 = 13.2-35.4 muM range, and the remaining compounds inactive. Consistent with the mechanism of action of the ADAMs as NNRTIs, they were inactive or displayed comparatively low activity versus HIV-2ROD. The replacement of the two aromatic methyl ester substituents in one of the most active ADAMs (EC50 = 0.6 muM) with two methyl thioester groups resulted in an increase in plasma half-life from 5.8 to 55.3 min, while maintaining the antiviral potency at the EC50 = 1.8 muM level. At the same time, the bis(thioester) modification was less cytotoxic to uninfected MT-4 cells, with a CC50 of >224 muM versus 160 muM for the parent compound.

  DOI：

  10.1021/jm049916x