Methyl 3-fluoro-5-[1-(3-fluoro-4-methoxy-5-methoxycarbonyl-phenyl)-6-methoxy-6-oxo-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-fluoro-5-[1-(3-fluoro-4-methoxy-5-methoxycarbonyl-phenyl)-6-methoxy-6-oxo-hex-1-enyl]-2-methoxy-benzoate
• 英文别名: methyl 3-fluoro-5-[1-(3-fluoro-4-methoxy-5-methoxycarbonylphenyl)-6-methoxy-6-oxohex-1-enyl]-2-methoxybenzoate
• 化学式: C₂₅H₂₆F₂O₈
• 分子量: 492.473
• InChiKey: FWLIBLPXBNVZCW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  35
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  97.4
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  3-氟-2-羟基苯甲酸 在 chromium(VI) oxide 、 tetrachlorobis(tetrahydrofuran)titanium(IV) 、 硫酸 、 乙酸酐 、 potassium carbonate 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 丙酮 为溶剂， 反应 46.75h， 生成 Methyl 3-fluoro-5-[1-(3-fluoro-4-methoxy-5-methoxycarbonyl-phenyl)-6-methoxy-6-oxo-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

• The Biological Effects of Structural Variation at the Meta Position of the Aromatic Rings and at the End of the Alkenyl Chain in the Alkenyldiarylmethane Series of Non-Nucleoside Reverse Transcriptase Inhibitors
  作者：Guozhang Xu、Mark Micklatcher、Maximilian A. Silvestri、Tracy L. Hartman、Jennifer Burrier、Mark C. Osterling、Heather Wargo、Jim A. Turpin、Robert W. Buckheit,、Mark Cushman

  DOI：10.1021/jm010212m

  日期：2001.11.1

  In an effort to elucidate a set of structure-activity relationships in the alkenyldiarylmethane (ADAM) series of non-nucleoside reverse transcriptase inhibitors, a number of modifications were made at two locations: (1) the meta positions of the two aromatic rings and (2) the end of the alkenyl chain. Forty-two new ADAMs were synthesized and evaluated for inhibition of the cytopathic effect of HIV-1(RF)

  为了阐明在烯基二芳基甲烷（ADAM）系列非核苷类逆转录酶抑制剂中的一系列结构活性关系，在两个位置进行了许多修饰：（1）两个芳环的间位和（ 2）烯基链的末端。合成了42种新的ADAM，并评估了它们在CEM-SS细胞培养中对HIV-1（RF）的细胞病变作用的抑制作用以及对HIV-1逆转录酶的抑制作用。发现芳族取代基的大小会影响抗HIV活性，Cl，CH（3）和Br取代基具有最佳活性，而较小（H和F）或较大（I和CF（3）则具有减弱的活性。 ））取代基。还发现烯基链末端的取代基会影响抗病毒活性，具有与甲基或乙基酯基团相关的最大活性，并且由于被高级酯，酰胺，硫化物，亚砜，砜，砜，酯，缩醛，酮，氨基甲酸酯，脲和硫脲取代而导致的活性降低。十二个新的ADAM显示出亚微摩尔EC（50）值，可抑制CEM-SS细胞中HIV-1（RF）的细胞病变作用。将选定的ADAM 19和21与先前发布的ADAM 15和17的