Methyl 3-chloro-5-[1-(3-chloro-4-methoxy-5-methoxycarbonyl-phenyl)-6-oxo-hex-1-enyl]-2-methoxy-benzoate | 252934-37-5

• 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: Methyl 3-chloro-5-[1-(3-chloro-4-methoxy-5-methoxycarbonyl-phenyl)-6-oxo-hex-1-enyl]-2-methoxy-benzoate
• 英文别名: methyl 3-chloro-5-[1-(3-chloro-4-methoxy-5-methoxycarbonylphenyl)-6-oxohex-1-enyl]-2-methoxybenzoate
• CAS: 252934-37-5
• 化学式: C₂₄H₂₄Cl₂O₇
• 分子量: 495.356
• InChiKey: AMHXOMTWYGECAQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  2.0
• 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：

  Methyl 3-chloro-5-[1-(3-chloro-4-methoxy-5-methoxycarbonyl-phenyl)-6-oxo-hex-1-enyl]-2-methoxy-benzoate 在 potassium cyanide 、 三乙酰氧基硼氢化钠 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 1,2-二氯乙烷 为溶剂， 反应 29.0h， 生成 N-(5α-cholestan-3β-yl)-6,6-bis(3'-carboxy-5'-chloro-4'-methoxyphenyl)-5-hexenylamine
  参考文献：
  名称：

  Synthesis and anti-HIV activity of cosalane analogues incorporating two dichlorodisalicylmethane pharmacophore fragments

  摘要：

  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.

  DOI：

  10.1016/s0968-0896(01)00152-3
• 作为产物：
  描述：

  3',3''-dichloro-4',4''-dimethoxy-5',5''-bis(methoxycarbonyl)-1,1-diphenyl-1-hexen-6-ol 在 草酰氯 、 二甲基亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 0.33h， 以79%的产率得到Methyl 3-chloro-5-[1-(3-chloro-4-methoxy-5-methoxycarbonyl-phenyl)-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
• 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.
• 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.