di(4-methoxy-3-methoxycarbonyl-5-methylphenyl) ketone | 381230-79-1

• 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: di(4-methoxy-3-methoxycarbonyl-5-methylphenyl) ketone
• 英文别名: Di[4-methoxy-3-(methoxycarbonyl)-5-methylphenyl]methanone；methyl 2-methoxy-5-(4-methoxy-3-methoxycarbonyl-5-methylbenzoyl)-3-methylbenzoate
• CAS: 381230-79-1
• 化学式: C₂₁H₂₂O₇
• 分子量: 386.401
• InChiKey: OSCZSURBEAFJBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  8
• 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：

  di(4-methoxy-3-methoxycarbonyl-5-methylphenyl) ketone 在 palladium on activated charcoal 四氢呋喃 、 氢气 、 四氯化钛 、 锌 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 15.0h， 生成 4-[Bis-(4-methoxy-3-methoxycarbonyl-5-methyl-phenyl)-methyl]-piperidine-1-carboxylic acid ethyl ester
  参考文献：
  名称：

  Synthesis of substituted diarylmethylenepiperidines (DAMPs), a novel class of anti-HIV agents

  摘要：

  Substituted diarymethylenepiperidines (DAMPs) were synthesized as conformationally restricted analogues of the alkenyldiarylmethane (ADAM) class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Although, like the ADAMs, the DAMPs were found to inhibit the cytopathic effect of HIV-1(RF) in CEM-SS cells, they were completely inactive as inhibitors of HIV-1 reverse transcriptase. The DAMPs were assessed for inhibition of HIV attachment and fusion. DAMP 14 was active in both assays with IC50 values of 26.5 muM (TI 3.8) and 12.1 muM (TI: > 8), respectively. DAMP 15 also inhibited HIV fusion with all IC50 12.8 muM (TI: > 6), but not virus attachment. However, attempts to verity inhibition of virus attachment and fusion as antiviral targets using time-of-addition experiments failed to confirm these observations, and instead identified all antiviral target Occurring after completion of reverse transcription. DAMPs 11, 12, 14, and 15 were found to inhibit virus replication if added 8 h post virus exposure, and DAMP 11 was equipotent at inhibition of virus replication if added 24 It after Virus addition. DAMPs 11, 12, and 15 did not inhibit virus replication in TNF-alpha induced latently infected U1 cells, a model for post-integrative antiviral targets. When tested in both 3' end-processing and strand-transfer assays in the presence of HIV-1 integrase. none of the DAMPs showed any inhibitory activity, indicating that HIV-1 integrase is not involved in the mechanism of the antiviral action. Thus, the DAMPs are novel conformationally restricted analogues of the previously published ADAM series with all unidentified antiviral target bounded by the completion of reverse transcription and virus integration. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00095-0
• 作为产物：
  描述：

  5-[(3-羧基-4-羟基-5-甲基苯基)甲基]-2-羟基-3-甲基苯甲酸 在 chromium(VI) oxide 、 potassium carbonate 、 溶剂黄146 作用下， 以 丙酮 为溶剂， 反应 38.0h， 生成 di(4-methoxy-3-methoxycarbonyl-5-methylphenyl) ketone
  参考文献：
  名称：

  在非核苷类逆转录酶抑制剂的烯基二芳基甲烷系列中，芳环的间位和烯基链末端的结构变异的生物学效应。

  摘要：

  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

  DOI：

  10.1021/jm010212m

文献信息

• Alkenyldiarylmethanes, Fused Analogs And Syntheses Thereof
  申请人：Cushman Mark S.

  公开号：US20080300288A1

  公开（公告）日：2008-12-04

  Non-nucleoside inhibitors of HIV-1 reverse transcriptase are described. Such inhibitors may be used as part of a combination therapy to treat HIV infection. Compounds described herein exhibit antiviral potency. In addition, compounds described herein exhibit metabolic stability. Also described herein are processes for preparing Non-nucleoside inhibitors of HIV-1 reverse transcriptase.

  HIV-1反转录酶的非核苷类抑制剂被描述。这些抑制剂可以作为治疗HIV感染的联合疗法的一部分使用。本文描述的化合物具有抗病毒效力。此外，本文描述的化合物具有代谢稳定性。本文还描述了制备HIV-1反转录酶非核苷类抑制剂的过程。
• [EN] ALKENYLDIARYLMETHANES, FUSED ANALOGS AND SYNTHESES THEREOF<br/>[FR] ALCENYLDIARYLMETHANES, ANALOGUES FONDUS ET SYNTHESE
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO2007005531A2

  公开（公告）日：2007-01-11

  [EN] Non-nucleoside inhibitors of HIV-I reverse transcriptase are described. Such inhibitors may be used as part of a combination therapy to treat HIV infection. Compounds described herein exhibit antiviral potency. In addition, compounds described herein exhibit metabolic stability. Also described herein are processes for preparing Non-nucleoside inhibitors of HIV-I reverse transcriptase.
  [FR] L'invention concerne des inhibiteurs non nucléosidiques de la transcriptase inverse du VIH-I. Ces inhibiteurs peuvent être partiellement impliqués dans une polythérapie visant à traiter l'infection à VIH. Les composés de l'invention possèdent en outre un effet antiviral puissant, et se caractérisent par une stabilité métabolique. Par ailleurs, l'invention concerne des procédés de préparation de ces inhibiteurs non nucléosidiques de la transcriptase inverse du VIH-I.
• Synthesis of substituted diarylmethylenepiperidines (DAMPs), a novel class of anti-HIV agents
  作者：Guozhang Xu、Arunachalam Kannan、Tracy L Hartman、Heather Wargo、Karen Watson、Jim A Turpin、Robert W Buckheit、Allison A Johnson、Yves Pommier、Mark Cushman

  DOI：10.1016/s0968-0896(02)00095-0

  日期：2002.8

  Substituted diarymethylenepiperidines (DAMPs) were synthesized as conformationally restricted analogues of the alkenyldiarylmethane (ADAM) class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Although, like the ADAMs, the DAMPs were found to inhibit the cytopathic effect of HIV-1(RF) in CEM-SS cells, they were completely inactive as inhibitors of HIV-1 reverse transcriptase. The DAMPs were assessed for inhibition of HIV attachment and fusion. DAMP 14 was active in both assays with IC50 values of 26.5 muM (TI 3.8) and 12.1 muM (TI: > 8), respectively. DAMP 15 also inhibited HIV fusion with all IC50 12.8 muM (TI: > 6), but not virus attachment. However, attempts to verity inhibition of virus attachment and fusion as antiviral targets using time-of-addition experiments failed to confirm these observations, and instead identified all antiviral target Occurring after completion of reverse transcription. DAMPs 11, 12, 14, and 15 were found to inhibit virus replication if added 8 h post virus exposure, and DAMP 11 was equipotent at inhibition of virus replication if added 24 It after Virus addition. DAMPs 11, 12, and 15 did not inhibit virus replication in TNF-alpha induced latently infected U1 cells, a model for post-integrative antiviral targets. When tested in both 3' end-processing and strand-transfer assays in the presence of HIV-1 integrase. none of the DAMPs showed any inhibitory activity, indicating that HIV-1 integrase is not involved in the mechanism of the antiviral action. Thus, the DAMPs are novel conformationally restricted analogues of the previously published ADAM series with all unidentified antiviral target bounded by the completion of reverse transcription and virus integration. (C) 2002 Elsevier Science Ltd. All rights reserved.
• 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