Ethyl 2-methyl-4-naphthalen-1-yl-3-oxobutanoate | 189057-84-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: Ethyl 2-methyl-4-naphthalen-1-yl-3-oxobutanoate
• CAS: 189057-84-9
• 化学式: C₁₇H₁₈O₃
• 分子量: 270.328
• InChiKey: USLJPVOPYNZYBY-UHFFFAOYSA-N

物化性质

• 沸点：
  395.4±17.0 °C(Predicted)
• 密度：
  1.126±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Ethyl 2-methyl-4-naphthalen-1-yl-3-oxobutanoate 在 sodium ethanolate 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (5-Methyl-4-naphthalen-1-ylmethyl-6-oxo-1,6-dihydro-pyrimidin-2-ylsulfanyl)-acetic acid ethyl ester
  参考文献：
  名称：

  5-Alkyl-2-[(aryl and alkyloxylcarbonylmethyl)thio]-6-(1-naphthylmethyl) pyrimidin-4(3H)-ones as an unique HIV reverse transcriptase inhibitors of S-DABO series

  摘要：

  The introduction of a beta-carbonyl group to the C-2 side chain of S-DABO led to the finding of a series of novel potent anti-HIV agent. Some derivatives proved to be highly effective in inhibiting HIV-1 replication at nanomolar concentrations. Furthermore, the novel S-DABOs differ from the classical NNRTIs in that some compounds are active against both HIV-1 and HIV-2. They might interfere with another target or at least act on RT in a different way as compared to typical NNRTIs. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.04.008
• 作为产物：
  描述：

  1-萘乙酸 、 3-乙氧基-2-甲基-3-氧代丙酸钾 在 N,N'-羰基二咪唑 、 三乙胺 、 magnesium chloride 作用下， 以 乙腈 为溶剂， 反应 2.5h， 生成 Ethyl 2-methyl-4-naphthalen-1-yl-3-oxobutanoate
  参考文献：
  名称：

  新型6-取代的5-取代的5-烷基-2-（芳基羰基甲硫基）嘧啶-4（3H）-酮的合成和生物学评估作为有效的非核苷HIV-1逆转录酶抑制剂。

  摘要：

  已经合成了一系列新的2-芳基羰基甲硫基-6-芳基甲基嘧啶-4（3H）-酮，并评估了其在MT-4细胞中的体外抗HIV活性。这些新化合物中的大多数显示出对野生型HIV-1的中等至有效活性，其EC（50）范围为8.97 microM至0.010 microM。其中，6-（3,5-二甲基苄基）类似物5p被确定为最有前途的化合物（EC（50）= 0.010 microM，SI> 31,800），具有与HIV-1双重突变体RT菌株K103N +的中等活性有关。 Y181C。这些新的同类物的构效关系得到了进一步的讨论。

  DOI：

  10.1016/j.bmc.2008.01.039

文献信息

• Dihydro(alkylthio)(naphthylmethyl)oxopyrimidines:  Novel Non-Nucleoside Reverse Transcriptase Inhibitors of the <i>S</i>-DABO Series
  作者：Antonello Mai、Marino Artico、Gianluca Sbardella、Silvana Quartarone、Silvio Massa、Anna G. Loi、Antonella De Montis、Franca Scintu、Monica Putzolu、Paolo La Colla

  DOI：10.1021/jm960802y

  日期：1997.5.1

  (S-DABOs). Chemical modifications at N-3, C-4, and C-6 of the pyrimidine ring were attempted with the aim of improving antiretroviral activity. In particular, replacement of the benzyl group with the 1-naphthylmethyl moiety enhanced the activity of S-DABOs, whereas N-3 alkylation and C=O transformation into C=S at position 4 of the pyrimidine ring led to compounds devoid of anti-HIV-1 activity. Lower

  已经合成了与2-（环己基硫基）-3,4-二氢-5-甲基-6-（3-甲基苄基）-4-氧嘧啶（3c，MC 639）相关的新型化合物，并已作为人免疫缺陷病毒类型的抑制剂进行了测试-1（HIV-1）。硫脲与芳基甲基乙酰乙酸乙酯反应，得到5-烷基-6-（芳基甲基）-3,4-二氢-2-巯基-4-氧嘧啶，然后在硫原子上烷基化，得到所需的2-烷硫基或2-环烷硫基衍生物（S-DABO）。为了改善抗逆转录病毒活性，尝试了在嘧啶环的N-3，C-4和C-6处进行化学修饰。特别是，用1-萘甲基甲基部分取代苄基可增强S-DABO的活性，而在嘧啶环的4位上N-3烷基化和C = O转化为C = S则导致化合物缺乏抗HIV-1活性。当1-萘甲基被异构体2-萘甲基取代时，通常观察到较低的活性。最具活性的化合物在低微摩尔范围内显示活性，其EC50值可与奈韦拉平相当。
• Synthesis and Biological Evaluation of a Series of 2-((1-substituted-1<i>H</i>-1,2,3-triazol-4-yl)methylthio)-6-(naphthalen-1-ylmethyl)pyrimidin-4(3<i>H</i>)-one As Potential HIV-1 Inhibitors
  作者：Zengjun Fang、Dongwei Kang、Lingzi Zhang、Boshi Huang、Huiqing Liu、Christophe Pannecouque、Erik De Clercq、Peng Zhan、Xinyong Liu

  DOI：10.1111/cbdd.12524

  日期：2015.10

  synthesized using the simple and efficient CuAAC reaction, and biologically evaluated as inhibitors of HIV‐1. Among them, the most active HIV‐1 inhibitor was compound 4‐((4‐((4‐(2,6‐dichlorobenzyl)‐5‐methyl‐6‐oxo‐1,6‐dihydropyrimidin‐2‐ylthio)methyl)‐1H‐1,2,3‐triazol‐1‐yl)methyl)benzenesulfonamide (B5b7), which exhibited similar HIV‐1 inhibitory potency (EC50 = 3.22 μm) compared with 3TC (EC50 = 2.24 μm)

  使用简单有效的CuAAC反应合成了一系列在C-2侧链上具有取代的1,2,3-三唑部分的新型S-DABO衍生物，并对其进行了生物学评估，将其作为HIV-1的抑制剂。其中最活跃的HIV-1抑制剂是化合物4-（（4-（（4-（2,6-二氯苄基）-5-甲基-6-氧代-1,6-二氢嘧啶-2-基硫基）甲基） -1H-1,2,3-三唑-1-基）甲基）苯磺酰胺（B5b7） ，其表现出类似的HIV-1抑制效力（EC 50  = 3.22  μ米）与3TC（EC相比50  = 2.24  μ米）。这些化合物均未显示出对HIV-2复制的抑制作用。简要讨论了这些新衍生物的初步构效关系（SAR）。
• Nonnucleoside HIV-1 Reverse Transcriptase Inhibitors: Part I. Synthesis and Structure-Activity Relationship of 1-Alkoxymethyl-5-alkyl-6-naphthylmethyl Uracils as HEPT Analogues
  作者：Ge Meng、Fen-Er Chen、Erik De Clercq、Jan Balzarini、Christophe Pannecouque

  DOI：10.1248/cpb.51.779

  日期：——

  1-Alkoxymethyl-5-alkyl-6-naphthylmethyl uracils, which are novel 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) analogues, were synthesized for evaluation as selective and potent nonnucleoside human immunodeficiency virus (HIV)-1 reverse transcriptase inhibitors. The anti-HIV-1 activity of these compounds was assayed in vitro using HIV-1 infected MT-4 and CEM bioassays. The EC50, CC50 and SI were recorded and calculated. The appropriate position, especially in the 1-position of the naphthyl ring, led to dramatic increases in potency, in both MT-4 and CEM cellular assays. The most important compounds in this series, 1-ethoxymethyl-5-isopropyl-6-(1-naphthylmethyl)thymine 8l (IC50=17 nM, CC50=38332 nM, SI=2229) and 1-benzyloxymethyl-5-ethyl-6-(1-naphthylmethyl)thymine 8n (IC50=17 nM, CC50=32560 nM, SI=1889) were significantly more potent than HEPT (EC50=7.0 μM, CD50=740 μM) in the anti-HIV-1 in vitro cellular assay.

  合成了新型 1-[(2-羟乙氧基)甲基]-6-(苯硫基)胸腺嘧啶（HEPT）类似物--1-烷氧基甲基-5-烷基-6-萘甲基尿嘧啶，并将其评估为选择性和强效的非核苷类人类免疫缺陷病毒（HIV）-1 逆转录酶抑制剂。这些化合物的抗 HIV-1 活性是通过体外 HIV-1 感染 MT-4 和 CEM 生物测定法进行的。记录并计算了 EC50、CC50 和 SI。在 MT-4 和 CEM 细胞实验中，适当的位置，尤其是萘环的 1 位，可使药效显著提高。该系列中最重要的化合物是 1-乙氧基甲基-5-异丙基-6-（1-萘甲基）胸腺嘧啶 8l（IC50=17 nM，CC50=38332 nM、SI=2229）和 1-苄氧基甲基-5-乙基-6-(1-萘甲基)胸腺嘧啶 8n（IC50=17 nM，CC50=32560 nM，SI=1889）明显比 HEPT（EC50=7.0 μM，CD50=740 μM）明显更有效。
• Discovery of Dihydro-Alkyloxy-Benzyl-Oxopyrimidines as Promising Anti-Influenza Virus Agents
  作者：Mingyan Yu、Ailin Liu、Guanhua Du、Lieve Naesens、Evelien Vanderlinden、Erik De Clercq、Xinyong Liu

  DOI：10.1111/j.1747-0285.2011.01180.x

  日期：2011.10

  and A/H3N2 subtype, respectively) and influenza B viruses (EC50: 33 μm). The antiviral mechanism of action of these dihydro‐alkyloxy‐benzyl‐oxopyrimidine derivatives must be quite different from that of the currently approved anti‐influenza virus drugs that target the viral M2 or neuraminidase proteins. The dihydro‐alkyloxy‐benzyl‐oxopyrimidine derivatives represent a new avenue for further optimization

  合成了一系列新颖的二氢-烷氧基-苄基-氧嘧啶衍生物，并评估了它们在Madin-Darby犬肾细胞中对流感病毒的活性。四个二氢-烷氧基苄基oxopyrimidine衍生物（4A1，4A2，4A3，和4D1）显示对流感病毒有效的活性。其中，化合物4A3与抗流感A宽的活性最有前途的引线（抗病毒EC 50倍的图9和18的值 μ米分别用于A / H1N1和A / H3N2亚型）和B型流感病毒（EC 50：33  μ米）。这些二氢-烷氧基-苄基-氧嘧啶衍生物的抗病毒作用机制必须与目前批准的针对病毒M2或神经氨酸酶蛋白的抗流感病毒药物完全不同。二氢烷氧基苄基氧嘧啶衍生物代表了进一步优化和开发新型抗流感病毒剂的新途径。
• Synthesis and anti-HIV-1 activity of S-dihydro(alkyloxy)benzyloxypyrimidine derivatives
  作者：Zhi-Kun Rao、Jing Long、Cong Li、Sui-Shuan Zhang、Mei He、Ling-Cheng Ou、Yong-Tang Zheng、Yan-Ping He

  DOI：10.1007/s00706-007-0834-8

  日期：2008.8

  Several 2-heteroaryl-, 2-heteroarylcarbonylmethyl-, 2-arylcarbonylmethyl, and 2-arylethyl derivatives of S-dihydro(alkyloxy)benzyloxypyrimidines have been synthesized and the anti-HIV activities of these compounds were tested in C8166 cell and against RT enzyme. It was found that some of these compounds showed good activity against HIV-1 (EC50 = 0.014-0.8 mu M) with low toxicity (CC50 value of 222-564 mu M) and high selectivity (SI value of 278-37743). The structure-activity relationships (SAR) of these compounds have also been discussed.