2-乙基-4-(萘-1-基)-3-氧代丁酸乙酯 | 194808-41-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 2-乙基-4-(萘-1-基)-3-氧代丁酸乙酯
• 英文名称: 2-Ethyl-4-naphthalen-1-yl-3-oxo-butyric acid ethyl ester
• 英文别名: Ethyl 2-ethyl-4-naphthalen-1-yl-3-oxobutanoate
• CAS: 194808-41-8
• 化学式: C₁₈H₂₀O₃
• 分子量: 284.355
• InChiKey: CLGAEIBZBUYLCO-UHFFFAOYSA-N

物化性质

• 熔点：
  188-191 °C(Solv: ethanol (64-17-5))
• 沸点：
  408.6±20.0 °C(Predicted)
• 密度：
  1.109±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 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：

  2-乙基-4-(萘-1-基)-3-氧代丁酸乙酯 在 sodium 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 (5-Ethyl-6-naphthalen-1-ylmethyl-4-oxo-1,4-dihydro-pyrimidin-2-ylsulfanyl)-acetic acid methyl ester
  参考文献：
  名称：

  HEPT和DABO的抗HIV活性萘类似物。

  摘要：

  将5-乙基-6-（1-萘甲基）尿嘧啶和5-乙基-6-（1-萘甲基）-2-硫尿嘧啶烷基化，分别得到。N-1和S2是乙氧基甲基和甲硫基甲基尿嘧啶衍生物。还用溴乙酸甲酯将5-乙基-6-（1-萘甲基）-2-硫尿嘧啶烷基化。产品显示出对HIV-1的活性，而N-1烷基化衍生物确实具有很高的活性。

  DOI：

  10.3891/acta.chem.scand.51-0426
• 作为产物：
  描述：

  1-萘乙腈 、 2-溴丁酸乙酯 在 锌 、 盐酸 作用下， 以 四氢呋喃 为溶剂， 反应 1.92h， 以60%的产率得到2-乙基-4-(萘-1-基)-3-氧代丁酸乙酯
  参考文献：
  名称：

  Nonnucleoside HIV-1 Reverse Transcriptase Inhibitors: Part I. Synthesis and Structure-Activity Relationship of 1-Alkoxymethyl-5-alkyl-6-naphthylmethyl Uracils as HEPT Analogues

  摘要：

  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。

  DOI：

  10.1248/cpb.51.779

文献信息

• 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 Biological Evaluation of 6-Substituted 5-Alkyl-2-(phenylaminocarbonylmethylthio)pyrimidin-4(3H)-ones as Potent HIV-1 NNRTIs
  作者：Mingyan Yu、Zhenyu Li、Shuai Liu、Erkang Fan、Christophe Pannecouque、Erik De Clercq、Xinyong Liu

  DOI：10.1002/cmdc.201000555

  日期：2011.5.2

  A series of new 5‐alkyl‐2‐phenylaminocarbonylmethylthiopyrimidin‐4(3H)‐ones bearing variously substituted arylmethyl moieties at the C6 position of the pyrimidine ring were synthesized and evaluated for anti‐HIV activity in MT‐4 cells. Most of these new congeners exhibited moderate to good activities against the wild‐type virus, with EC50 values in the range of 1.40–0.19 μM. Among them, 2‐[(4‐cyan

  合成了一系列新的5-烷基-2-苯基氨基羰基甲基硫嘧啶-4（3 H）-在嘧啶环的C6位带有不同取代的芳基甲基的部分，并评估了其在MT-4细胞中的抗HIV活性。大多数这些新的同系物表现出中度到对野生型病毒的创先争优活动，与EC 50个在1.40-0.19μ的范围值中号。其中2-[（（4-氰基苯基氨基）羰基甲硫基] -6-（2-氯-6-氟苄基）-5-乙基嘧啶-4（3 H）-一4 b6是被赋予最高的宽泛度的化合物之一。光谱HIV-1的抑制活性，以EC 50个为0.19±0.005μ值中号对野生型病毒，1.05±0.24μ中号（双重抵抗）的E138K应变，和2.38±0.13μ中号（4.5倍的抗性）压靠在Y181C菌株。此外，使用选定的衍生物进行了针对野生型HIV-1 RT的逆转录酶（RT）抑制试验，证实了这些化合物的主要靶标是HIV-1 RT，并且这些新的S -DABO类似物充当了非核苷RT。抑制
• 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.
• Synthesis and in vitro anti-HIV evaluation of a new series of 6-arylmethyl-substituted S-DABOs as potential non-nucleoside HIV-1 reverse transcriptase inhibitors
  作者：Yue-Ping Wang、Fen-Er Chen、Erik De Clercq、Jan Balzarini、Christophe Pannecouque

  DOI：10.1016/j.ejmech.2008.06.028

  日期：2009.3

  A series of new 5-alkyl-2-benzylsulfanylpyrimidin-4(3H)-ones (5a-y) bearing different substituted arylmethyl moieties at the C-6 position of the pyrimidine core have been synthesized and evaluated for their in vitro activities against HIV-1 and HIV-2 in MT-4 cell cultures. The majority of the title compounds showed moderate to good activities against HIV-1 with an IC50 range from 6.67 mu M to 0.12 mu M. Among them, 6-(3,5-dimethylbenzy]) analogue 5q exhibited the most potent anti-HIV-1 activity (IC50 = 0.12 mu M, SI > 2642), which was about 40-fold more active than the reference compounds 1-[(2-hydroxyethoxy)methyl]-6-(phenylsulfanyl)thymine (HEPT) and 2',3'-dideoxyinosine (DDI). The structure-activity relationships (SARs) of these new congeners were further discussed. (C) 2008 Elsevier Masson SAS. All rights reserved.
• 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
  作者：Yanping He、Fener Chen、Guangfu Sun、Yueping Wang、Erik De Clercq、Jan Balzarini、Christophe Pannecouque

  DOI：10.1016/j.bmcl.2004.04.008

  日期：2004.6

  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.