6-[(3,5-二甲基苯基)甲基]-1-(乙氧基甲基)-5-乙基嘧啶-2,4-二酮 | 136160-30-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 6-[(3,5-二甲基苯基)甲基]-1-(乙氧基甲基)-5-乙基嘧啶-2,4-二酮
• 英文名称: 5-ethyl-1-ethoxymethyl-6-(3,5-dimethylbenzyl)uracil
• 英文别名: 1-Ethoxymethyl-5-ethyl-6-(3,5-dimethylbenzyl)uracil；6-[(3,5-dimethylphenyl)methyl]-1-(ethoxymethyl)-5-ethylpyrimidine-2,4-dione
• CAS: 136160-30-0
• 化学式: C₁₈H₂₄N₂O₃
• 分子量: 316.4
• InChiKey: LNEPZLRCYLNOIU-UHFFFAOYSA-N

物化性质

• 密度：
  1.111±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  6-(3,5-dimethylbenzyl)-5-ethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione 在 硫酸氢铵 、 三氟甲磺酸三甲基硅酯 作用下， 以 乙腈 为溶剂， 反应 5.0h， 生成 6-[(3,5-二甲基苯基)甲基]-1-(乙氧基甲基)-5-乙基嘧啶-2,4-二酮
  参考文献：
  名称：

  1-[（2-羟基乙氧基）甲基] -6-（苯硫基）胸腺嘧啶的新型6-苄基尿嘧啶类似物的合成及有效的抗HIV-1活性。

  摘要：

  由相应的芳基乙腈和2-溴酸酯合成2-烷基-4-芳基-3-氧代丁酸乙酯。丁酸酯与硫脲的缩合，然后用氯乙酸处理，得到5-烷基-6-（芳基甲基）尿嘧啶。使用三氟甲磺酸三甲基甲硅烷基酯（TMS三氟甲磺酸酯）作为催化剂，将尿嘧啶与乙缩醛缩合，得到无环的5-烷基-6-（芳基甲基）尿嘧啶衍生物。还将6-苄基-5-乙基尿嘧啶与5-O-（叔丁基二苯基甲硅烷基）-2-脱氧-3-O-（苯氧硫羰基+++）-α，β-D-赤型戊呋喃糖苷缩合，然后进行巴顿还原脱保护，得到6-苄基-5-乙基-2′，3′-二脱氧尿苷的异构体。用烷基氯甲基硫化物将尿嘧啶烷基化，得到了HEPT的新硫代类似物。测试了所有新的N1取代的尿嘧啶对HIV-1的活性，

  DOI：

  10.1021/jm9600499

文献信息

• [EN] 4'-ALLENE-SUBSTITUTED NUCLEOSIDE DERIVATIVES<br/>[FR] DÉRIVÉS DE NUCLÉOSIDES 4'-ALLÈNE-SUBSTITUÉS
  申请人：ENANTA PHARM INC

  公开号：WO2010030858A1

  公开（公告）日：2010-03-18

  The present invention discloses compounds of formula (I), or its β-L enantiomer, or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, solvate, prodrug, or combination thereof: Formula (I) which inhibit, preventing or treating abnormal cellular proliferation and/or a viral infection, particularly by HIV, HCV or HBV. Consequently, the compounds of the present invention interfere with the replication cycle of a virus and are also useful as antiviral agents, or interfere with host cellular biochemical process and are also useful as antiproliferative agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from viral infection and/or cell proliferation. The invention also relates to methods of treating a viral infection and/or cell proliferation in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention relates to novel antiviral/anti-proliferative compounds represented herein above, pharmaceutical compositions comprising such compounds, and methods for the treatment or prophylaxis of viral infection in a subject in need of such therapy with said compounds.

  本发明揭示了化合物的结构式（I），或其β-L对映体，或药学上可接受的盐、酯、立体异构体、互变异构体、溶剂合物、前药或其组合物：结构式（I），其能够抑制、预防或治疗异常细胞增殖和/或病毒感染，特别是HIV、HCV或HBV。因此，本发明的化合物干扰病毒的复制周期，并且也可作为抗病毒剂使用，或干扰宿主细胞的生化过程，也可作为抗增殖剂使用。本发明还涉及包含上述化合物的药物组合物，用于治疗患有病毒感染和/或细胞增殖的受试者。该发明还涉及通过给患有病毒感染和/或细胞增殖的受试者使用包含本发明化合物的药物组合物来治疗病毒感染和/或细胞增殖的方法。本发明涉及上述新型抗病毒/抗增殖化合物，包括这些化合物的药物组合物和治疗或预防需要此类化疗的受试者的病毒感染的方法。
• NUCLEOSIDE PHOSPHONATE DERIVATIVES
  申请人：Or Yat Sun

  公开号：US20090274686A1

  公开（公告）日：2009-11-05

  The present invention discloses compounds of formula (I) or (II), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit, preventing or treating abnormal cellular proliferation and/or a viral infection, particularly by HIV, HCV or HBV. Consequently, the compounds of the present invention interfere with the replication cycle of a virus and are also useful as antiviral agents, or interfere with host cellular biochemical process and are also useful as antiproliferative agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from viral infection and/or cell proliferation. The invention also relates to methods of treating a viral infection and/or cell proliferation in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention relates to novel antiviral/anti-proliferative compounds represented herein above, pharmaceutical compositions comprising such compounds, and methods for the treatment or prophylaxis of viral infection in a subject in need of such therapy with said compounds.

  本发明揭示了化合物的公式(I)或(II)，或其药学上可接受的盐、酯或前药：这些化合物抑制、预防或治疗异常细胞增殖和/或病毒感染，特别是HIV、HCV或HBV。因此，本发明的化合物干扰病毒的复制周期，同时也可用作抗病毒剂，或干扰宿主细胞的生化过程，同时也可用作抗增殖剂。本发明还涉及包含上述化合物的药物组合物，用于治疗患有病毒感染和/或细胞增殖的受试者。该发明还涉及通过给予包含本发明化合物的药物组合物来治疗受试者的病毒感染和/或细胞增殖的方法。本发明涉及上述新型抗病毒/抗增殖化合物，包括含有这些化合物的药物组合物，以及用于治疗或预防受试者的病毒感染的方法。
• 2'-CHLOROACETYLENYL SUBSTITUTED NUCLEOSIDE DERIVATIVES
  申请人：Wang Guoqiang

  公开号：US20130078217A1

  公开（公告）日：2013-03-28

  The present invention relates to 2′-chloroacetylenyl-substituted nucleoside derivatives of the general formula (I): As well as pharmaceutical compositions comprising such compounds and methods to treat or prevent an HIV infection, HBV infection, HCV infection or abnormal cellular proliferation, comprising administering said compounds or compositions. In addition, the present invention includes processes for the preparation of such compounds, and the related β-D and β-L-nucleoside derivatives.

  本发明涉及通式（I）的2'-氯乙炔基取代核苷衍生物，以及包含这些化合物的药物组合物和治疗或预防HIV感染、HBV感染、HCV感染或异常细胞增殖的方法，包括给予这些化合物或组合物。此外，本发明还包括用于制备这些化合物的方法，以及相关的β-D和β-L-核苷衍生物。
• [EN] NUCLEOSIDE AND NUCLEOTIDE DERIVATIVES<br/>[FR] DÉRIVÉS DE NUCLÉOSIDES ET DE NUCLÉOTIDES
  申请人：ENANTA PHARM INC

  公开号：WO2016033164A1

  公开（公告）日：2016-03-03

  The present invention discloses compounds of formula (I), or a pharmaceutically acceptable salt thereof: (I) which inhibit, preventing or treating abnormal cellular proliferation and/or a viral infection, particularly by HIV, HCV or HBV. Consequently, the compounds of the present invention interfere with the replication cycle of a virus and are also useful as antiviral agents, or interfere with host cellular biochemical process and are also useful as antiproliferative agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from viral infection and/or cell proliferation. The invention also relates to methods of treating a viral infection and/or cell proliferation in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention relates to novel antiviral/anti-proliferative compounds represented herein above, pharmaceutical compositions comprising such compounds, and methods for the treatment or prophylaxis of viral infection in a subject in need of such therapy with said compounds.

  本发明揭示了化合物(I)或其药学上可接受的盐，该化合物可抑制、预防或治疗异常细胞增殖和/或病毒感染，特别是HIV、HCV或HBV感染。因此，本发明的化合物干扰病毒的复制周期，也可用作抗病毒剂，或干扰宿主细胞的生化过程，也可用作抗增殖剂。本发明还涉及包含上述化合物的制药组合物，用于治疗患有病毒感染和/或细胞增殖的受试者。本发明还涉及通过给予包含本发明化合物的制药组合物来治疗受试者的病毒感染和/或细胞增殖的方法。本发明涉及上述新型抗病毒/抗增殖化合物，包括这些化合物的制药组合物，以及使用这些化合物治疗或预防受需要的受试者的病毒感染的方法。
• Synthesis and Antiviral Activity of 6-Benzyl Analogs of 1-[(2-Hydroxyethoxy)methyl]-5-(phenylthio)thymine (HEPT) as Potent and Selective Anti-HIV-1 Agents
  作者：Hiromichi Tanaka、Hideaki Takashima、Masaru Ubasawa、Kouichi Sekiya、Naoko Inouye、Masanori Baba、Shiro Shigeta、Richard T. Walker、Erik De Clercq、Tadashi Miyasaka

  DOI：10.1021/jm00015a008

  日期：1995.7

  5-isopropyl-2-thiouracil derivatives 13 and 14 by the above procedure following oxidative hydrolysis of the thione. Preparation of the target 5-alkyl-1-(alkoxymethyl)-6-benzyluracil derivatives 27-34 was carried out by acetylation of 9-14 followed by Pd-catalyzed hydrogenolysis. The 1-butyl- (37 and 39) and 1-(2-methoxyl)- (38 and 40) 5-alkyl-6-benzyluracils were synthesized by 1-alkylation of the 3-phenacyl

  合成了1-[（（2-羟基乙氧基）甲基] -6-（苯硫基）胸腺嘧啶（1; HEPT）的几种6-苄基类似物，并评估了它们的抗HIV-1活性。LDA（二异丙基氨基锂）锂化5-乙基尿嘧啶衍生物7和8，随后与芳基醛反应，得到6-（芳基羟甲基）-5-乙基尿嘧啶衍生物9-12。在硫酮氧化水解之后，通过上述程序由5-异丙基-2-硫尿嘧啶衍生物13和14制备6-（芳基羟甲基）-5-异丙基尿嘧啶衍生物15-18。通过9-14的乙酰化，然后Pd催化的氢解，进行目标5-烷基-1-（烷氧基甲基）-6-苄基尿嘧啶衍生物27-34的制备。1-丁基-（37和39）和1-（2-甲氧基）-（38和40）5-烷基-6-苄基尿嘧啶是通过将3-苯甲酰基衍生物35和36与卤代烷进行1-烷基化反应合成的通过去保护3-苯甲酰基。在这项研究中合成的化合物在亚微摩尔至纳摩尔浓度范围内抑制MT-4细胞中的HIV-1复制。从这一系列化合物中，选