5-ethyl-6-(3,5-dimethylphenyl)thio-2,4-pyrimidinedione | 171048-61-6

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 5-ethyl-6-(3,5-dimethylphenyl)thio-2,4-pyrimidinedione
• 英文别名: 5-ethyl-6-(3,5-dimethylphenylthio)-2,4-pyrimidinedione；6-(3,5-dimethylphenyl)sulfanyl-5-ethyl-1H-pyrimidine-2,4-dione
• CAS: 171048-61-6
• 化学式: C₁₄H₁₆N₂O₂S
• 分子量: 276.359
• InChiKey: KNGPWBDWLKEHMI-UHFFFAOYSA-N

物化性质

• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  83.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-ethyl-6-(3,5-dimethylphenyl)thio-2,4-pyrimidinedione 在 N-甲基吗啉 、 sodium hydroxide 、 2-氯-4,6-二甲氧基-1,3,5-三嗪 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 31.0h， 生成 2',3'-dideoxy-4-N-[N-13-[6-(3,5-dimethylphenylthio)-5-ethyl-1-(5-oxopentyl)uracil]-13-azadodecyl]cytidine
  参考文献：
  名称：

  Synthesis and Evaluation of “AZT-HEPT”, “AZT-Pyridinone”, and “ddC-HEPT” Conjugates as Inhibitors of HIV Reverse Transcriptase

  摘要：

  To test the concept that HIV reverse transcriptase could be effectively inhibited by "mixed site inhibitors", a series of seven conjugates containing both a nucleoside analogue component(AZT 1, ddC 2) and a nonnucleoside type inhibitor (HEPT analogue 12, pyridinone 27) were synthesized and evaluated for their ability to block HIV replication. The (N-3 and C-5)AZT-HEPT conjugates 15, 22, and 23 displayed 2-5 mu M anti-HIV activity, but they had no effect on the replication of HIV-2 or the HIV-1 strain with the Y181C mutation. The (C-5)AZT-pyridinone conjugates 34-37 were found to be inactive. In marked contrast, the ddC-HEPT molecule 26 displayed the same potency (EC50 = 0.45 mu M) against HTV-1 (wild type and the Y181C nevirapine-resistant strain) and HIV-2 in cell culture. No synergistic effect was-observed for these bis-substrate inhibitors, suggesting that the two individual inhibitor components in these molecules do not bind simultaneously in their respective sites. Interestingly, however, the results indicate that the AZT-HEPT conjugates and the ddC-HEPT derivative 26 inhibit reverse transcriptase (RT) in an opposite manner. One explanation for this difference is that the former compounds interact preferentially with the hydrophobic pocket in RT, whereas 26 (after supposed triphosphorylation) inhibits RT through binding in the catalytic site.

  DOI：

  10.1021/jm991125l
• 作为产物：
  描述：

  2,4,6-三氯-5-乙基嘧啶 在 氢氧化钾 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 5.5h， 生成 5-ethyl-6-(3,5-dimethylphenyl)thio-2,4-pyrimidinedione
  参考文献：
  名称：

  某些 6-(芳硫基)尿嘧啶作为潜在抗病毒剂的合成

  摘要：

  摘要 通过6-氯尿嘧啶或5-乙基-6-氯尿嘧啶与相应的苯硫酚衍生物在吡啶或乙醇氢氧化钾中缩合制备了一系列6-(芳硫基)尿嘧啶。测试合成的化合物的抗病毒活性。一些 5-乙基-6-（芳硫基）尿嘧啶衍生物 10a-g 对乙型肝炎病毒 (HBV) 和 HIV-1 病毒显示出中等活性。

  DOI：

  10.1080/10426500108040231

文献信息

• Synthesis and Anti-HIV Activity of Novel N-1 Side Chain-Modified Analogs of 1-[(2-Hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT)
  作者：Renée Pontikis、Rachid Benhida、Anne-Marie Aubertin、David S. Grierson、Claude Monneret

  DOI：10.1021/jm960765a

  日期：1997.6.1

  1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (1, HEPT) were synthesized and evaluated for their anti-HIV-1 activity. In particular, the influence of substitution of the terminal hydroxy group of the acyclic structure of HEPT and the structural rigidity of this side chain were investigated. Halo (7, 8), azido (9), and amino (10-15) derivatives were synthesized from HEPT via the p-tosylate derivative 6. Acylation

  合成了一系列33种N-1的1-[（（2-羟基乙氧基）甲基] -6-（苯硫基）胸腺嘧啶（1，HEPT）的N-1侧链修饰的类似物，并评估了它们的抗HIV-1活性。特别地，研究了HEPT的无环结构的末端羟基的取代和该侧链的结构刚性的影响。经由对甲苯磺酸酯衍生物6由HEPT合成卤代（7、8），叠氮基（9）和氨基（10-15）衍生物。伯胺15的酰化提供了酰胺基类似物16-20。通过在三正丁基膦的存在下使HEPT或6-（2-吡啶硫基）类似物23与二芳基二硫化物反应来制备二芳基衍生物26-29。化合物39-41，其中N-1侧链通过掺入E-构型的双键而硬化，
• Antiviral substituted pyrimidinedione homocarbocyclic nucleoside
  申请人：Samjin Pharmaceutical Co., Ltd

  公开号：US05922727A1

  公开（公告）日：1999-07-13

  The present invention relates to novel compound of general formula (I) and pharmaceutically acceptable salts thereof, and process for the preparation of such derivatives and to pharmaceutical compositions containing the same as active ingredients. ##STR1## wherein R.sub.1, R.sub.2, and R.sub.3 represents independently hydrogen atom, halogen atom, C.sub.1 -C.sub.10 alkyl, C.sub.1 -C.sub.10 thioalkyl, C.sub.3 -C.sub.8 optionally substituted cyclicalkyl, unsaturated alkyl, substituted alkyl hydroxyl or aryl hydroxyl, C.sub.1 -C.sub.10 alkylamine, nitro, C.sub.1 -C.sub.4 lower ester, C.sub.1 -C.sub.4 lower alkoxy, C.sub.1 -C.sub.4 lower thioalkoxy; Z represents oxygen atom, sulfur atom, carbon atom and carbonyl group; X represents oxygen atom, sulfur atom; n represents an integer of 1-3; and (sub)cycloalk(en)yl represents ##STR2## in which R.sub.4 and R.sub.5 represents independently hydrogen atom, hydroxymethyl, protected hydroxymethyl, benzyl, substituted carbonyl, substituted alkylsulfonyl or arylsulfonyl, substituted silyl or the like.

  本发明涉及一般式(I)的新化合物及其药学上可接受的盐，以及制备这类衍生物的方法和含有其作为活性成分的药物组合物。其中，R.sub.1、R.sub.2和R.sub.3分别表示氢原子、卤原子、C.sub.1-C.sub.10烷基、C.sub.1-C.sub.10硫代烷基、C.sub.3-C.sub.8可选择地取代的环烷基、不饱和烷基、取代烷基羟基或芳基羟基、C.sub.1-C.sub.10烷基胺、硝基、C.sub.1-C.sub.4较低酯、C.sub.1-C.sub.4较低烷氧基、C.sub.1-C.sub.4较低硫代烷氧基；Z表示氧原子、硫原子、碳原子和羰基；X表示氧原子、硫原子；n表示1-3的整数；(亚)环烷基表示##STR2## 其中R.sub.4和R.sub.5分别独立表示氢原子、羟甲基、保护羟甲基、苄基、取代的羰基、取代的烷基磺酰基或芳基磺酰基、取代的硅烷基或类似物。
• [EN] NOVEL ANTIVIRAL 2,4-PYRIMIDINEDIONE DERIVATIVES AND PROCESSES FOR THE PREPARATION THEREOF<br/>[FR] NOUVEAUX DERIVES ANTIVIRAUX DE 2,4-PYRIMIDINEDIONE ET LEURS PROCEDES DE PREPARATION
  申请人：KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY

  公开号：WO1995018109A1

  公开（公告）日：1995-07-06

  (EN) Novel 2,4-pyrimidinedione compounds, and pharmaceutically acceptable salts thereof which possess good antiviral activities, and specifically represented by formula (I) wherein: R1 represents an unsubstituted or substituted alkyl group represented by CH2CH=CR5R6 or an unsubstituted or substituted propargyl group represented by CH2C$m(Z)CR7 wherein R5, R6 and R7 are each independently a hydrogen atom; a methyl group optionally substituted with a halogen atom, or a C1-10 carbonyloxy, hydroxy, azido, cyano, optionally substituted amino, optionally substituted phosphonyl, optionally substituted phenyl, C3-10 heteroaryl, C1-3 alkoxy or benzyloxy radical; a C2-10 alkyl or alkenyl group; a cyclopropyl group; an optionally substituted phenyl group; a C3-10 heteroaryl group; a C1-10 ester group; or an optionally substituted C1-10 alkylamide group; R2 represents a halogen atom, an optionally substituted C1-5 alkyl, C3-6 cycloalkyl, C2-8 alkenyl, C2-8 alkynyl group or a benzyl group; R3 and R4 represent independently a hydrogen or halogen atom, or a hydroxy, C1-3 alkyl, fluoromethyl, C1-3 alkoxy, amino, C2-6 alkylester or C2-7 alkylamide group; A represents an oxygen or sulfur atom; Z represents an oxygen or sulfur atom; a carbonyl group; an amino group; or a methylene group optionally substituted with at least one selected from the group consisting of a halogen atom, and a cyano, hydroxy, azido, amino, C1-3 alkylamide, C1-4 ester, and nitro groups.(FR) Nouveaux composés de 2,4-pyrimidinedione, et leurs sels pharmaceutiquement acceptables présentant de bonnes activités antivirales, répondant à la formule (I), dans laquelle R1 représente un groupe allyle éventuellement substitué représenté par CH2CH=CR5R6, ou un groupe propargyle éventuellement substitué représenté par CH2C$m(Z)CR7, où R5, R6 et R7, indépendamment les uns des autres, représentent un atome d'hydrogène; un groupe méthyle éventuellement substitué par un atome d'halogène, ou un radical carbonyloxy C1-10, hydroxy, azido, cyano, amino éventuellement substitué, phosphonyle éventuellement substitué, phényle éventuellement substitué, hétéroaryle C3-10, alcoxy C1-3 ou benzyloxy; un groupe alcényle ou alkyle C2-10; un groupe cyclopropyle; un groupe phényle éventuellement substitué; un groupe hétéroaryle C3-10; un groupe ester C1-10; ou un groupe alkylamide C1-10 éventuellement substitué; R2 représente un atome d'halogène, un groupe alkyle C1-5, cycloalkyle C3-6, alcényle C2-8 ou alcynyle C2-8 éventuellement substitué, ou un groupe benzyle; R3 et R4, indépendamment l'un de l'autre, représentent un atome d'hydrogène ou d'halogène, ou un groupe hydroxy, alkyle C1-3, fluorométhyle, alcoxy C1-3, amino, alkylester C2-6 ou alkylamide C2-7; A représente un atome d'oxygène ou de soufre; Z représente un atome d'oxygène ou de soufre; un groupe carbonyle; un groupe amino; ou un groupe méthylène éventuellement substitué par au moins un élément sélectionné dans le groupe constitué d'un atome d'halogène et de groupes cyano, hydroxy, azido, amino, alkylamide C1-3, ester C1-4 et nitro.

  （中文）一种新的2,4-嘧啶二酮化合物及其药物可接受的盐，具有良好的抗病毒活性，特别是由式（I）所表示的化合物，其中：R1表示未取代或取代的烷基，由CH2CH = CR5R6表示，或未取代或取代的丙炔基，由CH2C $ m（Z）CR7表示，其中R5，R6和R7各自独立地表示氢原子; 一种甲基基团，可选地取代卤素原子，或C1-10羰氧基，羟基，偶氮基，氰基，可选地取代的氨基，可选地取代的磷酸基，可选地取代的苯基，C3-10杂环基，C1-3烷氧基或苄氧基基团; C2-10烷基或烯基基团; 环丙基基团; 可选地取代的苯基基团; C3-10杂环基团; C1-10酯基团; 或可选地取代的C1-10烷基酰胺基团; R2表示卤素原子，可选地取代的C1-5烷基，C3-6环烷基，C2-8烯基，C2-8炔基或苄基; R3和R4独立地表示氢或卤素原子，或羟基，C1-3烷基，氟甲基，C1-3烷氧基，氨基，C2-6烷基酯基或C2-7烷基酰胺基; A表示氧或硫原子; Z表示氧或硫原子; 羰基基团; 氨基; 或至少取代一个选自卤素原子和氰基，羟基，偶氮基，氨基，C1-3烷基酰胺基，C1-4酯基和硝基的甲基基团的亚甲基基团。
• [EN] ANTIVIRAL PYRIMIDINEDIONE DERIVATIVES AND PROCESS FOR THE PREPARATION THEREOF<br/>[FR] DERIVES DE PYRIMIDINEDIONE, A PROPRIETE ANTIVIRALE, ET PROCEDE DE PREPARATION ASSOCIE
  申请人：SAMJIN PHARM CO LTD

  公开号：WO2000061564A1

  公开（公告）日：2000-10-19

  The present invention relates to pyrimidinedione derivatives of following formula (I) which are useful as antiviral agents, especially as agents for treatment of AIDS, pharmaceutically acceptable salts thereof, process for the preparation thereof and pharmaceutical compositions containing the same, wherein R represents cyclopropyl; cyclobutyl; cyclohexyl; unsubstituted or mono-, di- or tri-substituted phenyl with a group selected from hydroxy, C1-C4 alkyl, C1-C4 alkoxy, halogen, trifluoromethyl, cyano and amino; 1- or 2-naphthyl; 9-anthracenyl; 2-anthraquinonyl; unsubstituted or substituted pyridyl with a group selected from C1-C4 alkyl, C1-C4 alkoxy, cyano and halogen; 2-, 3- or 4-quinolinyl; oxiranyl; 1-benzotriazolyl; 2-benzoxazolyl; furanyl substituted with C1-C4 alkoxycarbonyl; C1-C4 alkylcarbonyl; or benzoyl, R1 represents halogen or C1-C4 alkyl, R2 and R3 represent independently hydrogen or C1-C4 alkyl, X represents oxygen atom, and Y represents oxygen atom, sulfur atom or carbonyl.

  本发明涉及以下式（I）的嘧啶二酮衍生物，其可用作抗病毒剂，尤其是用于治疗艾滋病的药物，其药学上可接受的盐，其制备方法以及包含其的制药组合物，其中R代表环丙基；环丁基；环己基；未取代或取代的苯基，所述苯基带有从羟基，C1-C4烷基，C1-C4烷氧基，卤素，三氟甲基，氰基和氨基中选择的基团; 1-或2-萘基；9-蒽基；2-蒽醌基；未取代或取代的吡啶基，所述吡啶基带有从C1-C4烷基，C1-C4烷氧基，氰基和卤素中选择的基团；2-，3-或4-喹啉基；环氧乙基基；1-苯并三氮唑基；2-苯并噁唑基；被C1-C4烷氧羰基，C1-C4烷基羰基或苯甲酰基取代的呋喃基，R1代表卤素或C1-C4烷基，R2和R3独立地代表氢或C1-C4烷基，X代表氧原子，Y代表氧原子，硫原子或羰基。
• [EN] NEW ANTIVIRAL SUBSTITUTED PYRIMIDINEDIONE HOMOCARBOCYCLIC NUCLEOSIDE DERIVATIVES AND METHODS FOR THE PREPARATION THEREOF AND COMPOSITIONS CONTAINING THE SAME AS ACTIVE INGREDIENTS<br/>[FR] NOUVEAUX DERIVES NUCLEOSIDIQUES HOMOCARBOCYCLIQUES DE PYRIMIDINEDIONE SUBSTITUEE, LEURS PROCEDES DE PREPARATION, ET COMPOSITIONS LES RENFERMANT A TITRE D'INGREDIENTS ACTIFS
  申请人：SAMJIN PHARMACEUTICAL CO., LTD.

  公开号：WO1997030979A1

  公开（公告）日：1997-08-28

  (EN) The present invention relates to novel compound of general formula (I) and pharmaceutically acceptable salts thereof, and process for the preparation of such derivatives and to pharmaceutical compositions containing the same as active ingredients, wherein R1, R2 and R3 represent independently hydrogen atom, halogen atom, C1-C10 alkyl, C1-C10 thioalkyl, C3-C8 optionally substituted cyclicalkyl, unsaturated alkyl, substituted alkyl hydroxyl or aryl hydroxyl, C1-C10 alkylamine, nitro, C1-C4 lower ester, C1-C4 lower alkoxy, C1-C4 lower thioalkoxy; Z represents oxygen atom, sulfur atom, carbon atom and carbonyl group; X represents oxygen atom, sulfur atom; n represents an integer of 1-3; and (sub)cycloalk(en)yl represents (a) or (b), in which (a) represents (c), (d), (e), or (f) in which R4 and R5 represent independently hydrogen atom, hydroxymethyl, protected hydroxymethyl, benzyl, substituted carbonyl, substituted alkylsulfonyl or arylsulfonyl, substituted silyl or the like.(FR) Nouveau composé répondant à la formule générale (I), ses sels pharmaceutiquement acceptables, procédé de préparation de dérivés de ce type, et compositions pharmaceutiques les renfermant à titre d'ingrédients actifs. Dans la formule générale (I), R1, R2 et R3, indépendamment les uns des autres, représentent un atome d'hydrogène, un atome d'halogène, alkyle C1-10, thioalkyle C1-10, cycloalkyle C3-8 éventuellement substitué, alkyle insaturé, alkylhydroxyle ou arylhydroxyle substitué, alkylamine C1-10, nitro, ester inférieur C1-4, alcoxy inférieur C1-4 ou thioalcoxy inférieur C1-4; Z représente un atome d'oxygène, un atome de soufre, un atome de carbone ou un groupe carbonyle; X représente un atome d'oxygène ou un atome de soufre; n est un entier compris entre 1 et 3; et (sous)cycloalkyle ou (sous)cycloalcényle représente (a) ou (b), où (a) représente (c), (d), (e) ou (f), où R4 et R5, indépendamment l'un de l'autre, représentent un atome d'hydrogène, hydroxyméthyle, hydroxyméthyle protégé, benzyle, carbonyle substitué, alkylsulfonyle ou arylsulfonyle substitué, silyle substitué ou analogue.

  本发明涉及一种新的通式（I）化合物及其药学上可接受的盐，以及制备这些衍生物的方法和包含它们作为活性成分的制药组合物。其中，R1、R2和R3独立地表示氢原子、卤素原子、C1-C10烷基、C1-C10硫代烷基、C3-C8可选取代的环烷基、不饱和烷基、取代烷基羟基或芳基羟基、C1-C10烷基胺、硝基、C1-C4低酯、C1-C4低烷氧基、C1-C4低硫代烷氧基；Z表示氧原子、硫原子、碳原子和羰基基团；X表示氧原子、硫原子；n表示1-3的整数；(亚)环烷基或(亚)环烯基表示(a)或(b)，其中(a)表示(c)、(d)、(e)或(f)，其中R4和R5独立地表示氢原子、羟甲基、保护羟甲基、苄基、取代的羰基、取代的烷基磺酰基或芳基磺酰基、取代的硅基或类似物。