5,6-diamino-3-methyl-1-phenyluracil | 50786-93-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5,6-diamino-3-methyl-1-phenyluracil
• 英文别名: 5,6-diamino-3-methyl-1-phenyl-1H-pyrimidine-2,4-dione；5,6-Diamino-3-methyl-1-phenyl-1H-pyrimidin-2,4-dion；5,6-diamino-3-methyl-1-phenyl-2,4-(1H, 3H)-pyrimidinedione；1-Methyl-3-phenyl-4,5-diamino-uracil；5,6-diamino-3-methyl-1-phenylpyrimidine-2,4-dione
• CAS: 50786-93-1
• 化学式: C₁₁H₁₂N₄O₂
• 分子量: 232.242
• InChiKey: VPIHNUGBRDLODE-UHFFFAOYSA-N

物化性质

• 沸点：
  345.3±52.0 °C(Predicted)
• 密度：
  1.364±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  92.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5,6-diamino-3-methyl-1-phenyluracil 在 乙醇 作用下， 以 丁酸酐 为溶剂， 反应 16.0h， 生成 3,7-dihydro-1-methyl-3-phenyl-8-propyl-1H-purine-2,6-dione
  参考文献：
  名称：

  Xanthine derivatives

  摘要：

  本发明提供的化合物的公式为##STR1##或其生理上可接受的盐，其中R.sup.1为甲基、乙基或正丙基，R.sup.2为甲基或正丙基，R.sup.3为##STR2##其制备方法；用于其制备的中间体；含有至少其中一种化合物的药物制剂；以及它们在过敏和支气管哮喘的治疗中的用途。

  公开号：

  US04233303A1
• 作为产物：
  描述：

  N-甲-N’-苯脲 在 盐酸 、 sodium hydroxide 、 乙酸酐 、 sodium nitrite 作用下， 以 溶剂黄146 为溶剂， 生成 5,6-diamino-3-methyl-1-phenyluracil
  参考文献：
  名称：

  CX-659S及其相关化合物对迟发型超敏反应的抑制作用及其合成与生物学评价。

  摘要：

  为了找到对延迟型超敏反应（DTH）反应具有抑制活性的新型非甾体化合物，我们使用氯化吡啶（PC）诱导的小鼠接触超敏反应（CHR）在小鼠中进行了随机筛选，发现化合物1为铅复合。然后，我们合成并评估了一系列广泛的针对尿嘧啶和抗氧化部分的5-羧酰胺基尿嘧啶衍生物。其中，我们发现受阻酚部分对于展示其活性是必要的。特别地，发现具有维生素E的部分结构的化合物28a-28c通过口服和局部给药都具有针对DTH反应的有效活性。化合物28c对脂质过氧化具有抗氧化活性，IC50为5.9 microM。

  DOI：

  10.1016/s0968-0896(00)00126-7

文献信息

• Inhibitory Activities of Novel Pyrimidine Derivatives on the Contact Hypersensitivity Reaction.
  作者：Yoshiaki Isobe、Masanori Tobe、Yoshifumi Inoue、Yuso Goto、Fumihiro Obara、Masakazu Isobe、Hideya Hayashi

  DOI：10.1248/cpb.51.309

  日期：——

  In order to obtain novel topically applied anti-inflammatory compounds containing an inexpensive anti-oxidative moiety without chirality, we synthesized compound 2c derivatives having a di-tert-butylphenol moiety, and evaluated by topical administration their anti-inflammatory potentials on picryl chloride-(PC) induced contact hypersensitivity reaction (CHR) in mice. In the course of our structure–activity relationship (SAR) studies on the pyrimidine or the anti-oxidative moiety and the linker between them, the most potent compounds (10, 11) were obtained by the insertion of a C2 unit in compound 2c. The potencies of these compounds were 2-fold greater than that of 1. Compounds 10 and 11 were considered to be useful lead compounds having inexpensive anti-oxidative moieties without chirality.

  为了获得含有经济实用的无手性抗氧化基团的新型局部抗炎化合物，我们合成了含二叔丁基苯酚基团的化合物2c衍生物，并通过局部给药在小鼠中评估了它们对接触性超敏反应（CHR）的抗炎潜力，该反应由二硝基氯苯（PC）诱发。在以嘧啶基团或抗氧化基团及其之间的连接链为研究对象的结构活性关系（SAR）研究过程中，通过在化合物2c中插入一个C2单元，得到了效力最强的化合物（10，11）。这些化合物的效力比1号化合物高出2倍。化合物10和11被认为是具有经济实用的无手性抗氧化基团的有用先导化合物。
• 1-arylpyrimidine derivatives and pharmaceutical use thereof
  申请人：Japan Energy Corporation

  公开号：US05661153A1

  公开（公告）日：1997-08-26

  The present invention relates to 1-arylpyrimidine derivatives represented by general formula (I): ##STR1## wherein R.sub.1 is H, alkyl or aralkyl; Ar is 1-naphthyl, or a substituted or unsubstituted phenyl group; R.sub.4 is a substituted phenyl, a substituted styryl, 1-methylcyclohexyl, 4-methylcyclohexyl, 4-oxo-4H-pyran-2-yl or 2-oxo-2H-pyran-5-yl group; R.sub.5 and R.sub.6 are each independently H or alkyl; R.sub.3 is H, and R.sub.7 and R.sub.8 are combined together to be oxo, or else R.sub.3 and R.sub.7 are combined together to be another direct bond, and R.sub.5 and R.sub.8 are combined together to be a direct bond, or pharmaceutically acceptable salts thereof; and methods for treating allergic diseases with such compounds.

  本发明涉及由通用公式(I)表示的1-芳基嘧啶衍生物：##STR1## 其中R.sub.1是H，烷基或芳烷基；Ar是1-萘基，或一个取代的或未取代的苯基；R.sub.4是一个取代的苯基，一个取代的苯乙烯基，1-甲基环己基，4-甲基环己基，4-氧代-4H-吡喃-2-基或2-氧代-2H-吡喃-5-基团；R.sub.5和R.sub.6各自独立是H或烷基；R.sub.3是H，R.sub.7和R.sub.8组合在一起形成氧代，或者R.sub.3和R.sub.7组合在一起形成另一个直接键，R.sub.5和R.sub.8组合在一起形成一个直接键，或其药用可接受盐；以及使用此类化合物治疗过敏性疾病的方法。
• Synthesis and Activity of a Metabolite of (S)-6-Amino-5-(6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxamido)-3-methyl-1-phenyl-2,4-(1H,3H)-pyrimidinedione (CX-659S).
  作者：Yoshiaki Isobe、Masanori Tobe、Osamu Takahashi、Yuso Goto、Yoshifumi Inoue、Fumihiro Obara、Masami Tsuchiya、Hideya Hayashi

  DOI：10.1248/cpb.50.1418

  日期：——

  CX-659S (1) [(S)-6-amino-5-(6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxamido)-3-methyl-1-phenyl-2,4-(1H,3H)-pyrimidinedione], has been developed as a new type anti-inflammatory agent for the treatment of dermatitis. The structure of a major metabolite of CX-659S was determined as (S)-6-amino-5-[2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxo-1,4-cyclohexadienyl)butanamide]-3-methyl-1-phenyl-2,4-(1H,3H)-pyrimidinedione (2) by direct comparison with the synthesized authentic compound. The anti-inflammatory activity of 2 was equipotent with that of 1 on the contact hypersensitivity reaction (CHR) induced by picryl chloride (PC) in mice, suggesting that compound 2 contributes, at least in part, to the anti-inflammatory activity of CX-659S.

  CX-659S (1) [(S)-6-氨基-5-(6-羟基-2,5,7,8-四甲基苯并二氢吡喃-2-甲酰胺基)-3-甲基-1-苯基-2,4-( 1H,3H)-嘧啶二酮]已被开发为治疗皮炎的新型抗炎剂。 CX-659S的主要代谢物的结构被确定为(S)-6-amino-5-[2-羟基-2-甲基-4-(2,4,5-trimethyl-3,6-dioxo-1) ,4-环己二烯基)丁酰胺]-3-甲基-1-苯基-2,4-(1H,3H)-嘧啶二酮(2)通过与合成的真实化合物直接比较。在小鼠体内由苦基氯 (PC) 诱导的接触性超敏反应 (CHR) 中，2 的抗炎活性与 1 的抗炎活性相当，表明化合物 2 至少部分有助于 CX 的抗炎活性-659S。
• Hydroquinone derivative and pharmaceutical use thereof
  申请人：Japan Energy Corporation

  公开号：US05821247A1

  公开（公告）日：1998-10-13

  Disclosed is a hydroquinone derivative or a pharmaceutically acceptable salt thereof, the hydroquinone derivative being represented by formula (I): ##STR1## wherein R.sup.1 is a phenyl group which is unsubstituted or substituted with a substituent or substituents each independently selected from the group consisting of a halogen atom, a C1-4 alkyl group and a C1-4 alkoxy group; R.sup.2 is a hydrogen atom or a C1-4 alkyl group; each of R.sup.3 and R.sup.4 is independently a hydrogen atom or a C1-4 alkyl group; R.sup.5 is a hydrogen atom or a C1-4 alkyl group; each of R.sup.6, R.sup.7 and R.sup.8 is independently a hydrogen atom or a C1-4 alkyl group; P is a hydroxyl group; Q is a hydroxyl group, a C1-4 alkoxy group, a C1-18 acyloxy group or an oxo group; P may form together with Q an ether bond; R is a hydroxyl group, a C1-4 alkoxy group, a C1-18 acyloxy group or an oxo group, provided that when one of said Q and said R is an oxo group, the other is also an oxo group; X is a single bond, an --NR.sup.10 --group or a --CH.sub.2 --NR.sup.10 --group in which R.sup.10 is a hydrogen atom or a C1-4 alkyl group; Y is a methylene group or a carbonyl group; and dotted bonds in a six membered ring represent that said six membered ring has the maximum number of double bonds.

  本发明涉及一种羟基苯醌衍生物或其药学上可接受的盐，该羟基苯醌衍生物由公式（I）表示：##STR1##其中，R.sup.1是苯基，其未取代或被取代为取自卤原子、C1-4烷基和C1-4烷氧基的各自独立的取代基；R.sup.2是氢原子或C1-4烷基；R.sup.3和R.sup.4各自独立地是氢原子或C1-4烷基；R.sup.5是氢原子或C1-4烷基；R.sup.6，R.sup.7和R.sup.8各自独立地是氢原子或C1-4烷基；P是羟基；Q是羟基、C1-4烷氧基、C1-18酰氧基或氧代基；P可以与Q共同形成醚键；R是羟基、C1-4烷氧基、C1-18酰氧基或氧代基，但当Q和R中的一个为氧代基时，另一个也为氧代基；X是单键、--NR.sup.10--基团或--CH.sub.2--NR.sup.10--基团，其中R.sup.10是氢原子或C1-4烷基；Y是亚甲基基团或羰基基团；六元环中的点状键表示该六元环具有最大数量的双键。
• 1-Arylpyrimidine derivatives and pharmaceutical use thereof
  申请人：JAPAN ENERGY CORPORATION

  公开号：EP0700908A1

  公开（公告）日：1996-03-13

  The present invention relates to pyrimidine derivatives of the formula (I): wherein    R₁ is H, alkyl or aralkyl;    Ar is 1-naphthyl, or a substituted or unsubstituted phenyl group;    R₄ is a substituted phenyl, a substituted styryl, 1-methylcyclohexyl, 4-methylcyclohexyl, 4-oxo-4H-pyran-2-yl or 2-oxo-2H-pyran-5-yl group;    R₅ and R₆ are each independently H or alkyl;    R₃ is H, and R₇ and R₈ are combined together to be oxo, or else R₃ and R₇ are combined together to be another direct bond, and R₅ and R₈ ar combined together to be a direct bond, or pharmaceutically acceptable salts thereof; and the use of such compounds in the treatment of an allergic disease.

  本发明涉及式（I）的嘧啶衍生物： 其中 R₁ 是 H、烷基或芳烷基； Ar 是 1-萘基或取代或未取代的苯基； R₄ 是取代的苯基、取代的苯乙烯基、1-甲基环己基、4-甲基环己基、4-氧代-4H-吡喃-2-基或 2-氧代-2H-吡喃-5-基； R₅ 和 R₆ 各自独立地为 H 或烷基； R₃为H，且R₇和R₈结合在一起为氧代，或者R₃和R₇结合在一起为另一个直接键，且R₅和R₈结合在一起为一个直接键，或其药学上可接受的盐；以及此类化合物在治疗过敏性疾病中的用途。