4-Amino-5-ethyl-1-((2R,4S,5R)-4-hydroxy-5-hydroxymethyl-3-methylene-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one | 129532-04-3

• 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: 4-Amino-5-ethyl-1-((2R,4S,5R)-4-hydroxy-5-hydroxymethyl-3-methylene-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one
• 英文别名: 4-amino-5-ethyl-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-3-methylideneoxolan-2-yl]pyrimidin-2-one
• CAS: 129532-04-3
• 化学式: C₁₂H₁₇N₃O₄
• 分子量: 267.285
• InChiKey: QDPAMGCFBHETGN-WCABBAIRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-<2-deoxy-2-methylidene-3,5-O-(tetraisopropyldisiloxane-1,3-diyl)-β-D-ribofuranosyl>-5-ethyluracil 在 四丁基氟化铵 、 氨 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 4-Amino-5-ethyl-1-((2R,4S,5R)-4-hydroxy-5-hydroxymethyl-3-methylene-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one
  参考文献：
  名称：

  核苷和核苷酸。97.合成新的广谱抗肿瘤核苷，2'-脱氧-2'-亚甲基胞苷（DMDC）及其衍生物。

  摘要：

  通过Wittig反应，由相应的2'-酮嘧啶核苷3和8合成了一种新型的抗肿瘤核苷2'-脱氧-2'-亚甲基胞苷（DMDC）。在反应过程中，我们发现中间体甜菜碱可以从过量的三苯基溴化pick中挑出质子形成2'-on盐5和10，并可以进一步转化为2'-脱氧-2'-亚甲基通过氢化钠处理得到核苷4和9。还从相应的5-取代的尿苷12a-f，h合成了各种5-取代的DMDC衍生物19a-e，h及其尿嘧啶同类物16a-h。其中，DMDC以及2'-脱氧-2'-亚甲基-5-氟胞苷（19a）对培养的鼠L1210细胞显示出有效的抗白血病活性。还检查了与1-β-D-阿拉伯呋喃糖基胞嘧啶胞嘧啶和5-氟尿嘧啶相比，DMDC和19a对培养的各种人类肿瘤细胞的活性。还描述了DMDC对L1210的体内抗肿瘤活性。

  DOI：

  10.1021/jm00106a049

文献信息

• 2'-Methylidenepyrimidin nucleoside compounds, their use and method for production thereof.
  申请人：YOSHITOMI PHARMACEUTICAL INDUSTRIES, LTD.

  公开号：EP0360018A1

  公开（公告）日：1990-03-28

  2′-Methylidenepyrimidine nucleoside compounds of the general formula : wherein R¹ stands for amino or hydroxy group; R² stands for a halogen or a lower alkyl when R¹ is amino or R² stands for an alkyl having 2 to 4 carbon atoms, an alkynyl having 2 to 4 carbon atoms or a haloalkyl when R¹ is hydroxy group; and R³ stands for hydrogen or a phosphoric acid residue, or salts thereof, anticancer compositions containing one or more of these compounds and methods for production of these compounds. Said compounds and salts thereof exhibit noticeable antitumor activities and are useful as anticancers.

  通式为...的2′-亚甲基嘧啶核苷化合物 其中R¹代表氨基或羟基；当R¹为氨基时，R²代表卤素或低级烷基；当R¹为羟基时，R²代表具有2至4个碳原子的烷基、具有2至4个碳原子的炔基或卤代烷基；R³代表氢或磷酸残基，或其盐、含有一种或多种这些化合物的抗癌组合物以及生产这些化合物的方法。 上述化合物及其盐类具有明显的抗肿瘤活性，可用作抗癌剂。
• Pyrimidine 2'-methylidene nucleoside compounds
  申请人：YAMASA SHOYU CO., LTD.

  公开号：EP0373485A1

  公开（公告）日：1990-06-20

  Pyrimidine 2′-deoxy-2′-methylidene nucleoside compounds : wherein R¹ represents amino, hydroxy, silylamino, silyloxy, acylamino or acyloxy; R² represents hydrogen, halogen, a lower alkyl, a lower alkenyl, a lower alkynyl or haloalkyl; R³ and R⁴ represent the same or different hydrogen, silyl, acyl or aminoacyl, or a pharmaceutically acceptable salt or hydrate thereof, except that R¹ is amino or hydroxy, and both of R³ and R⁴ are hydrogen. Said compounds possess excellent antitumor and antiviral activities, thus providing novel anticancer and antiviral agent.

  嘧啶 2′-脱氧-2′-亚甲基核苷化合物 ： 其中，R¹代表氨基、羟基、水硅烷基、水硅烷氧基、酰氨基或酰氧基；R²代表氢、卤素、低级烷基、低级烯基、低级炔基或卤代烷基；R³和R⁴代表相同或不同的氢、水硅烷基、酰基或氨基酰基，或其药学上可接受的盐或水合物，但R¹为氨基或羟基，R³和R⁴均为氢。 上述化合物具有优异的抗肿瘤和抗病毒活性，从而提供了新型抗癌剂和抗病毒剂。
• 2'-Methylidenepyrimidine Nucleoside Compounds, their use and method for production thereof
  申请人：YOSHITOMI PHARMACEUTICAL INDUSTRIES, LTD.

  公开号：EP0566162A1

  公开（公告）日：1993-10-20

  2'-Methylidenepyrimidine nucleoside compounds of the general formula : wherein R¹ stands for amino or hydroxy group; R² stands for a halogen or a lower alkyl when R¹ is amino or R² stands for an alkyl having 2 to 4 carbon atoms, an alkynyl having 2 to 4 carbon atoms or a haloalkyl when R¹ is hydroxy group; and R³ stands for hydrogen or a phosphoric acid residue, or salts thereof, anticancer compositions containing one or more of these compounds and methods for production of these compounds. Said compounds and salts thereof exhibit noticeable antitumor activities and are useful as anticancers.

  通式为...的 2'-亚甲基嘧啶核苷化合物 其中R¹代表氨基或羟基；R²代表卤素或低级烷基（当R¹为氨基时），或R²代表具有2至4个碳原子的烷基、具有2至4个碳原子的炔基、或卤代烷基（当R¹为羟基时）；以及R³代表氢或磷酸残基，或它们的盐、含有一种或多种这些化合物的抗癌组合物以及生产这些化合物的方法。 上述化合物及其盐类具有明显的抗肿瘤活性，可用作抗癌剂。
• COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF LIVER DISORDERS
  申请人：IDENIX Pharmaceuticals, Inc.

  公开号：EP2107909A2

  公开（公告）日：2009-10-14
• Compounds and pharmaceutical compositions for the treatment of liver disorders
  申请人：Sommadossi Jean-Pierre

  公开号：US20080261913A1

  公开（公告）日：2008-10-23

  Provided herein are compounds, compositions and methods for the treatment of liver disorders, including liver cancer and metabolic diseases, such as diabetes, hyperlipidemia, atherosclerosis, and obesity. Specifically, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-cancer agents.