5-Chloro-1-((2R,4S,5R)-4-hydroxy-5-hydroxymethyl-3-methylene-tetrahydro-furan-2-yl)-1H-pyrimidine-2,4-dione | 119410-96-7

• 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-Chloro-1-((2R,4S,5R)-4-hydroxy-5-hydroxymethyl-3-methylene-tetrahydro-furan-2-yl)-1H-pyrimidine-2,4-dione
• 英文别名: 2'-Methylidene-2'-deoxy-5-chlorouridine；5-chloro-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-3-methylideneoxolan-2-yl]pyrimidine-2,4-dione
• CAS: 119410-96-7
• 化学式: C₁₀H₁₁ClN₂O₅
• 分子量: 274.661
• InChiKey: JZLACCZKTTXRTJ-BKPPORCPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  5

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-chlorouracil 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 以91%的产率得到5-Chloro-1-((2R,4S,5R)-4-hydroxy-5-hydroxymethyl-3-methylene-tetrahydro-furan-2-yl)-1H-pyrimidine-2,4-dione
  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'-alkylidenepyrimidine nucleoside derivatives, process for production
  申请人：Yamasa Shoyu Kabushiki Kaisha

  公开号：US05430139A1

  公开（公告）日：1995-07-04

  Disclosed are novel 2'-alkylidenepyrimidine nucleoside derivatives represented by formula [I]: ##STR1## R.sup.1 is an amino group or a hydroxy group, R.sup.2 is a hydrogen atom, a halogen atom or a lower alkyl group, R.sup.3 is a hydrogen atom or a lower alkyl group, and R.sup.4 is a hydrogen atom or a phosphate residue, or salts thereof. These novel compounds can be produced from uridine or cytidine derivatives by alkylidenating the 2'-position in the sugar moiety thereof with Wittig's reagent. Furthermore, the compounds have remarkable antiviral activities and therefore can provide novel antiviral agents.

  本发明涉及一种新型2'-烷基亚嘧啶核苷衍生物，其化学式表示为[I]：##STR1##其中R.sup.1是氨基或羟基，R.sup.2是氢原子、卤原子或低碳基，R.sup.3是氢原子或低碳基，R.sup.4是氢原子或磷酸盐残基或其盐。这些新化合物可以通过使用Wittig试剂烷基化糖基中的2'-位点，从脲苷或胞苷衍生物中制备而来。此外，这些化合物具有显著的抗病毒活性，因此可以提供新的抗病毒药物。
• 2'-alkylidenepyrimidine nucleoside compounds and a process for
  申请人：Yamasa Shoyu Kabushiki Kaisha

  公开号：US05300636A1

  公开（公告）日：1994-04-05

  Disclosed are novel 2'-alkylidenepyrimidine nucleoside derivatives represented by formula [I]: ##STR1## wherein R.sup.1 is an amino group or a hydroxy group, R.sup.2 is a hydrogen atom, a halogen atom or a lower alkyl group, R.sup.3 is a hydrogen atom or a lower alkyl group, and R.sup.4 is a hydrogen atom or a phosphate residue, or salts thereof. These novel compounds can be produced from uridine or cytidine derivatives by alkylidenating the 2'-position in the sugar moiety thereof with Wittig's reagent. Furthermore, the compounds have remarkable antiviral activities and therefore can provide novel antiviral agents.

  本发明涉及一种新型2'-烷基亚嘧啶核苷衍生物，其化学式为[I]：##STR1##其中，R.sup.1是氨基或羟基，R.sup.2是氢原子、卤素原子或低碳基，R.sup.3是氢原子或低碳基，R.sup.4是氢原子或磷酸盐残基，或其盐。这些新型化合物可以通过使用维特格试剂在尿苷或胞苷衍生物的糖基上烷基化2'-位置而制得。此外，这些化合物具有显著的抗病毒活性，因此可以提供新型抗病毒剂。
• 2'-ALKYLIDENEPYRIMIDINE NUCLEOSIDE DERIVATIVES, PROCESS FOR THEIR PREPARATION, AND THEIR USE
  申请人：Yamasa Shoyu Kabushiki Kaisha

  公开号：EP0310673A1

  公开（公告）日：1989-04-12

  Novel 2'-alkylidenepyrimidine nucleoside derivatives represented by formula (I) or salts thereof are disclosed, wherein R1 represents an amino group or a hydroxy group, R2 represents a hydrogen atom, a halogen atom or a lower alkyl group, R3 represents a hydrogen atom or a lower alkyl group, and R4 represents a hydrogen atom or a phosphoric acid residue. These novel compounds may be prepared by using a uridine or cytidine derivative as the starting material and introducing an alkylidene group into the 2'-position of the sugar moiety with a Wittig reagent. These compounds have an excellent antiviral effect, thus providing novel antiviral drugs.

  由式(I)表示的新型 2'-烷基亚嘧啶核苷衍生物 或其盐，其中 R1 代表氨基或羟基，R2 代表氢原子、卤素原子或低级烷基，R3 代表氢原子或低级烷基，R4 代表氢原子或磷酸残基。这些新型化合物的制备方法是：以尿苷或胞苷衍生物为起始原料，用维蒂希试剂在糖分子的 2'- 位上引入亚烷基。这些化合物具有极佳的抗病毒效果，从而提供了新型抗病毒药物。
• 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。
• UEDA, TOHRU;MATSUDA, AKIRA;YOSHIMURA, YUICHI;TAKENUKI, KENJI, NUCLEOSIDES AND NUCLEOTIDES, 8,(1989) N-6, C. 743-752
  作者：UEDA, TOHRU、MATSUDA, AKIRA、YOSHIMURA, YUICHI、TAKENUKI, KENJI

  DOI：——

  日期：——