2'-C-cyano-2'-deoxy-1-β-D-ribo-pentofuranosylcytosine

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 2'-C-cyano-2'-deoxy-1-β-D-ribo-pentofuranosylcytosine
• 英文别名: 2'-C-cyano-2'-deoxy-1-β-D-ribofuranosylcytosine；2'-Cyano-2'-deoxycytidine；(2R,3R,4S,5R)-2-(4-amino-2-oxopyrimidin-1-yl)-4-hydroxy-5-(hydroxymethyl)oxolane-3-carbonitrile
• 化学式: C₁₀H₁₂N₄O₄
• 分子量: 252.23
• InChiKey: DCYBPMFXJCWXNB-MTSNSDSCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  132
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  棕榈酸酐 、 2'-C-cyano-2'-deoxy-1-β-D-ribo-pentofuranosylcytosine 在 甲醇 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以to afford 860.9 mg of the title compound as fine white needles的产率得到2'-Cyano-2'-deoxy-N4-palmitoylcytidine
  参考文献：
  名称：

  Pyrimidine nucleoside derivatives having anti-tumor activity, their

  摘要：

  化合物的结构式（I）：##STR1## 其中：R.sup.1、R.sup.2和R.sup.3独立地选自氢原子、可选取代的烷酰基团和烯基羰基基团的群，前提是R.sup.1、R.sup.2和R.sup.3中至少有一个代表具有5到24个碳原子的未取代烷酰基团，所述取代烷酰基团或所述烯基羰基基团；R.sup.4和R.sup.5中的一个代表氢原子，另一个代表氰基；具有有价值的抗肿瘤活性。

  公开号：

  US05691319A1
• 作为产物：
  描述：

  (2R,3S,4S,5R)-2-(4-氨基-2-氧代嘧啶-1-基)-4-羟基-5-(羟基甲基)四氢呋喃-3-甲腈盐酸盐 在 Tris-HCl buffer 作用下， 反应 6.0h， 以28%的产率得到1,4-anhydro-2-C-cyano-2-deoxy-D-erythropent-1-enitol
  参考文献：
  名称：

  核苷和核苷酸。141.一种新的抗肿瘤核苷2'-C-氰基-2'-脱氧-1-β-D-阿拉伯糖基-戊呋喃糖基胞嘧啶在碱性介质中的化学稳定性：2'-C-氰基-2'-脱氧-1的形成-β-D-核糖-呋喃糖基胞嘧啶及其抗肿瘤活性。

  摘要：

  我们设计了2'-C-氰基-2'-脱氧-1-β-D-阿拉伯糖基呋喃呋喃糖基胞嘧啶（CNDAC）作为潜在的基于机制的DNA链断裂核苷，显示出对多种肿瘤细胞有效的抑制作用体外和体内人类肿瘤细胞系。在测量CNDAC的2'α-质子的pKa时，我们发现CNDAC被差向为2'-C-氰基-2'-脱氧-1-β-D-核糖-戊呋喃糖基胞嘧啶（CNDC），同时伴随着两个CNDAC的降解CNDC合成胞嘧啶和1,4-脱水-2-C-氰基-2-脱氧-D-赤藓基-1-烯醇。这些反应的动力学分析表明，CNDAC和CNDC酸性2'质子的抽象引发了反应，并迅速达到平衡。在平衡状态下，CNDAC和CNDC的浓度比约为3：5。发现这些核苷的伴随降解相当缓慢。用CNDAC在D2O缓冲液中进行氘掺入实验表明，β-消除反应的机理是E1cB型。这些差向异构和降解反应甚至在中性条件（pH 7.5）下也发现，并且也发生在RPMI 1640细胞培

  DOI：

  10.1021/jm00017a023

文献信息

• AGENT FOR PREVENTING OR TREATING PANCREAS CANCER, OVARY CANCER OR LIVER CANCER CONTAINING NOVEL WATER-SOLUBLE PRODRUG
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP1938823A1

  公开（公告）日：2008-07-02

  Preventive or therapeutic agents for pancreatic cancer, ovarian cancer, or liver cancer of the present invention comprise a water-soluble prodrug represented by formula 1 described below, or a pharmaceutically acceptable salt, or a hydrate or solvate of the prodrug or pharmaceutically acceptable salt, (wherein, R1 represents a hydrogen atom, or a C1-C6 alkyl group; W represents a divalent group comprising a tertiary amino group or a divalent group comprising a sulfonyl group, and Y represents a residue of a compound represented by Y-OH comprising an alcoholic hydroxyl group, wherein said Y-OH is a camptothecin, a taxane, or an anticancer nucleotide).

  预防或治疗胰腺癌、卵巢癌或肝癌的本发明药剂包括下述式子所代表的水溶性前药，或者前药的药用可接受盐，或者前药或药用可接受盐的水合物或溶剂化合物， （其中， R1代表氢原子，或者C1-C6烷基； W代表包含三级胺基团或含磺酰基团的二价基团，以及 Y代表由Y-OH所代表的化合物残基，包括含有醇羟基的醇羟基化合物残基，其中所述的Y-OH是一种喜树碱、紫杉醇或抗癌核苷酸）。
• 2'-C-Cyano-2'-deoxy-1-β-D-arabinofuranosylcytosine (CNDAC): A Mechanism-Based DNA-Strand-Breaking Antitumor Nucleoside1
  作者：Akira Matsuda、Atsushi Azuma

  DOI：10.1080/15257779508012407

  日期：1995.5.1

  of action of 2′-C-cyano-2′-deoxy-1-β-d-arabinofuranosylcytosine (CNDAC) has been examined. CNDAC was designed as a potentially DNA-self-strand-breaking nucleoside. It had potent antitumor effects against various solid tumors in vitro as well as in vivo. Using a chain-extension method with Vent (exo−) DNA polymerase and a short primer/template system, we found that 5′-triphosphate of CNDAC (CNDACTP) was

  摘要研究了2'-C-氰基-2'-脱氧-1-β-d-阿拉伯呋喃糖基胞嘧啶（CNDAC）的抗肿瘤作用机理。CNDAC被设计为潜在的DNA自链断裂核苷。它在体内外对各种实体瘤都有有效的抗肿瘤作用。使用具有Vent（exo-）DNA聚合酶和短引物/模板系统的链延伸方法，我们发现CNDAC（CNDACTP）的5'-三磷酸在模板中与鸟嘌呤残基相对的位点掺入引物中。含有CNDAC的引物在3'-末端进行进一步的链延伸反应后，未观察到链延长。因此，CNDACTP似乎起了链终止剂的作用。引物中3'-末端的结构分析表明2'-C-氰基-2'，3'-二氢-2'，3′-二脱氧胞苷（ddCNC）与CNDAC和2′-C-氰基-2′-脱氧-1-β-d-呋喃呋喃糖基胞嘧啶（CNDC）一起。引物3'端中ddCNC的存在是由于核苷酸inc。的自链断裂。
• Method for identifying an enzyme to design anti-cancer compounds
  申请人：——

  公开号：US20030138864A1

  公开（公告）日：2003-07-24

  The present invention relates to a method for identification of enzymes that are preferentially expressed in certain tumor tissue as compared with rapidly growing normal cells or tissue, use of said enzymes for the compound design to generate an active anti-cancer substance selectively in tumor tissue, compounds designed based on said enzymes, their pharmaceutically acceptable salts as well as pharmaceutical composition thereof.

  本发明涉及一种酶的鉴定方法，该酶在某些肿瘤组织中与快速生长的正常细胞或组织相比表达优势，利用该酶设计化合物以在肿瘤组织中选择性地生成活性抗癌物质，基于该酶设计的化合物、其药学上可接受的盐以及药物组成物。
• Pyrimidine nucleoside derivatives having anti-tumor activity, their preparation and use
  申请人：Sankyo Company Limited

  公开号：EP0536936A1

  公开（公告）日：1993-04-14

  Compounds of formula (I): [in which: R¹, R² and R³ are the same or different and each represents a hydrogen atom, an optionally substituted alkanoyl group or an alkenylcarbonyl group, provided that at least one of R¹, R² and R³ represents an unsubstituted alkanoyl group having from 5 to 24 carbon atoms, said substituted alkanoyl group or said alkenylcarbonyl group; and one of R⁴ and R⁵ represents a hydrogen atom and the other represents a cyano group]; have valuable anti-tumour activity.

  式子（I）的化合物：[其中：R¹、R²和R³相同或不同，每个代表氢原子、可选取代的脂肪酰基团或烯基羰基团，前提是至少有一个R¹、R²和R³代表有5到24个碳原子的未取代脂肪酰基团，或者是所述取代的脂肪酰基团或所述烯基羰基团；R⁴和R⁵中的一个代表氢原子，另一个代表氰基]，具有有价值的抗肿瘤活性。
• Novel Water-Soluble Prodrugs
  申请人：Umeda Isao

  公开号：US20080015157A1

  公开（公告）日：2008-01-17

  An objective of the present invention is to provide water-soluble prodrugs that can be administered parenterally, and which show excellent water solubility and small interspecies or individual differences and are rapidly converted to the active form by chemical conversion. This invention provides water-soluble prodrugs represented by formula (1), or pharmaceutically acceptable salts, or hydrates or solvates thereof, (wherein, R 1 represents a hydrogen atom, or C1-C6 alkyl group; W represents a divalent group comprising a tertiary amino group or sulfonyl group; and Y represents a residue of a compound represented by Y—OH comprising an alcoholic hydroxyl group).

  本发明的目的是提供可经由肌肉注射给药的水溶性前药，其具有优异的水溶性、小的种间或个体差异，并且可通过化学转化迅速转化为活性形式。本发明提供了由式(1)表示的水溶性前药，或其药学上可接受的盐、水合物或溶剂化物，其中R1代表氢原子或C1-C6烷基；W代表包含三级胺基或磺酰基的二价基团；Y代表由Y-OH表示的化合物的残基，该化合物包括醇羟基。