(4R)-5'-O-cis-[4-(pyridin-4yl)-2-oxido-1,3,2-dioxaphosphorinan-2yl]-cytosine-β-D-arabinofuranoside

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: (4R)-5'-O-cis-[4-(pyridin-4yl)-2-oxido-1,3,2-dioxaphosphorinan-2yl]-cytosine-β-D-arabinofuranoside
• 英文别名: 5'-O-cis-[4-(pyridin-4yl)-2-oxido-1,3,2-dioxaphosphorinan-2yl]-cytosine-β-D-arabinofuranoside；2(1H)-pyrimidinone, 4'-amino-1-[5-O-[(2S,4R)-2-oxido-4-(4-pyridinyl)-1,3,2-dioxaphosphorinan-2-yl]-β-D-arabinofuranosyl]；4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-[[(2S,4R)-2-oxo-4-pyridin-4-yl-1,3,2lambda5-dioxaphosphinan-2-yl]oxymethyl]oxolan-2-yl]pyrimidin-2-one；4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-[[(2S,4R)-2-oxo-4-pyridin-4-yl-1,3,2λ5-dioxaphosphinan-2-yl]oxymethyl]oxolan-2-yl]pyrimidin-2-one
• 化学式: C₁₇H₂₁N₄O₈P
• 分子量: 440.35
• InChiKey: HOAHIHGOMCBTFW-VMRWEBHKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  166
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  阿糖胞苷 在 咪唑 、 盐酸 、 4-二甲氨基吡啶 、 叔丁基氯化镁 作用下， 以 四氢呋喃 、 吡啶 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 (4R)-5'-O-cis-[4-(pyridin-4yl)-2-oxido-1,3,2-dioxaphosphorinan-2yl]-cytosine-β-D-arabinofuranoside
  参考文献：
  名称：

  EP3730504

  摘要：

  公开号：

文献信息

• Novel cytarabine monophosphate prodrugs
  申请人：——

  公开号：US20040092476A1

  公开（公告）日：2004-05-13

  Compounds of Formula I, their preparation and uses are described: 1 wherein: M and V are cis to one another and MH is cytarabine; the 5′ oxygen of said cytarabine is attached to the phosphorus; V is 4-pyridyl; and pharmaceutically acceptable prodrugs and salts thereof.

  式I的化合物，其制备和用途如下所述： 其中： M和V相对于彼此为顺式，MH为紫杉醇； 所述紫杉醇的5′氧原子连接到磷； V为4-吡啶基； 以及其药用可接受的前药和盐。
• Synthesis and Characterization of a Novel Liver-Targeted Prodrug of Cytosine-1-β-<scp>d</scp>-arabinofuranoside Monophosphate for the Treatment of Hepatocellular Carcinoma
  作者：Serge H. Boyer、Zhili Sun、Hongjian Jiang、Julie Esterbrook、Jorge E. Gómez-Galeno、William Craigo、K. Raja Reddy、Bheemarao G. Ugarkar、Deidre A. MacKenna、Mark D. Erion

  DOI：10.1021/jm0607449

  日期：2006.12.1

  Cytotoxic nucleosides have proven to be ineffective for the treatment of hepatocellular carcinoma (HCC) due, in part, to their inadequate conversion to their active nucleoside triphosphates (NTP) in the liver tumor and high conversion in other tissues. These characteristics lead to poor efficacy, high toxicity, and a drug class associated with an unacceptable therapeutic index. Cyclic 1-aryl-1,3-propanyl phosphate prodrugs selectively release the monophosphate of a nucleoside (NMP) into CYP3A4-expressing cells, such as hepatocytes, while leaving the prodrug intact in plasma and extrahepatic tissues. This prodrug strategy was applied to the monophosphate of the well-known cytotoxic nucleoside cytosine-1-beta-D-arabinofuranoside (cytarabine, araC). Compound 19S (MB07133), in mice, achieves good liver targeting compared to araC, generating > 19-fold higher cytarabine triphosphate (araCTP) levels in the liver than levels of araC in the plasma and > 12-fold higher araCTP levels in the liver than in the bone marrow, representing a > 120-fold and > 28-fold improvement, respectively, over araC administration.
• CYTARABINE PRODRUG NUCLEOSIDE CYCLIC PHOSPHATE COMPOUND BASED ON LIVERSPECIFIC DELIVERY AND USE
  申请人：ZHEJIANG PALO ALTO PHARMACEUTICALS, INC.

  公开号：US20200317711A1

  公开（公告）日：2020-10-08

  Disclosed are an anticancer prodrug nucleoside cyclic phosphate compound based on liver-specific delivery (LSD) technology and the use thereof, in particular, provided are a compound of formula (I) and an isomer, a pharmaceutically acceptable salt, a hydrate, a solvate and a corresponding pharmaceutical composition thereof, and the use of the compound alone or in combination with other anticancer drugs against cancer, especially in treating hepatic carcinoma (HCC).
• US7553826B2
  申请人：——

  公开号：US7553826B2

  公开（公告）日：2009-06-30
• EP3730504
  申请人：——

  公开号：——

  公开（公告）日：——