(+)-(4R)-trans-2-(4-nitrophenoxy)-2-oxido-4-(pyridin-4-yl)-1,3,2-dioxaphosphorinane | 685111-94-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (+)-(4R)-trans-2-(4-nitrophenoxy)-2-oxido-4-(pyridin-4-yl)-1,3,2-dioxaphosphorinane
• 英文别名: (4R)-(+)-(4-pyridyl)-2-(4-nitrophenoxy)-2-oxo-1,3,2-dioxaphosphorinane；(2S,4R)-2-(4-nitrophenoxy)-4-pyridin-4-yl-1,3,2lambda5-dioxaphosphinane 2-oxide；(2S,4R)-2-(4-nitrophenoxy)-4-pyridin-4-yl-1,3,2λ5-dioxaphosphinane 2-oxide
• CAS: 685111-94-8
• 化学式: C₁₄H₁₃N₂O₆P
• 分子量: 336.241
• InChiKey: HKSUSEMODQDQMJ-QKFKETGDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  104
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (+)-(4R)-trans-2-(4-nitrophenoxy)-2-oxido-4-(pyridin-4-yl)-1,3,2-dioxaphosphorinane 在 叔丁基氯化镁 、 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 反应 34.5h， 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：

  Synthesis and Characterization of a Novel Liver-Targeted Prodrug of Cytosine-1-β-d-arabinofuranoside Monophosphate for the Treatment of Hepatocellular Carcinoma

  摘要：

  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.

  DOI：

  10.1021/jm0607449
• 作为产物：
  描述：

  3-羟基-3-(吡啶-4-基)丙酸乙酯 在 吡啶 、 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 24.5h， 生成 (+)-(4R)-trans-2-(4-nitrophenoxy)-2-oxido-4-(pyridin-4-yl)-1,3,2-dioxaphosphorinane
  参考文献：
  名称：

  Synthesis and Characterization of a Novel Liver-Targeted Prodrug of Cytosine-1-β-d-arabinofuranoside Monophosphate for the Treatment of Hepatocellular Carcinoma

  摘要：

  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.

  DOI：

  10.1021/jm0607449

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。
• EP3733669
  申请人：——

  公开号：——

  公开（公告）日：——
• EP3730508
  申请人：——

  公开号：——

  公开（公告）日：——
• US7553826B2
  申请人：——

  公开号：US7553826B2

  公开（公告）日：2009-06-30