(±)-4-(3-chloro-4-fluorophenyl)-2-(4-nitrophenoxy)-1,3,2-dioxaphosphinane-2-oxide

• 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: (±)-4-(3-chloro-4-fluorophenyl)-2-(4-nitrophenoxy)-1,3,2-dioxaphosphinane-2-oxide
• 英文别名: trans-4-(3-chloro-4-fluorophenyl)-2-(4-nitrophenoxy)-2-oxo-1,3,2-dioxaphosphorinane；4-(3-Chloro-4-fluorophenyl)-2-(4-nitrophenoxy)-1,3,2lambda5-dioxaphosphinane 2-oxide；4-(3-chloro-4-fluorophenyl)-2-(4-nitrophenoxy)-1,3,2λ5-dioxaphosphinane 2-oxide
• 化学式: C₁₅H₁₂ClFNO₆P
• 分子量: 387.689
• InChiKey: NWMZFFNVGCLWDO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  90.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (±)-4-(3-chloro-4-fluorophenyl)-2-(4-nitrophenoxy)-1,3,2-dioxaphosphinane-2-oxide 在 叔丁基氯化镁 、 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 36.5h， 生成 5'-O-cis-[4-(3-chloro-4-fluorophenyl)-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-氯-4-氟苯甲醛 在 sodium tetrahydroborate 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 为溶剂， 反应 6.5h， 生成 (±)-4-(3-chloro-4-fluorophenyl)-2-(4-nitrophenoxy)-1,3,2-dioxaphosphinane-2-oxide
  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 2'-C-methyl nucleoside derivatives
  申请人：Reddy Raja K.

  公开号：US20050182252A1

  公开（公告）日：2005-08-18

  Compounds of Formula I, stereoisomers, and pharmaceutically acceptable salts or prodrugs thereof, their preparation, and their uses for the treatment of hepatitis C viral infection are described:

  化合物I的配方、立体异构体以及其药用可接受的盐或前药，它们的制备以及它们用于治疗丙型肝炎病毒感染的用途被描述：
• [EN] NICOTINAMIDE MONONUCLEOTIDE DERIVATIVES AND THEIR USES<br/>[FR] DÉRIVÉS DE NICOTINAMIDE MONONUCLÉOTIDE ET LEUR UTILISATIONS
  申请人：METROBIOTECH LLC

  公开号：WO2017024255A1

  公开（公告）日：2017-02-09

  The invention relates to compositions of nicotinamide mononucleotide derivatives and their methods of use. The invention also relates to methods of preparing nicotinamide mononucleotide derivatives. The invention relates to pharmaceutical compositions and nutritional supplements containing a nicotinamide mononucleotide derivative. The invention relates to methods of using nicotinamide mononucleotide derivatives that promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for treating diseases and improving cell and tissue survival.

  本发明涉及烟酰胺单核苷酸衍生物的组合物及其使用方法。本发明还涉及制备烟酰胺单核苷酸衍生物的方法。本发明涉及含有烟酰胺单核苷酸衍生物的药物组合物和营养补充剂。本发明涉及使用烟酰胺单核苷酸衍生物的方法，促进细胞和组织中烟酰胺腺嘌呤二核苷酸（NAD+）水平的增加，用于治疗疾病和改善细胞和组织的存活。
• [EN] 2 '-C-METHYL NUCLEOSIDES CONTAINING A CYCLIC PHOSPHATE DIESTER OF 1, 3-PROPANEDIOL (2-OXO-[1, 3, 2]-DIOXAPHOSPHORINANE) AT POSITION 5'<br/>[FR] NUCLÉOSIDES 2'-C-MÉTHYL COMPRENANT UN DIESTER DE PHOSPHATE CYCLIQUE DE 1,3-PROPANEDIOL (2-OXO-[1,3,2]-DIOXAPHOSPHORINANE À LA POSITION 5'
  申请人：LIGAND PHARM INC

  公开号：WO2013106344A1

  公开（公告）日：2013-07-18

  2'-C-methyl nucleosides containing a 5'-monophosphate ester (a cyclic phosphate ester of 1,3-propanediol or 2-oxo-[1,3,2]-dioxaphos-phorinane) Compositions and methods relating to 2'-C-methyl nucleosides containing a 5'-monophosphate ester (a cyclic phosphate ester of 1,3-propanediol or 2-oxo-[1,3,2]-dioxaphosphorinane) are provided. In some embodiments, the novel compounds are useful to treat viral infections. In particular, 2'-C-methyl nucleoside 5'-monophosphate derivative compounds, stereoisomers, and pharmaceutically acceptable salts or prodrugs thereof, their preparation, and their uses for the treatment of hepatitis C virus (HCV) are described. The compounds have the following formulas:

  提供了与2'-C-甲基核苷酸含有5'-单磷酸酯（1,3-丙二醇环状磷酸酯或2-氧-[1,3,2]-二氧杂磷杂环磷酸酯）相关的组合物和方法。在某些实施例中，这些新型化合物有助于治疗病毒感染。具体地，描述了2'-C-甲基核苷酸5'-单磷酸衍生物化合物、立体异构体及其药学上可接受的盐或前药的制备以及它们用于治疗丙型肝炎病毒（HCV）的用途。这些化合物具有以下公式：
• Novel cyclic phosphate diesters of 1,3-propane-1-aryl diols and their use in preparing prodrugs
  申请人：——

  公开号：US20040192651A1

  公开（公告）日：2004-09-30

  Compounds of Formula I, their preparation and synthetic intermediates, and their use in the synthesis of prodrugs: 1 wherein: V and L are trans relative to one another; V is selected from group consisting of carbocyclic aryl, substituted carbocyclic aryl, heteroaryl, and substituted heteroaryl; and L is a leaving group selected from the group consisting of halogen, alkyl sulfonate, aryloxy optionally substituted with 1-2 substituents, N-containing heteroaryl, and N-hydroxy-nitrogen containing heteroaryl; and salts thereof.

  公式I的化合物，它们的制备和合成中间体，以及它们在前药合成中的应用： 其中： V和L是相对于彼此的反式； V选自群组，包括碳环芳基，取代的碳环芳基，杂环芳基和取代的杂环芳基； L是离去基，选自群组，包括卤素，烷基磺酸盐，取代1-2个取代基的芳氧基，含氮杂环和含N-羟基-氮杂环； 以及它们的盐。
• Nicotinamide mononucleotide derivatives and their uses
  申请人：Metro International Biotech, LLC

  公开号：US10548913B2

  公开（公告）日：2020-02-04

  The invention relates to compositions of nicotinamide mononucleotide derivatives and their methods of use. The invention also relates to methods of preparing nicotinamide mononucleotide derivatives. The invention relates to pharmaceutical compositions and nutritional supplements containing a nicotinamide mononucleotide derivative. The invention relates to methods of using nicotinamide mononucleotide derivatives that promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for treating diseases and improving cell and tissue survival.

  本发明涉及烟酰胺单核苷酸衍生物的组合物及其使用方法。本发明还涉及制备烟酰胺单核苷酸衍生物的方法。本发明涉及含有烟酰胺单核苷酸衍生物的药物组合物和营养补充剂。本发明涉及使用烟酰胺单核苷酸衍生物的方法，该衍生物可促进细胞和组织中烟酰胺腺嘌呤二核苷酸（NAD+）细胞内水平的增加，用于治疗疾病和改善细胞和组织存活率。