(4S)-4-(3-chlorophenyl)-2-(4-nitrophenoxy)-1,3,2-dioxaphosphinane 2-oxide | 883989-35-3

• 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: (4S)-4-(3-chlorophenyl)-2-(4-nitrophenoxy)-1,3,2-dioxaphosphinane 2-oxide
• 英文别名: (4S)-4-(3-chlorophenyl)-2-(4-nitrophenoxy)-1,3,2lambda5-dioxaphosphinane 2-oxide；(4S)-4-(3-chlorophenyl)-2-(4-nitrophenoxy)-1,3,2λ5-dioxaphosphinane 2-oxide
• CAS: 883989-35-3
• 化学式: C₁₅H₁₃ClNO₆P
• 分子量: 369.698
• InChiKey: LTBCYGZGEUORSW-FZADBTJQSA-N

物化性质

• 沸点：
  477.7±45.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 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：
  6

反应信息

• 作为反应物：
  描述：

  (4S)-4-(3-chlorophenyl)-2-(4-nitrophenoxy)-1,3,2-dioxaphosphinane 2-oxide 在 氟化铵 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 mineral oil 为溶剂， 反应 27.0h， 生成
  参考文献：
  名称：

  [EN] A PRODRUG PLATFORM USEFUL TO DELIVER AMINES, AMIDES AND PHENOLS
  [FR] PLATE-FORME DE PROMÉDICAMENTS UTILE POUR ADMINISTRER DES AMINES, DES AMIDES ET DES PHÉNOLS

  摘要：

  本文提供了一种用于传递药用活性胺、酰胺和酚的前药平台，以及它们在诊断、预防和/或治疗各种疾病中的用途。与母药（例如吉西他滨）相比，前药在整体安全性方面表现出明显改善（疗效指数（TI）改善），尤其是在肝脏方面。

  公开号：

  WO2021032075A1
• 作为产物：
  描述：

  1-(3-chlorophenyl)-1,3-propanediol 在 对硝基苯酚 、 三氟甲磺酸三甲基硅酯 、 三乙胺 、 六甲基二硅氮烷 作用下， 以 四氢呋喃 为溶剂， 生成 (4S)-4-(3-chlorophenyl)-2-(4-nitrophenoxy)-1,3,2-dioxaphosphinane 2-oxide
  参考文献：
  名称：

  Phosphoramidate and phosphate prodrugs of (−)-β-d-(2R,4R)-dioxolane-thymine: Synthesis, anti-HIV activity and stability studies

  摘要：

  A series of phosphoramidate and phosphate prodrugs of DOT were synthesized via dichlorophosphate or H-phosphonate chemistry and evaluated for their anti-HIV activity against LAI M 184V mutants in PBM cells as well as for their cytotoxicity. The antiviral and cytotoxic profiles of the prodrugs were compared with that of the parent compound (DOT), and it was found that four aryl phosphoramidates 5, 18, 20, and 26 showed a significant enhancement (8- to 12-fold) in anti-HIV activity without cytotoxicity. Chemical stability of these prodrugs was evaluated in phosphate buffer at pH values of biological relevance (i.e., pH 2.0 and 7.4). Enzymatic hydrolysis was also studied in esterase or lipase in buffer solution. Chemical stability studies indicate that the phosphoramidates have good chemical stability at pH 2.0 and at pH 7.4 phosphate buffer. Phosphoramidate prodrugs were hydrolyzed in vitro by esterase or lipase and found to be better substrates for lipases than for esterases. 1,3-Diol cyclic phosphates showed potent anti-HIV activity without increasing the cytotoxicity compared with that of DOT and have good chemical and enzymatic stability. Long-chain lipid phosphates, although showed potent anti-HIV activity, exhibited increased cytotoxicity. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.11.008

文献信息

• 一种乐伐替尼衍生物及制备方法和用途
  申请人：四川海思科制药有限公司

  公开号：CN110590839B

  公开（公告）日：2022-04-05

  本发明涉及一种通式(I)所示化合物及其立体异构体或药学上可接受的盐，以及在制备用于抗肿瘤的药物中的应用，通式(I)化合物的结构为Q‑L‑R1，其基团定义与说明书定义一致。
• [EN] PHOSPHORUS-CONTAINING PRODRUGS OF GEMCITABINE<br/>[FR] PROMÉDICAMENTS CONTENANT DU PHOSPHORE DE GEMCITABINE
  申请人：SHANGHAI CHANGCHENGYIYAOKEJI COMPANY LTD

  公开号：WO2020001475A1

  公开（公告）日：2020-01-02

  This invention relates to phosphorus-containing prodrugs of gemcitabine and their use in the treatment of cancer and viral infectious diseases. Compared with the parent drug (i.e., Gemcitabine), the prodrugs of present invention show a significant overall safety improvement (therapeutic index (TI) improvement), especially in liver.

  这项发明涉及含磷前药的吉西他滨及其在癌症和病毒感染性疾病治疗中的应用。与母药（即吉西他滨）相比，本发明的前药在整体安全性方面表现出显著改善（治疗指数（TI）改善），尤其是在肝脏方面。
• 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：
• 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。
• NOVEL CYCLIC PHOSPHATE DIESTERS OF 1,3-PROPANE-1-ARYL DIOLS AND THEIR USE IN PREPARING PRODRUGS
  申请人：Metabasis Therapeutics, Inc.

  公开号：EP1556393B1

  公开（公告）日：2013-12-25