3-(2-氯乙基)八氢-2-羟基-1,3,6,2-氧杂二氮杂磷杂八环 2-氧化物 | 158401-52-6

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 中文名称: 3-(2-氯乙基)八氢-2-羟基-1,3,6,2-氧杂二氮杂磷杂八环 2-氧化物
• 中文别名: 3-(2-氯乙基)八氢-2-羟基-1,3,6,2-氧杂二氮杂磷杂八环2-氧化物；环磷酰胺相关化合物B
• 英文名称: 3-(2-Chloroethyl)octahydro-2-hydroxy-1,3,6,2-oxadiazaphosphonine 2-oxide
• 英文别名: 3-(2-Chloroethyl)-2-oxo-2-hydroxy-1,3,6,2-oxadiazaphosphonane；chloroethyl-2-oxo-2-hydroxy-1,3,6,2-oxadiazaphosphonane；3-(2-Chloroethyl)-2-hydroxy-1,3,6,2-oxadiazaphosphonane 2-oxide；3-(2-chloroethyl)-2-hydroxy-1,3,6,2λ5-oxadiazaphosphonane 2-oxide
• CAS: 158401-52-6
• 化学式: C₇H₁₆ClN₂O₃P
• 分子量: 242.642
• InChiKey: SIMWMEHPUXRDQD-UHFFFAOYSA-N

物化性质

• 熔点：
  >190°C (dec.)
• 沸点：
  371.0±52.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)
• 溶解度：
  可微溶于水

计算性质

• 辛醇/水分配系数(LogP)：
  -2.8
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  61.8
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• WGK Germany：
  3
• 储存条件：
  -20°C，密封保存，并保持干燥。

反应信息

• 作为产物：
  描述：

  环磷酰胺 在 sodium cacodylate buffer 作用下， 反应 4.0h， 生成 3-(2-氯乙基)八氢-2-羟基-1,3,6,2-氧杂二氮杂磷杂八环 2-氧化物
  参考文献：
  名称：

  Chemical and Biological Evaluation of Hydrolysis Products of Cyclophosphamide

  摘要：

  P-31 NMR spectroscopy was used to study the products of the decomposition of cyclophosphamide (1) in buffered solutions at pH's ranging between 1.2 and 8.6 at 20 degrees C and at pH 7.4 at 37 degrees C. At pH 1.2, 1 undergoes a rapid breakdown (t(1/2) = 1.4 days) of the two P-N bonds, giving compounds 2 [HN(CH2CH2Cl)(2)] and 3 [H2N(CH2)(3)OP(O)(OH)(2)] as hydrochlorides. No intermediates were detected. At pH's between 5.4 and 8.6, hydrolysis of 1 during 17 days leads to the sole and previously unknown nine-membered ring compound 13. 13 results from the intramolecular alkylation of 1 giving the bicyclic compound 7 followed by the exothermal hydrolytic breakdown of the P-N bond of its six-membered ring. At pH 2.2 and 3.4, the two hydrolytic pathways coexist since, beside compounds 2 and 3, the hydrochloride of compound 9 [Cl(CH2)(2)NH(CH2)(2)NH(CH2)(3)OP(O)(OH)(2)] is formed, resulting from the acid-catalyzed breakdown of the P-N bond in the nine-membered ring compound 13. At pH 2.2, the presence of chloride ion affected neither the stability of 1 nor the contribution of the two competing hydrolytic pathways. At pH's ranging from 3.4 to 8.6, there is little degradation of 1 since more than 95% of initial 1 was still present after 7 days at 20 degrees C. Under physiological conditions (pH 7.4, 37 degrees C) after 6 days, 45% of 1 is hydrolyzed (t(1/2) = 6.6 days), leading essentially (30% of initial 1) to the nine-membered ring compound 13. The rate of hydrolysis of 13 and the nature of its hydrolysis products were found to depend on pH over the range 0-8.6. After a single ip injection to mice, compounds 3, 9, and 13 were less toxic than 1. They did not exhibit any direct cytotoxic efficacy on the colony-forming capacity of L1210 cells in vitro, and they had no antitumor activity in vivo against P388 leukemia.

  DOI：

  10.1021/jm00049a018

文献信息

• METHOD FOR HYDRATING LYOPHILIZED CYCLOPHOSPHAMIDE COMPOSITION AND PRODUCT THEREOF
  申请人：Sinotherapeutics Inc.

  公开号：EP3831366A1

  公开（公告）日：2021-06-09

  Provided are a hydration method for a lyophilized cyclophosphamide composition and a composition and preparation prepared thereby. The hydration method comprises: (a) providing an aqueous solution comprising cyclophosphamide and an optional pharmaceutically acceptable excipient; (b) freeze-drying the solution to obtain a lyophilized composition; and (c) hydrating the lyophilized composition by using liquid water to obtain the product.

  本发明提供了一种用于冻干环磷酰胺组合物的水合方法以及由此制备的组合物和制剂。水合方法包括：(a) 提供包含环磷酰胺和任选的药学上可接受的赋形剂的水溶液；(b) 冷冻干燥溶液以获得冻干组合物；(c) 使用液态水水合冻干组合物以获得产品。
• Stable liquid formulations of cyclophosphamide and its impurities
  申请人：DR. REDDY'S LABORATORIES LIMITED

  公开号：US10849916B2

  公开（公告）日：2020-12-01

  The present invention relates to novel impurities of cyclophosphamide having structure V, VI or VII, stabilized form of these novel impurities, a process of preparing a stabilized form and isolating thereof. The invention also relates cyclophosphamide formulations which include cyclophosphamide, at least one pharmaceutically acceptable excipient, and a certain level of these impurities having structure V, VI or VII. The invention further relate to method of using such stable liquid formulations of cyclophosphamide for parenteral administration in treating various cancer disorders.

  本发明涉及具有 V、VI 或 VII 结构的新型环磷酰胺杂质、这些新型杂质的稳定形式、制备稳定形式的工艺及其分离。本发明还涉及环磷酰胺制剂，其中包括环磷酰胺、至少一种药学上可接受的赋形剂和一定含量的具有 V、VI 或 VII 结构的这些杂质。本发明还涉及使用这种稳定的环磷酰胺液体制剂进行肠外给药治疗各种癌症疾病的方法。
• Stable ready to use cyclophosphamide liquid formulations
  申请人：LEIUTIS PHARMACEUTICALS PVT. LTD.

  公开号：US10993952B2

  公开（公告）日：2021-05-04

  The present invention relates to stable ready to use liquid formulations of Cyclophosphamide for parenteral use. The ready to use composition comprises Cyclophosphamide dissolved in a solvent system comprising a solvent, cosolvent(s) and antioxidant(s).

  本发明涉及肠外用环磷酰胺的稳定即用型液体制剂。即用型组合物包括溶解在由溶剂、共溶剂和抗氧化剂组成的溶剂体系中的环磷酰胺。
• Stable liquid formulations of cyclophosphamide and processes to prepare the same
  申请人：DR. REDDY'S LABORATORIES LIMITED

  公开号：US11382923B2

  公开（公告）日：2022-07-12

  The present invention relates to stable liquid pharmaceutical formulations of cyclophosphamide comprising cyclophosphamide and at least one pharmaceutically acceptable excipient wherein moisture content of the liquid formulation is less than about 2.0% by weight. The invention further relates to stable liquid formulations of cyclophosphamide prepared by a process comprising a step of reducing the moisture content from cyclophosphamide or liquid compositions of cyclophosphamide or both. The invention further relate to method of using such stable liquid formulations of cyclophosphamide for parenteral administration either as ready-to-use or ready-to-dilute for treating various cancer disorders.

  本发明涉及稳定的环磷酰胺液体药物制剂，该制剂由环磷酰胺和至少一种药学上可接受的赋形剂组成，其中液体制剂的水分含量按重量计小于约2.0%。本发明进一步涉及稳定的环磷酰胺液体制剂，其制备过程包括降低环磷酰胺或环磷酰胺液体组合物或两者的水分含量的步骤。本发明进一步涉及使用这种稳定的环磷酰胺液体制剂进行肠外给药的方法，这种制剂可以是即用型的，也可以是稀释型的，用于治疗各种癌症疾病。
• [EN] METHOD FOR HYDRATING LYOPHILIZED CYCLOPHOSPHAMIDE COMPOSITION AND PRODUCT THEREOF<br/>[FR] PROCÉDÉ D'HYDRATATION D'UNE COMPOSITION DE CYCLOPHOSPHAMIDE LYOPHILISÉE ET PRODUIT ASSOCIÉ<br/>[ZH] 一种水化环磷酰胺冻干组合物的方法及其产品
  申请人：SINOTHERAPEUTICS INC

  公开号：WO2020025069A1

  公开（公告）日：2020-02-06

  一种冻干环磷酰胺组合物的水化方法及其制备得到的组合物和制剂。该水化方法包括：(a)提供含有环磷酰胺以及任选存在的药学上可接受的辅料的水溶液；(b)将所述溶液冷冻干燥以获得冻干组合物；(c)使用液态水将所述冻干组合物水化，即得。