羟基苯达莫司汀 | 109882-27-1

• 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 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 羟基苯达莫司汀
• 中文别名: 羟基苯达莫司汀杂质
• 英文名称: 4-[5-[(2-chloroethyl)-(2-hydroxy-ethyl)amino]-1-methyl-benzimidazo-2-yl]-butanoic acid
• 英文别名: 5-[(2-Chloroethyl)(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazole-2-butanoic acid；4-[5-[2-chloroethyl(2-hydroxyethyl)amino]-1-methylbenzimidazol-2-yl]butanoic acid
• CAS: 109882-27-1
• 化学式: C₁₆H₂₂ClN₃O₃
• 分子量: 339.822
• InChiKey: PFTRYOMJJKBZKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  78.6
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 海关编码：
  2933997500
• WGK Germany：
  3

制备方法与用途

用途

本品为羟基苯达莫司汀的杂质，主要用于作为杂质标准品和对照品。

反应信息

• 作为反应物：
  描述：

  重氮甲烷 、 羟基苯达莫司汀 以 甲醇 为溶剂， 生成 4-{5-[(2-Chloro-ethyl)-(2-hydroxy-ethyl)-amino]-1-methyl-1H-benzoimidazol-2-yl}-butyric acid methyl ester
  参考文献：
  名称：

  Werner; Letsch; Ihn, Pharmazie, 1987, vol. 42, # 4, p. 272 - 273

  摘要：

  DOI：
• 作为产物：
  描述：

  宾达氮芥 在 水 作用下， 反应 8.0h， 以81.6%的产率得到二羟基苯达莫司汀
  参考文献：
  名称：

  Optimization of the N-Lost Drugs Melphalan and Bendamustine: Synthesis and Cytotoxicity of a New Set of Dendrimer−Drug Conjugates as Tumor Therapeutic Agents

  摘要：

  Bendamustine and melphalan are very promising alkylating drugs with applicability in the treatment of various tumoral diseases, e.g., chronic lymphocytic leukemia (CLL) or breast cancer. However, numerous adverse effects limited their use. Therefore, 1,3,5-tris(3-aminopropyl)benzene (G0) and its G1 analogue 3,5-bis(3-aminopropyl)-N-(3-{3,5-bis[3-{3,5-bis(3-aminopropyl)benzoylamino}propyl]phenyl}propyl)benzamide were selected to design cytostatic drug-dendrimer conjugates to achieve tumor cell accumulation by endocytosis as already demonstrated for platinum complexes. The dendrimers act as carriers and an N-(2-hydroxyethyl)maleimide spacer between drug and carrier should guarantee a selective release of the cytostatics in the tumor cells. The resulting cytotoxicity was determined in vitro using the human MCF-7 and MDA-MB-231 breast cancer cell lines. It was demonstrated that melphalan caused cytotoxic effects depending on its free amino group (Boc protection strongly decreased the activity) but independent of a derivation of the carboxylic group (dendrimers and spacer binding). Esterification of bendamustine with the N-(2-hydroxyethyl)maleimide spacer strongly increased the hydrolytic stability of the N-lost moiety, so antiproliferative effects were yet observed in vitro.

  DOI：

  10.1021/bc900453f

文献信息

• PROCESS FOR THE PREPARATION OF BENDAMUSTINE HYDROCHLORIDE
  申请人：FRESENIUS KABI ONCOLOGY LIMITED

  公开号：US20140121383A1

  公开（公告）日：2014-05-01

  The present invention relates to an improved process for the synthesis of bendamustine, in particular, bendamustine hydrochloride of the formula (VI) and its intermediate 1-Methyl-5-[bis(2-chloroethyl)amino]-1H-benzimidazol-2-yl]lithium butanoate of formula (V), both having a purity of ≧99%, which is simple, convenient, economical, does not use hazardous chemicals and industrially viable.

  本发明涉及一种改进的苯达莫司汀合成工艺，特别是苯达莫司汀盐酸盐（化学式（VI））及其中间体1-甲基-5-[双(2-氯乙基)氨基]-1H-苯并咪唑-2-基]锂丁酸酯（化学式（V）），两者纯度≧99%，该工艺简单、方便、经济，不使用危险化学品且具有工业可行性。
• [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF BENDAMUSTINE HYDROCHLORIDE<br/>[FR] PROCÉDÉ AMÉLIORÉ DE PRÉPARATION D'HYDROCHLORURE DE BENDAMUSTINE
  申请人：FRESENIUS KABI ONCOLOGY LTD

  公开号：WO2013046223A1

  公开（公告）日：2013-04-04

  The present invention relates to an improved process for the synthesis of bendamustine, in particular, bendamustine hydrochloride of the formula (VI) and its intermediate 1 -Methyl-5-[bis(2-chloroethyl)amino]- 1H-benzimidazol-2-yl]lithium butanoate of formula(V), both having a purity of ≥99%, which is simple, convenient, economical, does not use hazardous chemicals and industrially viable.

  本发明涉及一种改进的苯达莫司汀合成工艺，特别是苯达莫司汀盐酸盐的合成，其化学式为(VI)，以及其中间体1-甲基-5-[双(2-氯乙基)氨基]-1H-苯并咪唑-2-基]锂丁酸盐，其化学式为(V)，两者纯度均≥99%，该工艺简单、方便、经济，不使用危险化学品且具有工业可行性。
• PROCESS FOR PREPARING BENDAMUS TINE HYDROCHLORIDE MONOHYDRATE
  申请人：Shrawat Vimal Kumar

  公开号：US20130217888A1

  公开（公告）日：2013-08-22

  The present invention provide processes for the preparation of Bendamustine hydrochloride monohydrate of formula (I) The present application also provides a process of purification of Bendamustine hydrochloride or monohydrate to get substantially pure Bendamustine hydrochloride monohydrate crystalline Form-SM. The said Bendamustine hydrochloride monohydrate crystalline Form-SM is characterized by X-ray powder diffraction pattern comprising at least 5 characteristic peaks selected from the XRPD 2 theta degrees peaks at 7.42, 10.60, 11.17, 16.43, 17.94, 22.89, 26.33, 28.77, 30.28, 31.92, 40.89±0.1 2θ°. The present application also provides a process for the preparation of Bendamustine hydrochloride monohydrate crystalline Form-SM useful in making pharmaceutical composition for the treatment of cancer or similar proliferative disorders.

  本发明提供了制备盐酸苯达莫司汀单水合物的方法，其化学式为(I)。本申请还提供了一种用于纯化盐酸苯达莫司汀或单水合物以获得基本纯净的苯达莫司汀单水合物结晶形式-SM的方法。所述的苯达莫司汀单水合物结晶形式-SM的特征是X射线粉末衍射图谱，包括至少5个特征峰，这些峰从XRPD 2θ角度的峰中选择，分别为7.42、10.60、11.17、16.43、17.94、22.89、26.33、28.77、30.28、31.92、40.89±0.12θ°。本申请还提供了一种制备盐酸苯达莫司汀单水合物结晶形式-SM的方法，用于制备用于治疗癌症或类似增殖性疾病的药物组合物。
• ESTERS OF BENDAMUSTINE AND RELATED COMPOUNDS, AND MEDICAL USE THEREOF
  申请人：Arevipharma GmbH

  公开号：US20130289032A1

  公开（公告）日：2013-10-31

  The present invention relates to particular esters of bendamustine and related compounds, and medical uses thereof.

  本发明涉及苯达莫司汀及其相关化合物的特定酯类，以及其医学用途。
• [EN] BENDAMUSTINE DERIVATIVES AND RELATED COMPOUNDS<br/>[FR] DÉRIVÉS DE BENDAMUSTINE ET SES COMPOSÉS
  申请人：SCHICKANEDER HELMUT

  公开号：WO2015091827A1

  公开（公告）日：2015-06-25

  The present invention relates to bendamustine derivatives and related compounds as well as their medical application.

  本发明涉及苯达莫司汀衍生物和相关化合物及其医学应用。