盐酸苯达莫司汀氯代二聚体杂质 | 1228551-91-4

• 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: 盐酸苯达莫司汀氯代二聚体杂质
• 英文名称: Bendamustine Chloro Dimer Impurity
• 英文别名: 4-[5-[2-[4-[5-[bis(2-chloroethyl)amino]-1-methylbenzimidazol-2-yl]butanoyloxy]ethyl-(2-chloroethyl)amino]-1-methylbenzimidazol-2-yl]butanoic acid
• CAS: 1228551-91-4
• 化学式: C₃₂H₄₁Cl₃N₆O₄
• 分子量: 680.1
• InChiKey: RSSXIQCZWSXHBO-UHFFFAOYSA-N

物化性质

• 熔点：
  >45°C (dec.)
• 溶解度：
  可溶于乙腈（少许）、DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  45
• 可旋转键数：
  20
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  8

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。
• METHODS FOR THE PREPARATION OF BENDAMUSTINE
  申请人：Gayring Anton H.

  公开号：US20130310571A1

  公开（公告）日：2013-11-21

  Improved methods for the preparation and purification of bendamustine hydrochloride are described; such as method of preparing bendamustine hydrochloride comprising contacting a compound of formula HBI: with thionyl chloride

  本文描述了制备和纯化氯化苯达莫司汀的改进方法，例如通过将化合物HBI的配方与氯化硫酰接触来制备氯化苯达莫司汀的方法。
• Lyophilized API preparation
  申请人：Azad Pharma AG

  公开号：EP2985038A1

  公开（公告）日：2016-02-17

  The present invention relates to lyophilized preparations comprising an active pharmaceutical ingredient (API) for pharmaceutical use as well as methods of preparing same.

  本发明涉及包含药用活性药物成分（API）的冻干制剂及其制备方法。
• Oral dosage forms of bendamustine and therapeutic use thereof
  申请人：ASTELLAS DEUTSCHLAND GMBH

  公开号：US10485787B2

  公开（公告）日：2019-11-26

  In the present invention there is provided a pharmaceutical composition for oral administration which comprises bendamustine or a pharmaceutically acceptable, ester, salt or solvate thereof as an active ingredient, and a pharmaceutically acceptable excipient and which shows a dissolution of the bendamustine of at least 60% in 20 minutes, 70% in 40 minutes and 80% in 60 minutes, as measured with a paddle apparatus at 50 rpm according to the European Pharmacopoeia in 500 ml of a dissolution medium at a pH of 1.5. The invention further relates to the above pharmaceutical composition for use for the oral treatment of a medical condition which is selected from chronic lymphocytic leukemia, acute lymphocytic leukaemia, chronic myelocytic leukaemia, acute myelocytic leukaemia, Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, breast cancer, ovarian cancer, small cell lung cancer and non-small cell lung cancer.

  本发明提供了一种用于口服给药的药物组合物，它包括作为活性成分的苯达莫司汀或其药学上可接受的酯类、盐类或溶解物，以及药学上可接受的赋形剂，并且根据《欧洲药典》，在500毫升pH值为1.5的溶解介质中，用桨叶仪器以50转/分的速度测量，苯达莫司汀在20分钟内的溶解度至少为60%，在40分钟内溶解度至少为70%，在60分钟内溶解度至少为80%。本发明进一步涉及上述药物组合物，用于口服治疗选自慢性淋巴细胞白血病、急性淋巴细胞白血病、慢性粒细胞白血病、急性粒细胞白血病、霍奇金病、非霍奇金淋巴瘤、多发性骨髓瘤、乳腺癌、卵巢癌、小细胞肺癌和非小细胞肺癌的病症。
• Oral dosage forms of bendamustine
  申请人：Astellas Deutschland GmbH

  公开号：US10543196B2

  公开（公告）日：2020-01-28

  In the present invention there is provided an oral pharmaceutical composition, comprising bendamustine or a pharmaceutically acceptable, ester, salt or solvate thereof as an active ingredient, and a pharmaceutically acceptable excipient, which is a pharmaceutically acceptable non-ionic surfactant, selected from the group consisting of polyethoxylated castor oil or derivative thereof and a block copolymer of ethylene oxide and propylene oxide.

  本发明提供了一种口服药物组合物，其中包含作为活性成分的苯达莫司汀或其药学上可接受的酯、盐或溶液，以及药学上可接受的赋形剂，即药学上可接受的非离子表面活性剂，该赋形剂选自聚乙氧基化蓖麻油或其衍生物以及环氧乙烷和环氧丙烷的嵌段共聚物组成的组。