雷洛昔芬N-氧化物 | 195454-31-0

• 物质功能分类: 生物 - 细胞培养 - 添加剂
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 雷洛昔芬N-氧化物
• 中文别名: 雷洛昔芬杂质C
• 英文名称: raloxifene N-oxide
• 英文别名: [2-(4-hydroxyphenyl)-6-hydroxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl) ethoxy]phenyl]methanone N-oxide；[6-hydroxy-2-(4-hydroxyphenyl)-1-benzothiophen-3-yl]-[4-[2-(1-oxidopiperidin-1-ium-1-yl)ethoxy]phenyl]methanone
• CAS: 195454-31-0
• 化学式: C₂₈H₂₇NO₅S
• 分子量: 489.592
• InChiKey: KNADIZJVEMEXLS-UHFFFAOYSA-N

物化性质

• 熔点：
  >180°C (dec.)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• WGK Germany：
  3

制备方法与用途

生物活性方面，Raloxifene N-氧化物是Raloxifene的氧化降解产物。

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  雷洛昔芬	Raloxifen	84449-90-1	C28H27NO4S	473.593

反应信息

• 作为产物：
  描述：

  盐酸雷洛昔芬 在 sodium hydroxide 、 双氧水 作用下， 以 甲醇 、 水 为溶剂， 以75%的产率得到雷洛昔芬N-氧化物
  参考文献：
  名称：

  Enrichment of Relevant Oxidative Degradation Products in Pharmaceuticals With Targeted Chemoselective Oxidation

  摘要：

  The ability to produce and isolate relatively pure amounts of relevant degradation products is key to several aspects of drug product development: (a) aid in the unambiguous structural identification of such degradation products, fulfilling regulatory requirements to develop safe formulations (International Conference on Harmonization Q3B and M7); (b) pursue as appropriate safety evaluations with such material, such as chronic toxicology or Ames testing; (c) for a specified degradation product in a late-stage regulatory filing, use pure and well-characterized material as the analytical standard. Producing such materials is often a resource-and time-intensive activity, either relying on the isolation of slowly formed degradation products from stressed drug product or by re-purposing the drug substance synthetic route. This problem is exacerbated if the material of interest is an oxidative degradation product, because typical oxidative stressing (H2O2 and radical initiators) tends to produce a myriad of irrelevant species beyond a certain stress threshold, greatly complicating attempts for isolating the relevant degradation product. In this article, we present reagents and methods that may allow the rapid and selective enrichment of active pharmaceutical ingredient with the desired oxidative degradation product, which can then be isolated and used for purposes described above. (c) 2019 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.xphs.2018.10.059

文献信息

• Benzothiophenes, formulations containing same, and methods
  申请人：ELI LILLY AND COMPANY

  公开号：EP0791591A1

  公开（公告）日：1997-08-27

  This invention provides pharmaceutical benzothiophene compounds of the formula wherein R1 is hydrogen, hydroxy, C1-C4 alkoxy, wherein Ar is optionally substituted phenyl, or -SO2(C4-C6 straight chain alkyl); R2 is R1, Cl or F; and R3 and R4 are, independently, C1-C4 alkyl or combine to form a C4-C6 polymethylene or, together with the nitrogen to which they are attached form morpholine, X is -CH2, -CHOH2-, -O-, or or a pharmaceutically acceptable salt or solvate thereof.

  本发明提供了如下式的药用苯并噻吩化合物 其中 R1 是氢、羟基、C1-C4 烷氧基、 其中 Ar 是任选取代的苯基，或 -SO2(C4-C6 直链烷基)； R2 是 R1、Cl 或 F；以及 R3 和 R4 独立地为 C1-C4 烷基，或结合形成 C4-C6 聚亚甲基，或与所连接的氮一起形成吗啉、 X是-CH2、-CHOH2-、-O-或 或其药学上可接受的盐或溶液。
• 2-Arylbenzo b thiophenes useful for the treatment of estrogen deprivation syndrome
  申请人：ELI LILLY AND COMPANY

  公开号：EP0920862A1

  公开（公告）日：1999-06-09

  This invention provides methods which are useful for the inhibition of the various medical conditions associated with estrogen deprivation syndrome including osteoporosis and hyperlipidemia utilizing compounds of formula I:

  本发明提供了利用式 I 化合物抑制与雌激素缺乏综合征有关的各种病症（包括骨质疏松症和高脂血症）的方法：
• Benzothiophenes, formulations containing same, and methods for their préparation
  申请人：ELI LILLY AND COMPANY

  公开号：EP0791591B1

  公开（公告）日：2001-08-29
• RALOXIFENE COMPOSITION
  申请人：Synthon B.V.

  公开号：EP2242483B1

  公开（公告）日：2013-02-20
• US6087378A
  申请人：——

  公开号：US6087378A

  公开（公告）日：2000-07-11