对乙氨基的代高通量多态性研究和对III形式的实验性衍生结构的研究
Matthew L Peterson1, Sherry L Morissette, Chris McNulty
1TransForm Pharmaceuticals, Inc., 610 Lincoln Street, Waltham, Massachusetts 02451, USA.
一个新的高通量结晶平台,CrystalMax,使得三种乙氨基晶体形式的制备和表征成为可能. 为难以获得的第三种形式提出了结构模型,解释了其具有挑战性的准备工作.
科学领域:
- 结晶科学是结晶的科学.
- 材料科学是一种材料科学.
- 制药科学 制药科学 制药科学
背景情况:
- 乙氨基表现出多态性,有三种已知的晶体形式.
- 描述和准备特定的多态体可能是具有挑战性的.
- 高通量方法为高效的多态选提供了潜力.
研究的目的:
- 开发和利用一个高通量结晶平台,用于乙氨基多态制剂的制备.
- 描述三种已知的乙氨基的晶体形式.
- 为了阐明难以捉摸的第三种乙氨基晶体形式的结构.
主要方法:
- 开发一个高通量结晶平台 (CrystalMax),集成设计软件,机器人处理和微分析.
- 使用各种超和驱动方法进行并行结晶实验.
- 粉末X射线衍射 (PXRD) 分析用于结构阐明.
- 计算建模用于结构假设生成.
主要成果:
- 使用CrystalMax.成功制备和表征了三种乙氨基晶体形式.
- PXRD数据提供了对第三种乙氨基多态的结构的见解.
- 为第三种形式提出的双层结构模型,由O-H...O(H) 键稳定.
- 拟议的结构有助于解释从溶液中获得这种形式的困难.
结论:
- CrystalMax平台对于高通量多态选和准备非常有效.
- 该研究提供了对第三种具有挑战性的乙氨基形式的结构性见解.
- 了解晶体结构和制备方法对于药物开发至关重要.
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