多成分結晶に溶剤を組み込むことによって誘発される同構造性の予測と観測
Aurora J Cruz Cabeza1, Graeme M Day, W D Samuel Motherwell
1The Pfizer Institute for Pharmaceutical Materials Science, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK.
Journal of the American Chemical Society
|November 9, 2006
まとめ
計算方法により,カルバマゼピンと,その二水分誘導体である酸の結晶構造が予測されました. 予期せぬことに,これらの異なる分子は同型共結晶を形成し,新しい製薬の可能性を明らかにしました.
科学分野:
- 医薬品科学 医薬品科学とは
- クリスタルグラフィーです.
- コンピューティング・ケミストリー
背景:
- カーバマゼピンの結晶構造は知られているが,その10,11-二水素誘導体は構造データがない.
- 医薬品の共結晶構造を予測することは,薬の開発において極めて重要です.
研究 の 目的:
- カルバマゼピンの結晶構造とその10,11-ジヒドロ誘導体と酸性酸の複合体を計算的に予測する.
- 同型共結晶形成の可能性を調査する.
主な方法:
- 計算モデリングを用いたインシリコ結晶構造の予測.
- 生成された結晶構造のイソモルフィズム分析.
主要な成果:
- カルバマゼピン酸と,その二水分派生体-酸エステンの共結晶の両方の妥当性の高い結晶構造の予測に成功しました.
- 親薬の分子の有意な差異にもかかわらず,結果として生成されたコクリスタルは同型であることが判明しました.
- 同型性は,水晶格子にエステル酸を組み込むことによって達成された.
結論:
- 計算方法は,新しい化合物であっても,医薬品の共結晶構造を予測するのに有効です.
- エセティック酸は,構造的に異なった製薬分子によるコ結晶の同型性を誘発することができる.
- この発見は,特別の性質を持つ固体形態の医薬品を設計するための新しい道を示唆しています.
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