サルフォナミド製薬剤によって導かれた異なったC-H機能化:薬剤発見のツールとしての後期段階の多様化
Hui-Xiong Dai1, Antonia F Stepan, Mark S Plummer
1Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Journal of the American Chemical Society
|April 15, 2011
まとめ
サルフォナミドは,C-H機能化を介して,薬剤の後期的な多様化を可能にします. このアプローチにより,既存の候補薬から,潜在的サイクロオキシゲネーゼII阻害剤などの新薬アナログの迅速な合成が可能になります.
科学分野:
- 薬用化学 薬用化学について
- オーガニック・シンセシス オーガニック・シンセシス
- ドラッグ・ディスカバリー・ディスカバリー・ドラッグ・ディスカバリー・ドラッグ・ディスカバリー
背景:
- 薬剤の発見は,鉛化合物の識別と同類の合成に依存しています.
- 一般的な薬理学者は,効率的なアナログ合成のためにC-H機能化を指示することができます.
- サルフォナミドは,セレコキシブを含む市販の薬剤における一般的な薬剤である.
研究 の 目的:
- 異なったC-H機能化によってスルフォナミドの後期的な多様化を実証する.
- サルフォナミドのC-H機能化反応の汎用性のあるセットを開発する.
- 新薬アナログ,特に潜在的なサイクロオキシゲネーゼII阻害剤を合成する.
主な方法:
- サルフォナミドC-Hの6つの異なる機能化反応を開発した. オレフィネーション,アリレーション,アルキレーション,ハロゲネーション,カルボキシレーション,カルボニレーション.
- サイト選択的なC-H機能化のためにスルフォナミドを誘導するグループ戦略を使用しました.
- サルフォナミドの薬剤候補に後期段階の多様化を適用した.
主要な成果:
- サルフォナミドの異なるC-H機能化が成功裏に実証されました.
- 潜在的サイクロオキシゲネーゼII阻害剤として新型セレコキシブアナログを合成した.
- 確立されたスルフォナミドは,C-H活性化のための効果的な指向グループである.
結論:
- サルフォナミドC-H機能化による後期段階の多様化は,薬剤発見の実行可能な戦略です.
- 開発された方法は,さまざまな薬物アナログを合成するのに広く有用です.
- サルフォナミド誘導群は,C-H活性化に効果があり,非対称な触媒の成功を反映しています.
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