フェニルチオノルスタチンの合成とBACE1阻害剤への導入
書誌事項
- タイトル別名
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- SYNTHESIS OF PHENYLTHIONORSTATINE AND ITS APPLICATION TO BACE1 INHIBITOR
説明
We reported potent and small-sized BACE1 inhibitors containing phenylnorstatine [(2R,3S)-3-amino-2-hydroxy-4-phenylbutyric acid; Pns] at P1 position as a transition-state mimic. We replaced the Pns by its thio-derivative. Herein, we present the synthesis of a novel phenylthionorstatine [(2R,3R)-3-amino-2-hydroxy-4-(phenylthio)butyric acid; Ptns] as a P1 moiety, and then, an application to the BACE1 inhibitors design. We have synthesized Ptns starting from readily available N-benzyloxycarbonyl-serine and after multistep reaction (including Weinreb amide formation, thiophenyl group introduction, through cyanohydrin derivative the transformation into the 2-hydroxy ester and then acid). Ptns was applied to SPPS (solid phase peptide synthesis). The peptide inhibitors of BACE1 containing Pns or Ptns at the P1 position, were adopted to enzyme assay and showed high BACE1 inhibitory activity.
収録刊行物
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- 反応と合成の進歩シンポジウム 発表要旨概要
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反応と合成の進歩シンポジウム 発表要旨概要 32 (0), 116-116, 2006
日本薬学会化学系薬学部会
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詳細情報 詳細情報について
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- CRID
- 1390001205634195968
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- NII論文ID
- 130006996462
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可
