Hydroxamates: Relationships between Structure and Plasma Stability

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• 作者：Marion Flipo ; Julie Charton ; Akila Hocine ; Sandrine Dassonneville ; Benoit Deprez ; Rebecca Deprez-Poulain
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：November 12, 2009
• 年：2009
• 卷：52
• 期：21
• 页码：6790-6802
• 全文大小：993K
• 年卷期：v.52,no.21(November 12, 2009)
• ISSN：1520-4804

文摘

Hydroxamates are valuable tools for chemical biology as well as interesting leads for medicinal chemistry. Although many hydroxamates display nanomolar activities against metalloproteases, only three hydroxamates have reached the market, among which is the HDAC inhibitor vorinostat. Failures in development are generally attributed to lack of selectivity, toxicity, or poor stability. To help medicinal chemists with respect to plasma stability, we have performed the first and preliminary study on structure−plasma stability for hydroxamates. We define some structural rules to predict or improve the plasma stability in the preclinical stage.