期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 52, 期 21, 页码 6790-6802出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm900648x
关键词
-
资金
- Fondation pour la Recherche Medicale, Nord-Pas-de-Calais [RAD07001EEA]
Hydroxamates are valuable tools for chemical biology as well its 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.
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