Irreversible 4-Aminopiperidine Transglutaminase 2 Inhibitors for Huntington's Disease
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- 作者：Michael E. Prime ; Frederick A. Brookfield ; Stephen M. Courtney ; Simon Gaines ; Richard W. Marston ; Osamu Ichihara ; Marie Li ; Darshan Vaidya ; Helen Williams ; Anna Pedret-Dunn ; Laura Reed ; Sabine Schaertl ; Leticia Toledo-Sherman ; Maria Beconi ; Douglas Macdonald ; Ignacio Mu帽oz-Sanjuan ; Celia Dominguez ; John Wityak
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2012
- 出版时间：September 13, 2012
- 年：2012
- 卷：3
- 期：9
- 页码：731-735
- 全文大小：323K
- 年卷期：v.3,no.9(September 13, 2012)
- ISSN：1948-5875
文摘
A new series of potent TG2 inhibitors are reported that employ a 4-aminopiperidine core bearing an acrylamide warhead. We establish the structure鈥揳ctivity relationship of this new series and report on the transglutaminase selectivity and in vitro ADME properties of selected compounds. We demonstrate that the compounds do not conjugate glutathione in an in vitro setting and have superior plasma stability over our previous series.