Structure-activity relationships of 2-arylquinazolin-4-ones as highly selective and potent inhibitors of the tankyrases
详细信息 查看全文
- 作者：Amit Nathubhaia ; a.nathubhai@bath.ac.uk" class="auth_mail" title="E-mail the corresponding author ; Teemu Haikarainenb ; Penelope C. Haywardc ; Silvia Muñ ; oz-Descalzod ; Andrew S. Thompsona ; Matthew D. Lloyda ; Lari Lehtiö ; b ; Michael D. Threadgilla
- 关键词：Tankyrase ; PARP ; 2-Arylquinazolin-4-one ; Wnt ; Hydrophobic cavity
- 刊名：European Journal of Medicinal Chemistry
- 出版年：2016
- 出版时间：8 August 2016
- 年：2016
- 卷：118
- 期：Complete
- 页码：316-327
- 全文大小：1343 K
文摘
- •
Structure-Activity Relationship of 2-arylquinazolin-4-ones as tankyrase inhibitors.
- •
8-Methyl group gives selectivity for tankyrases over PARP-1 and PARP-2.
- •
Polar groups at the 8-position give poor isoform-selectivity.
- •
Crystal structures rationalised the observed selectivity.
- •
Reveal a novel, potent and selective tankyrase and Wnt signalling inhibitor.