Design, synthesis, and biological evaluation of structurally modified isoindolinone and quinazolinone derivatives as hedgehog pathway inhibitors

详细信息    查看全文

• 作者：Deepak Bhattarai^a ; ¹ ; Joo Hyun Jung^b ; ¹ ; Seunghyeon Han^a ; Hankyu Lee^b ; Soo Jin Oh^c ; Hyuk Wan Ko^b ; ^{kohw@dongguk.edu} ; Kyeong Lee^a ; ^{Kaylee@dongguk.edu}
• 关键词：Quinazolinone ; Isoindolinone ; Hedgehog pathway ; Structure hopping ; Smoothened ; Gli
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2017
• 出版时间：5 January 2017
• 年：2017
• 卷：125
• 期：Complete
• 页码：1036-1050
• 全文大小：1889 K
• 卷排序：125

文摘

Quinazolinone and isoindolinone analogs were designed and prepared as Hh pathway inhibitors. Several analogs exhibited potent inhibitory activity up to nanomolar IC50. New quinazolinone derivatives suppressed Hh signaling by blocking Smo and Gli translocation into cilia. The representative quinazolinone derivatives preserved the inhibitory activity to vismodegib-resistant Smo mutants. Novel quinazolinone scaffolds can be a useful platform for the development of Hh pathway inhibitors.