Design, Structure鈥揂ctivity Relationship, and in Vivo Characterization of the Development Candidate NVP-HSP990

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• 作者：Christopher M. McBride ; Barry Levine ; Yi Xia ; Cornelia Bellamacina ; Timothy Machajewski ; Zhenhai Gao ; Paul Renhowe ; William Antonios-McCrea ; Paul Barsanti ; Kristin Brinner ; Abran Costales ; Brandon Doughan ; Xiaodong Lin ; Alicia Louie ; Maureen McKenna ; Kris Mendenhall ; Daniel Poon ; Alice Rico ; Michael Wang ; Teresa E. Williams ; Tinya Abrams ; Susan Fong ; Thomas Hendrickson ; Dachuan Lei ; Julie Lin ; Daniel Menezes ; Nancy Pryer ; Pietro Taverna ; Yongjin Xu ; Yasheen Zhou ; Cynthia M. Shafer
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：November 13, 2014
• 年：2014
• 卷：57
• 期：21
• 页码：9124-9129
• 全文大小：280K
• ISSN：1520-4804

文摘

Utilizing structure-based drug design, a novel dihydropyridopyrimidinone series which exhibited potent Hsp90 inhibition, good pharmacokinetics upon oral administration, and an excellent pharmacokinetic/pharmacodynamic relationship in vivo was developed from a commercial hit. The exploration of this series led to the selection of NVP-HSP990 as a development candidate.