Design, structure-activity relationship, and in vivo characterization of the development candidate NVP-HSP990

  • J Med Chem. 2014 Nov 13;57(21):9124-9. doi: 10.1021/jm501107q.
Christopher M McBride  1 ,  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
Affiliations
  • 1. Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research , 5300 Chiron Way, Emeryville, California 94608, United States.
PMID: 25368984 DOI: 10.1021/jm501107q
Abstract

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.

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