title: Design, structure-activity relationship, and in vivo characterization of the development candidate NVP-HSP990.
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.
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research , 5300 Chiron Way, Emeryville, California 94608, United States.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: McBride
authors.forename: Barry
authors.initials: B
authors.lastname: Levine
authors.forename: Yi
authors.initials: Y
authors.lastname: Xia
authors.forename: Cornelia
authors.initials: C
authors.lastname: Bellamacina
authors.forename: Timothy
authors.initials: T
authors.lastname: Machajewski
authors.forename: Zhenhai
authors.initials: Z
authors.lastname: Gao
authors.forename: Paul
authors.initials: P
authors.lastname: Renhowe
authors.forename: William
authors.initials: W
authors.lastname: Antonios-McCrea
authors.forename: Paul
authors.initials: P
authors.lastname: Barsanti
authors.forename: Kristin
authors.initials: K
authors.lastname: Brinner
authors.forename: Abran
authors.initials: A
authors.lastname: Costales
authors.forename: Brandon
authors.initials: B
authors.lastname: Doughan
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Lin
authors.forename: Alicia
authors.initials: A
authors.lastname: Louie
authors.forename: Maureen
authors.initials: M
authors.lastname: McKenna
authors.forename: Kris
authors.initials: K
authors.lastname: Mendenhall
authors.forename: Daniel
authors.initials: D
authors.lastname: Poon
authors.forename: Alice
authors.initials: A
authors.lastname: Rico
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.forename: Teresa E
authors.initials: TE
authors.lastname: Williams
authors.forename: Tinya
authors.initials: T
authors.lastname: Abrams
authors.forename: Susan
authors.initials: S
authors.lastname: Fong
authors.forename: Thomas
authors.initials: T
authors.lastname: Hendrickson
authors.forename: Dachuan
authors.initials: D
authors.lastname: Lei
authors.forename: Julie
authors.initials: J
authors.lastname: Lin
authors.forename: Daniel
authors.initials: D
authors.lastname: Menezes
authors.forename: Nancy
authors.initials: N
authors.lastname: Pryer
authors.forename: Pietro
authors.initials: P
authors.lastname: Taverna
authors.forename: Yongjin
authors.initials: Y
authors.lastname: Xu
authors.forename: Yasheen
authors.initials: Y
authors.lastname: Zhou
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Shafer
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D051379:Mice; D011728:Pyridones / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: C570862:2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido(4,3-d)pyrimidin-5(6H)-one; D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D011728:Pyridones; D011743:Pyrimidines