title: Potent and Selective Inhibitors of CK2 Kinase Identified through Structure-Guided Hybridization.
abstract: In this paper we describe a series of 3-cyano-5-aryl-7-aminopyrazolo[1,5-a]pyrimidine hits identified by kinase-focused subset screening as starting points for the structure-based design of conformationally constrained 6-acetamido-indole inhibitors of CK2. The synthesis, SAR, and effects of this novel series on Akt signaling and cell proliferation in vitro are described.
authors.affiliation: AstraZeneca , Oncology Innovative Medicines Unit, 35 Gatehouse Drive, Waltham, Massachusetts 02145, United States.
authors.forename: James E
authors.initials: JE
authors.lastname: Dowling
authors.affiliation: AstraZeneca , Oncology Innovative Medicines Unit, 35 Gatehouse Drive, Waltham, Massachusetts 02145, United States.
authors.forename: Claudio
authors.initials: C
authors.lastname: Chuaqui
authors.affiliation: AstraZeneca , Oncology Innovative Medicines Unit, 35 Gatehouse Drive, Waltham, Massachusetts 02145, United States.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Pontz
authors.affiliation: AstraZeneca , Oncology Innovative Medicines Unit, 35 Gatehouse Drive, Waltham, Massachusetts 02145, United States.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Lyne
authors.affiliation: AstraZeneca , Oncology Innovative Medicines Unit, 35 Gatehouse Drive, Waltham, Massachusetts 02145, United States.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Larsen
authors.affiliation: AstraZeneca , Oncology Innovative Medicines Unit, 35 Gatehouse Drive, Waltham, Massachusetts 02145, United States.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Block
authors.affiliation: AstraZeneca , Oncology Innovative Medicines Unit, 35 Gatehouse Drive, Waltham, Massachusetts 02145, United States.
authors.forename: Huawei
authors.initials: H
authors.lastname: Chen
authors.affiliation: AstraZeneca , Oncology Innovative Medicines Unit, 35 Gatehouse Drive, Waltham, Massachusetts 02145, United States.
authors.forename: Nancy
authors.initials: N
authors.lastname: Su
authors.affiliation: AstraZeneca , Oncology Innovative Medicines Unit, 35 Gatehouse Drive, Waltham, Massachusetts 02145, United States.
authors.forename: Allan
authors.initials: A
authors.lastname: Wu
authors.affiliation: AstraZeneca , Oncology Innovative Medicines Unit, 35 Gatehouse Drive, Waltham, Massachusetts 02145, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Russell
authors.affiliation: AstraZeneca , Oncology Innovative Medicines Unit, 35 Gatehouse Drive, Waltham, Massachusetts 02145, United States.
authors.forename: Hannah
authors.initials: H
authors.lastname: Pollard
authors.affiliation: AstraZeneca , Oncology Innovative Medicines Unit, 35 Gatehouse Drive, Waltham, Massachusetts 02145, United States.
authors.forename: John W
authors.initials: JW
authors.lastname: Lee
authors.affiliation: AstraZeneca , Oncology Innovative Medicines Unit, 35 Gatehouse Drive, Waltham, Massachusetts 02145, United States.
authors.forename: Bo
authors.initials: B
authors.lastname: Peng
authors.affiliation: AstraZeneca , Oncology Innovative Medicines Unit, 35 Gatehouse Drive, Waltham, Massachusetts 02145, United States.
authors.forename: Kumar
authors.initials: K
authors.lastname: Thakur
authors.affiliation: AstraZeneca , Oncology Innovative Medicines Unit, 35 Gatehouse Drive, Waltham, Massachusetts 02145, United States.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.affiliation: AstraZeneca , Oncology Innovative Medicines Unit, 35 Gatehouse Drive, Waltham, Massachusetts 02145, United States.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: AstraZeneca , Oncology Innovative Medicines Unit, 35 Gatehouse Drive, Waltham, Massachusetts 02145, United States.
authors.forename: Patrick
authors.initials: P
authors.lastname: Brassil
authors.affiliation: AstraZeneca , Oncology Innovative Medicines Unit, 35 Gatehouse Drive, Waltham, Massachusetts 02145, United States.
authors.forename: Vicki
authors.initials: V
authors.lastname: Racicot
authors.affiliation: AstraZeneca , Oncology Innovative Medicines Unit, 35 Gatehouse Drive, Waltham, Massachusetts 02145, United States.
authors.forename: Larry
authors.initials: L
authors.lastname: Bao
authors.affiliation: AstraZeneca , Oncology Innovative Medicines Unit, 35 Gatehouse Drive, Waltham, Massachusetts 02145, United States.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Denz
authors.affiliation: AstraZeneca , Oncology Innovative Medicines Unit, 35 Gatehouse Drive, Waltham, Massachusetts 02145, United States.
authors.forename: Emma
authors.initials: E
authors.lastname: Cooke
keywords: CK2; casein kinase; pyrazolo[1,5-a]pyrimidine; structure-based design