Referenced in: none

Automatically associated channels: Kv11.1

Title: Structure and Property Based Design of Pyrazolo[1,5-a]pyrimidine Inhibitors of CK2 Kinase with Activity in Vivo.

Authors: James E Dowling, Marat Alimzhanov, Larry Bao, Michael H Block, Claudio Chuaqui, Emma L Cooke, Christopher R Denz, Alex Hird, Shan Huang, Nicholas A Larsen, Bo Peng, Timothy W Pontz, Caroline Rivard-Costa, Jamal Carlos Saeh, Kumar Thakur, Qing Ye, Tao Zhang, Paul D Lyne

Journal, date & volume: ACS Med Chem Lett, 2013 Aug 8 , 4, 800-5

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24900749

Abstract
In this letter, we describe the design, synthesis, and structure-activity relationship of 5-anilinopyrazolo[1,5-a]pyrimidine inhibitors of CK2 kinase. Property-based optimization of early leads using the 7-oxetan-3-yl amino group led to a series of matched molecular pairs with lower lipophilicity, decreased affinity for human plasma proteins, and reduced binding to the hERG ion channel. Agents in this study were shown to modulate pAKT(S129), a direct substrate of CK2, in vitro and in vivo, and exhibited tumor growth inhibition when administered orally in a murine DLD-1 xenograft.