Channelpedia

PubMed 20006500


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kv11.1 , SK3



Title: Tetrasubstituted pyridines as potent and selective AKT inhibitors: Reduced CYP450 and hERG inhibition of aminopyridines.

Authors: Hong Lin, Dennis S Yamashita, Ren Xie, Jin Zeng, Wenyong Wang, Jack Leber, Igor G Safonov, Sharad Verma, Mei Li, Louis Lafrance, Joseph Venslavsky, Dennis Takata, Juan I Luengo, Jason A Kahana, Shuyun Zhang, Kimberly A Robell, Dana Levy, Rakesh Kumar, Anthony E Choudhry, Michael Schaber, Zhihong Lai, Barry S Brown, Brian T Donovan, Elisabeth A Minthorn, Kristin K Brown, Dirk A Heerding

Journal, date & volume: Bioorg. Med. Chem. Lett., 2010 Jan 15 , 20, 684-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20006500


Abstract
The synthesis and evaluation of tetrasubstituted aminopyridines, bearing novel azaindazole hinge binders, as potent AKT inhibitors are described. Compound 14c was identified as a potent AKT inhibitor that demonstrated reduced CYP450 inhibition and an improved developability profile compared to those of previously described trisubstituted pyridines. It also displayed dose-dependent inhibition of both phosphorylation of GSK3beta and tumor growth in a BT474 tumor xenograft model in mice.