Heather J Finlay, James A Johnson, John L Lloyd, Ji Jiang, James Neels, Prashantha Gunaga, Abhisek Banerjee, Naveen Dhondi, Anjaneya Chimalakonda, Sandhya Mandlekar, Mary Lee Conder, Harinath Sale, Dezhi Xing, Paul Levesque, Ruth R Wexler
A new series of phenylquinazoline inhibitors of Kv 1.5 is disclosed. The series was optimized for Kv 1.5 potency, selectivity versus hERG, pharmacokinetic exposure, and pharmacodynamic potency. 5-Phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine (13k) was identified as a potent and ion channel selective inhibitor with robust efficacy in the preclinical rat ventricular effective refractory period (VERP) model and the rabbit atrial effective refractory period (AERP) model.
September 8, 2016: ACS Medicinal Chemistry Letters