title: Discovery of 5-Phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine as a Potent I Kur Inhibitor.
abstract: 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.
authors.affiliation: Departments of Discovery Chemistry, Biology, and Preclinical Candidate Optimization, Bristol-Myers Squibb, Research and Development , P.O. Box 5400, Princeton, New Jersey 08543-5400, United States.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Finlay
authors.affiliation: Departments of Discovery Chemistry, Biology, and Preclinical Candidate Optimization, Bristol-Myers Squibb, Research and Development , P.O. Box 5400, Princeton, New Jersey 08543-5400, United States.
authors.forename: James A
authors.initials: JA
authors.lastname: Johnson
authors.affiliation: Departments of Discovery Chemistry, Biology, and Preclinical Candidate Optimization, Bristol-Myers Squibb, Research and Development , P.O. Box 5400, Princeton, New Jersey 08543-5400, United States.
authors.forename: John L
authors.initials: JL
authors.lastname: Lloyd
authors.affiliation: Departments of Discovery Chemistry, Biology, and Preclinical Candidate Optimization, Bristol-Myers Squibb, Research and Development , P.O. Box 5400, Princeton, New Jersey 08543-5400, United States.
authors.forename: Ji
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Departments of Discovery Chemistry, Biology, and Preclinical Candidate Optimization, Bristol-Myers Squibb, Research and Development , P.O. Box 5400, Princeton, New Jersey 08543-5400, United States.
authors.forename: James
authors.initials: J
authors.lastname: Neels
authors.affiliation: Departments of Discovery Chemistry, Biology, and Preclinical Candidate Optimization, Biocon Bristol-Myers Squibb Research Center (BBRC) , Bangalore 560099, India.
authors.forename: Prashantha
authors.initials: P
authors.lastname: Gunaga
authors.affiliation: Departments of Discovery Chemistry, Biology, and Preclinical Candidate Optimization, Biocon Bristol-Myers Squibb Research Center (BBRC) , Bangalore 560099, India.
authors.forename: Abhisek
authors.initials: A
authors.lastname: Banerjee
authors.affiliation: Departments of Discovery Chemistry, Biology, and Preclinical Candidate Optimization, Biocon Bristol-Myers Squibb Research Center (BBRC) , Bangalore 560099, India.
authors.forename: Naveen
authors.initials: N
authors.lastname: Dhondi
authors.affiliation: Departments of Discovery Chemistry, Biology, and Preclinical Candidate Optimization, Bristol-Myers Squibb, Research and Development , P.O. Box 5400, Princeton, New Jersey 08543-5400, United States.
authors.forename: Anjaneya
authors.initials: A
authors.lastname: Chimalakonda
authors.affiliation: Departments of Discovery Chemistry, Biology, and Preclinical Candidate Optimization, Biocon Bristol-Myers Squibb Research Center (BBRC) , Bangalore 560099, India.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Mandlekar
authors.affiliation: Departments of Discovery Chemistry, Biology, and Preclinical Candidate Optimization, Bristol-Myers Squibb, Research and Development , P.O. Box 5400, Princeton, New Jersey 08543-5400, United States.
authors.forename: Mary Lee
authors.initials: ML
authors.lastname: Conder
authors.affiliation: Departments of Discovery Chemistry, Biology, and Preclinical Candidate Optimization, Biocon Bristol-Myers Squibb Research Center (BBRC) , Bangalore 560099, India.
authors.forename: Harinath
authors.initials: H
authors.lastname: Sale
authors.affiliation: Departments of Discovery Chemistry, Biology, and Preclinical Candidate Optimization, Bristol-Myers Squibb, Research and Development , P.O. Box 5400, Princeton, New Jersey 08543-5400, United States.
authors.forename: Dezhi
authors.initials: D
authors.lastname: Xing
authors.affiliation: Departments of Discovery Chemistry, Biology, and Preclinical Candidate Optimization, Bristol-Myers Squibb, Research and Development , P.O. Box 5400, Princeton, New Jersey 08543-5400, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Levesque
authors.affiliation: Departments of Discovery Chemistry, Biology, and Preclinical Candidate Optimization, Bristol-Myers Squibb, Research and Development , P.O. Box 5400, Princeton, New Jersey 08543-5400, United States.
authors.forename: Ruth R
authors.initials: RR
authors.lastname: Wexler
keywords: Kv 1.5; atrial effective refractory period; phenylquinazoline; ventricular effective refractory period