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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.

SUBMITTER: Finlay HJ

PROVIDER: S-EPMC5018869 | biostudies-other | 2016 Sep

REPOSITORIES: biostudies-other

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Discovery of 5-Phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine as a Potent I Kur Inhibitor.

Finlay Heather J HJ Johnson James A JA Lloyd John L JL Jiang Ji J Neels James J Gunaga Prashantha P Banerjee Abhisek A Dhondi Naveen N Chimalakonda Anjaneya A Mandlekar Sandhya S Conder Mary Lee ML Sale Harinath H Xing Dezhi D Levesque Paul P Wexler Ruth R RR

ACS medicinal chemistry letters 20160609 9

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. ...[more]

PMID: 27660686

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Crystal structure of (pyridin-2-yl-methyl-idene)(tri-phenyl-meth-yl)amine.

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N-Cyclo-hexyl-N-{[3-(4,6-dimeth-oxy-pyrimidin-2-yl-oxy)pyridin-2-yl]meth-yl}4,6-dimeth-oxy-pyrimidin-2-amine.

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