Pyrrolidine amides of pyrazolodihydropyrimidines as potent and selective KV1.5 blockers

  • Bioorg Med Chem Lett. 2010 Feb 15;20(4):1436-9. doi: 10.1016/j.bmcl.2009.12.085.
John Lloyd  1 ,  Heather J Finlay ,  Wayne Vacarro ,  Tram Hyunh ,  Alexander Kover ,  Rao Bhandaru ,  Lin Yan ,  Karnail Atwal ,  Mary Lee Conder ,  Tonya Jenkins-West ,  Hong Shi ,  Christine Huang ,  Danshi Li ,  Huabin Sun ,  Paul Levesque
Affiliations
  • 1. Bristol-Myers Squibb Pharmaceutical Research and Development, Princeton, NJ 08543, USA. [email protected]
PMID: 20097068 DOI: 10.1016/j.bmcl.2009.12.085
Abstract

Design and synthesis of pyrazolodihydropyrimidines as KV1.5 blockers led to the discovery of 7d as a potent and selective antagonist. This compound showed atrial selective prolongation of effective refractory period in rabbits and was selected for clinical development.