Dihydropyrazolopyrimidines Containing Benzimidazoles As K(V)1.5 Potassium Channel Antagonists

Dihydropyrazolopyrimidines with a C6 heterocycle substituent were found to have high potency for block of K(V)1.5. Investigation of the substitution in the benzimidazole ring and the substituent in the 5-position of the dihydropyrazolopyrimidine ring produced 31 a with an IC50 for K(V)1.5 block of 0.030 mu M without significant block of other cardiac ion channels. This compound also showed good bioavailability in rats and robust pharmacodynamic effects in a rabbit model. (C) 2009 Elsevier Ltd. All rights reserved.