Dihydropyrazolopyrimidines containing benzimidazoles as KV1.5 potassium channel antagonists

Abstract 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 31a with an IC 50 for K V 1.5 block of 0.030 μM without significant block of other cardiac ion channels. This compound also showed good bioavailability in rats and robust pharmacodynamic effects in a rabbit model.