Dihydropyrazolopyrimidines Containing Benzimidazoles As K(V)1.5 Potassium Channel Antagonists
Bioorganic & Medicinal Chemistry Letters(2009)
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 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.
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Key words
I-Kur,K(V)1.5,Voltage gated potassium channel,Atrial fibrillation
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