Article ID Journal Published Year Pages File Type
1372011 Bioorganic & Medicinal Chemistry Letters 2009 5 Pages PDF
Abstract

Dihydropyrazolopyrimidines with a C6 heterocycle substituent were found to have high potency for block of KV1.5. Investigation of the substitution in the benzimidazole ring and the substituent in the 5-position of the dihydropyrazolopyrimidine ring produced 31a with an IC50 for KV1.5 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.

Graphical abstractKV1.5 blockers have the potential to be selective agents for the treatment of atrial fibrillation. Dihydropyrazolopyrimidines provide a template for the synthesis of potent and selective KV1.5 blockers.Figure optionsDownload full-size imageDownload as PowerPoint slide

Related Topics
Physical Sciences and Engineering Chemistry Organic Chemistry
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