Dihydropyrazolopyrimidines containing benzimidazoles as K_V1.5 potassium channel antagonists

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• 作者：John Lloyd ; Heather J. Finlay ; Karnail Atwal ; Alex ; er Kover ; Joseph Prol ; Lin Yan ; Rao Bh ; aru ; Wayne Vaccaro ; Tram Huynh ; Christine S. Huang ; MaryLee Conder ; Tonya Jenkins-West ; Huabin Sun ; Danshi Li
• 关键词：I_Kur ; K_V1.5 ; Voltage gated potassium channel ; Atrial fibrillation
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2009
• 出版时间：15 September 2009
• 年：2009
• 卷：19
• 期：18
• 页码：5469-5473
• 全文大小：555 K

文摘

Dihydropyrazolopyrimidines with a C6 heterocycle substituent were found to have high potency for block of K_V1.5. 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 K_V1.5 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.