Pseudosaccharin amines as potent and selective KV1.5 blockers
详细信息 查看全文
- 作者：John Lloyd ; Heather J. Finlay ; Alexander Kover ; James Johnson ; Zulan Pi ; Ji Jiang ; James Neels ; Cullen Cavallaro ; Ruth Wexler ; Mary Lee Conder ; Hong Shi ; Danshi Li ; Huabin Sun ; Anjaneya Chimalakonda ; Christine Huang ; Mark Salvati ; Paul Levesque
- 关键词：KV1.5 ; IKur ; Atrial fibrillation ; Phenethylamine ; AERP
- 刊名：Bioorganic & Medicinal Chemistry Letters
- 出版年：2015
- 出版时间：1 November 2015
- 年：2015
- 卷：25
- 期：21
- 页码：4983-4986
- 全文大小：685 K
文摘
Phenethyl aminoheterocycles like compound 1 were known to be potent IKur blockers although they lacked potency in vivo. Modification of the heterocycle led to the design and synthesis of pseudosaccharin amines. Compounds such as 14, 17d and 21c were found to be potent KV1.5 blockers and selective over other cardiac ion channels. These compounds had potent pharmacodynamic activity, however, they also showed off-target activities such as hemodynamic effects.