Pyrrolidine amides of pyrazolodihydropyrimidines as potent and selective Kv1.5 blockers

Design and synthesis of pyrazolodihydropyrimidines as KV1.5 blockers led to the discovery of 7d as a potent and selective antagonist. This compound showed atrial selective prolongation of effective refractory period in rabbits and was selected for clinical development.

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2010-02, Vol.20 (4), p.1436-1439
Main Authors: LLOYD, John, FINLAY, Heather J, HONG SHI, HUANG, Christine, DANSHI LI, HUABIN SUN, LEVESQUE, Paul, VACARRO, Wayne, HYUNH, Tram, KOVER, Alexander, BHANDARU, Rao, LIN YAN, ATWAL, Karnail, LEE CONDER, Mary, JENKINS-WEST, Tonya
Format: Article
Language:English
Subjects:
Amides - chemical synthesis
Amides - chemistry
Amides - pharmacology
Animals
Antiarythmic agents
Biological and medical sciences
Cardiovascular system
Dogs
Dose-Response Relationship, Drug
Inhibitory Concentration 50
Kv1.5 Potassium Channel - antagonists & inhibitors
Medical sciences
Molecular Structure
Pharmacology. Drug treatments
Potassium Channel Blockers - chemical synthesis
Potassium Channel Blockers - chemistry
Potassium Channel Blockers - pharmacology
Pyrazoles - pharmacology
Pyrrolidines - chemical synthesis
Pyrrolidines - chemistry
Pyrrolidines - pharmacology
Rabbits
Rats
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Description
Summary:Design and synthesis of pyrazolodihydropyrimidines as KV1.5 blockers led to the discovery of 7d as a potent and selective antagonist. This compound showed atrial selective prolongation of effective refractory period in rabbits and was selected for clinical development.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2009.12.085