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.
Lloyd
John
J
Bristol-Myers Squibb Pharmaceutical Research and Development, Princeton, NJ 08543, USA. john.lloyd@bms.com
Finlay
Heather J
HJ
Vacarro
Wayne
W
Hyunh
Tram
T
Kover
Alexander
A
Bhandaru
Rao
R
Yan
Lin
L
Atwal
Karnail
K
Conder
Mary Lee
ML
Jenkins-West
Tonya
T
Shi
Hong
H
Huang
Christine
C
Li
Danshi
D
Sun
Huabin
H
Levesque
Paul
P
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D051666:Kv1.5 Potassium Channel / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D026902:Potassium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology*; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats
D000577:Amides; D051666:Kv1.5 Potassium Channel; D026902:Potassium Channel Blockers; D011720:Pyrazoles; D011759:Pyrrolidines; C032519:pyrrolidine