title: Dihydropyrazolopyrimidines containing benzimidazoles as K(V)1.5 potassium channel antagonists.
abstract: Dihydropyrazolopyrimidines with a C6 heterocycle substituent were found to have high potency for block of K(V)1.5. 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(V)1.5 block of 0.030muM without significant block of other cardiac ion channels. This compound also showed good bioavailability in rats and robust pharmacodynamic effects in a rabbit model.
authors: Bristol-Myers Squibb, Pharmaceutical Research and Development, PO Box 5400, Princeton, NJ 08543-5400, USA. john.lloyd@bms.com
authors: John
authors: J
authors: Lloyd
authors: Heather J
authors: HJ
authors: Finlay
authors: Karnail
authors: K
authors: Atwal
authors: Alexander
authors: A
authors: Kover
authors: Joseph
authors: J
authors: Prol
authors: Lin
authors: L
authors: Yan
authors: Rao
authors: R
authors: Bhandaru
authors: Wayne
authors: W
authors: Vaccaro
authors: Tram
authors: T
authors: Huynh
authors: Christine S
authors: CS
authors: Huang
authors: Marylee
authors: M
authors: Conder
authors: Tonya
authors: T
authors: Jenkins-West
authors: Huabin
authors: H
authors: Sun
authors: Danshi
authors: D
authors: Li
authors: Paul
authors: P
authors: Levesque
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000188:drug therapy; D002460:Cell Line; D006801:Humans; D051666:Kv1.5 Potassium Channel / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011720:Pyrazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011743:Pyrimidines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D051666:Kv1.5 Potassium Channel; D026902:Potassium Channel Blockers; D011720:Pyrazoles; D011743:Pyrimidines; C031280:pyrazole