title: Pyrrolidine amides of pyrazolodihydropyrimidines as potent and selective KV1.5 blockers.
abstract: 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.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research and Development, Princeton, NJ 08543, USA. john.lloyd@bms.com
authors.forename: John
authors.initials: J
authors.lastname: Lloyd
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Finlay
authors.forename: Wayne
authors.initials: W
authors.lastname: Vacarro
authors.forename: Tram
authors.initials: T
authors.lastname: Hyunh
authors.forename: Alexander
authors.initials: A
authors.lastname: Kover
authors.forename: Rao
authors.initials: R
authors.lastname: Bhandaru
authors.forename: Lin
authors.initials: L
authors.lastname: Yan
authors.forename: Karnail
authors.initials: K
authors.lastname: Atwal
authors.forename: Mary Lee
authors.initials: ML
authors.lastname: Conder
authors.forename: Tonya
authors.initials: T
authors.lastname: Jenkins-West
authors.forename: Hong
authors.initials: H
authors.lastname: Shi
authors.forename: Christine
authors.initials: C
authors.lastname: Huang
authors.forename: Danshi
authors.initials: D
authors.lastname: Li
authors.forename: Huabin
authors.initials: H
authors.lastname: Sun
authors.forename: Paul
authors.initials: P
authors.lastname: Levesque
mesh_terms: 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
chemical_list: D000577:Amides; D051666:Kv1.5 Potassium Channel; D026902:Potassium Channel Blockers; D011720:Pyrazoles; D011759:Pyrrolidines; C032519:pyrrolidine