title: Triazolo and imidazo dihydropyrazolopyrimidine potassium channel antagonists.
abstract: Previously disclosed C6 amido and benzimidazole dihydropyrazolopyrimidines were potent and selective blockers of IKur current. Syntheses and SAR for C6 triazolo and imidazo dihydropyrazolopyrimidines series are described. Trifluoromethylcyclohexyl N(1) triazole, compound 51, was identified as a potent and selective Kv1.5 inhibitor with an acceptable PK and liability profile.
authors: Department of Discovery Chemistry, Bristol-Myers Squibb, Research and Development, PO Box 5400, Princeton, NJ 08543-5400, United States. heather.finlay@bms.com
authors: Heather J
authors: HJ
authors: Finlay
authors: Ji
authors: J
authors: Jiang
authors: Yolanda
authors: Y
authors: Caringal
authors: Alexander
authors: A
authors: Kover
authors: Mary Lee
authors: ML
authors: Conder
authors: Dezhi
authors: D
authors: Xing
authors: Paul
authors: P
authors: Levesque
authors: Timothy
authors: T
authors: Harper
authors: Mei Mann
authors: MM
authors: Hsueh
authors: Karnail
authors: K
authors: Atwal
authors: Michael
authors: M
authors: Blanar
authors: Ruth
authors: R
authors: Wexler
authors: John
authors: J
authors: Lloyd
mesh_terms: D000818:Animals; D002460:Cell Line; D007093:Imidazoles / Q000737:chemistry; D007536:Isomerism; D051666:Kv1.5 Potassium Channel / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D026902:Potassium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: C583194:7-(3,4-dichlorophenyl)-5-methyl-2-(trifluoromethyl)-6-(1-(4-(trifluoromethyl)cyclohexyl)-1H-1,2,4-triazol-5-yl)-4,7-dihydropyrazolo(1,5-a)pyrimidine; D007093:Imidazoles; D051666:Kv1.5 Potassium Channel; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011720:Pyrazoles; D011743:Pyrimidines; D014230:Triazoles; C031280:pyrazole; C029899:imidazole; C030986:pyrimidine