title: Pseudosaccharin amines as potent and selective KV1.5 blockers.
abstract: Phenethyl aminoheterocycles like compound 1 were known to be potent I(Kur) blockers although they lacked potency in vivo. Modification of the heterocycle led to the design and synthesis of pseudosaccharin amines. Compounds such as 14, 17d and 21c were found to be potent K(V)1.5 blockers and selective over other cardiac ion channels. These compounds had potent pharmacodynamic activity, however, they also showed off-target activities such as hemodynamic effects.
authors: Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08534-5400, USA.
authors: John
authors: J
authors: Lloyd
authors: Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08534-5400, USA.
authors: Heather J
authors: HJ
authors: Finlay
authors: Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08534-5400, USA.
authors: Alexander
authors: A
authors: Kover
authors: Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08534-5400, USA.
authors: James
authors: J
authors: Johnson
authors: Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08534-5400, USA.
authors: Zulan
authors: Z
authors: Pi
authors: Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08534-5400, USA.
authors: Ji
authors: J
authors: Jiang
authors: Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08534-5400, USA.
authors: James
authors: J
authors: Neels
authors: Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08534-5400, USA.
authors: Cullen
authors: C
authors: Cavallaro
authors: Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08534-5400, USA.
authors: Ruth
authors: R
authors: Wexler
authors: Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08534-5400, USA.
authors: Mary Lee
authors: ML
authors: Conder
authors: Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08534-5400, USA.
authors: Hong
authors: H
authors: Shi
authors: Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08534-5400, USA.
authors: Danshi
authors: D
authors: Li
authors: Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08534-5400, USA.
authors: Huabin
authors: H
authors: Sun
authors: Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08534-5400, USA.
authors: Anjaneya
authors: A
authors: Chimalakonda
authors: Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08534-5400, USA.
authors: Christine
authors: C
authors: Huang
authors: Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08534-5400, USA.
authors: Mark
authors: M
authors: Salvati
authors: Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08534-5400, USA.
authors: Paul
authors: P
authors: Levesque
mesh_terms: D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003510:Cyclohexanes / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051666:Kv1.5 Potassium Channel / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D026902:Potassium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D013141:Spiro Compounds / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D003510:Cyclohexanes; D051666:Kv1.5 Potassium Channel; D026902:Potassium Channel Blockers; D013141:Spiro Compounds
keywords: AERP; Atrial fibrillation; I(Kur); K(V)1.5; Phenethylamine