title: Initial SAR studies on apamin-displacing 2-aminothiazole blockers of calcium-activated small conductance potassium channels.
abstract: An initial SAR study on a series of apamin-displacing 2-aminothiazole K(Ca)2 channel blockers is described. Potent inhibitors such as N-(4-methylpyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (13) are disclosed, and for select members of the series, the relationship between the observed activity in a thallium flux, a binding and a whole-cell electrophysiology assay is presented.
authors.affiliation: Research and Development, Bristol Myers Squibb Co., 5 Research Parkway, Wallingford, CT 06492, USA. robert.gentles@bms.com
authors.forename: Robert G
authors.initials: RG
authors.lastname: Gentles
authors.forename: Katherine
authors.initials: K
authors.lastname: Grant-Young
authors.forename: Shuanghua
authors.initials: S
authors.lastname: Hu
authors.forename: Yazhong
authors.initials: Y
authors.lastname: Huang
authors.forename: Michael A
authors.initials: MA
authors.lastname: Poss
authors.forename: Charles
authors.initials: C
authors.lastname: Andres
authors.forename: Tracey
authors.initials: T
authors.lastname: Fiedler
authors.forename: Ronald
authors.initials: R
authors.lastname: Knox
authors.forename: Nicholas
authors.initials: N
authors.lastname: Lodge
authors.forename: C David
authors.initials: CD
authors.lastname: Weaver
authors.forename: David G
authors.initials: DG
authors.lastname: Harden
mesh_terms: D001030:Apamin / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D015394:Molecular Structure; D026902:Potassium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C532530:N-(4-methylpyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine; D026902:Potassium Channel Blockers; D011725:Pyridines; D051640:Small-Conductance Calcium-Activated Potassium Channels; D013844:Thiazoles; D001030:Apamin