title: Preliminary SAR studies on non-apamin-displacing 4-(aminomethylaryl)pyrrazolopyrimidine K(Ca) channel blockers.
abstract: An exploratory SAR study on a series of potent, non-apamin-displacing 4-(aminomethylaryl)pyrazolopyrimidine K(Ca) channel blockers is described and their selectivity against K(Ca) channel subtypes is reported. The most potent analog, 5-chloro-N-(thiophen-2-ylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine (24) displayed sub-micromolar activity in both a thallium flux and whole-cell electrophysiology assay and did not displace apamin in a competitive binding study.
authors.affiliation: Research and Development, Bristol Myers Squibb Co., 5 Research Parkway, Wallingford, CT, USA. robert.gentles@bms.com
authors.forename: Robert G
authors.initials: RG
authors.lastname: Gentles
authors.forename: Shuanghua
authors.initials: S
authors.lastname: Hu
authors.forename: Yazhong
authors.initials: Y
authors.lastname: Huang
authors.forename: Katherine
authors.initials: K
authors.lastname: Grant-Young
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 / Q000737:chemistry*; D001667:Binding, Competitive; D002460:Cell Line; D004594:Electrophysiology; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D026902:Potassium Channel Blockers / Q000737:chemistry*; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D020033:Protein Isoforms; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013793:Thallium / Q000737:chemistry
chemical_list: D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D020033:Protein Isoforms; D011720:Pyrazoles; D011743:Pyrimidines; D001030:Apamin; D013793:Thallium; C030986:pyrimidine