Ontology highlight
ABSTRACT:
SUBMITTER: Porter JD
PROVIDER: S-EPMC6858848 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
Porter Jacob D JD Vivas Oscar O Weaver C David CD Alsafran Abdulmohsen A DiMilo Elliot E Arnold Leggy A LA Dickson Eamonn J EJ Dockendorff Chris C
Bioorganic & medicinal chemistry letters 20190914 23
A set of novel Kv7.2/7.3 (KCNQ2/3) channel blockers was synthesized to address several liabilities of the known compounds XE991 (metabolic instability and CYP inhibition) and the clinical compound DMP 543 (acid instability, insolubility, and lipophilicity). Using the anthrone scaffold of the prior channel blockers, alternative heteroarylmethyl substituents were installed via enolate alkylation reactions. Incorporation of a pyridazine and a fluorinated pyridine gave an analog (compound 18, JDP-10 ...[more]