title: Halogen substituents on the aromatic moiety of the tetracaine scaffold improve potency of cyclic nucleotide-gated channel block.
abstract: A series of new tetracaine derivatives with substituents on the aromatic ring was prepared and evaluated for block of retinal rod cyclic nucleotide-gated (CNG) channels. Aromatic substitutions had little effect starting with the basic tetracaine scaffold, but electron-withdrawing substituents significantly improved the blocking potency of an octyl-tail derivative of tetracaine. In particular, halogen substitutions at either the 2- or 3-position on the ring resulted in compounds that were up to eight-fold more potent than the parent octyl-tail derivative and up to 50-fold more potent than tetracaine.
authors.affiliation: Department of Chemistry, Willamette University, 900 State Street, Salem, OR 97301, USA.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Kirk
authors.forename: Adriana L
authors.initials: AL
authors.lastname: Andrade
authors.forename: Kenneth
authors.initials: K
authors.lastname: Melich
authors.forename: Evan P
authors.initials: EP
authors.lastname: Jackson
authors.forename: Elysia
authors.initials: E
authors.lastname: Cuellar
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Karpen
mesh_terms: D054815:Cyclic Nucleotide-Gated Cation Channels / Q000037:antagonists & inhibitors*; D006219:Halogens / Q000737:chemistry*; D013748:Tetracaine / Q000737:chemistry*
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D006219:Halogens; D013748:Tetracaine