Halogen substituents on the aromatic moiety of the tetracaine scaffold improve potency of cyclic nucleotide-gated channel block.

Sarah R Kirk, Adriana L Andrade, Kenneth Melich, Evan P Jackson, Elysia Cuellar, Jeffrey W Karpen

Department of Chemistry, Willamette University, 900 State Street, Salem, OR 97301, USA.

Bioorganic & medicinal chemistry letters 2011 Nov 1

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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. Copyright © 2011 Elsevier Ltd. All rights reserved.

Citation

Sarah R Kirk, Adriana L Andrade, Kenneth Melich, Evan P Jackson, Elysia Cuellar, Jeffrey W Karpen. Halogen substituents on the aromatic moiety of the tetracaine scaffold improve potency of cyclic nucleotide-gated channel block. Bioorganic & medicinal chemistry letters. 2011 Nov 1;21(21):6417-9