Previous structure-activity relationship studies involving a series of lactone-based muscarinic ligands identified
a lead compound containing a diphenylmethylpiperazine moiety (4; IC50 = 340 nM). The purpose of the present work is to
investigate 1,3-benzodioxoles, 4,4-diethyl substituted tetrahydrofurans, 5-substituted oxazolidinones and chromones as
bioisosteric replacements for the lactone ring in a novel series of muscarinic ligands. The approach provided compounds
with improved % inhibition values and identified a non-selective muscarinic ligand with an IC50 value of 280 nM. The
structure-activity relationship for this new series will be discussed. Selected compounds were evaluated in preliminary assays
for subtype selectivity and were found to be non-selective.
Keywords: Bioisostere, oxazolidinone, 1, 3-benzodioxole, tetrahydrofuran, chromones.
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