Bioisosteric Replacement and Related Analogs in the Design, Synthesis and Evaluation of Ligands for Muscarinic Acetylcholine Receptors

Author(s): Richie R. Bhandare, Daniel J. Canney.

Journal Name: Medicinal Chemistry

Volume 10 , Issue 4 , 2014

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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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Article Details

Year: 2014
Page: [361 - 375]
Pages: 15
DOI: 10.2174/15734064113096660043
Price: $58

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