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

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

Volume: 10 Issue: 4

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

Affiliation:

Keywords: Bioisostere, oxazolidinone, 1, 3-benzodioxole, tetrahydrofuran, chromones.

Abstract: 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.

Cite this article as:

Bhandare R. Richie and Canney J. Daniel, Bioisosteric Replacement and Related Analogs in the Design, Synthesis and Evaluation of Ligands for Muscarinic Acetylcholine Receptors, Medicinal Chemistry 2014; 10 (4) . https://dx.doi.org/10.2174/15734064113096660043