Design and synthesis of muscarinic acetylcholine receptor (mAChR) antagonist: pharmacophore-based screening and structure-based optimization

摘要

This study describes screening of muscarinic acetylcholine receptors (mAChR) antagonist by pharmacophore modeling and optimization by molecular docking. A series of molecules was synthesized and evaluated for preliminary pharmacological activity on rat ileum. A molecule based on benzonitrile piperazine scaffold showed good tissue relaxation and blocking of neurotransmitter ACh in the ex vivo experiment.