Synthesis and SAR of N-(4-(4-alklylpiperazin-1-yl)phenyl)benzamides as muscarinic acetylcholine receptor subtype 1 (M1) anatgonists.

Abstract This Letter describes the synthesis and SAR, developed through an iterative analog library approach, of a novel series of selective M 1 mAChR antagonists, based on an N -(4-(4-alkylpiperazin-1-yl)phenyl)benzamide scaffold for the potential treatment of Parkinson’s disease, dystonia and other movement disorders. Compounds in this series possess M 1 antagonist IC 50 s in the 350 nM to >10 μM range with varying degrees of functional selectivity versus M 2 –M 5 .