Skip to main content

Weaver Lab

Synthesis and SAR of selective muscarinic acetylcholine receptor subtype 1 (M1 mAChR) antagonists.

AUTHORS

Lewis LML Michelle , Sheffler D Douglas , Williams R Richard , Bridges TM Thomas M , Kennedy JP J Phillip , Brogan JT J T , Mulder MJ Matthew J , Williams L Lyndsey , Nalywajko NT Natalia T , Niswender CM Colleen M , Weaver CD Charles D , Conn PJ P Jeffrey , Lindsley CW Craig W . Bioorganic & medicinal chemistry letters. 2008 2 1; 18(3). 885-90

ABSTRACT

This Letter describes the synthesis and SAR, developed through an iterative analogue library approach, of a novel series of selective M1 mAChR antagonists for the potential treatment of Parkinson’s disease, dystonia and other movement disorders. Compounds in this series possess M1 antagonist IC(50)s in the 441nM-19microM range with 8- to >340-fold functional selectivity versus rM2-rM5.

This Letter describes the synthesis and SAR, developed through an iterative analogue library approach, of a novel series of selective M1 mAChR antagonists for the potential treatment of Parkinson’s disease, dystonia and other movement disorders. Compounds in this series possess M1 antagonist IC(50)s in the 441nM-19microM range with 8- to >340-fold functional selectivity versus rM2-rM5.