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 microM range with varying degrees of functional selectivity versus M(2)-M(5).
2010 Elsevier Ltd. All rights reserved.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Benzamides / chemical synthesis
-
Benzamides / chemistry*
-
Benzamides / pharmacology*
-
CHO Cells
-
Cricetinae
-
Cricetulus
-
Dystonia / drug therapy
-
Humans
-
Mice
-
Molecular Sequence Data
-
Parkinson Disease / drug therapy
-
Receptor, Muscarinic M1 / antagonists & inhibitors*
-
Receptor, Muscarinic M1 / chemistry
-
Receptor, Muscarinic M1 / metabolism*
-
Structure-Activity Relationship
Substances
-
Benzamides
-
Receptor, Muscarinic M1