Synthesis and SAR of N-(4-(4-alklylpiperazin-1-yl)phenyl)benzamides as muscarinic acetylcholine receptor subtype 1 (M1) anatgonists.
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).
Miller
Nicole R
NR
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Daniels
R Nathan
RN
Lee
David
D
Conn
P Jeffrey
PJ
Lindsley
Craig W
CW
D000595:Amino Acid Sequence; D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004421:Dystonia / Q000188:drug therapy; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010300:Parkinson Disease / Q000188:drug therapy; D043643:Receptor, Muscarinic M1 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
D001549:Benzamides; D043643:Receptor, Muscarinic M1