title: 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 microM range with varying degrees of functional selectivity versus M(2)-M(5).
authors.affiliation: Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Miller
authors.forename: R Nathan
authors.initials: RN
authors.lastname: Daniels
authors.forename: David
authors.initials: D
authors.lastname: Lee
authors.forename: P Jeffrey
authors.initials: PJ
authors.lastname: Conn
authors.forename: Craig W
authors.initials: CW
authors.lastname: Lindsley
mesh_terms: 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
chemical_list: D001549:Benzamides; D043643:Receptor, Muscarinic M1