title: Synthesis and SAR of analogs of the M1 allosteric agonist TBPB. Part II: Amides, sulfonamides and ureas--the effect of capping the distal basic piperidine nitrogen.
abstract: This letter describes the further synthesis and SAR, developed through an iterative analog library approach, of analogs of the highly selective M1 allosteric agonist TBPB by deletion of the distal basic piperidine nitrogen by the formation of amides, sulfonamides and ureas. Despite the large change in basicity and topology, M1 selectivity was maintained.
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: Thomas M
authors.initials: TM
authors.lastname: Bridges
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Brady
authors.forename: P Jeffrey
authors.initials: PJ
authors.lastname: Conn
authors.forename: Craig W
authors.initials: CW
authors.lastname: Lindsley
mesh_terms: D000494:Allosteric Regulation; D000495:Allosteric Site; D000577:Amides / Q000737:chemistry*; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D008956:Models, Chemical; D009584:Nitrogen / Q000737:chemistry*; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry*; D043643:Receptor, Muscarinic M1 / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry*; D014508:Urea / Q000737:chemistry*
chemical_list: C532626:1-(1'-(2-methylbenzyl)-1,4'-bipiperidin-4-yl)-1H-benzo(d)imidazol-2-(3H)-one; D000577:Amides; D001562:Benzimidazoles; D010880:Piperidines; D043643:Receptor, Muscarinic M1; D013449:Sulfonamides; C032727:piperidine; D014508:Urea; D009584:Nitrogen