title: Synthesis and SAR of analogues of the M1 allosteric agonist TBPB. Part I: Exploration of alternative benzyl and privileged structure moieties.
abstract: This Letter describes the first account of the synthesis and SAR, developed through an iterative analogue library approach, of analogues of the highly selective M1 allosteric agonist TBPB. With slight structural changes, mAChR selectivity was maintained, but the degree of partial M1 agonism varied considerably.
authors.affiliation: Department of Pharmacology, Vanderbilt University Medical Center, 802 Robinson Research Building, Nashville, TN 37232, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Bridges
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Brady
authors.forename: J Phillip
authors.initials: JP
authors.lastname: Kennedy
authors.forename: R Nathan
authors.initials: RN
authors.lastname: Daniels
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Miller
authors.forename: Kwango
authors.initials: K
authors.lastname: Kim
authors.forename: Micah L
authors.initials: ML
authors.lastname: Breininger
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Gentry
authors.forename: John T
authors.initials: JT
authors.lastname: Brogan
authors.forename: Carrie K
authors.initials: CK
authors.lastname: Jones
authors.forename: P Jeffrey
authors.initials: PJ
authors.lastname: Conn
authors.forename: Craig W
authors.initials: CW
authors.lastname: Lindsley
mesh_terms: D000109:Acetylcholine / Q000737:chemistry; D000494:Allosteric Regulation; D000495:Allosteric Site; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry*; D001665:Binding Sites; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D008956:Models, Chemical; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry*; D043643:Receptor, Muscarinic M1 / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: C532626:1-(1'-(2-methylbenzyl)-1,4'-bipiperidin-4-yl)-1H-benzo(d)imidazol-2-(3H)-one; D001562:Benzimidazoles; D008024:Ligands; D010880:Piperidines; D043643:Receptor, Muscarinic M1; D000109:Acetylcholine