title: Development of a more highly selective M(1) antagonist from the continued optimization of the MLPCN Probe ML012.
abstract: This Letter describes the continued optimization of an MLPCN probe molecule (ML012) through an iterative parallel synthesis approach. After exploring extensive modifications throughout the parent structure, we arrived at a more highly M(1)-selective antagonist, compound 13l (VU0415248). Muscarinic subtype selectivity across all five human and rat receptors for 13l, along with rat selectivity for the lead compound (ML012), is presented.
authors.affiliation: Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Melancon
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Lamers
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Bridges
authors.forename: Gary A
authors.initials: GA
authors.lastname: Sulikowski
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Utley
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Sheffler
authors.forename: Meredith J
authors.initials: MJ
authors.lastname: Noetzel
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Morrison
authors.forename: J Scott
authors.initials: JS
authors.lastname: Daniels
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Niswender
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
authors.forename: Michael R
authors.initials: MR
authors.lastname: Wood
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015335:Molecular Probes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D043643:Receptor, Muscarinic M1 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D015335:Molecular Probes; D011804:Quinolines; D043643:Receptor, Muscarinic M1; D013449:Sulfonamides; C574450:VU0415248