title: Isatin replacements applied to the highly selective, muscarinic M1 PAM ML137: continued optimization of an MLPCN probe molecule.
abstract: This Letter describes the continued optimization of an MLPCN probe molecule (ML137) with a focused effort on the replacement/modification of the isatin moiety present in this highly selective M(1) PAM. A diverse range of structures were validated as viable replacements for the isatin, many of which engendered sizeable improvements in their ability to enhance the potency and efficacy of acetylcholine when compared to ML137. Muscarinic receptor subtype selectivity for the M(1) receptor was also maintained.
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: Michael S
authors.initials: MS
authors.lastname: Poslusney
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Gentry
authors.forename: James C
authors.initials: JC
authors.lastname: Tarr
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Sheffler
authors.forename: Margrith E
authors.initials: ME
authors.lastname: Mattmann
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Bridges
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Utley
authors.forename: J Scott
authors.initials: JS
authors.lastname: Daniels
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Niswender
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: D020128:Inhibitory Concentration 50; D007510:Isatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015335:Molecular Probes / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D043643:Receptor, Muscarinic M1 / Q000187:drug effects*
chemical_list: C581677:ML 137; D015335:Molecular Probes; D008996:Monoamine Oxidase Inhibitors; D043643:Receptor, Muscarinic M1; D007510:Isatin