title: Development of a highly selective, orally bioavailable and CNS penetrant M1 agonist derived from the MLPCN probe ML071.
abstract: Herein we report the discovery and SAR of a novel series of M(1) agonists based on the MLPCN probe, ML071. From this, VU0364572 emerged as a potent, orally bioavailable and CNS penetrant M(1) agonist with high selectivity, clean ancillary pharmacology and enantiospecific activity.
authors.affiliation: Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Evan P
authors.initials: EP
authors.lastname: Lebois
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Digby
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Sheffler
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Melancon
authors.forename: James C
authors.initials: JC
authors.lastname: Tarr
authors.forename: Hyekyung P
authors.initials: HP
authors.lastname: Cho
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Miller
authors.forename: Ryan
authors.initials: R
authors.lastname: Morrison
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Bridges
authors.forename: Zixiu
authors.initials: Z
authors.lastname: Xiang
authors.forename: J Scott
authors.initials: JS
authors.lastname: Daniels
authors.forename: Michael R
authors.initials: MR
authors.lastname: Wood
authors.forename: P Jeffrey
authors.initials: PJ
authors.lastname: Conn
authors.forename: Craig W
authors.initials: CW
authors.lastname: Lindsley
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002460:Cell Line; D002490:Central Nervous System / Q000378:metabolism*; D006801:Humans; D018721:Muscarinic Agonists / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D043643:Receptor, Muscarinic M1 / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D018721:Muscarinic Agonists; D043643:Receptor, Muscarinic M1