title: Design and synthesis of m1-selective muscarinic agonists: (R)-(-)-(Z)-1-Azabicyclo[2.2.1]heptan-3-one, O-(3-(3'-methoxyphenyl)-2-propynyl)oxime maleate (CI-1017), a functionally m1-selective muscarinic agonist.
abstract: The synthesis and SAR of a series of (Z)-(+/-)-1-azabicyclo[2.2. 1]heptan-3-one, O-(3-aryl-2-propynyl)oximes are described. The biochemistry and pharmacology of 24Z (PD 142505) and its enantiomers are highlighted. 24Z is functionally an m1-selective muscarinic agonist. Efficacy and m1 selectivity reside in the R enantiomer, (R)-24Z (CI-1017).
authors.affiliation: Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, Michigan 48106-1047, USA.
authors.forename: H
authors.initials: H
authors.lastname: Tecle
authors.forename: S D
authors.initials: SD
authors.lastname: Barrett
authors.forename: D J
authors.initials: DJ
authors.lastname: Lauffer
authors.forename: C
authors.initials: C
authors.lastname: Augelli-Szafran
authors.forename: M R
authors.initials: MR
authors.lastname: Brann
authors.forename: M J
authors.initials: MJ
authors.lastname: Callahan
authors.forename: B W
authors.initials: BW
authors.lastname: Caprathe
authors.forename: R E
authors.initials: RE
authors.lastname: Davis
authors.forename: P D
authors.initials: PD
authors.lastname: Doyle
authors.forename: D
authors.initials: D
authors.lastname: Eubanks
authors.forename: W
authors.initials: W
authors.lastname: Lipiniski
authors.forename: T
authors.initials: T
authors.lastname: Mirzadegan
authors.forename: W H
authors.initials: WH
authors.lastname: Moos
authors.forename: D W
authors.initials: DW
authors.lastname: Moreland
authors.forename: C B
authors.initials: CB
authors.lastname: Nelson
authors.forename: M R
authors.initials: MR
authors.lastname: Pavia
authors.forename: C
authors.initials: C
authors.lastname: Raby
authors.forename: R D
authors.initials: RD
authors.lastname: Schwarz
authors.forename: C J
authors.initials: CJ
authors.lastname: Spencer
authors.forename: A J
authors.initials: AJ
authors.lastname: Thomas
authors.forename: J C
authors.initials: JC
authors.lastname: Jaen
mesh_terms: D016475:3T3 Cells; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D016466:CHO Cells; D006224:Cricetinae; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D018721:Muscarinic Agonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D010091:Oximes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D007295:Inositol Phosphates; D018721:Muscarinic Agonists; D010091:Oximes; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; C096405:PD 142505-0028