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

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).