C(8)-substituted 1-azabicyclo[3.3.1]non-3-enes: a novel scaffold for muscarinic receptor ligands.
The [3.3.1]-bicyclic amine, exo-8-benzyloxymethyl-3-ethoxycarbonyl-4-hydroxy-1-azabicyclo[3.3.1]non-3-ene (1), has been shown to be a potent competitive antagonist against the hM(1)-hM(5) muscarinic receptors. This heterocyclic system has not been extensively evaluated despite the notable activities reported for other bicyclic amines. Synthetic strategies permitted the selective alteration of five structural sites in 1. Pharmacological evaluation demonstrated that modification of either the C(3) alkoxycarbonyl or the C(4) enol units in 1 gave compounds with high affinity for the hM(1)-hM(5) muscarinic receptors with selectivity for the hM(2) receptor.
Kim
Myoung Goo
MG
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360, USA.
Bodor
Erik T
ET
Harden
T Kendall
TK
Kohn
Harold
H
D000818:Animals; D001372:Aza Compounds / Q000737:chemistry / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000737:chemistry / Q000378:metabolism*; D019556:COS Cells; D008024:Ligands; D018727:Muscarinic Antagonists / Q000737:chemistry / Q000378:metabolism*; D013057:Spectrum Analysis
D001372:Aza Compounds; D001643:Bridged Bicyclo Compounds; D008024:Ligands; D018727:Muscarinic Antagonists