Synthesis and in vitro muscarinic activities of a series of 3-(pyrazol-3-yl)-1-azabicyclo[2.2.2]octanes.
A series of 3-(pyrazol-3-yl)-1-azabicyclo[2.2.2]octane derivatives C (Fig. 1) was synthesized and tested for muscarinic activity in receptor binding assays using [3H]-oxotremorine-M (OXO-M) and [3H]-pirenzepine (PZ) as ligands. Potential muscarinic agonistic or antagonistic properties of the compounds were determined using binding studies measuring their potencies to inhibit the binding of OXO-M and PZ. Preferential inhibition of OXO-M binding was used as an indicator for potential muscarinic agonistic properties; this potential was confirmed in functional studies on isolated organs.
Plate
R
R
Department of Medicinal Chemistry, N. V. Organon, Oss, The Netherlands. r.plate@organon.oss.akzonobel.nl
Plaum
M J
MJ
van der Hulst
R G
RG
de Boer
T
T
D000818:Animals; D001921:Brain / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D018678:Cholinergic Agents / Q000737:chemistry* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009795:Octanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats
D001643:Bridged Bicyclo Compounds; D018678:Cholinergic Agents; D009795:Octanes