Synthesis and in vitro muscarinic activities of a series of 1,3-diazacycloalkyl carboxaldehyde oxime derivatives.
A series of 1,3-diazacycloalkyl carboxaldehyde oxime derivatives 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
Ralf
R
Department of Medicinal Chemistry, N.V. Organon, PO Box 20, 5340 BH, Oss, The Netherlands. ralf.plate@organon.com
Jans
Christan G J M
CG
Plaum
Marc J M
MJ
de Boer
Thijs
T
D000818:Animals; D001115:Arecoline / Q000737:chemistry / Q000494:pharmacology; D001667:Binding, Competitive; D018678:Cholinergic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects; D007082:Ileum / Q000187:drug effects; D018721:Muscarinic Agonists / Q000138:chemical synthesis / Q000494:pharmacology; D010091:Oximes / Q000138:chemical synthesis / Q000494:pharmacology*; D011485:Protein Binding; D011869:Radioligand Assay; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism; D013329:Structure-Activity Relationship; D013552:Swine
D018678:Cholinergic Agents; D018721:Muscarinic Agonists; D010091:Oximes; D011976:Receptors, Muscarinic; D001115:Arecoline