Synthesis and muscarinic activities of O-[(Benzyl- or benzoyl-pyrazolyl)propynyl]-oximes of N-methylpiperidinone, 3-tropinone, and 3-quinuclidinone

The synthesis of O-propynyloximes of N-methylpiperidinone, 3-tropinone, and 3-quinuclidinone, containing several pyrazole frameworks is described, together with their muscarinic receptor affinities. Compounds derived from N-methylpiperidinone or 3-tropinone and N-(4-methoxybenzyl)- or N-(2,4,6-trime...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2003-05, Vol.11 (10), p.2263-2268
Main Authors: Rodrı́guez-Franco, Marı́a Isabel, Dorronsoro, Isabel, Castro, Ana, Martı́nez, Ana, Badı́a, Albert, Baños, Josep E
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cholinergic system
Isomerism
Magnetic Resonance Spectroscopy
Medical sciences
Models, Molecular
Molecular Structure
Muscarinic Agonists - chemical synthesis
Muscarinic Agonists - pharmacology
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Oximes - chemical synthesis
Oximes - pharmacology
Pharmacology. Drug treatments
Piperidines - chemistry
Pyrazoles - chemistry
Quinuclidines - chemistry
Radioligand Assay
Rats
Receptors, Muscarinic - drug effects
Structure-Activity Relationship
Tropanes - chemistry
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Summary:The synthesis of O-propynyloximes of N-methylpiperidinone, 3-tropinone, and 3-quinuclidinone, containing several pyrazole frameworks is described, together with their muscarinic receptor affinities. Compounds derived from N-methylpiperidinone or 3-tropinone and N-(4-methoxybenzyl)- or N-(2,4,6-trimethylbenzoyl)pyrazole showed moderate activity for muscarinic receptors in the rat central nervous system. A semi-empirical AM1 calculation has shown that the O-[(benzoyl-pyrazolyl)propynyl]-oximes of tropinone fit a previously described muscarinic pharmacophoric model, revealing structural features useful for the development of new muscarinic agents. The synthesis of O-propynyloximes of N-methylpiperidinone, 3-tropinone, and 3-quinuclidinone, containing several pyrazole frameworks, is described, together with their muscarinic receptor affinities.
ISSN:0968-0896
1464-3391
DOI:10.1016/S0968-0896(03)00111-1