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-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.
Rodríguez-Franco
María Isabel
MI
Instituto de Qíumica Médica (C.S.I.C.), Juan de la Cierva 3, 28006 Madrid, Spain. isabelrguez@iqm.csic.es
Dorronsoro
Isabel
I
Castro
Ana
A
Martínez
Ana
A
Badía
Albert
A
Baños
Josep E
JE
D000818:Animals; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D018721:Muscarinic Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D010091:Oximes / Q000138:chemical synthesis* / Q000494:pharmacology; D010880:Piperidines / Q000737:chemistry*; D011720:Pyrazoles / Q000737:chemistry; D011812:Quinuclidines / Q000737:chemistry*; D011869:Radioligand Assay; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014326:Tropanes / Q000737:chemistry*
D018721:Muscarinic Agonists; D010091:Oximes; D010880:Piperidines; D011720:Pyrazoles; D011812:Quinuclidines; D011976:Receptors, Muscarinic; D014326:Tropanes; C016808:3-tropinone