Novel pyrrolinones as N-methyl-D-aspartate receptor antagonists.
A series of oximes, deriving from 2-arylidene-pyrroline-3,4-diones (7, 8, 22, 23) has been prepared. The presence of tautomers in their solutions has been established by spectroscopic means. The compounds reacted with diazomethane chiefly by N-methylation forming nitrones (10, 11). The analogously prepared 2-arylidene-4-nitropyrrolin-3-ones (12, 13, 24, 25), formally derived from nitrotetramic acids, yielded nitronic acid esters (14, 15, 26) upon reaction with diazomethane. The structures were elucidated by spectral evidence and-in the case of compounds 10 and 20b-by X-ray diffraction analysis. The binding affinity of some of the new compounds toward the N-methyl-d-aspartate (NMDA) (glycine site) receptor has been measured thus providing the basis for further structure-activity relationship studies. Oxime 8b showed the highest binding potency (Ki= 9.2 microM).
Poschenrieder
Hermann
H
Department Pharmazie, Zentrum für Pharmaforschung, Universität München, Butenandtstr. 7, D-81377 München, Germany.
Stachel
Hans-Dietrich
HD
Höfner
Georg
G
Mayer
Peter
P
D001665:Binding Sites; D005998:Glycine / Q000378:metabolism; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D011758:Pyrroles; D016194:Receptors, N-Methyl-D-Aspartate; C013231:pyrroline; D005998:Glycine