Interactive multivariate modelling of 4-amino-2-carboxytetrahydroquinolines as antagonists of the glycine-site directed NMDA receptor-ion channel complex.
Multivariate quantitative conformation-activity relationships of a series of 4-amino-2-carboxytetrahydroquinolines have shown that the biological activity profile (inhibition of (3H)glycine binding to rat cortical membranes and antagonism of depolarizations due to N-methyl-D-aspartic acid (NMDA) in a rat cortical slice preparation) depends on the molar refraction of the substituents, the total energy related to the nitrogen atom and the carbon atom of the -NHCOR1 bridge of the lead molecule (Figure 1), and the 1.4 nonvalency energy. Diagnostic statistics shows that the model assumptions are approximately satisfied.
Mager
P P
PP
Institute of Pharmacology and Toxicology, University of Leipzig, Saxony, Germany.
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008956:Models, Chemical; D015233:Models, Statistical; D015999:Multivariate Analysis; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D007473:Ion Channels; D011804:Quinolines; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate