Novel NMDA antagonists: replacement of the pyridinium ring of 6,11-ethanobenzo[b]quinolizinium cations with heteroisoquinolinium cations.
Replacement of the pyridinium ring of 6,11-ethanobenzo[b]quinolizinium cations with thiazolium (4a and 4b) and N-methylimidazolium (4c and 4d) resulted in equipotent compounds in the [3H]TCP binding assay. The corresponding N-methyl-1,2,4-triazolium analogs were less potent in this assay. The thiazolium derivative 4b, with a Ki = 2.9 nM, is being evaluated as a possible neuroprotective N-methyl-D-aspartic acid (NMDA) antagonist.
Kumar
V
V
Department of Medicinal Chemistry, Sterling Winthrop Pharmaceuticals Research Division, Collegeville, Pennsylvania 19426-0900, USA.
Carabateas
P M
PM
Dority
J A
JA
Earley
W G
WG
Mallamo
J P
JP
Subramanyam
C
C
Aimone
L D
LD
Ault
B
B
DeHaven Hudkins
D L
DL
Miller
M S
MS
D000818:Animals; D002412:Cations; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D005260:Female; D008297:Male; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D011247:Pregnancy; D011726:Pyridinium Compounds / Q000737:chemistry* / Q000494:pharmacology; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology; D011807:Quinolizines / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D002412:Cations; D011726:Pyridinium Compounds; D011804:Quinolines; D011807:Quinolizines; D016194:Receptors, N-Methyl-D-Aspartate