Synthesis of 2-substituted-6,8-dichloro-3,4-dihydro-3-oxo-2H-1,4-benzothiazine-1,1-d ioxides and -1-oxides as glycine-NMDA receptor antagonists.
A number of 2-substituted-3,4-dihydro-3-oxo-6,8-dichloro-2H-1, 4-benzothiazine-1,1-dioxides (1-2a-b) and -1-oxides (3-4a-b) bioisosters of RPR 104632 in which the 3-carboxylic group was replaced by a carbonyl group were synthesized. Comparative in vitro pharmacological studies on this series of RPR 104632 analogs were performed using receptor binding assays. None of these compounds showed detectable binding affinity for the glycine-NMDA receptor.
Varano
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F
Dipartimento di Scienze Farmaceutiche, Università di Firenze, Italy.
Catarzi
D
D
Colotta
V
V
Filacchioni
G
G
Cecchi
L
L
Galli
A
A
Costagli
C
C
D000818:Animals; D001581:Benzothiadiazines / Q000737:chemistry; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010087:Oxides / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D013843:Thiazines / Q000138:chemical synthesis* / Q000494:pharmacology
D001581:Benzothiadiazines; D018691:Excitatory Amino Acid Antagonists; D010087:Oxides; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D013843:Thiazines; C103467:RPR 104632