4-Hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b] pyrimidine derivatives: synthesis and their biological evaluation for the glycine site acting on the N-methyl-D-aspartate (NMDA) receptor.
Bioisostere approach has been shown to be useful to augment potency or to modify certain physiological properties of a lead compound. Based upon well documented bioisosterism, an isosteric replacement of benzene ring of 4-hydroxy-2-quinolone compound (L-695902) with a thiophene moiety was carried out to prepare the title compounds, 4-hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b] pyrimidines 15. The resulting bioisosteric compounds 15 were evaluated for their antagonistic activity (binding assay) for NMDA receptor glycine site.
Hwang
K J
KJ
Department of Chemistry and Research Center of Bioactive Materials, College of Natural Science, Chonbuk National University, Chonju, Korea. Kijun@moak.chonbuk.ac.kr
Lee
T S
TS
Kim
K W
KW
Kim
B T
BT
Lee
C M
CM
Park
E Y
EY
Woo
R S
RS
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007211:Indoles / Q000378:metabolism; D008024:Ligands; D008297:Male; D011728:Pyridones / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D013570:Synaptic Membranes / Q000187:drug effects; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology*
D018691:Excitatory Amino Acid Antagonists; D007202:Indicators and Reagents; D007211:Indoles; D008024:Ligands; C101788:MDL 105519; D011728:Pyridones; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D013876:Thiophenes