|
KMID : 0043319970200040351
|
|
Archives of Pharmacal Research
1997 Volume.20 No. 4 p.351 ~ p.357
|
|
|
4-Substituted-kynurenic Acid Derivatives:A Novel Class of NMDA Receptor Glycine Site Antagonists
|
|
Kim Ran-Hee
Chung Yong-Jun
Lee Chang-Woo
Kong Jae-Yang
Jung Young-Sik
Seong Churl-Min
Park No-Sang
|
|
|
Abstract
|
|
|
|
A series of 4-substituted-kynurenic acid derivatives possessing several different substituents at C4-position which are consisted of both a flexible propyloxy chain and an adjunct several type of carbonyl groups has been synthesized and evaluated for their in vitro antagonist activity at the glycine site on the NMDA receptor. Of them, N-benzoylthiourea 15c and N-phenylthiourea 15a were found to have the best in vitro binding affinity with of 3.95 and , respectively. On the other hand, in compounds 12a-c and 13 the displacement of a thiourea group to an amide or a carbamate caused a significant decrease of the in vitro binding affinity. In the SAR study of the 4-substituted kynurenic acid derivatives, it was realized that the terminal substitution pattern on a flexible C4-propyloxy chain of kynurenic acid nucleus significantly influences on the binding affinity for glycine site; the binding affinity to the NMDA receptor might be increased by the introduction of a suitable electron rich substituent at C4 of kynurenic acid nucleus.
|
|
|
KEYWORD
|
|
|
NMDA receptor antagonists, Glycine modulatory site, [H]-Glycine displacement test, 4-Subsisuted-kynurenic acids
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|