Young Sik Jung

Bioisosterism: Interchange of 4-OH to 4-NH2 in vanillin or homovanillin ring of capsaicinoids

A series of 4-amino Capsaicin analogs15, 17 and19 were prepared to investigate the bioisosteric effect of 4-amino group, and all these compounds exhibited moderate or weak potency from their analgesic test. From our previous results and others, 4-hydroxyl group, as well as 3-methoxy substituent could be crucial for high analgesic activity. This biological result also shows that the activity is sensitive to alkyl chain length in hydrophobic region and the phenylacetic amides19 are more active than the corresponding urea derivatives17.

4-Substituted-kynurenic acid derivatives: A novel class of NMDA receptor glycine site antagonists

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 theirin vitro antagonist activity at the glycine site on the NMDA receptor. Of them, N-benzoylthiourea15c and N-phenylthiourea15a were found to have the bestin vitro binding affinity with IC50 of 3.95 and 6.04 μM, respectively. On the other hand, in compounds12a∼c and13 the displacement of a thiourea group to an amide or a carbamate caused a significant decrease of thein 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.