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

Abstract
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.