Bioorganic & Medicinal Chemistry 2012-05-01

Design and synthesis of 4-O-methylhonokiol analogs as inhibitors of cyclooxygenase-2 (COX-2) and PGF₁ production.

Bit Lee, Jae-Hwan Kwak, Shin-Won Huang, Jae-Yong Jang, Sanglae Lim, Young-Shin Kwak, Kiho Lee, Hyung Sook Kim, Sang-Bae Han, Jin-Tae Hong, Heesoon Lee, Sukgil Song, Seung-Yong Seo, Jae-Kyung Jung

Index: Bioorg. Med. Chem. 20(9) , 2860-8, (2012)

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Abstract

A series of novel 4-O-methylhonokiol analogs were synthesized in light of revealing structure-activity relationship for inhibitory effect of COX-2 enzyme. The key strategy of the molecular design was oriented towards modification of the potential metabolic soft spots (e.g., phenol and olefin) or by altering the polar surface area via incorporating heterocycles such as isoxazole and triazole. Most of all exhibited the inhibitory effects on COX-2 and PGF(1) production but not macrophage NO production. Especially, aryl carbamates 10 and 11 exhibited more potent inhibitory activity against COX-2 and PGF(1) production.Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.