Structure based optimization of chromen-based TNF-α converting enzyme (TACE) inhibitors on S1′ pocket and their quantitative structure–activity relationship ( …

JS Yang, K Chun, JE Park, M Cho, J Seo…

Index: Yang, Jee Sun; Chun, Kwangwoo; Park, Jung Eun; Cho, Misun; Seo, Jeongjea; Song, Doona; Yoon, Hongchul; Park, Chun-Ho; Joe, Bo-Young; Choi, Jong-Hee; Kim, Myung-Hwa; Han, Gyoonhee Bioorganic and Medicinal Chemistry, 2010 , vol. 18, # 24 p. 8618 - 8629

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Citation Number: 12

Abstract

A series of coumarin based TACE inhibitors were designed to bind in S1′ pocket of TACE enzyme based on their docking study. Twelve analogues were synthesized and most of compounds were active in vitro TACE enzyme inhibition as well as cellular TNF-α inhibition. Among these, 15l effectively inhibited the production of serum TNF-α by oral administration at a dose of 30mg/kg. Compound 15l also showed a good oral bioavailability at 42% and ...