Synthesis and SAR studies for the inhibition of TNF-alpha production. Part 2. 2-[3-(Cyclopentyloxy)-4-methoxyphenyl]-substituted-1-isoindolinone derivatives.
This study describes the synthesis and in vitro evaluation of 2-[3-(cyclopentyloxy)-4-methoxyphenyl]-1-isoindolinone derivatives substituted on benzene moiety of isoindoline ring for the inhibition of TNF-alpha production. From this study, we have found the 6-C position on isoindolinone ring is an optimal derivatization site. Among the compounds synthesized, 6-amino-2-[3-(cyclopentyloxy)-4-methoxyphenyl]-1-isoindolinone (6) was the most potent in inhibitory activity of TNF-alpha production in LPS-stimulated RAW264.7 cells.
Park
Joon Seok
JS
Institute of Bioscience & Biotechnology, Daewoong Pharm, Ltd, Yongin, Kyunggi-Do, Korea. joonchem@daewoong.co.kr
Moon
Seong Cheol
SC
Baik
Kyong Up
KU
Cho
Jae Youl
JY
Yoo
Eun Sook
ES
Byun
Young Seok
YS
Park
Myung Hwan
MH
Balk
Kyung Up
KU
D000818:Animals; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D007211:Indoles; D014409:Tumor Necrosis Factor-alpha