Structure-activity relationships of 6-hydroxy-7-methoxychroman-2-carboxylic acid N-(substituted)phenylamides as inhibitors of nuclear factor-kappaB activation.
A series of 6-hydroxy-7-methoxychroman-2-carboxylic acid N-substitutedphenylamides (2a-n) were synthesized and their ability to inhibit nuclear factor-kappaB activity was evaluated in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. While compounds bearing -OH, or -OCH3 substituents were inactive, compounds with -CH3, -CF3, or -Cl substituents were potent inhibitors (IC50: 6.0-60.2 microM). The most active compound, 2n, contained a 4-Cl substituent on the phenyl ring and was four times more potent than the compound KL-1156.
College of Pharmacy, Chungbuk National University, Cheongiu 361-763, Korea.
Jae-Hwan
JH
Kwak
Byung Hak
BH
Kim
Jae-Kyung
JK
Jung
Youngsoo
Y
Kim
Jungsook
J
Cho
Heesoon
H
Lee
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002839:Chromans / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection
C495393:6-hydroxy-7-methoxychroman-2-carboxylic acid phenylamide; D000893:Anti-Inflammatory Agents; D002839:Chromans; D008070:Lipopolysaccharides; D016328:NF-kappa B