Synthesis and nuclear factor-kappaB inhibitory activities of 6- or 7-methylchroman-2-carboxylic acid N-(substituted) phenylamides.
A series of 6- or 7-methylchroman-2-carboxylic acid N-(substituted) phenylamides (2a-s, 3a-s) were synthesized. Their abilities to inhibit nuclear factor-kappaB (NF-kappaB) activity were evaluated in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. Compounds with substituents such as -H, -CH(3), and -CF(3) on the phenyl ring were poor inhibitors of NF-kappaB. The most active NF-kappaB inhibitors contained 4-Cl (3s) and 4-OMe (3g) in the 7-methylchroman-2-carboxamide derivatives and 2-OH (2b) and 4-Cl (2s) in the 6-methylchroman-2-carboxamide derivatives (IC(50): 20.2-24.0 microM). These were slightly more potent than a reference compound, KL-1156 (1) (IC(50): 43.9 microM).
Kwak
Jae-Hwan
JH
College of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea.
Won
Sun-Woo
SW
Kim
Tae-Jeong
TJ
Yi
Wonhui
W
Choi
Eun-Hwa
EH
Kim
Seung-Chan
SC
Park
Hyunjeong
H
Roh
Eunmiri
E
Jung
Jae-Kyung
JK
Hwang
Bang Yeon
BY
Hong
Jin Tae
JT
Kim
Youngsoo
Y
Cho
Jungsook
J
Lee
Heesoon
H
D000818:Animals; D002460:Cell Line; D002839:Chromans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
C495393:6-hydroxy-7-methoxychroman-2-carboxylic acid phenylamide; D002839:Chromans; D008070:Lipopolysaccharides; D016328:NF-kappa B