A novel structural class of potent inhibitors of NF-kappa B activation: structure-activity relationships and biological effects of 6-aminoquinazoline derivatives.
In this study, we have investigated the roles of substituents on the terminal phenyl ring at the C(4)-position of the quinazoline core to complete the structure-activity relationships (SARs) of our NF-kappa B activation inhibitors. Among them, compound 12j afforded highly potent inhibitory activity toward NF-kappa B transcriptional activation with IC(50) value of 2 nM, along with an excellent in vivo efficacy by reducing the edema formation seen in carrageenin-induced inflammation of the rat hind paw.
Tobe
Masanori
M
Research Division, Sumitomo Pharmaceuticals Co., Ltd., 1-98 Kasugade Naka 3-Chome, Konohana-ku, Osaka 554-0022, Japan.
Isobe
Yoshiaki
Y
Tomizawa
Hideyuki
H
Nagasaki
Takahiro
T
Takahashi
Hirotada
H
Hayashi
Hideya
H
D000634:Aminoquinolines / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D007249:Inflammation / Q000139:chemically induced; D020128:Inhibitory Concentration 50; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011799:Quinazolines / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C492910:6-amino-4-(4-n-pentyloxy)phenethylaminoquinazoline; D000634:Aminoquinolines; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D011799:Quinazolines; D014409:Tumor Necrosis Factor-alpha; C032928:6-aminoquinoline; D002351:Carrageenan