Structure-activity relationships of quinazoline derivatives: dual-acting compounds with inhibitory activities toward both TNF-alpha production and T cell proliferation.
We synthesized 4-chlorophenethylaminoquinazoline derivatives and evaluated their inhibitory activities toward both TNF-alpha production and T cell proliferation responses. Compound 2f, containing a piperazine ring at the C(7)-position of the quinazoline ring, exhibited more potent inhibitory activities toward both than the lead compound la. A smaller N-substituent in the piperazine ring was required for inhibition of TNF-alpha production.
Tobe
M
M
Pharmaceuticals and Biotechnology Laboratory, Japan Energy Corporation, Saitama, Japan.
Isobe
Y
Y
Tomizawa
H
H
Matsumoto
M
M
Obara
F
F
Nagasaki
T
T
Hayashi
H
H
D000818:Animals; D018501:Antirheumatic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D018501:Antirheumatic Agents; D011799:Quinazolines; D014409:Tumor Necrosis Factor-alpha