Synthesis and topical antiinflammatory and antiallergic activities of antioxidant o-aminophenol derivatives.
In order to develop novel compounds for topical use possessing antiallergic as well as antiinflammatory activities, a series of o-aminophenol derivatives bearing H1-antihistaminic structures were synthesized and their effects were investigated on lipid peroxidation in rat brain homogenates, antiinflammatory effection arachidonic acid- and 12-O-tetradecanoylphorbol-13- acetate-induced mouse ear edema and antiallergic effect on 48-h homologous passive cutaneous anaphylaxis in rats. Furthermore, the effects of these compounds on delayed-type hypersensitivity reaction in mice were examined. Several N-monosubstituted amino-4-methylphenols were found to exert potent inhibitory activities in all of these assays. Of these compounds, 4m was chosen for further development as AD0261.
Sugiyama
N
N
Research Division, Green Cross Corporation, Osaka, Japan.
Akahoshi
F
F
Kuwahara
S
S
Kajii
M
M
Sakaue
Y
Y
Yakumaru
H
H
Sugiura
M
M
Fukaya
C
C
D000287:Administration, Topical; D000627:Aminophenols / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D001921:Brain / Q000187:drug effects; D004423:Ear; D004487:Edema / Q000188:drug therapy; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D006968:Hypersensitivity, Delayed / Q000188:drug therapy*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012882:Skin Tests; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000627:Aminophenols; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D006634:Histamine H1 Antagonists; C027667:2-aminophenol; D016718:Arachidonic Acid; D013755:Tetradecanoylphorbol Acetate