Studies on cerebral protective agents. VII. Synthesis of novel 4-arylazole derivatives with anti-anoxic activity.
Novel 4-arylazole (i.e. thiazole, oxazole, and imidazole) derivatives, possessing an amino moiety at the C-5 position of the azole ring, were prepared and tested for anti-anoxic (AA) activity in mice. Among them, 5-(4-methylpiperazin-1-yl)methyl-4-(3-nitrophenyl)-2-phenylthia zole (3b, FR75094) possessed significant AA activity (10 mg/kg, i.p. and 100 mg/kg, p.o., respectively), and was also effective on anti-lipid peroxidation (ALP) assay and inhibited arachidonate-induced cerebral edema in rats. Structure-activity relationships in regard to AA activity of this series of compounds are discussed.
Ohkubo
M
M
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Kuno
A
A
Sakai
H
H
Takasugi
H
H
D000818:Animals; D016718:Arachidonic Acid; D001929:Brain Edema / Q000139:chemically induced / Q000188:drug therapy; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002534:Hypoxia, Brain / Q000188:drug therapy*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D007928:Lethal Dose 50; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity
D007093:Imidazoles; D010080:Oxazoles; D013844:Thiazoles; D016718:Arachidonic Acid