Studies on cerebral protective agents. I. Novel 4-arylpyrimidine derivatives with anti-anoxic and anti-lipid peroxidation activities.
Novel 4-arylpyrimidine derivatives were synthesized by the oxidation of 4-aryl-1,4-dihydropyrimidines, and their effects on anti-anoxic (AA) activity in mice and anti-lipid peroxidation (ALP) activity in rat brain mitochondria were investigated. Among these compounds, ethyl 6-methyl-2-phenyl-4-(4-pyridyl)-5-pyrimidinecarboxylate (4b) has AA activity (10 mg/kg, i.p.) and ethyl 6-methyl-4-(3-nitrophenyl)-2-phenyl-5-pyrimidinecarboxylate (4f) has ALP activity (73% inhibition at 10(-5) g/ml). The latter compound (100 mg/kg, i.p.) was also effective on arachidonate-induced cerebral edema in rats with comparable potency to that of vitamin E.
Kuno
A
A
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Sugiyama
Y
Y
Katsuta
K
K
Kamitani
T
T
Takasugi
H
H
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001929:Brain Edema / Q000139:chemically induced / Q000188:drug therapy; D002534:Hypoxia, Brain / Q000188:drug therapy*; D015227:Lipid Peroxidation / Q000187:drug effects*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D011743:Pyrimidines / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D011743:Pyrimidines; D016718:Arachidonic Acid