Studies on Cerebral Protective Agents. III. Novel 4-Arylpyrimidine Derivatives with Anti-anoxic and Anti-lipid Peroxidation Activities. (3)

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Novel 4-arylpyrimidine derivatives, bearing an amino moiety in the C-5 or C-6 position of the pyrimidine ring, were synthesized and tested for anti-anoxic (AA) activity in mice. Among them, 6,7-dihydro-6-[2-(dimethylamino)-ethyl]-4-(3-nitrophenyl-2-phenyl-5H-pyrrolo[3,4-d]pyrimidine-5-one (2a, FR 75469) and 6-methyl-5-(4-methyl-piperazin-1-ylmethyl)-4-(3-nitrophenyl)-2-phenylpyrimidine (4c, FR 72707) had comparable potency 10-100mg/kg, i.p. and p.o.)to that of 6-methyl-5-(4-methylpiperazin-1-ylcarbonyl)-4-(3-nitrophenyl)-2-phenylpyrimidine (FK 360).These were also effective on anti-lipid peroxidation (ALP) assay and arachidonate-induced cerebral edema in rats.Structure-activiity relationship in regard to AA activity of this series of compounds are discussed. Three-dimensional molecular electrostatic potentials (3D-MEP) around the nitrogeneous basic moiety of FK 360 and 5-acetyl-6-(2-dimethylaminoethyl)-4-(3-nitrophenyl)-2-phenylpyrimidine (5f) were compared, and both electrostatic potential maps were similar.
社団法人日本薬学会の論文
1993-01-15