Studies on cerebral protective agents. V. Novel 4-(3-nitrophenyl)pyridine and 4-(3-nitrophenyl)pyrimidine derivatives with anti-anoxic activity.
Novel 4-(3-nitrophenyl)pyridine and 4-(3-nitrophenyl)pyrimidine derivatives, possessing three-atom linkages between basic nitrogen and at the C-5 (or C-3) position of the pyrimidine (or pyridine) ring, were synthesized and tested for anti-anoxic (AA) activity in mice. Among them, 6-methyl-4-(3-nitrophenyl)-2-phenyl-5-(pyrrolidinomethylcarbonylamino )pyrimidin e (10f) had the most potent AA activity (3.2 mg/kg, i.p.). Three-dimensional molecular electrostatic potentials (3D-MEP0 around the nitrogenous basic moiety of 6-methyl-5-(4-methylpiperazin-1-ylcarbonyl)-4-(3-nitrophenyl )-2-phenylpyrimidin e (FK 360) and 10f were compared. The negative zone of 10f is broader and deeper and positioned somewhat differently to that of FK 360, although there is a co-occupied spacial area in part.
Kuno
A
A
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Sakai
H
H
Ohkubo
M
M
Takasugi
H
H
D000818:Animals; D001929:Brain Edema / Q000139:chemically induced / Q000517:prevention & control; D002534:Hypoxia, Brain / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D013329:Structure-Activity Relationship
D011725:Pyridines; D011743:Pyrimidines