Ohkubo M, Kuno A, Sakai H, Takasugi H
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Chem Pharm Bull (Tokyo). 1995 Jun;43(6):947-54. doi: 10.1248/cpb.43.947.
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.
制备了在唑环C-5位带有氨基部分的新型4-芳基唑（即噻唑、恶唑和咪唑）衍生物，并在小鼠中测试其抗缺氧（AA）活性。其中，5-(4-甲基哌嗪-1-基)甲基-4-(3-硝基苯基)-2-苯基噻唑（3b，FR75094）具有显著的AA活性（分别为10mg/kg，腹腔注射和100mg/kg，口服），并且在抗脂质过氧化（ALP）试验中也有效，还能抑制花生四烯酸诱导的大鼠脑水肿。讨论了该系列化合物AA活性的构效关系。
