Novel 5-Substituted-1H-tetrazole Derivatives as Potent Glucose and Lipid Lowering Agents

概要

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A series of 5-(4-alkoxyphenylalkyl)-1H-tetrazole derivatives, containing an oxazole-based group at the alkoxy moiety, was prepared and their antidiabetic effects were evaluated in two genetically obese and diabetic animal models, KKA^y mice and Wistar fatty rats. Syntheses were performed by cyclization of the corresponding nitriles reacting with azide compounds. A large number of the 5-(4-alkoxyphenylalkyl)-1H-tetrazoles showed potent glucose and lipid lowering activities in KKA^y mice. In particular, 5-[3-[6-(5-methyl-2-phenyl-4-oxazolyl-methoxy)-3-pyridyl]propyl]-1H-tetrazole had potent glucose lowering activity(ED_<25>=0.0839 mg・ kg^<-1>・d^<-1>), being 72 times more active than pioglitazone hydrochloride(ED_<25>=6.0 mg・kg^<-1>・d^<-1>). This compound also showed strong glucose lowering(ED_<25>=0.0873 mg・kg^<-1>・d^<-1>)and lipid lowering effects(ED_<25>=0.0277 mg・kg^<-1>・d^<-1>)in Wistar fatty rats. The antidiabetic effects of this compound are considered to be due to its potent agonistic activity for peroxisome proliferafor-activated receptor γ(PPARγ)(EC_<50>=6.75 nм).
公益社団法人日本薬学会の論文
2002-01-01