ABSTRACT
Some analogues of (+/-)-N-methyl-N-¿1-[3-(4-fluorophenoxy)-2-hydroxy-propyl]-piperidin+ ++-4-yl¿ benzothiazol-2-amine (sabeluzole, CAS 104383-17-7), a series of 4-(l-naphthylamino)-piperidines (1a-1h), are potent inhibitors of both NADPH- and Fe(2+)-dependent lipid peroxidation (IC50 < 10 mumol/1). It was demonstrated that the naphthylaminopiperidine moiety is responsible for this effect due to its antioxidant property, verified by cyclic voltammetric studies.
Subject(s)
Lipid Peroxidation/drug effects , Piperidines/chemical synthesis , Animals , Electrochemistry , Iron/pharmacology , Male , Microsomes/drug effects , Microsomes/metabolism , NADP/metabolism , Piperidines/pharmacology , Rats , Rats, WistarSubject(s)
Anti-Ulcer Agents/pharmacology , Gastric Acid/metabolism , Piperidines/pharmacology , Thiazoles/pharmacology , Animals , Female , Rats , Rats, WistarABSTRACT
Several new bioanalogues of (+/-)-N-methyl-N-(1-[3-(4-fluorophenoxy)-2-hydroxy-propyl]piperidin++ +-4-yl) benzothiazol-2-amine (1, sabeluzole, CAS 104383-17-7) were prepared by reacting 1,2-epoxy-3-aryloxypropanes with 4-arylaminopiperidines. Some of these derivatives showed enhanced activity in the potassium cyanide hypoxia test and in the pentetrazol convulsion test in mice compared to 1.
