Masatoshi Sakae

Structure - Activity studies leading to ( - )1-(Benzofuran-2-yl)-2-propylaminopentane, (( - )BPAP), a highly potent, selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain

The catecholaminergic and serotoninergic neurons in the brain change their performance according to the physiological need via a catecholaminergic/serotoninergic activity enhancer (CAE/SAE) mechanism. Phenylethylamine (PEA), tyramine and tryptamine are the presently known endogenous CAE/SAE substances which enhance the impulse propagation mediated release of catecholamines and serotonin in the brain. A PEA derivative, (-)deprenyl (selegiline), known as a selective inhibitor of MAO-B, is for the time being the only CAE/SAE substance in clinical use. Aiming to develop a selective CAE/SAE substance much more potent than (-)deprenyl, a series of new 1-aryl-2-alkylaminoalkanes, structurally unrelated to PEA and the amphetamines, was designed and prepared. Among them, (-)1-(benzofuran-2-yl)-2-propylaminopentane ((-)BPAP) was selected as a promising candidate substance for further studies. (-)BPAP significantly enhanced in rats the impulse propagation mediated release of catecholamines and serotonin in the brain 30min after acute injection of 0.36nmol/kg sc. In the shuttle box, (-)BPAP was in rats about 130 times more potent than (-)deprenyl in antagonizing tetrabenazine induced inhibition of performance. (+/-)BPAP protected cultured hippocampal neurons from the neurotoxic effect of beta-amyloid in 10(-14)-10(-15)M concentration.

The Reaction of 3-Substituted 2-(N-Cyanoimino)thiazolidine Derivatives with Hydrazine: Novel Synthesis of Triazoles

The reaction of 3-substituted 2-(N-cyanoimino)thiazolidine (NCT) derivatives with hydrazine hydrate afforded two types of 1,2,4-triazoles via a selective C 2 -S or C 2 -N 3 bond fission, in which the selectivity was controlled by the N 3 -substituent

Unexpected O → S and N → S alkyl transfer reactions in the reaction of 3-alkyl-2-(N-cyanoimino)thiazolidines with sodium alkoxides: a new synthesis of cimetidine

Unexpected O → S and N → S alkyl transfer reactions were observed in the reaction of 3-alkyl-2-(N-cyanoimino)thiazolidines with sodium alkoxides, and a new synthetic method for cimetidine was developed using the N → S alkyl transfer reaction as a key step.