Japan Tobacco Inc.

Yoshitomi Pharmaceutical Industries, Ltd.

Kunio Iwata

Itsuo Uchida

Koji Kobayashi

Koretake Anami

Kazuhiko Nishii

Akira Saito

Junichi Haruta

Mutsuyoshi Matsushita

Katsuyoshi Hara

Noboru Furukawa

Shin Hara

Akihiro Yasuda

Hiroaki Hari

Novel proline derivatives of the following formula (I) ##STR1## wherein each symbol is as defined in the specification, which specifically inhibit prolyl endopeptidase activity and can be used for the prevention and/or treatment of dementia and amnesia as agents which act directly on the central symptoms of dementia.

Proline derivatives possessing prolyl endopeptidase-inhibitory activity

Novel peptide derivatives of the following formula ##STR1## wherein each symbol is as defined in the specification, pharmaceutically acceptable acid addition salts thereof and analogous copounds thereof. Since the derivatives and their pharmaceutically acceptable acid addition salts of the present invention possess stronger actions on central nervous system (e.g. antagonistic action against hypothermia, locomotor stimulant action, signal reflex stimulant action), they are of use as a therapeutic medicament for central nervous disorders such as impaired consciousness, depression, hypomnesia, the like in association association with schizophrenia, melancholia, senile dementia, sequelae of cerebrovascular disorders, head trauma, epilepsy and spinocerebellar degeneracy.

Histidyl peptide derivatives

Amino acid derivatives possessing prolyl endopeptidase-inhibitory

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Hatano, Japan

Kunio Iwata