Japan Tobacco Inc.

Yoshitomi Pharmaceutical Industries, Ltd.

Itsuo Uchida

Koji Kobayashi

Kunio Iwata

Koji Ando

Yasuki Yamada

Junichi Haruta

Katsuyoshi Hara

Koretake Anami

Kazuhiko Nishii

Shin Hara

Akihiro Yasuda

Saizo Shibata

Hiroyuki Abe

Masahiro Tanaka

Yoshihiro Watanabe

Akira Saito

Shunichi Manabe

John A Lawson

Mutsuyoshi Matsushita

Shinji Yata

Susumu Katoh

Noboru Furukawa

Kazuhiko Sakuma

Kazuhide Hayakawa

Minoru Akamatsu

Ikuro Nakamura

Kiyoshi Fukui

Shinsuke Sayama

Motohiro Kogayu

Hidetsura Cho

Hiroaki Hari

Kazuo Aisaka

Jun-ichi Haruta

Akira Ohta

Koichi Ozawa

Masashi Sasabuchi

Eiji Shirakawa

Katsuo Toide

Dioxacycloalkane compound having renin-inhibitory activity

Chroman derivative and pharmaceutical use thereof

Compound having prolyl endopeptidase inhibitory activity and

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

Compounds of the formula I ##STR1## are disclosed. In this formula, R is a member selected from the group consisting of --CR.sub.1 R.sub.2 R.sub.3, hydroxy, an alkoxy group having 1 to 4 carbon atoms and --NR.sub.4 R.sub.5, in which at most one of R.sub.1, R.sub.2 and R.sub.3 is hydrogen and the remainder are each independently selected from the group consisting of an alkyl group having 1 to 4 carbon atoms, an alkenyl group having 2 to 4 carbon atoms, an alkynyl group having 2 to 4 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms, a cycloalkylalkyl having 4 to 9 carbon atoms and a 3 to 6 membered cyclic ether; R.sub.4 and R.sub.5 are each independently hydrogen or an alkyl group having 1 to 4 carbon atoms; R.sub.6 and R.sub.7 are each independently hydrogen or an alkyl group having 1 to 4 carbon atoms; and R.sub.8 is hydrogen, an alkyl group having 1 to 4 carbon atoms, hydroxy, an alkoxy group having 1 to 4 carbon atoms or halogen. Salts of these compounds are also disclosed. Also disclosed are pharmaceutical compositions of these compounds with a pharmaceutically acceptable carrier, the use of these materials as N-methyl-D-aspartate receptor antagonists, processes for preparing these compounds and salts, and methods to treat cerebral diseases by administering an effective amount of these compounds, salts or compositions.

Benzomorphans useful as NMDA receptor antagonists

Oxazinone derivative

Cyclohexene derivative and method of producing the same

Method for preparing .alpha.-amino-.beta., .delta.-diol derivatives

1,3,2-dioxathiolane oxide derivative

4H-3,1-benzoxazin-4-one derivative

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

Growing community of inventors

Yokohama, Japan

Itsuo Uchida