Snow Brand Milk Products Co., Ltd.

Toshin Chemical Co., Ltd.

Susumu Ishiguro

Motohide Seya

Shin Nomoto

Masayuki Okue

Shinichi Shimada

Kenichi Ishibashi

Yuzo Yagi

Nobuo Ogane

Masamichi Nakakoshi

Yasuyoshi Takeshita

Fumitake Shimada

Noboru Kawaguchi

Shin'ichi Shimada

Tadayoshi Koyama

Hiroshi Nakamura

Yasunari Saito

Noboru Kwaguchi

Yasunari Saitou

Noriko Abe

Reiko Komaki

Naomi Kito

Toshio Itoh

Kunio Tomitsuka

Isoquinoline derivatives

Particular hexahydropyrano [3,2-b] [1,4] benzothiazine derivatives represented by the following general formula (I) or pharmaceutically acceptable acid-addition salts thereof. ##STR1## The compounds can facilitate the metabolic turnover of inositol phospholipids at a hippocampus playing an important part in memory, and improve cerebral function leading the memory. The compounds can be utilized as agents for activating brain metabolism and improving cerebral function.

Hexahydropyrano [3,2-B] [1,4] benzothiazine derivative

The invention provides novel compounds and salts thereof, have the structure ##STR1## wherein R.sub.1 is a guianidinobenzoyloxy group and R.sub.2 is a hydrogen atom, a hydroxy, cyano, --COR.sub.3 (wherein R.sub.3 is an amino or lower alkyl group) or --COOR.sub.4 group [wherein R.sub.4 is a hydrogen atom, lower alkyl, phenyl, benzyl or --CH.sub.2 CONR.sub.5 R.sub.6 group (wherein R.sub.5 and R.sub.6 are the same or different and selected from a hydrogen atom and lower alkyl groups)], and wherein R.sub.1 is a hydroxy group and wherein R.sub.2 is a --COR.sub.3 (wherein R.sub.3 is an amino or lower alkyl group) or --COOR.sub.4 group [wherein R.sub.4 is a (C.sub.1, C.sub.3 or C.sub.4) alkyl, phenyl, benzyl or --CH.sub.2 CONR.sub.5 R.sub.6 group (wherein R.sub.5 and R.sub.6 are the same or different and selected from a hydrogen atom and lower alkyl groups)]. The compounds, wherein R.sub.1 is a guanidinobenzoyloxy group, are useful protease inhibitors as anti-trypsin agents.

Isoquinoline derivatives and salts thereof

A novel and efficient method is proposed for the preparation of isosorbide-5-nitrate which is a promising medicinal compound for several diseases due to disorder in heart. The method comprises direct nitration of isosorbide with a concentrated nitric acid in a specific reaction medium containing an aromatic hydrocarbon solvent, e.g. benzene, in addition to conventional acetic acid and acetic anhydride. After neutralization of the reaction mixture and removal of the dinitrate as a byproduct therefrom, the reaction mixture is admixed with an aqueous solution of sodium hydroxide so that a sodium salt of isosorbide-5-nitrate is precipitated in the form of a hydrate, which is a novel compound not known in the prior art. This hydrate sodium salt is then decomposed with an acid to give the desired isosorbide-5-nitrate in a high yield.

Method for the preparation of isosorbide-5-nitrate and sodium

A novel and very elegant method is proposed for the preparation of N.sub.1 -(2-tetrahydrofuryl)-5-substituted or -unsubstituted uracil, especially, N.sub.1 -(2-tetrahydrofuryl)-5-fluorouracil, by the reaction of the corresponding 5-substituted uracil compound with 2,3-dihydrofuran. The reaction is performed in the presence of a chlorosilane compound, e.g. dimethyldichlorosilane, and a catalytic amount of an organic amine compound and can proceed very rapidly without disadvantageous side reactions to give the objective compound with high purity in a high yield.

Method for the preparation of derivatives of uracil

Growing community of inventors

Omiya, Japan

Susumu Ishiguro