Nisshin Flour Milling Co., Ltd.

Noriyoshi Sueda

Katsura Kogure

Kunio Nakagawa

Youziro Yoshino

Sizuo Himoto

Yoshiyuki Tahara

Makoto Yanai

Yoshikuni Suzuki

Nobuhiro Kinoshita

Toshiji Sugai

Toshihiro Takahashi

Hiroyasu Koyama

Norio Oshida

Shigeru Hiramoto

Hiroaki Yamada

Masahiro Tsuji

Masato Horigome

Masao Nagase

Koichi Katsuyama

Katsutoshi Miura

Kazuhiko Yamada

Yoko Tsukada

Fumihisa Nakata

Haruo Seto

Noboru Otake

Hitoshi Inoue

Masanori Sugita

Shinji Yokoyama

Yohei Natori

Tetsuo Sasaki

Hiroki Kato

Koichi Katasuyama

Ryotaro Kojima

Imide compounds having a propioloyl group or pharmaceutically acceptable salts thereof which exhibit potent activities to inhibit the production of Interleukin 1-.beta. and also the production of Tumor Necrosis Factor .alpha.. These imide compounds are useful as a prophylactic or therapeutic agent for inhibiting the production of Interleukin 1-.beta. and the production of Tumor Necrosis Factor .alpha., typically for such diseases as chronic rheumatism, sepsis, ulcerative colitis, Crohn's disease and many other related diseases in which Interleukin 1-.beta. and/or Tumor Necrosis Factor .alpha. would participate.

Imide derivatives for inhibiting the production of interleukin-1.beta.

Urea derivatives of formula (I) ##STR1## wherein the valuable groups are as defined in the specification, which possess both an ACAT inhibitory activity and an antioxidative activity. Those derivatives are useful in the prophylaxis and treatment of hypercholesterolemia and atherosclerosis.

Urea derivatives and their use as ACAT inhibitors

Urea derivatives of formula (1) ##STR1## wherein the valuable groups are as defined in the specification, which possess both an ACAT inhibitory activity and an antioxidative activity. Those derivatives are useful in the prophylaxis and treatment of hypercholesterolemia and atherosclerosis.

Disclosed is a rhodanine derivative of formula (I). A rhodanine derivative of formula (I) ##STR1## wherein R.sup.1 is hdyrogen, C.sub.1 -C.sub.8 alkyl, carboxyl(C.sub.1 -C.sub.4)alkyl or (C.sub.1 -C.sub.4)alkoxycarbonyl(C.sub.1 -C.sub.4)alkyl;

Rhodanine derivatives and pharmaceutical compositions

Compounds are described of formula (I) ##STR1## wherein R.sup.1 is a hydrogen atom, an alkyl group, an alkoxy group, a dialkylamino group or a halogen atom; n is 1 to 4; R.sup.2 is a hydrogen atom, an alkyl group, an unsubstituted or substituted aminoalkyl group, an acyl group, an unsubstituted or substituted aralkyl group, a carboxyalkyl group, an alkoxycarbonyalkyl group or ##STR2## wherein X is an unsubstituted or substituted-phenyl, -benzyl, -benzoyl or -furoyl group; A is -NR.sup.3 - where R.sup.3 is hydrogen or alkyl, an alkylene or an alkylidene; and B is a heterocyclic group selected from triazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzimidazolyl, benzothiazolyl, quinolyl and isoquinolyl, said heterocyclic group being optionally substituted by one or more alkyl, alkoxy, nitro or phenyl group, and the physiologically acceptable acid addition salts thereof. The compound of formula (I) are or cardiotonic activity and thus may be useful for the treatment of circulatory diseases.

Benzimidazole derivatives

Four different optical isomers of a new compound, 1-[2'-(o-methoxyphenoxy)-1'-methylethylamino]-3-(4'-isocarbostyriloxy)-2-p ropanol are now provided as new substances. These four optical isomers are now named as (2R, 1'S)-1-[2'-(o-methoxyphenoxy)-1'-methylethylamino]-3-(4'-isocarbostyriloxy )-2-propanol, (2S, 1'S)-1-[2'-(o-methoxyphenoxy)-1'-methylethylamino]-3-(4'-isocarbostyriloxy )-2-propanol, (2S, 1'R)-1-[2'-(o-methoxyphenoxy)-1'-methylethylamino]-3-(4'-isocarbostyriloxy )-2-propanol, and (2R, 1'R)-1-[2'-(o-methoxyphenoxy)-1'-methylethylamino]-3-(4'-isocarbostyriloxy )-2-propanol, respectively. These four optical isomers have different activities for their .beta.-adrenergic-blocking effect and .alpha.-adrenergic-blocking effect and are useful as valuable agents for therapeutic treatment of various cardiovascular diseases, as compared to an optically inactive racemic mixture of said isomer compounds. These four optical isomers may be produced and isolated from each other by chromatographing (1'S)- or (1'R)-N-[2'-(o-methoxyphenoxy)-1'-methylethyl]-5-(4'-isocarbostyriloxymeth yl)-2-oxazolidones to isolate either its (5R, 1'S)-isomer and its (5S, 1'S)-isomer, or its (5S, 1'R)-isomer and its (5R, 1'R)-isomer therefrom separately and then hydrolyzing each of these isolated isomers under alkaline conditions to obtain separately (2R, 1'S)-, (2S, 1'S)-, (2S, 1'R)- and (2R, 1'R)-1-[2'-(o-methoxyphenoxy)-1'-methylethylamino]-3-(4'-isocarbostyriloxy )-2-propanols.

Optically active isocarbostyril derivatives and a method of preparing

Compounds of the structure ##STR1## wherein X, R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are as herein defined, effective as .beta.-blockers and hypotensive agents, are described.

Isocarbostyril derivatives

The disclosure describes a microbiological process for the preparation of mycotrien-related compounds. The compounds are isolated and characterized by structural formula and other identifying data. The compounds are useful in the treatment of tumors.

Ansatrienols

2-Hydroxy-butenoic acid derivatives of the general formula: ##STR1## are described. These compounds have antiphlogistic activity.

Butenoic and pyruvic acid derivatives

A process for preparing 3-methyl-3-(substituted aryl)-pyruvic acid compounds by treating a glycidic acid ester compound of the formula, ##STR1## wherein R.sup.1 is a 4-biphenylyl, 4-clyclohexylphenyl, 3-phenoxyphenyl, 4'-fluoro-4-biphenylyl, 2-fluoro-4-biphenylyl or 3-benzoylphenyl group and R.sup.2 is a lower alkyl group or its corresponding free acid with a Lewis acid to form a 2-hydroxy-3-(substituted aryl)-3-butenoic acid ester and treating the resulting ester in an alcohol with an alkali metal alcoholate to form the pyruvic acid compounds. If desired, the pyruvic acid compounds can then be saponified to compounds of the formula, ##STR2## wherein R.sup.1 is as previously defined and which compounds are useful as anti-inflammatory agents.

Process for preparing a 2-methyl-(substituted aryl)-pyruvic acid compound

Process for preparing a 2-hydroxy-butenoic acid derivative of the general formula, ##STR1## wherein R.sup.1 is a group selected from aliphatic, alicyclic or aromatic radicals and R.sup.2 is a lower alkyl group by heating a glycidic acid derivative having the general formula, ##STR2## wherein R.sup.1 and R.sup.2 is as defined above or for preparing a pyruvic acid derivative of the general formula, ##STR3## wherein R.sup.1 and R.sup.2 are as defined above by heating the glycidic acid derivative of the above mentioned formula (I) or the 2-hydroxy-butenoic acid derivative of formula (II) in the presence of an electrophilic agent.

Process for producing a 2-hydroxy-3-butenoic acid derivative having the formula ##STR1## wherein R.sup.1 is an aliphatic, alicyclic or aromatic group and R.sup.2 is a lower alkyl group by treating a glycidic acid ester derivative having the formula ##STR2## wherein R.sup.1 and R.sup.2 are as defined above in the presence of an acid.

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Saitama-ken, Japan

Noriyoshi Sueda