Teijin Limited

Other

Teitin Limited

Seizi Kurozumi

Toshio Tanaka

Atsuo Hazato

Takeshi Toru

Kiyoshi Bannai

Makiko Kobayashi

Masaaki Suzuki

Sachio Ishimoto

Ryoji Noyori

Shuzi Miura

Takeo Oba

Noriaki Okamura

Satoshi Sugiura

Tatsuyuki Naruchi

Akira Ohtsu

Kenzo Watanabe

Yoshinori Kato

Masahiro Koga

Keiji Komoriya

Sadakazu Matsubara

Akira Yanagisawa

Shiro Ikegami

Toshio Kawagishi

Yutaka Mizushima

Toshio Wakabayashi

Yoshinobu Hashimoto

Toru Minoshima

Kenji Hoshina

Tamotsu Koyama

Masanori Fukushima

Yoshio Mori

Fukuyoshi Kamimoto

Kenzo Wantanabe

Satsohi Sugiura

Satoshi Asano

Akira Otsu

Shuji Miura

Makoto Ogawa

Yasuko Koshihara

Yasuko Yagyu

Yoko Shoji

Yasuhiro Torizawa

16(S)-Isocarbacyclins have been found to the useful in the treatment of liver and kidney diseases.

Isocarbocyclins for the treatment of liver and kidney diseases

A process for producing a 2,3-disubstituted-4-substituted cyclopentanone, an enantiomorph thereof, or a mixture of these in an arbitrary ratio. The process comprises (A) subjecting a 4-substituted-2-cyclopentenone, an enantiomorph thereof, or a mixture of these in an arbitrary ratio, and an organocopper compound to conjugate addition-reaction, and thereafter (B) reacting the resulting enolate intermediate with a halide in the presence of a phenyl organotin compound.

Process for producing 2,3-disubstituted-4-substituted cyclopentanones,

A 2,6,7-trisubstituted-3-methylenebicyclo-[3.3.0]octane of formula (I) or an enantiomer thereof, or a mixture of these in an arbitrary ratio. The compound is a key intermediate for preparation of isocarbacyclins which are useful as medicines for the circulatory system such as an antithrombotic agent, an antilipidemic agent, a hypotensive agent or an antiarterosclerotic agent.

2,6,7-trisubstituted-3-methylenebicyclo(3.3.0)-octanes, and process for

An isocarbacyclin derivative represented by the following formula: ##STR1## wherein R.sup.1 represents H or a linear or branched C.sub.1 -C.sub.10 alkyl group, R.sup.2 represents H, a methyl group or a vinyl group, and R.sup.3 represents an unsubstituted linear or branched C.sub.3 -C.sub.8 alkyl group or a C.sub.5 -C.sub.6 cycloalkyl group. and a pharmaceutaically acceptable salt thereof.

Isocarbacyclin derivative

An isocarbacyclin derivative represented by the following formula [VII'] ##STR1## wherein A represents, a hydrocarbylcarboxylate group, a carboxymethoxycarbonyl group, an amide group, an acyloxymethyl group or a hydroxymethyl group; R.sup.4 represents H, a methyl group or a vinyl group; R.sup.5 represents a (substituted)alkyl group, a phenyl group, a phenoxy group or a cycloalkyl group; R.sup.e22 and R.sup.e32 represent H or a hydroxyprotecting group; n is 0 or 1; and a pharmaceutically acceptable salt thereof.

Isocarbacyclin derivatives and their pharmaceutically acceptable salts

7-thiaprostaglandins E.sub.1 which are compounds represented by the following formula [I] or their enantiomers or mixtures thereof in any ratio: ##STR1## where R.sup.1 represents a hydrogen atom, a C.sub.1 -C.sub.10 alkyl group, a C.sub.2 -C.sub.20 alkenyl group, a substituted or unsubstituted phenyl group, a substituted or unsubstituted C.sub.3 -C.sub.10 cycloalkyl group, a substituted or unsubstituted phenyl (C.sub.1 -C.sub.2) alkyl group, or one equivalent cation; R.sup.2 and R.sup.3, which may be the same or different, represent a hydrogen atom, a tri (C.sub.1 -C.sub.7) hydrocarbon silyl group, or a group forming an acetal linkage together with an oxygen atom of a hydroxyl group; R.sup.4 represents a hydrogen atom, a methyl group or a vinyl group; R.sup.5 represents a linear or branched C.sub.3 -C.sub.8 alkyl group, a linear or branched C.sub.3 -C.sub.8 alkenyl group, a linear or branched C.sub.2 -C.sub.8 alkynyl group, a phenyl group which may be substituted, a phenoxy group which may be substituted, a C.sub.3 -C.sub.10 cycloalkyl group which may be substituted, or a linear or branched C.sub.1 -C.sub.5 alkyl group which may be substituted with a C.sub.1 -C.sub.6 alkoxy group, a phenyl group which may be substituted, a phenoxy group which may be substituted or a C.sub.3 -C.sub.10 cycloalkyl group which may be substituted; X represents an ethylene group, a vinylene group or an ethylene group; n represents 0 or 1; the expression represents an ethylene group or a vinylene group, provided that when n is o and x is an ethylene group, R.sup.5 is not a linear or branched C.sub.3 -C.sub.8 alkyl group or a C.sub.3 -C.sub.10 cycloalkyl group which may be substituted. Such compounds are especially useful for the treatment and prevention of digestive organ diseases such as a duodenal ulcer or a gastric ulcer.

7-thiaprostaglandins E, and process for producing same

A 2-cyclopentenone derivative represented by the following formula ##STR1## wherein R.sup.1 represents an alkyl group having 1 to 10 carbon atoms which may be substituted by a substituted or unsubstituted phenyl or phenoxy group, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are identical or different and each represents a hydrogen atom or a lower alkanoyl group, and the wavy line shows that the bonded state of the double bond is E or Z. This compound is useful for treating, for instance, malignant tumors.

2-cyclopentenone derivatives

The fat emulsions containing the prostaglandin I.sub.2 's expressed by the following formula (I): ##STR1## where X represents an oxygen atom to a methine group, Y is a carbon atom, Z represents a methylene or methine group; when X is an oxygen atom, the mode of Y-Z binding is a double bond of carbon-carbon, and when X is a methine group, the mode of X-Y binding is a double bond of carbon-carbon and Z is a methylene group; R.sub.1 represents a hydrogen atom or alkyl group, R.sub.2 represents a hydrogen atom or fluorine atom, and R.sub.3 represents a hydrogen atom, methyl group, ethyl group or vinyl group. R.sub.4 represents a substituted or unsubstituted alkyl group with 1-10 carbon atoms, a substituted or unsubstituted alkenyl group with 2-10 carbons atoms, a substituted or unsubstituted alkynyl group with 2-10 carbon atoms, or a substituted or unsubstituted cycloalkyl group with 3-8 carbon atoms; and n is zero (0) or an integer of value 1.

Fat emulsions containing isocarbacyclin

2-Substituted-2-cyclopentenones represented by the formula (I): ##STR1## wherein A is a hydroxyl group or ##STR2## and B is a hydrogen atom or A and B are bonded together to form one bonding arm;

2-substituted-2-cyclopentenones

1. An aromatic derivative having the formula (I) or the salt thereof: ##STR1## wherein R.sup.1 and R.sup.2 independently represent a hydrogen atom, hydroxyl, a halogen atom, or OR.sup.3 wherein R.sup.3 is C.sub.1 -C.sub.10 alkyl; A-B represents a hydrocarbon moiety having 1 to 10 carbon atoms and containing at least one double bond or a sulfur- or oxygen-containing hydrocarbon moiety having 1 to 10 carbon atoms; n is an integer of 2 to 4; X represents a group ##STR2## and Y represents a hydrogen atom; alkyl having 1 to 5 carbon atoms which may be substituted with aryl; alkenyl having 2 to 5 carbon atoms which may be substituted with aryl or aryl substituted with at least one C.sub.1 -C.sub.5 alkoxy; aryl which may be substituted with at least one carboxy or C.sub.1 -C.sub.5 alkoxycarbonyl or C.sub.1 -C.sub.5 alkoxy; provided that, when R.sup.1 and R.sup.2 are both hydrogen, the moiety --A--B--(CH.sub.2).sub.n --X--Y does not represent ##STR3## wherein n=2 to 4 and R.sup.4 is hydrogen or C.sub.1 -C.sub.5 alkyl.

Aromatic derivative and preparation method thereof

Process for producing bicyclo[3.3.0]octanes

A novel process for manufacturing 16-substituted .DELTA..sup.7 -prostaglandin Es, which include compounds expressed by the following formula (I), their enanantiomers, or their mixtures of arbitrary mixing ratio, ##STR1## wherein R.sup.1 indicates COOR.sup.2, CH.sub.2 OR.sup.3, or COCH.sub.2 OR.sup.3, in which R.sup.2 indicates a hydrogen atom, a substituted or unsubstituted C.sub.1 -C.sub.10 alkyl group, a substituted or unsubstituted C.sub.3 -C.sub.10 cycloalkyl group, or a substituted or unsubstituted phenyl group, and R.sup.3 indicates a hydrogen atom, a tri(C.sub.1 -C.sub.7) hydrocarbon silyl group, a group which forms an acetal bond together with the oxygen atom of a hydroxyl group, or a C.sub.2 -C.sub.7 acyl group; R.sup.4 and R.sup.5 are identical or different, each representing a hydrogen atom, a tri(C.sub.1 -C.sub.7) hydrocarbon silyl group, or a group which forms an acetal bond together with the oxygen atom of a hydroxyl group; R.sup.6 indicates a hydrogen atom, a C.sub.1 -C.sub.4 alkyl group, or a vinyl group; R.sup.7 indicates a linear or branched C.sub.3 -C.sub.8 alkyl group, an alkyenyl group, or an alkynyl group, which may contain an oxygen atom; a phenyl group, a phenoxy group, or a C.sub.3 - C.sub.10 cycloalkyl group, which may be substituted; or a linear or branched C.sub.1 -C.sub.5 alkyl group which is substituted by a C.sub.1 -C.sub.6 alkoxy group, a phenyl group, a phenoxy group, or a C.sub.3 -C.sub.10 cycloalkyl group, which may be substituted; and Y indicates CH.sub.2 X or XCH.sub.2, in which X represents an ethylene group, a cis -or trans-vinylene group, or an ethynylene group.

Process for producing 16-substituted prostaglandines

The present invention provides a process for the production of PGD.sub.2, wherein 7-hydroxy prostaglandin F.sub.2 .alpha. is treated with thiocarbonyl diimidazole or its analog and subjecting thus treated product to the reaction to deoxidize the hydroxyl group at the 7-position, the reaction to convert the hydroxyl group to a protecting group, and the reaction to oxidize the hydroxyl group at the 11-position, thus giving PGD.sub.2 at a high efficiency.

Process for production of prostaglandins D2

The present invention provides an industrially very advantageous process for producing prostaglandins E.sub.1 with fewer steps and in higher yield. The process comprises reacting a 7-hydroxyprostaglandin E with a reactive derivative of an organic sulfonic acid in the presence of a basic compound to form the corresponding 7-organic sulfonyloxyprostaglandin E, treating the resulting 7-organic sulfonyloxyprostaglandin E, after or without isolation, in the presence of a basic compound to form a .DELTA..sup.7 -prostaglandin E, thereafter selectively reducing the carbon-carbon unsaturated bond existing on the .alpha.-chain. Some of the 7-hydroxyprostaglandins E and .DELTA..sup.7 -prostaglandins E used in the process are novel compounds.

Process for prostaglandin E.sub.1 production, and novel delta

Process for producing 16-substituted prostaglandin es.

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Kokubunji, Japan

Seizi Kurozumi