Takeda Chemical Industries, Inc.

Isuke Imada

Masazumi Watanabe

Mitsuru Kawada

Hiroshi Morimoto

Shinji Terao

Hirosada Sugihara

Hisayoshi Okazaki

Mitsuru Shiraishi

Ichiro Azuma

Akinobu Nagaoka

Kazuaki Kitano

Yuichi Yamamura

Minoru Hirata

Tetsuya Okutani

Yoshio Nakao

Toshio Amano

Kazuhisa Sugimura

A novel benzoquinone derivative of the general formula: ##STR1## [wherein R.sub.1 and R.sub.2 are the same or different and each is methyl or methoxy; n is an integer of 0 to 21; m is 0 or 1, Z is a group of the formula: ##STR2## (wherein R.sub.3 and R.sub.4 are the same or different and each is hydrogen or an alkyl group which may optionally be substituted or, R.sub.3 and R.sub.4 together with the adjacent nitrogen atom form a morpholino group), a group of the formula: --COR.sub.5 (wherein R.sub.5 is an .alpha.-amino acid residue or a substituted or unsubstituted glucosamine residue), a group of the formula: ##STR3## (wherein R.sub.6 is a divalent hydrocarbon group of 1 to 3 carbon atoms), a group of the formula: ##STR4## (wherein R.sub.6 has the same meaning as defined above) or a group of the formula: ##STR5## (wherein l is an integer of 1 to 4 and R.sub.7 is hydroxy, methoxy or methyl)] has protocollagen-proline hydroxylase inhibiting activity, collagen biosynthesis inhibiting activity and 5-lipoxygenase suppressant activity, and is useful for the prevention and treatment of such diseases as pulmonary fibrosis, hepatocirrhosis, nephrosclerosis, arteriosclerosis, scleroderma, myelofibrosis and chronic arthritis or for the prevention and treatment of asthma, allergic rhinitis, urticaria, etc.

Benzoquinone derivatives and production thereof

Compounds of the formula: ##STR1## wherein l is an integer of 0 to 18, X is hydrogen, an alkyl having 1 to 4 carbon atoms or a carboxylic acyl having 2 to 4 carbon atoms and Y is a phenylene, a cycloalkylene having 3 to 7 carbon atoms or a group of the formula: ##STR2## in which m is an integer of 0 to 3, and R.sub.1 and R.sub.2 each is an alkyl having 1 to 4 carbon atoms, are novel compounds, possess circulatory disturbance-improving activity and inhibitory activity of the generation and release of SRS-A, and used for prophylactic or therapy of ischemic diseases such as cerebral apoplexy or allergic diseases.

Benzoquinone derivatives, their production and use

A novel benzoquinone derivative of the general formula: ##STR1## [wherein R.sub.1 and R.sub.2 are the same or different and each is methyl or methoxy; n is an integer of 0 to 21; m is 0 or 1, Z is a group of the formula: ##STR2## (wherein R.sub.3 and R.sub.4 are the same or different and each is hydrogen or an alkyl group which may optionally be substituted or, R.sub.3 and R.sub.4 together with the adjacent nitrogen atom form a morpholino group), a group of the formula: --COR.sub.5 (wherein R.sub.5 is an .alpha.-amino acid residue or a substituted or unsubstituted glucosamine residue), a group of the formula: ##STR3## (wherein R.sub.6 is a divalent hydrocarbon group of 1 to 3 carbon atoms), a group of the formula: ##STR4## (wherein R.sub.6 has the same meaning as defined above) or a group of the formula: --CH.dbd.CH).sub.l COR.sub.7 (wherein l is an integer of 1 to 4 and R.sub.7 is hydroxy, methoxy or methyl)] has protocollagen-proline hydroxylase inhibiting activity, collagen biosynthesis inhibiting activity and 5-lipoxygenase suppressant activity, and is useful for the prevention and treatment of such diseases as pulmonary fibrosis, hepatocirrhosis, nephrosclerosis, arteriosclerosis, scleroderma, myelofibrosis and chronic arthritis or for the prevention and treatment of asthma, allergic rhinitis, urticaria, etc.

An automatic analysis method of and apparatus for the full automation of an enzyme reaction analysis from the pretreatment step of the reaction to the data processing step, wherein the operation of the pretreatment step is arranged to be sequentially performed on many samples with full automation by the use of robots and computers to improve savings efficiency and measurement accuracy. Also, the pretreatment steps of weighing samples in many sample tubes, adding the given amount of solvent corresponding to the weighing value and placing the samples into the dissolution vessel to dissolve the sample in the solvent are adapted to be sequentially performed with full automation with the use of the robot, computer and electronic balance. Furthermore, the filtration, concentration and the injecting operations into the HPLC are automatically performed. The automatic apparatuses are coupled to each other so that the filtration, concentration, injecting operations are allowed to be sequentially performed with full automation using an on-line system.

Automatic analysis method and apparatus for enzyme reaction

A quinone compound of the formula: ##STR1## wherein R stands for an alkyl group of 1 to 22 carbon atoms having at its terminal end a hydroxyl group which may be protected, can be obtained with industrial advantage by allowing a compound of the formula: ##STR2## to react with a peroxide of a carboxylic acid of the formula:

Method of producing quinone derivatives

A compound of the general formul: ##STR1## wherein .alpha. .beta. means a saturated bond or a double bond; each R independently of one another is a methyl group or a methoxy group, or two R's taken together represent a group of --CH.dbd.CH--CH.dbd.CH--; n is zero or an integer of 1 through 9; when .alpha. .beta. is a saturated bond, R.sub.2 is a hydrogen atom or hydroxyl group, and when .alpha. .beta. is a double bond, R.sub.2 is a hydrogen atom; when .alpha. .beta. is a double bond or when R.sub.2 is a hydroxyl group, R.sub.1 is a carboxyl group, a group of CH.sub.2.sub.2m OH (wherein m is an integer of 1 through 3) or a group of ##STR2## (wherein m is an integer of 1 through 3); when .alpha. .beta. is a saturated bond and R.sup.2 is a hydrogen atom, R.sub.1 is a hydroxymethyl group or a group of ##STR3## (wherein m is an integer of 1 through 3) has pharmacological actions such as membrane stabilizing activity (e.g. lysosomal membrane stabilizing activity), mitochondrial electron transport activity, hypotensive activity, activity to inhibit cardiac hypertrophy, tracheal muscle relaxant activity, cerebral circulation improving activity and cerebral ischemia preventive activity and is of value in the prophylaxis and treatment of hypertension, cardiac failure, asthma, cerebral apoplexy and other diseases, as a cardiac failure remedy, bronchodilator, cerebral circulation improving agent or the like.

Quinine derivatines

A novel benzoquinone derivative of the general formula: ##STR1## wherein R.sub.1 and R.sub.2 are the same or different and each is methyl or methoxy; n is an integer of 0 to 21; m is 0 or 1, Z is a group of the formula: ##STR2## (wherein R.sub.3 and R.sub.4 are the same or different and each is hydrogen or an alkyl group which may optionally be substituted or, R.sub.3 and R.sub.4 together with the adjacent nitrogen atom form a morpholino group), a group of the formula: --COR.sub.5 (wherein R.sub.5 is an .alpha.-amino acid residue or a substituted or unsubstituted glucosamine residue), a group of the formula: ##STR3## (wherein R.sub.6 is a divalent hydrocarbon group of 1 to 3 carbon atoms), a group of the formula: ##STR4## (wherein R.sub.6 has the same meaning as defined above) or a group of the formula: ##STR5## (wherein l is an integer of 1 to 4 and R.sub.7 is hydroxy, methoxy or methyl) has protocollagen-proline hydroxylase inhibiting activity, collagen biosynthesis inhibiting activity and 5-lipoxygenase suppressant activity, and is useful for the prevention and treatment of such diseases as pulmonary fibrosis, hepatocirrhosis, nephrosclerosis, arteriosclerosis, scleroderma, myelofibrosis and chronic arthritis or for the prevention and treatment of asthma, allergic rhinitis, urticaria, etc.

Benzoquinone derivatives

A novel benzoquinone derivative of the general formula: ##STR1## [wherein R.sub.1 and R.sub.2 are the same or different and each is methyl or methoxy; n is an integer of 0 to 21; m is 0 or 1, Z is a group of the formula: (wherein R.sub.3 and R.sub.4 are the same or different and each is hydrogen or an alkyl group which may optionally be substituted or, R.sub.3 and R.sub.4 together with the adjacent nitrogen atom form a morpholino group), a group of the formula: --COR.sub.5 (wherein R.sub.5 is an .alpha.-amino acid residue or a substituted or unsubstituted glucosamine residue), a group of the formula: ##STR2## (wherein R.sub.6 is a divalent hydrocarbon group of 1 to 3 carbon atoms), a group of the formula: ##STR3## (wherein R.sub.6 has the same meaning as defined above) or a group of the formula: --CH.dbd.CH).sub.l COR.sub.7 (wherein l is an integer of 1 to 4 and R.sub.7 is hydroxy, methoxy or methyl)] has protocollagen-proline hydroxylase inhibiting activity, collagen biosynthesis inhibiting activity and 5-lipoxygenase suppressant activity, and is useful for the prevention and treatment of such diseases as pulmonary fibrosis, hepatocirrhosis, nephrosclerosis, arteriosclerosis, scleroderma, myelofibrosis and chronic arthritis or for the prevention and treatment of asthma, allergic rhinitis, urticaria, etc.

A compound of the formula: ##STR1## [wherein either one of R.sub.1 and R.sub.2 stands for hydrogen or SO.sub.3 H and the other is SO.sub.3 H, Z stands for ##STR2## (where m denotes an integer of 1-22, n denotes an integer of 0-21, R.sub.3 stands for hydrogen or an acyl group having 2 to 4 carbon atoms, and R.sub.4 is hydrogen or an alkyl group having 1 to 4 carbon atoms)] and pharmacologically acceptable salts thereof, which has various pharmacological actions such as antioxidative action, inhibitory action of SRS-A generation, immunoregulatory action, action on lysosome-membrane, cell-activating action, phosphodiesterase-inhibitory action, etc.

Hydroquinone sulfate derivatives and production thereof

Novel spirobenzofuranone compounds of the formula: ##STR1## wherein R is a hydrogen atom or a lower alkyl and --X-- is ##STR2## and a pharmaceutically acceptable salt thereof, have gastric secretion inhibitive, antiulcer activities, and are of value as drugs.

Spirobenzofuranones and their use in treating peptic ulcers

A novel benzoquinone derivative of the general formula: ##STR1## [wherein R.sub.1 and R.sub.2 are the same or different and each is methyl or methoxy; n is an integer of 0 to 21; m is 0 or 1, Z is a group of the formula: ##STR2## (wherein R.sub.3 and R.sub.4 are the same or different and each is hydrogen or an alkyl group which may optionally be substituted or, R.sub.3 and R.sub.4 together with the adjacent nitrogen atom form a morpholino group), a group of the formula: --COR.sub.5 (wherein R.sub.5 is an .alpha.-amino acid residue or a substituted or unsubstituted glucosamine residue), a group of the formula: ##STR3## (wherein R.sub.6 is a divalent hydrocarbon group of 1 to 3 carbon atoms), a group of the formula: ##STR4## (wherein R.sub.6 has the same meaning as defined above) or a group of the formula: --CH.dbd.CH.sub.l --COR.sub.7 (wherein l is an integer of 1 to 4 and R.sub.7 is hydroxy, methoxy or methyl)] has protocollagen-proline hydroxylase inhibiting activity, collagen biosynthesis inhibiting activity and 5-lipoxygenase suppressant activity, and is useful for the prevention and treatment of such diseases as pulmonary fibrosis, hepatocirrhosis, nephrosclerosis, arteriosclerosis, scleroderma, myelofibrosis and chronic arthritis or for the prevention and treatment of asthma, allergic rhinitis, urticaria, etc.

Novel compounds of the formulae ##STR1## wherein R represents lower alkyl or lower alkoxy, A represents --CH.sub.2 --, --CO-- or ##STR2## n represents an integer of 1 to 8, X represents hydrogen or hydroxyl which may be protected and Y represents hydroxyl which may be protected, and their esters show an excellent action on the lysosomal membranes of cells, and exhibit excellent pharmacological activities such as physiologic host defense control activity, especially immuno-potentiating activity.

Aralkyl carboxylic acid compounds in compositions for potentiating

Compounds of the formula ##STR1## wherein A is methylene or carbonyl, n is an integer of 2 to 21, inclusive, and R is hydrogen or lower alkyl, are effective for the prophylaxis or treatment of mammals suffering from fibrosis due to excessive collagen accumulation.

Antifibrotic agent

A compound of the general formula ##STR1## wherein n is an integer of 10 to 21, inclusive; R is H or lower alkyl having 1 to 4 carbon atoms has pharmaceutical activities such as hypotensive, tissue metabolism stimulating, immuno-regulatory, lysosomal membrane stabilizing and SRS-A production inhibitory activities and is useful as a heart failure remedy, cerebral circulation disturbance remedy, immuno-regulator, and antiallergic drug.

Quinone carboxylic acids and ester derivatives

A mammal suffering from ischemic disease such as cerebral apoplexy, cardiac insufficiency, renal insufficiency due to vascular changes, etc. is remedied by administering to said mammal an effective amount of a compound of the formula: ##STR1## wherein n is an integer of from 4 to 22.

Growing community of inventors

Izumi, Japan

Isuke Imada