Mitsubishi Chemical Industries Limited

Mitsubishi Kasei Corporation

Hiromi Okushima

Makio Kobayashi

Rikizo Furuya

Akihiro Narimatsu

Yoshimi Kitada

Tetsuo Sekiya

Shinichiro Fujimori

Shinya Inoue

Kazuo Suzuki

Kohei Umezu

Shuzo Hayakawa

Chiaki Hyodo

Akihiro Tobe

Issei Nitta

Tetsuro Shimpuku

Junko Hayashi

Asami Seino

Naoya Satoh

Miyuki Morita

Isao Shimooda

Hideki Bessho

Disclosed are antihypertensive pharmaceutical compositions and compounds which include the thiocarbamoylacetonitrile having the formula: ##STR1## wherein: R.sup.1 is selected from the group consisting of hydrogen, a C.sub.1 to C.sub.6 alkyl, a C.sub.3 to C.sub.6 cycloalkyl or --(CH.sub.2).sub.n --A (where A is selected from the group consisting of a C.sub.6 to C.sub.12 aryl, a 5- or 6-membered heterocyclic group or a fused heterocyclic group constituted by 9 or 10 atoms, each of which may be substituted by at least one substitute group selected from a C.sub.1 to C.sub.6 alkyl and a halogen and n is 0 or an integer of 1 to 6),

Antihypertensive thiocarbamoylascetonitrile compounds

A novel 1-phenylalkyl-3-phenylurea derivative represented by the following formula (I): ##STR1## wherein R.sup.1 and R.sup.5 represent independently hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.5 alkoxyl or halo; R.sup.2 represents hydrogen or C.sub.1 -C.sub.15 alkyl; R.sup.3 represents C.sub.1 -C.sub.15 alkyl or R.sup.3 represents together with R.sup.2 C.sub.2 -C.sub.9 alkylene; R.sup.4 and R.sup.5 represent independently C.sub.1 -C.sub.5 alkyl, C.sub.1 -C.sub.5 alkoxyl or halo; X represents oxygen or sulfur; Y represents --O--(CH.sub.2).sub.l --O-- wherein l is an integer of 1 to 3 or --(CH.sub.2).sub.p -- wherein p is an integer of 3 to 5; m is 0 or an integer of 1 to 5; and n is 0 or an integer of 1 to 3, is provided. The 1-phenylalkyl-3-phenylurea derivative (I) have the action of reducing cholesterol in blood by ACAT inhibition, and therefore, useful for treating hyperlipemia and atherosclerosis.

1-phenylalkyl-3-phenylurea derivative

Novel 1-phenylakyl-3-phenylurea derivatives represented by the following formula (I): ##STR1## wherein R.sup.1 is an alkyl group of 1 to 8 carbon atoms, an alkoxy group of 1 to 5 carbon atoms or a halogen atom, R.sup.2 is an alkyl group of 1 to 15 carbon atoms, each of R.sup.3 and R.sup.4 is independently an alkyl group of 1 to 5 carbon atoms, m is an integer of 1 to 3, and n is 0 or 1, are provided. The compounds are potent in reducing the cholesterol level in serum, and useful for treating hyperlipemia and atherosclerosis.

1-phenylalkyl-3-phenylurea derivatives

There is disclosed an aminobenzenesulfonic acid derivative of the formula: ##STR1## wherein R.sub.1 represents hydrogen atom, a C.sub.1 -C.sub.6 alkyl group, a C.sub.3 -C.sub.7 cycloalkyl group, a C.sub.1 -C.sub.4 halogenated alkyl group, a halogen atom or a C.sub.6 -C.sub.12 aryl group, R.sub.2 represents hydrogen atom, a C.sub.1 -C.sub.6 alkyl group or a C.sub.7 -C.sub.12 aralkyl group which may have at least one substituent selected from cyano group, nitro group, C.sub.1 -C.sub.6 alkoxy groups, halogen atoms, C.sub.1 -C.sub.6 alkyl groups and amino groups, and n represents an integer of 1 to 4, of a pharmaceutically acceptable salt thereof.

Aminobenzenesulfonic acid derivatives

There are provided novel pyridazinone derivatives having the general formula (I): ##STR1## wherein A represents 5- or 6-membered heterocyclic ring having 1-3 nitrogen atoms, which may be substituted by at least one member selected from the group consisting of C.sub.1-5 alkyl, cyano, hydroxyl, C.sub.1-5 alkoxyl, amino, C.sub.1-5 alkylamino, C.sub.2-6 dialkylamino, C.sub.2-5 acylamino, carboxyl, C.sub.2-5 alkoxycarbonyl and carbamoyl, and R.sup.1 and R.sup.2 independently represent hydrogen atom or C.sub.1-5 alkyl or R.sup.1 and R.sup.2 may form together C.sub.1-5 alkylene, and salts thereof.

Pyridazinone derivatives and salts thereof

Piperazinyl carbonyl phenyl pyridazinone derivatives useful as

There are provided novel pyridazinone derivatives having the general formula (I): ##STR1## wherein A represents 5- or 6-membered heterocyclic ring having 1-3 nitrogen atoms, which may be substituted by at least one member selected from the group consisting of C.sub.1-5 alkyl, cyano, hydroxyl, C.sub.1-5 alkoxy, amino, C.sub.1-5 alkylamino, C.sub.2-6 dialkylamino, C.sub.2-5 acylamino, carboxyl, C.sub.2-5 alkoxycarbonyl and carbamoyl, and R.sup.1 and R.sup.2 independently represent hydrogen atom or C.sub.1-5 alkyl or R.sup.1 and R.sup.2 may form together C.sub.1-5 alkylene, and salts thereof.

Pyridazinone derivatives and salts thereof as cardiac stimulants

A 7.alpha.-acylthio-4-en-3-oxosteroid such as 7.alpha.-acetylthio-17-hydroxy-3-oxo-17.alpha.-pregn-4-ene-21-carboxylic acid .gamma.-lactone (spironolactone) which is an antialdosteronic diuretic effective in therapy is prepared by contacting a steroidal material which contains a 7.beta.-acylthio-4-en-3-oxosteroid with a thiocarboxylic acid.

Method for preparing 7.alpha.-acylthio-4-en-3-oxosteroids

An alkali metal salt of a 3-(17.beta.-hydroxyandrosten-3-one 3-acetal-17.alpha.-yl)propiolic acid which is useful as an intermediate in the preparation of 3-(3-oxo-7.alpha.-acetylthio-17.beta.-hydroxyandrost-4-en-17.alpha.-yl)-pr opiolactone (spironolactone) as antialdosteronic diuretics and hypotensive agents is prepared by reacting a 17.beta.-hydroxypregnen-20-yn-3-one 3-acetal (I) with an alkali metal dimsyl (II) to give an alkali metal salt of the 17.beta.-hydroxypregnen-20-yn-3-one 3-acetal (III), and reacting the compound (III) with carbon dioxide followed by hydrolysis.

Process for preparing steroid-carboxylates

A steroidal 7.alpha.-acylthio-4-en-3-one is produced by adding a thiocarboxylic acid to a steroidal 4,6-dien-3-one in the presence of a strong acid in a neutral organic solvent.

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Kawasaki, Japan

Hiromi Okushima