Kureha Kagaku Kogyo Kabushiki Kaisha

Kureha Chemical Industry Company, Limited

Kureha Kagaku Kogyo K.k.

Hiroyuki Enari

Satoru Kumazawa

Nobuo Sato

Mikiro Yanaka

Atsushi Ito

Toshihide Saishoji

Susumu Shimizu

Michihito Ise

Fuyuhiko Nishijima

Toru Yamazaki

Toshikazu Dewa

Susumu Ikeda

Hiroshi Takahashi

Shigeru Suzuki

Mikio Sugano

Shiro Yamazaki

Yutaka Konai

Hiroshi Maruoka

Masahiro Hamada

Takashi Yamauchi

Takayuki Tanonaka

Masayo Ito

Uichi Akiba

Toshihide Saishojo

Benzimidazole derivative

Cardiac diseases improving method

This invention relates to cardiac diseases improving agents substantially free from antagonistic action to type 1 receptor of angiotensin II which participates to hypotensive action. Particularly, this invention relates to cardiac diseases improving agents composed of effective ingredients of aromatic compounds or pharmacologically acceptable salts thereof shown by below mentioned general formula. ##STR1## (wherein, substituents thereof typically include, R.sup.1, R.sup.4, R.sup.13 representing hydrogen atom, an alkyl group, a haloalkyl group and so forth, R.sup.8 representing --CO--, --SO.sub.2 -- or single bond, R.sup.2 representing a 3-7 membered aliphatic cyclic amino group having at least one nitrogen atom, R.sup.7 representing --CO-- or --SO.sub.2 --, and R.sup.12 representing N-substituted valeramido group.)

Cardiac diseases improving agents

An aromatic compound of the formula (I): ##STR1## specifically, for example, 3-��(4-carboxyphenyl)methyl!valeramido!-4-dimethylaminobenzoic acid 4'-methylpiperazide, or a salt thereof, and a pharmaceutical composition comprising said aromatic compound or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent which provides sufficiently effective alleviation of renal dysfunction without affecting blood pressure at a low blood concentration.

Aromatic compound and pharmaceutical composition

A benzene derivative of the formula (I): ##STR1## wherein R.sup.1 is hydrogen, C.sub.1-6 -alkyl, C.sub.1-6 -haloalkyl, --NH.sub.2, --NHR.sup.21 ; R.sup.2 is hydroxyl, --OR.sup.22, three- to seven-membered saturated cycloaliphatic amino optionally interrupted by one or more nitrogen, oxygen or sulfur atoms, --NHR.sup.23, --N(R.sup.24).sub.2, --NH.sub.2 ; R.sup.4 is hydrogen, C.sub.1-6 -alkyl, or --C(.dbd.O)R.sup.25 ; R.sup.7 is --CO--, --SO.sub.2 --; R.sup.8 is --CO--, single bond; R.sup.12 is --R.sup.11 --R.sup.5 ; R.sup.11 is --N(R.sup.5)--, --NH--, --O--, --N(R.sup.26)--, --N(C(.dbd.O)R.sup.27)--, --N(C(.dbd.O)NH.sub.2)--, --N(C(.dbd.O)NHR.sup.28)--; R.sup.13 is hydrogen, C.sub.1-6 -alkyl, C.sub.1-6 -haloalkyl, --NHC(.dbd.O)(CH.sub.2).sub.m C.sub.6 H.sub.5, --NHC(.dbd.O)R.sup.29, --NHC(.dbd.O)CH(C.sub.6 H.sub.5).sub.2, --NH.sub.2, --NHR.sup.30, --(CH.sub.2).sub.n C.sub.6 H.sub.5 ; Z is C, CH, N; A is CH, N; R.sup.5 is hydrogen, --CH.sub.2 C.sub.6 H.sub.4 COOH, --CH.sub.2 C.sub.6 H.sub.4 COOR.sup.31, --CH.sub.2 C.sub.6 H.sub.4 OH, --CH.sub.2 C.sub.6 H.sub.4 OR.sup.32, --CH.sub.2 C.sub.6 H.sub.4 NH.sub.2, --CH.sub.2 C.sub.6 H.sub.4 N(R.sup.33).sub.2, --CH.sub.2 C.sub.6 H.sub.4 -azole, --CH.sub.2 C.sub.6 H.sub.4 NHR.sup.34, --CH.sub.2 C.sub.6 H.sub.4 C.sub.6 H.sub.4 R.sup.14 ; R.sup.14 is azole, --COOH; R.sup.21 to R.sup.34 are independently C.sub.1-6 -alkyl or C.sub.1-6 -haloalkyl; m is 0 to 6; n is 0 to 6; t is 0 or 1, with the proviso that when Z is N, R.sup.5 is hydrogen, --CH.sub.2 C.sub.6 H.sub.4 COOH, --CH.sub.2 C.sub.6 H.sub.4 COOR.sup.31, --CH.sub.2 C.sub.6 H.sub.4 OH, --CH.sub.2 C.sub.6 H.sub.4 OR.sup.32, --CH.sub.2 C.sub.6 H.sub.4 NH.sub.2, --CH.sub.2 C.sub.6 H.sub.4 N(R.sup.33).sub.2, --CH.sub.2 C.sub.6 H.sub.4 -azole, or --CH.sub.2 C.sub.6 H.sub.4 NHR.sup.34, or a salt thereof, and a pharmaceutical composition comprising said benzene derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier are disclosed.

Benzene derivatives and pharmaceutical composition

A benzene derivative of the formula (I): ##STR1## wherein R.sup.1 is hydrogen, C.sub.1-6 -alkyl, C.sub.1-6 -haloalkyl, --NH.sub.2, --NHR.sup.21 ; R.sup.2 is hydroxyl, --OR.sup.22, three- to seven-membered saturated cycloaliphatic amino optionally interrupted by one or more nitrogen, oxygen or sulfur atoms, --NHR.sup.23, --N(R.sup.24).sub.2, --NH.sub.2 ; R.sup.4 is hydrogen, C.sub.1-6 -alkyl, or --C(.dbd.O)R.sup.25 ; R.sup.7 is --CO--, --SO.sub.2 --; R.sup.8 is --CO--, single bond; R.sup.12 is --R.sup.11 --R.sup.5 ; R.sup.11 is --N(R.sup.5)--, --NH--, --O--, --N(R.sup.26)--, --N(C(.dbd.O)R.sup.27)--, --N(C(.dbd.O)NH.sub.2)--, --N(C(.dbd.O)NHR.sup.28)--; R.sup.13 is hydrogen, C.sub.1-6 -alkyl, C.sub.1-6 -haloalkyl, --NHC(.dbd.O) (CH.sub.2).sub.m C.sub.6 H.sub.5, --NHC(.dbd.O) R.sup.29, --NHC(.dbd.O)CH(C.sub.6 H.sub.5).sub.2, --NH.sub.2, --NHR.sup.30, --(CH.sub.2).sub.n C.sub.6 H.sub.5 ; Z is C, CH, N; A is CH, N; R.sup.5 is hydrogen, --CH.sub.2 C.sub.6 H.sub.4 COOH, --CH.sub.2 C.sub.6 H.sub.4 COOR.sup.31, --CH.sub.2 C.sub.6 H.sub.4 OH, --CH.sub.2 C.sub.6 H.sub.4 OR.sup.32, --CH.sub.2 C.sub.6 H.sub.4 NH.sub.2, --CH.sub.2 C.sub.6 H.sub.4 N(R.sup.33).sub.2, --CH.sub.2 C.sub.6 H.sub.4 -azole, --CH.sub.2 C.sub.6 H.sub.4 NHR.sup.34, --CH.sub.2 C.sub.6 H.sub.4 C.sub.6 H.sub.4 R.sup.14 ; R.sup.14 is azole, --COOH; R.sup.21 to R.sup.34 are independently C.sub.1-6 -alkyl or C.sub.1-6 -haloalkyl; m is 0 to 6; n is 0 to 6; t is 0 or 1, with the proviso that when Z is N, R.sup.5 is hydrogen, --CH.sub.2 C.sub.6 H.sub.4 COOH, --CH.sub.2 C.sub.6 H.sub.4 COOR.sup.31, --CH.sub.2 C.sub.6 H.sub.4 OH, --CH.sub.2 C.sub.6 H.sub.4 OR.sup.32, --CH.sub.2 C.sub.6 H.sub.4 NH.sub.2, --CH.sub.2 C.sub.6 H.sub.4 N(R.sup.33).sub.2, --CH.sub.2 C.sub.6 H.sub.4 -azole, or --CH.sub.2 C.sub.6 H.sub.4 NHR.sup.34, or a salt thereof, and a pharmaceutical composition comprising said benzene derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier are disclosed.

A benzimidazolesulfonamide derivative of the formula (I): ##STR1## wherein R.sup.1 is an alkyl group of 1 to 6 carbon atoms or a haloalkyl group of 1 to 6 carbon atoms; R.sup.2 is a hydrogen atom, an alkyl group of 1 to 6 carbon atoms, a haloalkyl group of 1 to 6 carbon atoms, --OR.sup.4, --O(CH.sub.2).sub.m C.sub.6 H.sub.5, --(CH.sub.2).sub.n C.sub.6 H.sub.5, --NH.sub.2, --NHR.sup.5, --NHC (.dbd.O)R.sup.6, --N(R.sup.7).sub.2, --NHC(.dbd.O) (CH.sub.2).sub.p C.sub.6 H.sub.5, or --NHC(.dbd.O)CH(C.sub.6 H.sub.5).sub.2 ; R.sup.3 is an azole group, --COOH, --COOR.sup.8, or --SO.sub.3 H; A is --O--, --NH--, or --S(O).sub.q --; R.sup.4, R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are independently an alkyl group of to 6 carbon atoms; m, n, and p are independently 0 or an integer of 1 to 6; and q is 0, 1, or 2, or a salt thereof; and a pharmaceutical composition comprising the above compound are disclosed. The compound exhibits a stable and strong antagonism to angiotensin II.

Benzimidazolesulfonamide derivatives and pharmaceutical composition

A pyrimidine derivative of the formula (I): ##STR1## wherein R.sup.1 is a hydrogen atom, alkyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, or --NHR.sup.11 group; R.sup.2 is a hydrogen or halogen atom, alkyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, --(CH.sub.2).sub.m C.sub.6 H.sub.5, --NH.sub.2, --NHR.sup.12, --NH(CH.sub.2).sub.n C.sub.6 H.sub.5, --NH(CH.sub.2).sub.p C.sub.6 H.sub.4 --OR.sup.13, --N(R.sup.14)(CH.sub.2).sub.q C.sub.6 H.sub.5, --NHC(.dbd.O)R.sup.15, --NHC(.dbd.O)(CH.sub.2).sub.r C.sub.6 H.sub.5, --NHC(.dbd.O)CH(C.sub.6 H.sub.5).sub.2, --OR.sup.16, or --O(CH.sub.2).sub.s C.sub.6 H.sub.5 group; R.sup.3 is --COOH, --COOR.sup.17, hydroxyl, --OR.sup.18, --NH.sub.2, --N(R.sup.19).sub.2, --NHR.sup.20, azole, or sulfonic acid group; R.sup.11 is alkyl of 1 to 6 carbon atoms or haloalkyl of 1 to 6 carbon atoms; R.sup.12, R.sup.13, R.sup.14, R.sup.15, R.sup.16, R.sup.17, R.sup.18, R.sup.19, and R.sup.20 are independently alkyl of 1 to 6 carbon atoms; m is 0 or an integer of 1 to 6; n is 0 or an integer of 1 to 6; p is 0 or an integer of 1 to 6; q is 0 or an integer of 1 to 6; r is 0 or an integer of 1 to 6; and s is 0 or an integer of 1 to 6, or a salt thereof, and a pharmaceutical composition comprising said pyrimidine derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier are disclosed.

Pyrimidine derivatives and pharmaceutical composition

This invention provides a simple process for production of an (azolylmethyl)(biphenylmethyl)cyclopentanol derivative represented by the following formula (I) in a good yield. This process comprises, as described in the following reaction formula, reacting an (azolylmethyl)(halogenophenylmethyl)cyclopentanol derivative represented by the following formula (II) with a benzene derivative represented by the following formula (III) by light irradiation. ##STR1## wherein X denotes a halogen atom, R.sup.1 and R.sup.2 denote independently a hydrogen atom or a C1-C5 alkyl group, R.sup.3 denotes a C1-C5 alkyl group, n means an integer of 0-2, and A represents CH or N.

Process for production of (azolylmethyl)-(biphenylmethyl)cyclopentanol

Disclosed herein are an azole derivative represented by the formula (I): ##STR1## wherein R.sup.1 and R.sup.2 respectively represent a (C.sub.1 -C.sub.5) alkyl group or a hydrogen atom; X represents a halogen atom, a (C.sub.1-C.sub.5) alkyl group or a phenyl group; n represents an integer of from 0 to 2 and A represents a nitrogen atom or a CH, provided that R.sup.1 is not a hydrogen atom when R.sup.2 is a hydrogen atom, a process for producing the azole derivative represented by the formula (I), and an agricultural and horticultural composition containing the azole derivative represented by the formula (I).

Cyclopentanecarboxylic acid derivatives useful for producing azole

Disclosed herein are 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid amide derivatives having a high antagonistic activity against angiotensin II and a high specificity to angiotensin II receptors, intermediates for preparing the derivatives, and antagonists against angiotensin II comprising the derivatives.

4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid amide

Disclosed herein are an azole derivative represented by the formula (I): ##STR1## wherein R.sup.1 and R.sup.2 respectively represent a (C.sub.1 -C.sub.5) alkyl group or a hydrogen atom; X represents a halogen atom, a (C.sub.1 -C.sub.5) alkyl group or a phenyl group; n represents an integer of from 0 to 2 and A represents a nitrogen atom or a CH, provided that R.sup.1 is not a hydrogen atom when R.sup.2 is a hydrogen atom, a process for producing the azole derivative represented by the formula(I),and an agricultural and horticultural composition containing the azole derivative represented by the formula(I).

Oxirane derivatives useful for making fungicidal azole compounds

Disclosed herein are an azole derivative represented by the formula(I): ##STR1## wherein R.sup.1 and R.sup.2 respectively represent a (C.sub.1 -C.sub.5) alkyl group or a hydrogen atom; X represents a halogen atom, a (C.sub.1 -C.sub.5) alkyl group or a phenyl group; n represents an integer of from 0 to 2 and A represents a nitrogen atom or a CH, provided that R.sup.1 is not a hydrogen atom when R.sup.2 is a hydrogen atom, a process for producing the azole derivative represented by the formula(I), and an agricultural and horticultural composition containing the azole derivative represented by the formula(I).

Cyclopentanone derivatives

Disclosed herein are an azole derivative represented by the formula (I): ##STR1## wherein R.sup.1 and R.sup.2 respectively represent a (C.sub.1 -C.sub.5) alkyl group or a hydrogen atom; X represents a halogen atom, a (C.sub.1 -C.sub.5) alkyl group or a phenyl group; n represents an integer of from 0 to 2 and A represents a nitrogen atom or a CH, provided that R.sup.1 is not a hydrogen atom when R.sup.2 is a hydrogen atom, a process for producing the azole derivative represented by the formula (I), and an agricultural and horticultural composition containing the azole derivative represented by the formula (I).

Growing community of inventors

Tokyo, Japan

Hiroyuki Enari