Ono Pharmaceutical Co., Ltd.

Kissei Pharmaceutical Co., Ltd.

Tadao Tanouchi

Masaki Hayashi

Masanori Kawamura

Hiroshi Terashima

Fumio Hirata

Takeshi Morimura

Tetsuya Mohri

Akio Ajima

Isao Ohyama

Hiroyuki Ito

Takanori Okada

Seiji Kori

Yoichi Iguchi

Ikuo Kajiwara

Satoshi Shigeoka

Masaki Havashi

The rhodanine derivatives of the general formula: ##STR1## [wherein (I) R.sup.1 and R.sup.2 are taken together to represent a tetramethylene or pentamethylene group; (II) R.sup.1 represents a hydrogen atom, and R.sup.2 represents (1) a cycloalkyl or cycloalkenyl group of 4-7 carbon atoms which is unsubstituted or substituted by at least one alkyl group of 1-4 carbon atoms, (2) an anthryl or naphthyl group, (3) a phenyl group which is unsubstituted or substituted by at least one of (a) halogen atom, (b) trifluoromethyl group, (c) hydroxyl group, (d) nitro group, (e) carboxyl group, (f) amino group which may be substituted by alkyl group(s) of 1-4 carbon atoms, (g) alkyl, alkoxy or alkylthio group of 1-5 carbon atoms, (h) phenyl group, (i) heterocyclic group containing at least one of nitrogen, oxygen and sulfur atoms which is unsubstituted or substituted by at least one of the above-described substituents (a) to (h), and (j) alkyl group of 1-4 carbon atoms which is substituted by at least one of the above-described substituents (c), (h) and (i), (4) a heterocyclic group containing at least one of nitrogen, oxygen and sulfur atoms which is unsubstituted or substituted by at least one of oxo group and the above-described substituents (a) to (h) and (j), or (5) a ##STR2## (wherein R.sup.4 represents a hydrogen atom, a halogen atom, phenyl group or an alkyl group of 1-5 carbon atoms; and R.sup.5 represents a hydrogen atom, a phenyl group or an alkyl group of 1-5 carbon atoms) or ##STR3## or (III) R.sup.1 and R.sup.2, which may be the same or different with each other, each represents a phenyl group which is unsubstituted or substituted by at least one of the above-described substituents (a) to (j); and R.sup.3 represents a hydrogen atom, an alkyl group of 1-12 carbon atoms, an aralkyl group of 7-13 carbon atoms, a cycloalkyl or cycloalkenyl group of 4-7 carbon atoms which is unsubstituted or substituted by at least one alkyl group of 1-4 carbon atoms, or a phenyl group which is unsubstituted or substituted by at least one of the above-described substituents (a) to (j)] and, when R.sup.3 represents a hydrogen atom, non-toxic salts of the acids possess a strong inhibitory activity on aldose reductase, and are useful for the prevention and treatment of nerve disturbances such as neuralgia, retinopathy, diabetic cataract and renal disturbances such as tubular nephropathy.

Rhodanine derivatives, process for their preparation, and aldose

The rhodanine derivatives of the general formula: ##STR1## [wherein (I) R.sup.1 and R.sup.2 are taken together to represent a tetramethylene or pentamethylene group; (II) R.sup.1 represents a hydrogen atom, and R.sup.2 represents (1) a cycloalkyl or cycloalkenyl group of 4-7 carbon atoms which is unsubstituted or substituted by at least one alkyl group of 1-4 carbon atoms, (2) an anthryl or naphthyl group, (3) a phenyl group which is unsubstituted or substituted by at least one of (a) halogen atom, (b) trifluoromethyl group, (c) hydroxyl group, (d) nitro group, (e) carboxyl group, (f) amino group which may be substituted by alkyl group(s) of 1-4 carbon atoms, (g) alkyl, alkoxy or alkylthio group of 1-5 carbon atoms, (h) phenyl group, (i) heterocyclic group containing at least one of nitrogen, oxygen and sulfur atoms which is unsubstituted or substituted by at least one of the above-described substituents (a) to (h), and (j) alkyl group of 1-4 carbon atoms which is substituted by at least one of the above-described substituents (c), (h) and (i), (4) a heterocyclic group containing at least one of nitrogen, oxygen and sulfur atoms which is unsubstituted or substituted by at least one of oxo group and the above-described substituents (a) to (h) and (j), or (5) a ##STR2## group (wherein R.sup.4 represents a hydrogen atom, a halogen atom, phenyl group or an alkyl group of 1-5 carbon atoms; and R.sup.5 represents a hydrogen atom, a phenyl group or an alkyl group of 1-5 carbon atoms) or ##STR3## group; or (III) R.sup.1 and R.sup.2, which may be the same or different with each other, each represents a phenyl group which is unsubstituted or substituted by at least one of the above-described substituents (a) to (j); and R.sup.3 represents a hydrogen atom, an alkyl group of 1-12 carbon atoms, an aralkyl group of 7-13 carbon atoms, a cycloalkyl or cycloalkenyl group of 4-7 carbon atoms which is unsubstituted or substituted by at least one alkyl group of 1-4 carbon atoms, or a phenyl group which is unsubstituted or substituted by at least one of the above-described substituents (a) to (j)] and, when R.sup.3 represents hydrogen atom, non-toxic salts of the acids possess a strong inhibitory activity on aldose reductase, and are useful for the prevention and treatment of nerve disturbances such as neuralgia, retinopathy, diabetic cataract and renal disturbances such as tubular nephropathy.

The rhodanine derivatives of the general formula: ##STR1## wherein (I) R.sup.1 and R.sup.2 are taken together to represent a tetramethylene or pentamethylene group; (II) R.sup.1 represents a hydrogen atom, and R.sup.2 represents (1) a cycloalkyl or cycloalkenyl group of 4-7 carbon atoms which is unsubstituted or substituted by at least one alkyl group of 1-4 carbon atoms, (2) an anthryl or naphthyl group, (3) a phenyl group which is unsubstituted or substituted, (4) a heterocyclic group containing at least one of nitrogen, oxygen and sulfur atoms which is unsubstituted or substituted (5) a ##STR2## group (wherein R.sup.4 represents a hydrogen atom, a halogen atom, phenyl group or an alkyl group of 1-5 carbon atoms; and R.sup.5 represents a hydrogen atom, a phenyl group or an alkyl group of 1-5 carbon atoms) or ##STR3## group; or (III) R.sup.1 and R.sup.2, which may be the same or different with each other, each represents a phenyl group which is unsubstituted or substituted; and R.sup.3 represents a hydrogen atom, an alkyl group of 1-12 carbon atoms, an aralkyl group of 7-13 carbon atoms, a cycloalkyl or cycloalkenyl group of 4-7 carbon atoms which is unsubstituted or substituted by at least one alkyl group of 1-4 carbon atoms, or a phenyl group which is unsubstituted or substituted, possess a strong inhibitory activity on aldose reductase.

The rhodanine derivatives of the general formula: ##STR1## possess a strong inhibitory activity on aldose reductase, and are useful for the prevention and treatment of nerve disturbances such as neuralgia, retinopathy, diabetic cataract and renal disturbances such as tubular nephropathy.

Rhodanine derivatives

The pyridine derivatives of the general formula: ##STR1## [wherein A represents an alkylene group containing from 1 to 5 carbon atoms unsubstituted or substituted by a hydroxy group, B represents a single bond, or an oxygen or sulphur atom, or an alkylene group containing from 1 to 5 carbon atoms, D represents a single bond, or an alkylene group containing from 1 to 5 carbon atoms, E represents a grouping of the formula: ##STR2## (in which R.sup.6 represents a hydrogen atoms, or an alkyl group containing from 1 to 4 carbon atoms), Z represents a single bond, or an ethynylene group, or a grouping of the formula: ##STR3## in which R.sup.2 represents a hydrogen atom, or an alkyl group containing from 1 to 4 carbon atoms, R.sup.3 represents a hydrogen, bromine or chlorine atom, or an alkyl group containing from 1 to 4 carbon atoms, the symbol  represents a single or double bond, the carbon atom attached to R.sup.2 binds to B, and the carbon atom attached to R.sup.3 binds to D, R.sup.1 represents a hydroxy group, or a grouping of the formula: --COOR.sup.4 or --COSR.sup.4, in which R.sup.4 represents a hydrogen atom, or an alkyl group containing from 1 to 12 carbon atoms, or an aralkyl group containing from 7 to 13 carbon atoms, or a cycloalkyl group containing from 4 to 7 carbon atoms unsubstituted or substituted by at least one alkyl group containing from 1 to 4 carbon atoms, or a phenyl group unsubstituted or substituted by at least one halogen atom, trifluoromethyl group, alkyl or alkoxy or alkylthio group containing from 1 to 4 carbon atoms, nitro or phenyl group, R.sup.5 represents a hydrogen atom, or an alkyl group containing from 1 to 4 carbon atoms, with the proviso that, when B represents an oxygen or sulphur atom, Z represents a single bond and D represents an alkylene group containing from 1 to 5 carbon atoms], and non-toxic acid addition salts thereof and, when R.sup.1 represents a carboxy or thiocarboxy group, non-toxic salts thereof, possess a strong inhibitory activity on thromboxane synthetase from rabbit platelet microsomes, and are useful as therapeutically active agents for the treatment or prevention of inflammation, hypertension, thrombus, cerebral apoplexy, asthma, myocardial infarction, cardiostenosis, and cerebral infarction.

Pyridine alkyl benzoic and thenoic acid compounds and their

The imidazole derivatives of the general formula: ##STR1## (wherein R.sup.1 represents a hydrogen atom or straight- or branched-chain alkyl group of 1 to 4 carbon atoms), or pharmaceutically acceptable non-toxic salts thereof, which have a specifically inhibitory effect on the biosynthesis of thromboxane A.sub.2 (abbreviated as TXA.sub.2 hereafter) and are, therefore, useful as treating agents for disease caused by TXA.sub.2 such as inflammation, cerebral apoplexy, miocardial infarction, acute cardiac death, cardiostenosis and thrombus etc.

1-(7-Carboxy-2-octynyl)imidazole derivatives, pharmaceutical

The imidazole derivatives of the general formula: ##STR1## wherein R.sup.1 represents a hydrogen atom, or a straight- or branched-chain alkyl group containing from 1 to 12 carbon atoms, R.sup.2 represents a hydrogen atom, or a straight- or branched-chain alkyl group containing from 1 to 4 carbon atoms, R.sup.3 represents a straight- or branched-chain alkyl group containing from 1 to 10 carbon atoms, and m and n, which may be the same or different, each represent zero, or an integer of 1 to 10, and non-toxic acid addition salts thereof, and, when R.sup.1 represents a hydrogen atom, non-toxic salts thereof, are new compounds. These compounds have a strong inhibitory effect on thromboxane synthetase from rabbit platelet microsomes, and are useful as therapeutically active agents for inflammation, hypertension, thrombus, cerebral apoplexy and asthma.

1-Substituted imidazole derivatives

The imidazole derivatives of the general formula: ##STR1## [wherein m represents an integer of 4 to 9, R.sup.1 represents a hydrogen atom or a straight- or branched-chain alkyl group containing from 1 to 12 carbon atoms, and one of R.sup.2 and R.sup.3 represents a hydrogen atom, and the other represents a halogen atom or a phenyl group, or R.sup.2 and R.sup.3 together represent --(CH.sub.2).sub.n --(in which n represents an integer of 4 to 6) or represent .dbd.CH.sub.2 ] and non-toxic salts thereof, which have a specifically inhibitory effect on the biosynthesis of thromboxane A.sub.2 (abbreviated as TXA.sub.2 hereafter) and are, therefore, useful as treating agents for diseases caused by TXA.sub.2 such as inflammation, cerebral apoplexy, myocardial infarction, acute cardiac death, cardiostenosis and thrombus etc.

Carboxy-imidazole derivatives, compositions and use

The pyridine derivatives of the general formula: ##STR1## [wherein A represents an alkylene group containing from 1 to 5 carbon atoms unsubstituted or substituted by a hydroxy group, B represents a single bond, or an oxygen or sulphur atom, or an alkylene group containing from 1 to 5 carbon atoms, D represents a single bond, or an alkylene group containing from 1 to 5 carbon atoms, E represents a grouping of the formula: ##STR2## (in which R.sup.6 represents a hydrogen atom, or an alkyl group containing from 1 to 4 carbon atoms), Z represents a single bond, or an ethynylene group, or a grouping of the formula: ##STR3## in which R.sup.2 represents a hydrogen atom, or an alkyl group containing from 1 to 4 carbon atoms, R.sup.3 represents a hydrogen, bromine or chlorine atom, or an alkyl group containing from 1 to 4 carbon atoms, the symbol  represents a single or double bond, the carbon atom attached to R.sup.2 binds to B, and the carbon atom attached to R.sup.3 binds to D, R.sup.1 represents a hydroxy group, or a grouping of the formula: --COOR.sup.4 or --COSR.sup.4, in which R.sup.4 represents a hydrogen atom, or an alkyl group containing from 1 to 12 carbon atoms, or an aralkyl group containing from 7 to 13 carbon atoms, or a cycloalkyl group containing from 4 to 7 carbon atoms unsubstituted or substituted by at least one alkyl group containing from 1 to 4 carbon atoms, or a phenyl group unsubstituted or substituted by at least one halogen atom, trifluoromethyl group, alkyl or alkoxy or alkylthio group containing from 1 to 4 carbon atoms, nitro or phenyl group, R.sup.5 represents a hydrogen atom, or an alkyl group containing from 1 to 4 carbon atoms, with the proviso that, when B represents an oxygen or sulphur atom, Z represents a single bond and D represents an alkylene group containing from 1 to 5 carbon atoms], and non-toxic acid addition salts thereof and, when R.sup.1 represents a carboxy or thiocarboxy group, non-toxic salts thereof, possess a strong inhibitory activity on thromboxane synthetase from rabbit platelet microsomes, and are useful as therapeutically active agents in the prevention and treatment of inflammation, hypertension, thrombus, cerebral apoplexy, asthma, myocardial infarction, cardiostenosis, cerebral infarction and acute cardiac death.

Pyridine derivatives

The pyridine derivatives of the general formula: ##STR1## [wherein A represents an alkylene group containing from 1 to 5 carbon atoms unsubstituted or substituted by a hydroxy group, B represents a single bond, or an oxygen or sulphur atom, or an alkylene group containing from 1 to 5 carbon atoms, D represents a single bond, or an alkylene group containing from 1 to 5 carbon atoms, R represents a grouping of the formula: ##STR2## (in which R.sup.6 represents a hydrogen atom, or an alkyl group containing from 1 to 4 carbon atoms), Z represents a single bond, or an ethynylene group, or a grouping of the formula: ##STR3## in which R.sup.2 represents a hydrogen atom, or an alkyl group containing from 1 to 4 carbon atoms, R.sup.3 represents a hydrogen, bromine or chlorine atom, or an alkyl group containing from 1 to 4 carbom atoms; the symbol  represents a single or double bond, the carbon atom attached to R.sup.2 binds to B, and the carbon atom attached to R.sup.3 binds to D, R.sup.1 represents a hydroxy group, or a grouping of the formula: --COOR.sup.4 or --COSR.sup.4, in which R.sup.4 represents a hydrogen atom, or an alkyl group containing from 1 to 12 carbon atoms, or an aralkyl group containing from 7 to 13 carbon atoms, or a cycloalkyl group containing from 4 to 7 carbon atoms unsubstituted or substituted by at least one alkyl group containing from 1 to 4 carbon atoms, or a phenyl unsubstituted or substituted by at least one halogen atom, trifluoromethyl group, alkyl or alkoxy or alkylthio group containing from 1 to 4 carbon atoms, nitro or phenyl group, R.sup.5 represents a hydrogen atom, or an alkyl group containing from 1 to 4 carbon atoms, with the proviso that, when B represents an oxygen or sulphur atom, Z represents a single bond and D represents an alkylene group containing from 1 to 5 carbon atoms], and non-toxic acid addition salts thereof and, when R.sup.1 represents a carboxy or thiocarboxy group, non-toxic salts thereof, possess a strong inhibitory activity on thromboxane synthetase from rabbit platelet microsomes, and are useful as therapeutically active agents in the prevention or treatment of inflammation, hypertension, thrombus, cerebral apoplexy, asthma, myocardial infarction, cardiostenosis, cerebral infarction and acute cardiac death.

The imidazole derivatives of the general formula: ##STR1## wherein R.sup.1 represents a hydrogen atom, or a straight- or branched-chain alkyl group containing from 1 to 12 carbon atoms, the symbol .dbd. represents a double bond that bond is E or Z, or a triple bond, and m and n, which may be the same or different, each represent zero, or an integer of 1 to 10, and non-toxic acid addition salts thereof, and, when R.sup.1 represents a hydrogen atom, non-toxic salts thereof are new compounds. These compounds have a strong inhibitory effect on thromboxane synthetase from rabbit platelet microsomes, and are useful as therapeutically active agents for inflammation, hypertension, thrombus, cerebral apoplexy and asthma.

1-Substituted imidazoles for inhibition of thromboxane synthetase

Prostaglandin analogues of the formula: ##STR1## wherein X represents oxygen or sulphur, R.sup.1 and R.sup.2 each represent hydrogen or alkyl of from 1 to 3 carbon atoms, alkenyl of from 2 to 4 carbon atoms or trifluoromethyl, and the double bonds depicted in positions C.sub.5 -C.sub.6 and C.sub.13 -C.sub.14 are cis and trans respectively. These compounds are indicated in the treatment of impaired fertility, induction of labor or termination of pregnancy in females.

Prostaglandin analogues

Prostaglandin compounds of the formula: ##STR1## wherein A represents a grouping of formula II, III or IV indicated below and (i)R.sub.1 represents an unsubstituted n-butyl, n-pentyl, n-hexyl or n-heptyl radical, or such a radical carrying one, two or three alkyl substituents of 1 to 4 carbon atoms, or R.sub.1 represents a methyl, ethyl, propyl or butyl radical carrying a phenyl, cyclohexyl or cyclopentyl substituent, R.sub.2 represents a hydrogen atom or an alkyl radical of 1 to 4 carbon atoms, and R.sub.3 represents a hydrogen atom, or (ii) R.sub.1 represents n-butyl, or n-butyl or n-pentyl carrying one, two or three alkyl substituents of 1 to 4 carbon atoms, or R.sub.1 represents a methyl, ethyl, propyl or butyl radical carrying a phenyl, cyclohexyl or cyclopentyl substituent, R.sub.2 represents a hydrogen atom or an alkyl radical of 1 to 4 carbon atoms, and R.sub.3 represents an alkyl radical of 1 to 4 carbon atoms are disclosed. These compounds exhibit characteristic prostaglandin-like activity.

Prostaglandin compounds of the formula: ##SPC1## Wherein A represents a grouping of formula II, III or IV indicated below and (i)R.sub.1 represents an unsubstituted n-butyl, n-pentyl, n-hexyl or n-heptyl radical, or such a radical carrying one, two or three alkyl substituents of 1 to 4 carbon atoms, or R.sub.1 represents a methyl, ethyl, propyl or butyl radical carrying a phenyl, cyclohexyl or cyclopentyl substituent, R.sub.2 represents a hydrogen atom or an alkyl radical of 1 to 4 carbon atoms, and R.sub.3 represents a hydrogen atom, or (ii) R.sub.1 represents n-butyl, or n-butyl or n-pentyl carrying one, two or three alkyl substituents of 1 to 4 carbon atoms, or R.sub.1 represents a methyl, ethyl, propyl or butyl radical carrying a phenyl, cyclohexyl or cyclopentyl substituent, R.sub.2 represents a hydrogen atom or an alkyl radical of 1 to 4 carbon atoms, and R.sub.3 represents an alkyl radical of 1 to 4 carbon atoms are disclosed. These compounds exhibit characteristic prostaglandin-like activity.

Growing community of inventors

Takatsuki, Japan

Tadao Tanouchi