US4734416A — Pharmaceutically useful carbostyril derivatives

Claim 1

Independent Claim 251 words

A carbostyril derivative represented by the formula, ##STR25## wherein R 1 is a hydrogen atom, an alkyl group having 1 to 6 carbon alkynyl group having 2 to 4 carbon atoms or a phenyl alkyl group having an alkylene group having 1 to 4 carbon atoms; R 2 is a hydrogen atom; R 3 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; R 4 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; R 5 is a phenyl group which may be substituted by 1 to 3 identical or different groups selected from the group consisting of a halogen atom, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms; X is a halogen atom; n is 0 or an integer of 1 or 2; Q is an integer of 2; l and m are respectively 0 or an integer of 1 to 6, but the sum of l and m should not exceed 6; the carbon-carbon bond at the 3- and 4-positions in the carbostyril skeleton in a single or double bond; the substituted position of the side chain of ##STR26## is any one of the 4-, 5-, 6-, 7- or 8-positions; or an acid addition salt thereof, with the proviso that when said side chain is substituted at the 4-position and said carbon-carbon bond at the 3- or 4-positions is a double bond, then R 2 does not exist.

Claim 2

Dependent Claim 251 words

A carbostyril derivative represented by the formula, ##STR25## wherein R 1 is a hydrogen atom, an alkyl group having 1 to 6 carbon alkynyl group having 2 to 4 carbon atoms or a phenyl alkyl group having an alkylene group having 1 to 4 carbon atoms; R 2 is a hydrogen atom; R 3 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; R 4 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; R 5 is a phenyl group which may be substituted by 1 to 3 identical or different groups selected from the group consisting of a halogen atom, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms; X is a halogen atom; n is 0 or an integer of 1 or 2; Q is an integer of 2; l and m are respectively 0 or an integer of 1 to 6, but the sum of l and m should not exceed 6; the carbon-carbon bond at the 3- and 4-positions in the carbostyril skeleton in a single or double bond; the substituted position of the side chain of ##STR26## is any one of the 4-, 5-, 6-, 7- or 8-positions; or an acid addition salt thereof, with the proviso that when said side chain is substituted at the 4-position and said carbon-carbon bond at the 3- or 4-positions is a double bond, then R 2 does not exist.

Claim 3

Dependent Claim 34 words

A carbostyril derivative or an acid addition salt thereof according to claim 1, wherein the substituted position of the side chain represented by the formula, ##STR27## is 5- or 7-position in the carbostyril skeleton.

Claim 4

Dependent Claim 35 words

A carbostyril derivative or an acid addition salt thereof according to claim 1, wherein the substituted position of the side chain represented by the formula, ##STR28## is 4-, 6- or 8-position in the carbostyril skeleton.

Claim 5

Dependent Claim 32 words

A carbostyril derivative or an acid addition salt thereof according to claim 2, wherein the substituted position of the side chain represented by the formula, ##STR29## is 5-position in the carbostyril skeleton.

Claim 6

Dependent Claim 32 words

A carbostyril derivative or an acid addition salt thereof according to claim 2, wherein the substituted position of the side chain represented by the formula, ##STR30## is 7-position in the carbostyril skeleton.

Claim 7

Dependent Claim 1 words

7-[3-(4-Phenylpiperazinyl)propoxy]-3,4-dihydrocarbostyril.

Claim 8

Dependent Claim 1 words

7-[3-(4-Phenylpiperazinyl)propoxy]-3,4-dihydrocarbostyril.

Claim 9

Dependent Claim 1 words

7-{3-[4-(2-Methoxyphenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril.

Claim 10

Dependent Claim 1 words

7-{3-[4-(2-Methoxyphenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril.

Claim 11

Dependent Claim 1 words

7-{3-[4-(3-Chlorophenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril.

Claim 12

Dependent Claim 1 words

7-{3-[4-(3-Chlorophenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril.

Claim 13

Dependent Claim 1 words

7-{3-[4-(2-Fluorophenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril.

Claim 14

Dependent Claim 1 words

7-{3-[4-(2-Fluorophenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril.

Claim 15

Dependent Claim 1 words

7-[3-(4-Phenylpiperazinyl)propoxy]carbostyril.

Claim 16

Dependent Claim 1 words

7-[3-(4-Phenylpiperazinyl)propoxy]carbostyril.

Claim 17

Dependent Claim 1 words

7-{3-[4-(2-Ethoxyphenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril.

Claim 18

Dependent Claim 1 words

7-{3-[4-(2-Ethoxyphenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril.

Claim 19

Dependent Claim 1 words

1-Methyl-7-[3-(4-phenylpiperazinyl)propoxy]-3,4-dihydrocarbostyril.

Claim 20

Dependent Claim 1 words

1-Methyl-7-[3-(4-phenylpiperazinyl)propoxy]-3,4-dihydrocarbostyril.

Claim 21

Dependent Claim 1 words

7-[4-(4-Phenylpiperazinyl)butoxy]-3,4-dihydrocarbostyril.

Claim 22

Dependent Claim 1 words

7-[4-(4-Phenylpiperazinyl)butoxy]-3,4-dihydrocarbostyril.

Claim 23

Dependent Claim 1 words

5-[3-(4-Phenylpiperazinyl)propoxy]-3,4-dihydrocarbostyril.

Claim 24

Dependent Claim 1 words

5-[3-(4-Phenylpiperazinyl)propoxy]-3,4-dihydrocarbostyril.

Claim 25

Dependent Claim 1 words

6-[3-(4-Phenylpiperazinyl)propoxy]carbostyril.

Claim 26

Dependent Claim 1 words

6-[3-(4-Phenylpiperazinyl)propoxy]carbostyril.

Claim 27

Dependent Claim 1 words

7-{3-[4-(2-Chlorophenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril.

Claim 28

Dependent Claim 1 words

7-{3-[4-(2-Chlorophenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril.

Claim 29

Dependent Claim 1 words

8-Bromo-5-[3-(4-phenylpiperazinyl)propoxy]carbostyril.

Claim 30

Dependent Claim 1 words

8-Bromo-5-[3-(4-phenylpiperazinyl)propoxy]carbostyril.

Claim 31

Dependent Claim 1 words

7-{3-[4-(2-Methoxyphenyl)piperazinyl]propoxy}carbostyril.

Claim 32

Dependent Claim 1 words

7-{3-[4-(2-Methoxyphenyl)piperazinyl]propoxy}carbostyril.

Claim 33

Dependent Claim 1 words

7-{3-[4-(4-Methylphenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril.

Claim 34

Dependent Claim 1 words

7-{3-[4-(4-Methylphenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril.

Claim 35

Dependent Claim 1 words

1-Benzyl-5-[3-(4-phenylpiperazinyl)propoxy]-3,4-dihydrocarbostyril.

Claim 36

Dependent Claim 1 words

1-Benzyl-5-[3-(4-phenylpiperazinyl)propoxy]-3,4-dihydrocarbostyril.

Claim 37

Dependent Claim 31 words

A central nervous controlling agent, containing a suitable amount of a carbostyril derivative or acid addition salt thereof according to claim 1 as an active ingredient and a pharmaceutically acceptable carrier.

Claim 38

Dependent Claim 22 words

A carbostyril derivative or an acid addition salt thereof according to claim 1 or 2, wherein R 1 is a hydrogen atom.

Claim 39

Dependent Claim 59 words

A carbostyril derivative or an acid addition salt thereof according to claim 1, wherein R 1 is an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 4 carbon atoms, an alkynyl group having 2 to 4 carbon atoms or a phenyl alkyl group having an alkylene group having 1 to 4 carbon atoms.

Claim 40

Dependent Claim 26 words

A carbostyril derivative or an acid addition salt thereof according to claim 1 or 2, wherein R 1 is a hydrogen atom and n is 0.

Claim 41

Dependent Claim 113 words

A carbostyril derivative or a salt thereof as claimed in claim 1, wherein the carbon-carbon bond at the 3- and 4-positions in the carbostyril skeleton is a single bond, the substituted position of the side chain of ##STR31## is the 6-position, l and m are each 1, R 4 is hydrogen, n is 0, R 1 denotes a hydrogen atom or a C 1 -C 6 alkyl group, R 5 denotes a phenyl group having one to three, identical or different substituents selected from the group consisting of a C 1 -C 4 -alkyl group, a C 1 -C 4 -alkoxy group and a halogen atom and R 3 denotes a hydrogen atom.

Claim 42

Dependent Claim 53 words

A carbostyril derivative or a salt thereof as claimed in claim 25, wherein R 5 is a phenyl group which is substituted by a group selected from the group consisting of a halogen atom, an alkyl group having 1 to 3 carbon atoms and an alkoxy group having 1 to 3 carbon atoms.

Claim 43

Dependent Claim 16 words

A composition having a central nervous controlling effect comprising a compound as defined in claim 26.

Claim 44

Dependent Claim 39 words

The method of treating a human patient to produce a central nervous controlling effect which comprises orally administering to said patient a dosage of about 40 ug to 2 mg/kg day of a compound as defined in claim 26.

Claim 45

Dependent Claim 39 words

The method of treating a human patient to produce a central nervous controlling effect which comprises intravenously administering to said patient a dosage of about 40 ug to 2 mg/kg day of a compound as defined in claim 26.

Claim 46

Dependent Claim 17 words

The compound of claim 1 wherein R 5 is a phenyl group substituted by two halogen atoms.

Claim 47

Dependent Claim 1 words

5-{3-[4-(2-Ethoxyphenyl)piperazinyl]propoxy}3,4-dihydrocarbostyril.

Claim 48

Dependent Claim 1 words

5-{3-[4-(2-Ethoxyphenyl)piperazinyl]propoxy}3,4-dihydrocarbostyril.

Claim 49

Dependent Claim 11 words

A carbostyril derivative in accordance with claim 1 consisting of: 7-{3-[4-(3-Fluorophenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril.

Claim 50

Dependent Claim 103 words

A (4-substituted-piperazin-1-yl)alkoxy-2-oxo-1,2-dihydroquinoline of the formula: ##STR32## in which R 1 is a hydrogen atom or an alkyl radical with 1 to 6 carbon atoms, R 3 is a hydrogen atom or an alkyl radical having 1 to 4 carbon atoms, R 4 is a hydrogen atom, a halogen atom, or an alkyl or alkoxy radical with 1 to 4 carbon atoms, n is 2, 3, 4 or 5 and A is a valency bond or a methylene radical with the proviso that when A is a methylene radical, R 4 is a hydrogen atom; or a salt thereof with a pharmacologically acceptable acid.

Claim 51

Dependent Claim 103 words

A (4-substituted-piperazin-1-yl)alkoxy-2-oxo-1,2-dihydroquinoline of the formula: ##STR32## in which R 1 is a hydrogen atom or an alkyl radical with 1 to 6 carbon atoms, R 3 is a hydrogen atom or an alkyl radical having 1 to 4 carbon atoms, R 4 is a hydrogen atom, a halogen atom, or an alkyl or alkoxy radical with 1 to 4 carbon atoms, n is 2, 3, 4 or 5 and A is a valency bond or a methylene radical with the proviso that when A is a methylene radical, R 4 is a hydrogen atom; or a salt thereof with a pharmacologically acceptable acid.

Claim 52

Dependent Claim 142 words

A carbostyril derivative or a salt thereof as claimed in claim 1, wherein R 1 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; R 3 is a hydrogen atom; R 4 is a hydrogen atom; R 5 is a phenyl group which may be substituted by a group selected from the group consisting of a halogen atom, an alkyl group having 1 to 4 carbon atoms, and an alkoxy group having 1 to 4 carbon atoms; n is 0; l and m are respectively 0 or an integer, wherein the sum of l and m is from 1 to 4; the carbon-carbon bond at the 3- and 4-positions in the carbostyril skeleton is a double bond; and the substituted position of the side chain of ##STR33## is any one of the 5-, 6-, 7- or 8-positions.

Claim 53

Dependent Claim 75 words

A compound or salt thereof according to claim 34 in which R 1 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; R 2 is a hydrogen atom; and R 5 is a phenyl group which may be substituted by a group selected from the group consisting of a chlorine atom, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms.

Claim 54

Dependent Claim 61 words

A compound or salt thereof according to claim 33 wherein such compound is ##STR34## in which R 3 is a hydrogen atom or a methyl radical, R 4 is a hydrogen atom or a chlorine atom, and A is a valency bond or methylene radical, with the proviso that when A is a methylene radical, R 4 is a hydrogen atom.

Claim 55

Dependent Claim 32 words

A compound or salt thereof according to claim 33 wherein such compound is ##STR35## in which R 3 is a hydrogen atom or a methyl radical, and A is a valency bond.

Claim 56

Dependent Claim 36 words

A compound or salt thereof according to claim 33 wherein such compound is: ##STR36## in which R 3 is a hydrogen atom or a methyl radical, and A is a valency bond or a methylene radical.

Claim 57

Dependent Claim 32 words

A compound or salt thereof according to claim 33 wherein such compound is: ##STR37## in which R 3 is a hydrogen atom or a methyl radical, and A is a valency bond.

Claim 58

Dependent Claim 25 words

A composition having an antihistaminic and a central nervous controlling effect comprising an effective amount of a compound or salt as defined in claim 34.

Claim 59

Dependent Claim 37 words

A method of treating a patient to produce a central nervous controlling effect or an antihistaminic effect comprising the step of administering to said patient an effective amount of a compound or salt according to claim 34.

Claim 60

Dependent Claim 254 words

A carbostyril derivative represented by the formula, ##STR38## wherein R 1 is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 4 carbon atoms, an alkynyl group having 2 to 4 carbon atoms or a phenyl alkyl group having an alkylene group having 1 to 4 carbon atoms; R 2 is an alkyl group having 1 to 4 carbon atoms or a phenyl group; R 3 is a hydrogen atom, a hydroxy group, an alkyl group having 1 to 4 carbon atoms, an alkanoyloxy group having 1 to 4 carbon atoms or a 3,4,5-trimethoxybenzoyloxy group; R 4 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; R 5 is a phenyl group which may be substituted by 1 to 3 identical or different groups selected from the group consisting of a halogen atom, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms; X is a halogen atom; n is 0 or an integer of 1 to 2; Q is an integer of 2, l and m are respectively 0 or an integer of 1 to 6, but the sum of l and m should not exceed 6; the carbon-carbon bond at the 3- and 4-positions in the carbostyril skeleton is a single or double bond; the substituted position of the side chain of ##STR39## is any one of the 5-, 6-, 7- or 8-positions; or an acid addition salt thereof.

Claim 61

Dependent Claim 254 words

A carbostyril derivative represented by the formula, ##STR38## wherein R 1 is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 4 carbon atoms, an alkynyl group having 2 to 4 carbon atoms or a phenyl alkyl group having an alkylene group having 1 to 4 carbon atoms; R 2 is an alkyl group having 1 to 4 carbon atoms or a phenyl group; R 3 is a hydrogen atom, a hydroxy group, an alkyl group having 1 to 4 carbon atoms, an alkanoyloxy group having 1 to 4 carbon atoms or a 3,4,5-trimethoxybenzoyloxy group; R 4 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; R 5 is a phenyl group which may be substituted by 1 to 3 identical or different groups selected from the group consisting of a halogen atom, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms; X is a halogen atom; n is 0 or an integer of 1 to 2; Q is an integer of 2, l and m are respectively 0 or an integer of 1 to 6, but the sum of l and m should not exceed 6; the carbon-carbon bond at the 3- and 4-positions in the carbostyril skeleton is a single or double bond; the substituted position of the side chain of ##STR39## is any one of the 5-, 6-, 7- or 8-positions; or an acid addition salt thereof.

Claim 62

Dependent Claim 30 words

A carbostyril derivative or an acid addition salt thereof according to claim 42, wherein R 3 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.

Claim 63

Dependent Claim 33 words

A carbostyril derivative or an acid addition salt thereof according to claim 42, wherein R 3 is a hydroxy group, an alkanoyloxy group having 1 to 4 carbon atoms or a 3,4,5-trimethoxybenzoyloxy group.

Claim 64

Dependent Claim 34 words

A carbostyril derivative or an acid addition salt thereof according to claim 43, wherein the substituted position of the side chain represented by the formula, ##STR40## is 5- or 7-position in the carbostyril skeleton.

Claim 65

Dependent Claim 34 words

A carbostyril derivative or an acid addition salt thereof according to claim 43, wherein the substituted position of the side chain represented by the formula, ##STR41## is 6- or 8-position in the carbostyril skeleton.

Claim 66

Dependent Claim 32 words

A carbostyril derivative or an acid addition salt thereof according to claim 45, wherein the substituted position of the side chain represented by the formula, ##STR42## is 5-position in the carbostyril skeleton.

Claim 67

Dependent Claim 32 words

A carbostyril derivative or an acid addition salt thereof according to claim 45, wherein the substituted position of the side chain represented by the formula, ##STR43## is 7-position in the carbostyril skeleton.

Claim 68

Dependent Claim 34 words

A pharmaceutical composition useful as an antihistaminic agent, containing a suitable amount of carbostyril derivative or an acid addition salt thereof according to claim 42 as an active ingredient and a pharmaceutically acceptable carrier.

Claim 69

Independent Claim 371 words

A method for producing an antihistaminic effect in a mammal comprising the step of administering to the mammal for producing said antihistaminic effect a pharmaceutical composition containing a suitable amount of a carbostyril derivative represented by the formula, ##STR44## wherein R 1 is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 4 carbon atoms, an alkynyl group having 2 to 4 carbon atoms or a phenyl alkyl group having an alkylene group having 1 to 4 carbon atoms; R 2 is a hydrogen atom, an alkyl group having 1 to 4 carbon atoms or a phenyl group; R 3 is a hydrogen atom, a hydroxy group, an alkyl group having 1 to 4 carbon atoms, an alkanoyloxy group having 1 to 4 carbon atoms or a 3,4,5-trimethoxybenzoyloxy group; R 4 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; R 5 is a cycloalkyl group having 3 to 8 carbon atoms, a phenyl group which may be substituted by 1 to 3 identical or different groups selected from the group consisting of a halogen atom, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms, a substituted alkyl group having 1 to 4 carbon atoms, having one hydroxy group, phenyl group or alkanoyloxy group having 1 to 4 carbon atoms as the substituent, an alkanoyl group having 1 to 4 carbon atoms or a benzoyl group; X is a halogen atom; n is 0 or an integer of 1 or 2; Q is an integer of 2; l and m are respectively 0 or an integer of 1 to 6, but the sum of l and m should not exceed 6; the carbon-carbon bond at the 3- and 4-positions in the carbostyril skeleton is a single or double bond; the substituted position of the side chain of ##STR45## is any one of the 4-, 5-, 6-, 7-, or 8-positions; or an acid addition salt thereof, with the proviso that when said side chain is substituted at the 4-position and said carbon-carbon bond at the 3- and 4-positions is a double bond, then R 2 does not exist.

Claim 70

Independent Claim 371 words

A method for producing an antihistaminic effect in a mammal comprising the step of administering to the mammal for producing said antihistaminic effect a pharmaceutical composition containing a suitable amount of a carbostyril derivative represented by the formula, ##STR44## wherein R 1 is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 4 carbon atoms, an alkynyl group having 2 to 4 carbon atoms or a phenyl alkyl group having an alkylene group having 1 to 4 carbon atoms; R 2 is a hydrogen atom, an alkyl group having 1 to 4 carbon atoms or a phenyl group; R 3 is a hydrogen atom, a hydroxy group, an alkyl group having 1 to 4 carbon atoms, an alkanoyloxy group having 1 to 4 carbon atoms or a 3,4,5-trimethoxybenzoyloxy group; R 4 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; R 5 is a cycloalkyl group having 3 to 8 carbon atoms, a phenyl group which may be substituted by 1 to 3 identical or different groups selected from the group consisting of a halogen atom, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms, a substituted alkyl group having 1 to 4 carbon atoms, having one hydroxy group, phenyl group or alkanoyloxy group having 1 to 4 carbon atoms as the substituent, an alkanoyl group having 1 to 4 carbon atoms or a benzoyl group; X is a halogen atom; n is 0 or an integer of 1 or 2; Q is an integer of 2; l and m are respectively 0 or an integer of 1 to 6, but the sum of l and m should not exceed 6; the carbon-carbon bond at the 3- and 4-positions in the carbostyril skeleton is a single or double bond; the substituted position of the side chain of ##STR45## is any one of the 4-, 5-, 6-, 7-, or 8-positions; or an acid addition salt thereof, with the proviso that when said side chain is substituted at the 4-position and said carbon-carbon bond at the 3- and 4-positions is a double bond, then R 2 does not exist.

Claim 71

Dependent Claim 22 words

The method of claim 50, wherein R 3 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.

Claim 72

Dependent Claim 25 words

The method of claim 50, wherein R 3 is a hydroxy group, an alkanoyloxy group having 1 to 4 carbon atoms or a 3,4,5-trimethoxybenzoyloxy group.

Claim 73

Dependent Claim 52 words

The method of claim 51, wherein R 5 is a phenyl group which may be substituted by 1 to 3 identical or different groups selected from the group consisting of a halogen atom, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms.

Claim 74

Dependent Claim 26 words

The method of claim 51, wherein R 5 is a substituted alkyl group having 1 to 4 carbon atoms, having one phenyl group as the substituent.

Claim 75

Dependent Claim 57 words

The method of claim 51, wherein R 5 is a cycloalkyl group having 3 to 8 carbon atoms; a substituted alkyl group having 1 to 4 carbon atoms having one hydroxy group or alkanoyloxy group having 1 to 4 carbon atoms as the substituent; an alkanoyl group having 1 to 4 carbon atoms or a benzoyl group.

Claim 76

Dependent Claim 52 words

The method of claim 52, wherein R 5 is a phenyl group which may be substituted by 1 to 3 identical or different groups selected from the group consisting of a halogen atom, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms.

Claim 77

Dependent Claim 59 words

The method of claim 52, wherein R 5 is a cycloalkyl group having 3 to 8 carbon atoms; a substituted alkyl group having 1 to 4 carbon atoms having one hydroxy group, phenyl group or alkanoyloxy group having 1 to 4 carbon atoms as the substituent; an alkanoyl group having 1 to 4 carbon atoms or a benzoyl group.

Claim 78

Dependent Claim 26 words

The method of claim 53, wherein the substituted position of the side chain represented by the formula, ##STR46## is 5- or 7-position in the carbostyril skeleton.

Claim 79

Dependent Claim 27 words

The method of claim 53, wherein the substituted position of the side chain represented by the formula, ##STR47## is 4-, 6- or 8-position in the carbostyril skeleton.

Claim 80

Dependent Claim 24 words

The method of claim 58, wherein the substituted position of the side chain represented by the formula, ##STR48## is 5-position in the carbostyril skeleton.

Claim 81

Dependent Claim 24 words

The method of claim 58, wherein the substituted position of the side chain represented by the formula, ##STR49## is 7-position in the carbostyril skeleton.

Claim 82

Dependent Claim 280 words

A carbostyril derivative represented by the formula, ##STR50## wherein R 1 is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 4 carbon atoms, an alkynyl group having 2 to 4 carbon atoms or a phenyl alkyl group having an alkylene group having 1 to 4 carbon atoms; R 2 is a hydrogen atom, a C 1 -C 4 alkyl group; R 3 is a hydrogen atom, a hydroxy group, an alkyl group having 1 to 4 carbon atoms, an alkanoyloxy group having 1 to 4 carbon atoms or a 3,4,5-trimethoxybenzoyloxy group; R 4 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; R 5 is a cycloalkyl group having 3 to 8 carbon atoms, a substituted alkyl group having 1 to 4 carbon atoms, having one phenyl group as the substituent, an alkanoyl group having 1 to 4 carbon atoms or a benzoyl group; X is a halogen atom; n is 0 or an integer of 1 or 2; Q is an integer of 2; l and m are respectively 0 or an integer of 1 to 6, but the sum of l and m should not exceed 6; the carbon-carbon bond at the 3- and 4-positions in the carbostyril skeleton is a single or double bond; the substituted position of the side chain of ##STR51## is any one of the 4-, 5-, 6-, 7-, or 8-positions; or an acid addition salt thereof, with the proviso that when said side chain is substituted at the 4-position and said carbon-carbon bond at the 3- and 4-positions is a double bond, then R 2 does not exist.

Claim 83

Dependent Claim 280 words

A carbostyril derivative represented by the formula, ##STR50## wherein R 1 is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 4 carbon atoms, an alkynyl group having 2 to 4 carbon atoms or a phenyl alkyl group having an alkylene group having 1 to 4 carbon atoms; R 2 is a hydrogen atom, a C 1 -C 4 alkyl group; R 3 is a hydrogen atom, a hydroxy group, an alkyl group having 1 to 4 carbon atoms, an alkanoyloxy group having 1 to 4 carbon atoms or a 3,4,5-trimethoxybenzoyloxy group; R 4 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; R 5 is a cycloalkyl group having 3 to 8 carbon atoms, a substituted alkyl group having 1 to 4 carbon atoms, having one phenyl group as the substituent, an alkanoyl group having 1 to 4 carbon atoms or a benzoyl group; X is a halogen atom; n is 0 or an integer of 1 or 2; Q is an integer of 2; l and m are respectively 0 or an integer of 1 to 6, but the sum of l and m should not exceed 6; the carbon-carbon bond at the 3- and 4-positions in the carbostyril skeleton is a single or double bond; the substituted position of the side chain of ##STR51## is any one of the 4-, 5-, 6-, 7-, or 8-positions; or an acid addition salt thereof, with the proviso that when said side chain is substituted at the 4-position and said carbon-carbon bond at the 3- and 4-positions is a double bond, then R 2 does not exist.

Claim 84

Dependent Claim 30 words

A carbostyril derivative or an acid addition salt thereof according to claim 62, wherein R 3 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.

Claim 85

Dependent Claim 33 words

A carbostyril derivative or an acid addition salt thereof according to claim 62, wherein R 3 is a hydroxy group, an alkanoyloxy group having 1 to 4 carbon atoms or a 3,4,5-trimethoxybenzoyloxy group.

Claim 86

Dependent Claim 34 words

A carbostyril derivative or an acid addition salt thereof according to claim 63, wherein the substituted position of the side chain represented by the formula, ##STR52## is 5- or 7-position in the carbostyril skeleton.

Claim 87

Dependent Claim 35 words

A carbostyril derivative or an acid addition salt thereof according to claim 63, wherein the substituted position of the side chain represented by the formula, ##STR53## is 4-, 6- or 8-position in the carbostyril skeleton.

Claim 88

Dependent Claim 32 words

A carbostyril derivative or an acid addition salt thereof according to claim 63, wherein the substituted position of the side chain represented by the formula, ##STR54## is 5-position in the carbostyril skeleton.

Claim 89

Dependent Claim 32 words

A carbostyril derivative or an acid addition salt thereof according to claim 63, wherein the substituted position of the side chain represented by the formula, ##STR55## is 7-position in the carbostyril skeleton.

Claim 90

Dependent Claim 33 words

A pharmaceutical composition usable as an antihistaminic agent, containing a suitable amount of the carbostyril derivative or acid addition salt thereof of claim 62 as an active ingredient and a pharmaceutically acceptable carrier.

Claim 91

Dependent Claim 1 words

7-[3-(4-Benzylpiperazinyl)propoxy]-3,4-dihydrocarbostyril.

Claim 92

Dependent Claim 1 words

7-[3-(4-Benzylpiperazinyl)propoxy]-3,4-dihydrocarbostyril.

Claim 93

Dependent Claim 1 words

7-[3-(4-Cyclohexylpiperazinyl)propoxy]-3,4-dihydrocarbostyril.

Claim 94

Dependent Claim 1 words

7-[3-(4-Cyclohexylpiperazinyl)propoxy]-3,4-dihydrocarbostyril.

Claim 95

Dependent Claim 1 words

5-[3-(4-Benzylpiperazinyl)propoxy]-3,4-dihydrocarbostyril.

Claim 96

Dependent Claim 1 words

5-[3-(4-Benzylpiperazinyl)propoxy]-3,4-dihydrocarbostyril.

Claim 97

Dependent Claim 1 words

5-[3-(4-Benzoylpiperazinyl)propoxy]-3,4-dihydrocarbostyril.

Claim 98

Dependent Claim 1 words

5-[3-(4-Benzoylpiperazinyl)propoxy]-3,4-dihydrocarbostyril.

Claim 99

Dependent Claim 34 words

The method of treating a human patient to produce a central nervous controlling effect which comprises administering to said patient an effective dosage of a compound or salt thereof as defined in claim 26.

Claim 100

Dependent Claim 35 words

The method of treating a human patient to produce a central nervous controlling effect which comprises orally administering to said patient an effective dosage of a compound or salt thereof as defined in claim 26.

Claim 101

Dependent Claim 35 words

The method of treating a human patient to produce a central nervous controlling effect which comprises intravenously administering to said patient an effective dosage of a compound or salt thereof as defined in claim 26.

Claim 102

Dependent Claim 25 words

A composition having an antihistaminic and a central nervous controlling effect comprising an effective amount of a compound or salt as defined in claim 26.

Claim 103

Dependent Claim 37 words

A method of treating a patient to produce a central nervous controlling effect or an antihistaminic effect comprising the step of administering to said patient an effective amount of a compound or salt according to claim 26.

Claim 104

Dependent Claim 33 words

A (4-substituted-piperazin-1-yl)alkoxy-2-oxo,1,2-dihydroquinoline or a salt thereof as claimed in claim 33, wherein R 4 is a hydrogen atom, a halogen atom, or an alkyl or alkoxy group having 1 to 3 carbon atoms.

Claim 105

Dependent Claim 25 words

A composition having an antihistaminic and a central nervous controlling effect comprising an effective amount of a compound or salt as defined in claim 79.

Claim 106

Dependent Claim 37 words

A method of treating a patient to produce a central nervous controlling effect or an antihistaminic effect comprising the step of administering to said patient an effective amount of a compound or salt according to claim 79.

Claim 107

Dependent Claim 25 words

A (4-substituted-piperazin-1-yl)alkoxy-2-oxo-1,2-dihydroquinoline or a salt thereof as claimed in claim 33, in which R 4 is a hydrogen atom, and A is a methylene radical.

Claim 108

Dependent Claim 27 words

A compound or salt thereof according to claim 82, in which R 1 is a hydrogen atom or an alkyl radical with 1 to 4 carbon atoms.

Claim 109

Dependent Claim 33 words

A compound or salt thereof according to claim 82, wherein such compound is ##STR56## in which R 3 is a hydrogen atom or a methyl radical, and R 4 is a hydrogen atom.

Claim 110

Dependent Claim 26 words

A compound or salt thereof according to claim 82 wherein such compound is ##STR57## in which R 3 is a hydrogen atom or a methyl radical.

Claim 111

Dependent Claim 26 words

A compound or salt thereof according to claim 82 wherein such compound is: ##STR58## in which R 3 is a hydrogen atom or a methyl radical.

Claim 112

Dependent Claim 26 words

A compound or salt thereof according to claim 82 wherein such compound is: ##STR59## in which R 3 is a hydrogen atom or a methyl radical.

Claim 113

Dependent Claim 25 words

A composition having an antihistaminic and a central nervous controlling effect comprising an effective amount of a compound or salt as defined in claim 82.

Claim 114

Dependent Claim 37 words

A method of treating a patient to produce a central nervous controlling effect or an antihistaminic effect comprising the step of administering to said patient an effective amount of a compound or salt according to claim 82.

Claim 115

Dependent Claim 30 words

The method according to claim 89, wherein said compound is: ##STR60## in which R 3 is a hydrogen atom or a methyl radical, and R 4 is a hydrogen atom.

Claim 116

Dependent Claim 18 words

A (4-substituted-piperazin-1-yl)alkoxy-2-oxo-1,2-dihydroquinoline or a salt thereof as claimed in claim 33, in which A is a valency bond.

Claim 117

Dependent Claim 25 words

A composition having an antihistaminic and a central nervous controlling effect comprising an effective amount of a compound or salt as defined in claim 91.

Claim 118

Dependent Claim 37 words

A method of treating a patient to produce a central nervous controlling effect or an antihistaminic effect comprising the step of administering to said patient an effective amount of a compound or salt according to claim 91.

Claim 119

Dependent Claim 66 words

The compound of claim 1, wherein R 1 , R 2 , R 3 and R 4 are hydrogen atoms; l and m are each 1; Q is 2; R 5 is a phenyl group containing 1 to 3 identical or different substituents selected from an alkyl group having 1 to 4 carbon atoms; and the side chain on the carbostyril skeleton is in the 7-position.

Claim 120

Dependent Claim 19 words

The compound of claim 94, wherein the R 5 substituted phenyl group contains two methyl groups as the substituents.

Claim 121

Dependent Claim 19 words

The compound of claim 94, wherein the R 5 substituted phenyl group contains one methyl group as the substituent.

Claim 122

Dependent Claim 9 words

The compound of claim 95, wherein n is 0.

Claim 123

Dependent Claim 9 words

The compound of claim 96, wherein n is 0.

Claim 124

Dependent Claim 9 words

An acid-addition salt of the compound of claim 94.

Claim 125

Dependent Claim 68 words

The compound of claim 1, wherein R 1 , R 2 , R 3 and R 4 are hydrogen atoms; l and m are each 1; n is 0; Q is 2; R 5 is a phenyl group containing one halogen atom; the side chain on the carbostyril skeleton is in the 7-position; and there is a single bond between the 3- and 4-positions in the carbostyril skeleton.

Claim 126

Dependent Claim 15 words

The compound of claim 100, wherein the R 5 halogen substituent is a chlorine atom.

Claim 127

Dependent Claim 15 words

The compound of claim 100, wherein the R 5 halogen substituent is a fluorine atom.

Claim 128

Dependent Claim 90 words

The compound of claim 1, wherein R 1 , R 2 , R 3 and R 4 are hydrogen; l and m are each 1; n is 0; Q is 2; R 5 is a phenyl group containing 1 to 3 identical or different substituents selected from the group consisting of a halogen atom and an alkyl group having 1 to 4 carbon atoms; the side chain on the carbostyril skeleton is in the 7-position and there is a single bond between the 3- and 4-positions in the carbostyril skeleton.

Claim 129

Dependent Claim 15 words

The compound of claim 103, wherein the R 5 substituted phenyl group is 4-chloro-3-methylphenyl group.

Claim 130

Dependent Claim 79 words

The compound of claim 1, wherein R 1 , R 2 , R 3 and R 4 are hydrogen atoms; l and m are each 1; Q is 2; n is 0; R 5 is a phenyl group containing 1 to 3 identical or different substituents selected from a halogen atom; the side chain on the carbostyril skeleton is in the 5-position; and the carbon-carbon bond between the 3- and 4-positions in the carbostyril skeleton is a single bond.

Claim 131

Dependent Claim 15 words

The compound of claim 105, wherein the R 5 halogen substituent is a fluorine atom.

Claim 132

Dependent Claim 1 words

7-{3-[4-(4-Chlorophenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril.

Claim 133

Dependent Claim 1 words

7-{3-[4-(4-Chlorophenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril.

Claim 134

Dependent Claim 1 words

7-{3-[4-(3,4-Dimethylphenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril.

Claim 135

Dependent Claim 1 words

7-{3-[4-(3,4-Dimethylphenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril.

Claim 136

Dependent Claim 1 words

5-{3-[4-(2-Fluorophenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril.

Claim 137

Dependent Claim 1 words

5-{3-[4-(2-Fluorophenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril.

Claim 138

Dependent Claim 22 words

The compound of claim 95, wherein the carbon-carbon bond at the 3- and 4-positions in the carbostyril skeleton is a double bond.

Claim 139

Dependent Claim 22 words

A phenylpiperazine compound in accordance with claim 25, wherein said compound is selected from the group consisting of 6-{3-[4-(4-methylphenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril, 6-{3-[4-(4-bromophenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril, and 1-methyl-6-{3-[4-(4-methylphenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril.

Claim 140

Dependent Claim 25 words

A compound in accordance with claim 33, wherein said compound is selected from the group consisting of, 5-[2-(4-phenylpiperazinyl)ethoxy]carbostyril, 7-[2-(4-phenylpiperazinyl)ethoxy]carbostyril, 8-[2-(4-phenylpiperazinyl)ethoxy]carbostyril, 5-[3-(4-phenylpiperazinyl)propoxy]carbostyril, 5-[4-(4-phenylpiperazinyl)propoxy]carbostyril, 7-[4-(4-phenylpiperazinyl)butoxy]carbostyril, 6-[5-(4-phenylpiperazinyl)pentyloxy]carbostyril, 8-[5-(4-phenylpiperazinyl)pentyloxy]carbostyril.

Claim 141

Dependent Claim 25 words

A compound in accordance with claim 33, wherein said compound is selected from the group consisting of, 1-methyl-5-[2-(4-phenylpiperazinyl)ethoxy]carbostyril, 1-methyl-6-[3-(4-phenylpiperazinyl)propoxy]carbostyril, 1-methyl-7-[3-(4-phenylpiperazinyl)propoxy]carbostyril, 1-hexyl-6-[3-(4-phenylpiperazinyl)propoxy]carbostyril, 1-methyl-5-{3-[4-(4-chlorophenyl)piperazinyl]propoxy}-carbostyril, 1-methyl-6-{3-[4-(4-methylphenyl)piperazinyl]propoxy}-carbostyril, and 1-methyl-7-{3-[4-(4-methoxyphenyl)piperazinyl]propoxy}-carbostyril.

Claim 142

Dependent Claim 33 words

A compound or salt thereof in accordance with claim 33, wherein said compound or salt is selected from the group consisting of, 5-{3-[4-(2-methoxyphenyl)piperazinyl]propoxy}carbostyril, 5-{3-[4-(3-methylphenyl)piperazinyl]propoxy}carbostyril, 6-{3-[4-(4-methylphenyl)piperazinyl]propoxy}carbostyril, 7-{2-[4-(4-propylphenyl)piperazinyl]ethoxy}carbostyril, 5-{3-[4-(4-chlorophenyl)piperazinyl]propoxy}carbostyril, 6-{3-[4-(4-bromophenyl)piperazinyl]propoxy}carbostyril, 7-{2-[4-(2-chlorophenyl)piperazinyl]ethoxy}carbostyril, 6-{3-[4-(2-methoxyphenyl)piperazinyl]propoxy}carbostyril.dihydrochloride, 8-{3-[4-(2-methoxyphenyl)piperazinyl]propoxy}carbostyril.dihydrochloride, and 7-{3-[4-(3-chlorophenyl)piperazinyl]propoxy}carbostyril.

Claim 143

Dependent Claim 24 words

A carbostyril derivative in accordance with claim 42, wherein said compound is selected from the group consisting of, 4-methyl-7-[3-(4-phenylpiperazinyl)propoxy]-3,4-dihydro-carbostyril 4-phenyl-7-[3-(4-phenylpiperazinyl)propoxy]carbostyril, 4-phenyl-7-[3-(4-phenylpiperazinyl)propoxy]-3,4-dihydro-carbostyril, 4-phenyl-7-{3-[4-(2-methoxyphenyl)piperazinyl]propoxy}-carbostyril, and 4-methyl-7-[3-(4-phenylpiperazinyl)propoxy]carbostyril.

Claim 144

Dependent Claim 26 words

The method of claim 50, wherein the carbostyril derivative is selected from the group consisting of: 7-[3-(4-phenylpiperazinyl)propoxy]-3,4-dihydrocarbostryril, 7-[3-(4-phenylpiperazinyl)propoxy]carbostyril, 1-Methyl-7-[3-(4-phenylpiperazinyl)propoxy]-3,4-dihydrocarbostyril, 7-[4-(4-phenylpiperazinyl)butoxy]-3,4-dihydrocarbostyril, 5-[3-(4-phenylpiperazinyl)propoxy]-3,4-dihydrocarbostyril, 6-[3-(4-phenylpiperazinyl)propoxy]carbostyril, 8-bromo-5-[3-(4-phenylpiperazinyl]propoxy]carbostyril, 7-[3-(4-benzylpiperazinyl)propoxy]-3,4-dihydrocarbostyril, and 1-benzyl-5-[3-(4-phenylpiperazinyl)propoxy]-3,4-dihydrocarbostyril.

Claim 145

Dependent Claim 24 words

The method of claim 50, wherein the carbostyril derivative is selected from the group consisting of: 7-{3-[4-(2-methoxyphenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril, 7-{3-[4-(3-chlorophenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril, 7-{3-[4-(2-fluorophenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril, 7-{3-[4-(2-ethyoxyphenyl)piperazinyl]propoxy}-3,4-hydrocarbostyril, 7-{3-[4-(2-chlorophenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril, 7-{3-[4-(2-methoxyphenyl)piperazinyl]propoxy}carbostyril and 7-{3-[4-(4-methylphenyl)piperazinyl]propoxy}-3,4-dihydrocarbostyril.

Claim 146

Dependent Claim 19 words

The method of claim 50, wherein the carbostyril derivative is selected from the group consisting of: 7-[2-hydroxy-3-(4-phenylpiperazinyl)propoxy]-3,4-dihydrocarbostyril, and 1-benzyl-5-[2-hydroxy-3-(4-phenylpiperazinyl)propoxy]-3,4-dihydrocarbostyril.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1991-03-29	1991-09-28	1992-03-29	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	1995-03-29	1995-09-28	1996-03-29	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	1999-03-29	1999-09-28	2000-03-29	$7700.00	Window Closed / Lapsed

Pharmaceutically useful carbostyril derivatives

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