4-Hydroxy-2-quinolinone-3-carboxylic acids and salts thereof

Claim 3

The method of claim 1 in which R p and R p ' are independently hydrogen, fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, nitro or trifluoromethyl.

Claim 4

The method of claim 2 in which R p o is alkyl.

Claim 5

The method of claim 2 in which R p o is alkenyl.

Claim 6

The method of claim 2 in which R p o is hydrogen.

Claim 7

The method of claim 2 in which R p o is cycloalkyl.

Claim 8

The method of claim 2 in which R p o is alkynyl.

Claim 9

The method of claim 2 in which R p o is cycloalkylalkyl.

Claim 10

The method of claim 2 in which R p o is ##STR9##

Claim 11

The method of claim 9 in which n is 0.

Claim 12

The method of claim 9 in which n is 1.

Claim 13

The method of claim 1 in which the compound is in free acid form.

Claim 14

The method of claim 2 in which R p and R p ' are each alkoxy.

Claim 15

The method of claim 13 in which R p and R p ' represent 6,7-dialkoxy.

Claim 16

The method of claim 14 in which R p and R p ' represent 6,7-dimethoxy.

Claim 17

The method of claim 4 in which R p o is allyl.

Claim 18

The method of claim 16 in which R p and R p ' represent 6,7-dimethoxy.

Claim 19

The method of claim 3 in which R p and R p ' represent 6,7-dimethoxy.

Claim 20

The method of claim 5 in which R p is fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms and R p ' is fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms or akoxy of 1 to 4 carbon atoms.

Claim 21

The method of claim 3 in which R p and R p ' are independently hydrogen, fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms.

Claim 22

The method of claim 19 in which the compound is 6,7-dimethoxy-4-hydroxy-2-quinolinone-3-carboxylic acid.

Claim 23

The method of claim 20 in which the compound is 1-methyl-4-hydroxy-2-quinolinone-3-carboxylic acid.

Claim 24

The method of claim 4 in which the compound is 1-allyl-4-hydroxy-2-quinolinone-3-carboxylic acid.

Claim 25

The method of claim 18 in which the compound is 1-allyl-6,7-dimethoxy-4-hydroxy-2-quinolinone-3-carboxylic acid.

Claim 26

The method of claim 2 in which the compound is 6-methyl-4-hydroxy-2-quinolinone-3-carboxylic acid.

Claim 27

The method of claim 20 in which the compound is 1-methyl-6-chloro-4-hydroxy-2-quinolinone-3-carboxylic acid.

Claim 28

The method of claim 11 in which the compound is 1-(p-fluorobenzyl)-4-hydroxy-2-quinolinone-3-carboxylic acid.

Claim 29

The method of claim 18 in which the compound is 1-methyl-6,7-dimethoxy-4-hydroxy-2-quinolinone-3-carboxylic acid.

Claim 30

The method of claim 1 in which R p and R p ' together form 6,7-methylenedioxy.

Claim 31

The method of claim 20 in which R p o is allyl.

Claim 32

The method of claim 21 in which the compound is 1-allyl-6,7-methylenedioxy-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester.

Claim 33

The method of claim 1 in which the compound is administered at a daily dosage of from 40 to 800 milligrams.

Claim 34

A pharmaceutical composition comprising in unit dosage form a pharmaceutically acceptable carrier and an amount effective to relieve allergic conditions due to histamine release of a compound having in free acid form the formula: ##STR10## wherein R p o is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 3 to 6 carbon atoms, alkynyl of 3 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, cycloalkylalkyl in which the cycloalkyl is of 3 to 6 carbon atoms and the alkyl portion is of 1 to 2 carbon atoms, or ##STR11## n--is 0 to 1, Y and Y'--are independently hydrogen, fluoro, chloro, bromo, alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, trifluoromethyl or nitro, with the proviso that only one of Y and Y' can be from the group consisting of nitro and trifluoromethyl, and R p and R p '--are independently hydrogen, fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, nitro or trifluoromethyl, or R p and R p ' together form 6,7-methylenedioxy, with the proviso that only one of R p and R p ' can be from the group consisting of nitro and trifluoromethyl, with the further proviso that the unsaturation in any alkenyl or alkynyl is on other than the alpha carbon atom; or a mono- or di-salt form thereof in which the salt forming cation is a pharmaceutically acceptable cation.

Claim 35

A pharmaceutical composition comprising in unit dosage form a pharmaceutically acceptable carrier and an amount effective to relieve allergic conditions due to histamine release of a compound having in free acid form the formula: ##STR10## wherein R p o is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 3 to 6 carbon atoms, alkynyl of 3 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, cycloalkylalkyl in which the cycloalkyl is of 3 to 6 carbon atoms and the alkyl portion is of 1 to 2 carbon atoms, or ##STR11## n--is 0 to 1, Y and Y'--are independently hydrogen, fluoro, chloro, bromo, alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, trifluoromethyl or nitro, with the proviso that only one of Y and Y' can be from the group consisting of nitro and trifluoromethyl, and R p and R p '--are independently hydrogen, fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, nitro or trifluoromethyl, or R p and R p ' together form 6,7-methylenedioxy, with the proviso that only one of R p and R p ' can be from the group consisting of nitro and trifluoromethyl, with the further proviso that the unsaturation in any alkenyl or alkynyl is on other than the alpha carbon atom; or a mono- or di-salt form thereof in which the salt forming cation is a pharmaceutically acceptable cation.

Claim 36

The composition of claim 33 in which R p and R p ' are independently hydrogen, fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, nitro or trifluoromethyl.

Claim 37

A composition of claim 34 in which R p o is alkyl.

Claim 38

A composition of claim 34 in which R p o is alkenyl.

Claim 39

A composition of claim 34 in which R p o is hydrogen.

Claim 40

A composition of claim 34 in which R p o is cycloalkyl.

Claim 41

A composition of claim 34 in which R p o is alkynyl.

Claim 42

A composition of claim 34 in which R p o is cycloalkylalkyl.

Claim 43

A composition of claim 34 in which R p o is ##STR12##

Claim 44

A composition of claim 41 in which n is 0.

Claim 45

A composition of claim 41 in which n is 1.

Claim 46

A composition of claim 33 in which the compound is in free acid form.

Claim 47

A composition of claim 33 in which R p and R p ' are each alkoxy.

Claim 48

A composition of claim 45 in which R p and R p ' represent 6,7-dialkoxy.

Claim 49

A composition of claim 46 in which R p and R p ' represent 6,7-dimethoxy.

Claim 50

A composition of claim 36 in which R p o is allyl.

Claim 51

A composition of claim 48 in which R p and R p ' represent 6,7-dimethoxy.

Claim 52

A composition of claim 35 in which R p and R p ' represent 6,7-dimethoxy.

Claim 53

A composition of claim 37 in which R p is fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms and R p ' is fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms.

Claim 54

A composition of claim 35 in which R p and R p ' are independently hydrogen, fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms.

Claim 55

A composition of claim 51 in which the compound is 6,7-dimethoxy-4-hydroxy-2-quinolinone-3-carboxylic acid.

Claim 56

A composition of claim 52 in which the compound is 1-methyl-4-hydroxy-2-quinolinone-3-carboxylic acid.

Claim 57

A composition of claim 36 in which the compound is 1-allyl-4-hydroxy-2-quinolinone-3-carboxylic acid.

Claim 58

A composition of claim 50 in which the compound is 1-allyl-6,7-dimethoxy-4-hydroxy-2-quinolinone-3-carboxylic acid.

Claim 59

A composition of claim 34 in which the compound is 6-methyl-4-hydroxy-2-quinolinone-3-carboxylic acid.

Claim 60

A composition of claim 52 in which the compound is 1-methyl-6-chloro-4-hydroxy-2-quinolinone-3-carboxylic acid.

Claim 61

A composition of claim 43 in which the compound is 1-(p-fluorobenzyl)-4-hydroxy-2-quinolinone-3-carboxylic acid.

Claim 62

A composition of claim 50 in which the compound is 1-methyl-6,7-dimethoxy-4-hydroxy-2-quinolinone-3-carboxylic acid.

Claim 63

A composition of claim 33 in which R p and R p ' together form 6,7-methylenedioxy.

Claim 64

A composition of claim 61 in which R p o is allyl.

Claim 65

A composition of claim 62 in which the compound is 1-allyl-6,7-methylenedioxy-4-hydroxy-2-quinolinone-3-carboxylic acid.

Claim 66

A composition of claim 33 containing the compound in an amount of from 10 to 400 milligrams and a solid carrier.