Pharmaceutical preparation and use of 4-hydroxy-2-quinolinone-3-carboxylic acid esters

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 ##STR20##

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 M p is hydrogen.

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 alkoxy 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 ethyl ester.

Claim 23

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

Claim 24

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

Claim 25

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

Claim 26

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

Claim 27

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

Claim 28

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

Claim 29

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

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 N-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 60 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 of the formula: ##STR21## wherein R 9 is alkyl of 1 to 4 carbon atoms, 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 or 2 carbon atoms, or ##STR22## M p is hydrogen or a pharmaceutically acceptable cation, n is 0 or 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.

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 of the formula: ##STR21## wherein R 9 is alkyl of 1 to 4 carbon atoms, 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 or 2 carbon atoms, or ##STR22## M p is hydrogen or a pharmaceutically acceptable cation, n is 0 or 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.

Claim 36

A 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 ##STR23##

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 M p is hydrogen.

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 ethyl ester.

Claim 56

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

Claim 57

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

Claim 58

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

Claim 59

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

Claim 60

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

Claim 61

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

Claim 62

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

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 N-allyl-6,7-methylenedioxy-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester.

Claim 66

A composition of claim 33 containing the compound in an amount of from 15 to 400 milligrams and a solid carrier.

Claim 67

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

Claim 68

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

Claim 69

The method of claim 16 in which R p is alkyl of 1 to 4 carbon atoms in the 7-position and R p ' is alkoxy of 1 or 2 carbon atoms in the 6-position.

Claim 70

The method of claim 67 in which the compound is N-allyl-6-methoxy-7-ethyl-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester.

Claim 71

The method of claim 67 in which the compound is N-allyl-6-methoxy-7-methyl-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester.