Claims
- 1. The method of treating allergic conditions due to histamine release comprising administering to a mammal in need of such treatment an allergy treating effective amount of a compound of the formula: ##STR18## wherein R.sub.9 is alkyl of 1 to 4 carbon atoms,
- R.sub.p.sup.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 ##STR19## M.sub.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.sub.p and R.sub.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.sub.p and R.sub.p 40 together form 6,7-methylenedioxy, with the proviso that only one of R.sub.p and R.sub.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.
- 2. The method of claim 1 in which R.sub.p and R.sub.p ' are independently hydrogen, fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, nitro or trifluoromethyl.
- 3. The method of claim 2 in which R.sub.p.sup.o is alkyl.
- 4. The method of claim 2 in which R.sub.p.sup.o is alkenyl.
- 5. The method of claim 2 in which R.sub.p.sup.o is hydrogen.
- 6. The method of claim 2 in which R.sub.p.sup.o is cycloalkyl.
- 7. The method of claim 2 in which R.sub.p.sup.o is alkynyl.
- 8. The method of claim 2 in which R.sub.p.sup.o is cycloalkylalkyl.
- 9. The method of claim 2 in which R.sub.p.sup.o is ##STR20##
- 10. The method of claim 9 in which n is 0.
- 11. The method of claim 9 in which n is 1.
- 12. The method of claim 1 in which M.sub.p is hydrogen.
- 13. The method of claim 2 in which R.sub.p and R.sub.p ' are each alkoxy.
- 14. The method of claim 13 in which R.sub.p and R.sub.p ' represent 6,7-dialkoxy.
- 15. The method of claim 14 in which R.sub.p and R.sub.p ' represent 6,7-dimethoxy.
- 16. The method of claim 4 in which R.sub.p.sup.o is allyl.
- 17. The method of claim 16 in which R.sub.p and R.sub.p ' represent 6,7-dimethoxy.
- 18. The method of claim 3 in which R.sub.p and R.sub.p ' represent 6,7-dimethoxy.
- 19. The method of claim 5 in which R.sub.p is fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms and R.sub.p ' is fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms.
- 20. The method of claim 3 in which R.sub.p and R.sub.p ' are independently hydrogen, fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms.
- 21. The method of claim 19 in which the compound is 6,7-dimethoxy-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester.
- 22. The method of claim 20 in which the compound is N-methyl-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester.
- 23. The method of claim 4 in which the compound is N-allyl-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester.
- 24. The method of claim 18 in which the compound is N-allyl-6,7-dimethoxy-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester.
- 25. The method of claim 2 in which the compound is 6-methyl-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester.
- 26. The method of claim 20 in which the compound is N-methyl-6-chloro-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester.
- 27. The method of claim 11 in which the compound is N-(p-fluorobenzyl)-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester.
- 28. The method of claim 18 in which the compound is N-methyl-6,7-dimethoxy-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester.
- 29. The method of claim 1 in which R.sub.p and R.sub.p ' together form 6,7-methylenedioxy.
- 30. The method of claim 20 in which R.sub.p.sup.o is allyl.
- 31. The method of claim 21 in which the compound is N-allyl-6,7-methylenedioxy-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester.
- 32. The method of claim 1 in which the compound is administered at a daily dosage of from 60 to 800 milligrams.
- 33. 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.sub.9 is alkyl of 1 to 4 carbon atoms,
- R.sub.p.sup.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.sub.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.sub.p and R.sub.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.sub.p and R.sub.p ' together form 6,7-methylenedioxy, with the proviso that only one of R.sub.p and R.sub.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.
- 34. A composition of claim 33 in which R.sub.p and R.sub.p ' are independently hydrogen, fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, nitro or trifluoromethyl.
- 35. A composition of claim 34 in which R.sub.p.sup.o is alkyl.
- 36. A composition of claim 34 in which R.sub.p.sup.o is alkenyl.
- 37. A composition of claim 34 in which R.sub.p.sup.o is hydrogen.
- 38. A composition of claim 34 in which R.sub.p.sup.o is cycloalkyl.
- 39. A composition of claim 34 in which R.sub.p.sup.o is alkynyl.
- 40. A composition of claim 34 in which R.sub.p.sup.o is cycloalkylalkyl.
- 41. A composition of claim 34 in which R.sub.p.sup.o is ##STR23##
- 42. A composition of claim 41 in which n is 0.
- 43. A composition of claim 41 in which n is 1.
- 44. A composition of claim 33 in which M.sub.p is hydrogen.
- 45. A composition of claim 33 in which R.sub.p and R.sub.p ' are each alkoxy.
- 46. A composition of claim 45 in which R.sub.p and R.sub.p ' represent 6,7-dialkoxy.
- 47. A composition of claim 46 in which R.sub.p and R.sub.p ' represent 6,7-dimethoxy.
- 48. A composition of claim 36 in which R.sub.p.sup.o is allyl.
- 49. A composition of claim 48 in which R.sub.p and R.sub.p ' represent 6,7-dimethoxy.
- 50. A composition of claim 35 in which R.sub.p and R.sub.p ' represent 6,7-dimethoxy.
- 51. A composition of claim 37 in which R.sub.p is fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms and R.sub.p ' is fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms.
- 52. A composition of claim 35 in which R.sub.p and R.sub.p ' are independently hydrogen, fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms.
- 53. A composition of claim 51 in which the compound is 6,7-dimethoxy-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester.
- 54. A composition of claim 52 in which the compound is N-methyl-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester.
- 55. A composition of claim 36 in which the compound is N-allyl-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester.
- 56. A composition of claim 50 in which the compound is N-allyl-6,7-dimethoxy-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester.
- 57. A composition of claim 34 in which the compound is 6-methyl-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester.
- 58. A composition of claim 52 in which the compound is N-methyl-6-chloro-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester.
- 59. A composition of claim 43 in which the compound is N-(p-fluorobenzyl)-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester.
- 60. A composition of claim 50 in which the compound is N-methyl-6,7-dimethoxy-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester.
- 61. A composition of claim 33 in which R.sub.p and R.sub.p ' together form 6,7-methylenedioxy.
- 62. A composition of claim 61 in which R.sub.p.sup.o is allyl.
- 63. A composition of claim 62 in which the compound is N-allyl-6,7-methylenedioxy-4-hydroxy-2-quinolinone-3-carboxylic acid ethyl ester.
- 64. A composition of claim 33 containing the compound in an amount of from 15 to 400 milligrams and a solid carrier.
- 65. 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.
- 66. 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.
- 67. The method of claim 16 in which R.sub.p is alkyl of 1 to 4 carbon atoms in the 7-position and R.sub.p ' is alkoxy of 1 or 2 carbon atoms in the 6-position.
- 68. 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.
- 69. 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.
Priority Claims (1)
Number |
Date |
Country |
Kind |
14933/73 |
Oct 1973 |
CHX |
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DISCLOSURE OF THE INVENTION
This application is a continuation-in-part of application Ser. No. 662,148, filed Feb. 27, 1976, which in turn is a continuation-in-part of application Ser. No. 557,984, filed Mar. 12, 1975, which is a divisional of application Ser. No. 454,070, filed Mar. 25, 1974, which in turn is a continuation-in-part of application Ser. No. 303,099, filed Nov. 2, 1972, and of application Ser. No. 392,082, filed Aug. 27, 1973, now all abandoned.
US Referenced Citations (5)
Number |
Name |
Date |
Kind |
3657223 |
Hellerbach et al. |
Apr 1972 |
|
3772301 |
Strandtmann |
Nov 1973 |
|
3772305 |
Hellerbach et al. |
Nov 1973 |
|
4107310 |
Allais etal. |
Aug 1978 |
|
4119720 |
Hardtmann |
Oct 1978 |
|
Foreign Referenced Citations (4)
Number |
Date |
Country |
2421121 |
Jan 1975 |
DEX |
2705446 |
Aug 1977 |
DEX |
74-06271 |
Sep 1975 |
ZAX |
1504709 |
Mar 1978 |
GBX |
Non-Patent Literature Citations (7)
Entry |
McCorkindale, Tetrahedron, 1961, vol. 14, pp. 223-229. |
Coutts et al., Chem. Abst., 1962, vol. 57, p. 5891(e). |
Brown, Ibid, 1955, vol. 50, p. 1010(c). |
Burger, Medicinal Chemistry, 1963, p. 42 (Interscience Pub. Co.). |
Asahina et al., Berich. Deutchen Chem. Gessellschaft, vol. 63, 1930, pp.2052ff. |
Grundon et al., Source not available, (1955), pp. 4284-4290. |
Brown, "Australian J. Chem.", (1954), vol. 8, pp. 348-377. |
Related Publications (1)
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Number |
Date |
Country |
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392082 |
Aug 1973 |
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Divisions (1)
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Number |
Date |
Country |
Parent |
454070 |
Mar 1974 |
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Continuation in Parts (3)
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Number |
Date |
Country |
Parent |
662148 |
Feb 1976 |
|
Parent |
557984 |
Mar 1975 |
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Parent |
303099 |
Nov 1972 |
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