SUBSTITUTED CHROMONE-3-CARBONITRILES, CARBOXAMIDES AND CARBOXYLIC ACIDS

• US 3,862,143 A
• Filed: 12/04/1972
• Issued: 01/21/1975
• Est. Priority Date: 12/04/1972
• Status: Expired due to Term

• Current Assignee: Maximilian Von Strandtmann, Richard E Brown, Sylvester Klutchko
• Original Assignee: Maximilian Von Strandtmann, Richard E Brown, Sylvester Klutchko
• Inventors: Klutchko, Sylvester, Brown, Richard E., Von Strandtmann, Maximilian
• Primary Examiner(s): Ford, John M.
• Application Number:
  US05/312,154
• Time in Patent Office: 778 Days
• Field of Search: 260/345.2,345.5
• US Class Current: 549/401
• CPC Class Codes: A61K 31/35 having six-membered rings with one oxygen as the only ring hetero atom
• CPC Class Codes: C07D 311/22 with oxygen or sulfur atoms directly attached in position 4
• CPC Class Codes: C07D 311/24 with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2

Abstract

WHEREIN X has the same meaning as given above; and wherein R2 and Z together may form a substituted pyrrole ring; and the corresponding non-toxic, pharmaceutically acceptable salts. These compounds are useful in the management of allergic conditions such as allergic bronchitis. Certain of these compounds may also be used as anti-secretory agents.

WHEREIN X represents amino, N-lower-alkylamino, hydroxylamino, N-lower-alkylhydroxylamino, ureido, piperidino, or anilino, with the proviso that when R2 represents hydrogen, Z represents cyano or

WHEREIN R1 represents hydrogen, halogen, lower alkyl, hydroxy, lower alkoxy, or acyloxy; R2 represents hydrogen, lower alkyl, fluorinated lower alkyl, alkoxycarbonyl, carboxy, or lower alkyl carboxylic acid; Z represents cyano, carboxy, alkoxycarbonyl, or

Substituted chromone-3-carbonitriles, carboxamides and carboxylic acids having the structural formula:

Claims

2. A compound according to claim 1 wherein R1 represents hydrogen, halogen, lower alkoxy, hydroxy or acetoxy;

R2 represents hydrogen, lower alkyl, trifluoromethyl, lower alkoxycarbonyl, carboxy, or lower alkyl carboxylic acid;

Z represents cyano, carboxy, lower alkoxycarbonyl or

3. A compound according to claim 2 wherein R1 represents hydrogen, halogen, lower alkoxy, hydroxy or acetoxy;

R2 represents hydrogen, lower alkyl, trifluoromethyl, lower alkoxycarbonyl, carboxy or lower alkyl carboxylic acid; and

Z represents cyano, or

4. A compound according to claim 3 wherein R1 is in position number 6, 7, or 8 on the chromone ring.

5. A compound according to claim 3 wherein R1 represents hydrogen, halogen, lower alkoxy, hydroxy, or acetoxy;

R2 represents hydrogen, lower alkyl, trifluoromethyl, lower alkoxycarbonyl, carboxy or lower alkyl carboxylic acid; and

Z represents cyano.

6. A compound according to claim 2 wherein R1 represents hydrogen, halogen, lower alkoxy, hydroxy or acetoxy;

R2 represents lower alkyl, trifluoromethyl, lower alkoxycarbonyl, carboxy or lower alkyl carboxylic acid; and

Z represents cyano, carboxy, lower alkoxycarbonyl or

7. A compound according to claim 6 wherein R1 is in position number 6, 7, or 8 on the chromone ring.

8. A compound according to claim 3 which is 7-hydroxy-4-oxo-4H-1-benzopyran-3-carbonitrile acetate.

9. A compound according to claim 3 which is 7-hydroxy-4-oxo-4H-1-benzopyran-3-carbonitrile.

10. A compound according to claim 3 which is the sodium salt of 4-oxo-4H-1-benzopyran-3-carbohydroxamate.

11. A compound according to claim 3 which is N-isopropyl-4-oxo-4H-1-benzopyran-3-carboxamide.

12. A compound according to claim 3 which is ((4-oxo-4H-1-benzopyran-3-yl)carbonyl)urea.

13. A compound according to claim 3 which is N-methyl-4-oxo-4H-1-benzopyran-3-carbohydroxamic acid.

14. A compound according to claim 3 which is 4-oxo-4H-1-benzopyran-3-carboxamide.

15. A compound according to claim 3 which is 4-oxo-4H-1-benzopyran-3-carbonitrile.

16. A compound according to claim 3 which is 6-bromo-4-oxo-4H--benzopyran-3-carbonitrile.

17. A compound according to claim 3 which is 8-methoxy-4-oxo-4H-1-benzopyran-3-carbonitrile.

18. A compound according to claim 6 which is 7-hydroxy-2-methyl-4-oxo-4H-1-benzopyran-3-carboxylic acid.

19. A compound according to claim 6 which is 3-carboxy-7-hydroxy-4-oxo-4H-1-benzopyran-2-propionic acid.

20. A compound according to claim 6 which is 7-hydroxy-4-oxo-4H-1-benzopyran-2,3-dicarboxylic acid.

21. A compound according to claim 6 which is 7-hydroxy-4-oxo-2-methyl-4H-1-benzopyran-3-carbonitrile acetate.

22. A compound according to claim 6 which is 7-hydroxy-4-oxo-2-methyl-4H-1-benzopyran-3-carbonitrile.

23. A compound according to claim 6 which is 3-cyano-7-hydroxy-4-oxo-4H-1-benzopyran-2-propionic acid.

24. A compound according to claim 6 which is 7-hydroxy-4-oxo-2-(trifluoromethyl)-4H-1-benzopyran-3-carbonitrile.

25. A compound according to claim 6 which is ethyl 3-cyano-7-hydroxy-4-oxo-4H-1-benzopyran-2-carboxylate.

26. A compound according to claim 6 which is 7-hydroxy-4-oxo-2-methyl-4H-1-benzopyran-3-carboxamide.

27. A compound according to claim 6 which is 7-hydroxy-4-oxo-2-(trifluoromethyl)-4H-1-benzopyran-3-carboxamide.

28. A compound according to claim 6 which is ethyl 3-carbamoyl-7-hydroxy-4-oxo-4H-1-benzopyran-2-carboxylate.

29. A compound according to claim 6 which is 2-methyl-4-oxo-4H-1-benzopyran-3-carboxylic acid.

30. A compound according to claim 6 which is methyl 2-methyl-4-oxo-4H-1-benzopyran-3-carboxylate.