Bicyclic heterocyclic compounds pharmaceutical compositions containing these compounds, their use and process for preparing the same

• US 8,343,982 B2
• Filed: 12/06/2010
• Issued: 01/01/2013
• Est. Priority Date: 03/30/2002
• Status: Expired due to Term

• Current Assignee: Boehringer Ingelheim Pharma GmbH & Company Kg (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim Pharma GmbH & Company Kg (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Himmelsbach, Frank, Jung, Birgit, Solca, Flavio
• Primary Examiner(s): Padmanabhan, Sreeni
• Assistant Examiner(s): Pihonak, Sarah
• Application Number:
  US12/961,109
• Publication Number:
  US 20110077246A1
• Time in Patent Office: 757 Days
• Field of Search: 514/266.4, 544/283
• US Class Current: 514/266.4
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 11/14 Antitussive agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C07D 239/94 Nitrogen atoms
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 491/08 Bridged systems

Abstract

The present invention relates methods for treating disease conditions selected from the list consisting of benign or malignant tumors, diseases of the airways and lungs, diseases of the gastrointestinal tract, the bile duct and the gall bladder by administration to a patient in need thereof of a therapeutically effective amount of a bicyclic heterocyclic groups of general formula

wherein said substituents are as defined herein.

Claims

1. A method of treating inflammatory diseases of the airways selected from the group consisting of chronic bronchitis, chronic obstructive bronchitis, asthma, bronchiectasis, allergic or non-allergic rhinitis or sinusitis, cystic fibrosis, alpha1-antitrypsin deficiency, coughs, pulmonary emphysema, pulmonary fibrosis and hyperreactive airways, said method comprising administering to a patient in need of such treatment an effective amount of a compound selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(morpholin-4-yl)carbonyl]-piperidin-4-yl-oxy}-7-methoxy-quinazoline

2. The method according to claim 1 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-(cis-4-{N-[(morpholin-4-yl)carbonyl]-N-methyl-amino}-cyclohexan-1-yloxy)-7-methoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

3. The method according to claim 1 wherein the inflammatory disease of the airways is selected from the group consisting of chronic bronchitis and chronic obstructive bronchitis.

4. The method according to claim 3 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-(cis-4-{N-[(morpholin-4-yl)carbonyl]-N-methyl-amino}-cyclohexan-1-yloxy)-7-methoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

5. The method according to claim 1 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(morpholin-4-yl)carbonyl]-piperidin-4-yl-oxy}-7-methoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

6. The method according to claim 3 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(morpholin-4-yl)carbonyl]-piperidin-4-yl-oxy}-7-methoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

7. The method according to claim 1 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-[cis-4-(N-dimethylaminocarbonyl-N-methyl-amino)-cyclohexan-1-yloxy]-7-methoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

8. The method according to claim 3 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-[cis-4-(N-dimethylaminocarbonyl-N-methyl-amino)-cyclohexan-1-yloxy]-7-methoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

9. The method according to claim 1 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-(3-methanesulphonylamino-cyclohexan-1-yloxy)-7-methoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

10. The method according to claim 3 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-(3-methanesulphonylamino-cyclohexan-1-yloxy)-7-methoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

11. The method according to claim 1 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-[cis-4-(N-dimethylaminosulphonyl-N-methyl-amino)-cyclohexan-1-yloxy]-7-methoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

12. The method according to claim 3 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-[cis-4-(N-dimethylaminosulphonyl-N-methyl-amino)-cyclohexan-1-yloxy]-7-methoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

13. The method according to claim 1 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-methanesulphonyl-piperidin-4-yloxy)-7-ethoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

14. The method according to claim 3 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-methanesulphonyl-piperidin-4-yloxy)-7-ethoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

15. The method according to claim 1 wherein the compound is selected from the group consisting of

4-[(3-ethynyl-phenyl)amino]-6-[1-(2-methoxy-acetyl)-piperidin-4-yloxy]-7-methoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

16. The method according to claim 3 wherein the compound is selected from the group consisting of

4-[(3-ethynyl-phenyl)amino]-6-[1-(2-methoxy-acetyl)-piperidin-4-yloxy]-7-methoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

17. The method according to claim 1 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-methylcarbonyl-piperidin-4-yloxy)-7-methoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

18. The method according to claim 3 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-methylcarbonyl-piperidin-4-yloxy)-7-methoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

19. The method according to claim 1 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(morpholin-4-yl)carbonyl]-piperidin-4-yloxy}-7-ethoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

20. The method according to claim 3 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(morpholin-4-yl)carbonyl]-piperidin-4-yloxy}-7-ethoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

21. The method according to claim 1 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-[1-(2-methoxy-acetyl)-piperidin-4-yloxy]-7-ethoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

22. The method according to claim 3 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-[1-(2-methoxy-acetyl)-piperidin-4-yloxy]-7-ethoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

23. The method according to claim 1 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-methanesulphonyl-piperidin-4-yloxy)-7-(2-methoxy-ethoxy)-quinazoline,

and the pharmaceutically acceptable salts thereof.

24. The method according to claim 3 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-methanesulphonyl-piperidin-4-yloxy)-7-(2-methoxy-ethoxy)-quinazoline,

and the pharmaceutically acceptable salts thereof.

25. The method according to claim 1 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(morpholin-4-yl)carbonyl]-piperidin-4-yloxy}-7-(2-methoxy-ethoxy)-quinazoline,

and the pharmaceutically acceptable salts thereof.

26. The method according to claim 3 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(morpholin-4-yl)carbonyl]-piperidin-4-yloxy}-7-(2-methoxy-ethoxy)-quinazoline,

and the pharmaceutically acceptable salts thereof.

27. The method according to claim 1 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-[1-(2-methoxy-acetyl)-piperidin-4-yloxy]-7-(2-methoxy-ethoxy)-quinazoline,

and the pharmaceutically acceptable salts thereof.

28. The method according to claim 3 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-[1-(2-methoxy-acetyl)-piperidin-4-yloxy]-7-(2-methoxy-ethoxy)-quinazoline,

and the pharmaceutically acceptable salts thereof.

29. The method according to claim 1 wherein the compound is selected from the group consisting of

4-[(3-ethynyl-phenyl)amino]-6-{1-[(morpholin-4-yl)carbonyl]-piperidin-4-yloxy}-7-methoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

30. The method according to claim 3 wherein the compound is selected from the group consisting of

4-[(3-ethynyl-phenyl)amino]-6-{1-[(morpholin-4-yl)carbonyl]-piperidin-4-yloxy}-7-methoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

31. The method according to claim 1 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-[trans-4-(N-methanesulphonyl-N-methyl-amino)-cyclohexan-1-yloxy]-7-methoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

32. The method according to claim 3 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-[trans-4-{N-methanesulphonyl-N-methyl-amino}-cyclohexan-1-yloxy]-7-methoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

33. The method according to claim 1 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-(trans-4-{N-[(morpholin-4-yl)carbonyl]-N-methyl-amino}-cyclohexan-1-yloxy)-7-methoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.

34. The method according to claim 3 wherein the compound is selected from the group consisting of

4-[(3-chloro-4-fluoro-phenyl)amino]-6-(trans-4-{N-[(morpholin-4-yl)carbonyl]-N-methyl-amino}-cyclohexan-1-yloxy)-7-methoxy-quinazoline,

and the pharmaceutically acceptable salts thereof.