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

• US 20090036676A1
• Filed: 02/26/2008
• Published: 02/05/2009
• Est. Priority Date: 03/30/2002
• Status: Active Grant

• Current Assignee: Birgit Jung, Flavio Solca, Frank Himmelsbach
• Original Assignee: Birgit Jung, Flavio Solca, Frank Himmelsbach
• Inventors: Solca, Flavio, Himmelsbach, Frank, Jung, Birgit
• Granted Patent: US 7,910,731 B2
• Time in Patent Office: Days
• US Class Current: 544/119
• 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 compound selected from the list consisting of

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

4-{[3-methyl-4-(pyridin-3-yloxy)-phenyl]amino)-6-(1-methanesulphonyl-piperidin-4-yloxy)-7-methoxy-quinazoline-methanesulphonate;

4-[(3-chloro-4-fluoro-phenyl)amino]-6-(tetrahydropyran-4-yloxy)-7-(2-acetylamino-ethoxy)-quinazolin;

4-[(3-chloro-4-fluoro-phenyl)amino]-6-(tetrahydropyran-4-yloxy)-7-(2-methanesulphonylamino-ethoxy)-quinazoline.

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 defined as 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(morpholin-4-yl)carbonyl]-piperidin-4-yloxy}-7-methoxy-quinazoline or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 defined as 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[cis-4-(N-dimethylaminocarbonyl-N-methyl-amino)-cyclohexan-1-yloxy]-7-methoxy-quinazoline or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 defined as 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(3-methanesulphonylamino-cyclohexan-1-yloxy)-7-methoxy-quinazoline or a pharmaceutically acceptable salt thereof.

5. The compound of claim 1 defined as 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[cis-4-(N-dimethylaminosulphonyl-N-methyl-amino)-cyclohexan-1-yloxy]-7-methoxy-quinazoline or a pharmaceutically acceptable salt thereof.

6. The compound of claim 1 defined as 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-methanesulphonyl-piperidin-4-yloxy)-7-ethoxy-quinazoline or a pharmaceutically acceptable salt thereof.

7. The compound of claim 1 defined as 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(cis-4-{N-[(morpholin-4-yl)carbonyl]-N-methyl-amino}-cyclohexan-1-yloxy)-7-methoxy-quinazoline or a pharmaceutically acceptable salt thereof.

8. The compound of claim 1 defined as 4-[(3-ethynyl-phenyl)amino]-6-[1-(2-methoxy-acetyl)-piperidin-4-yloxy]-7-methoxy-quinazoline or a pharmaceutically acceptable salt thereof.

9. The compound of claim 1 defined as 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-methylcarbonyl-piperidin-4-yloxy)-7-methoxy-quinazoline or a pharmaceutically acceptable salt thereof.

10. The compound of claim 1 defined as 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(morpholin-4-yl)carbonyl]-piperidin-4-yloxy}-7-ethoxy-quinazoline or a pharmaceutically acceptable salt thereof.

11. The compound of claim 1 defined as 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[1-(2-methoxy-acetyl)-piperidin-4-yloxy]-7-ethoxy-quinazoline or a pharmaceutically acceptable salt thereof.

12. The compound of claim 1 defined as 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-methanesulphonyl-piperidin-4-yloxy)-7-(2-methoxy-ethoxy)-quinazoline or a pharmaceutically acceptable salt thereof.

13. The compound of claim 1 defined as 4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(morpholin-4-yl)carbonyl]-piperidin-4-yloxy}-7-(2-methoxy-ethoxy)-quinazoline or a pharmaceutically acceptable salt thereof.

14. The compound of claim 1 defined as 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[1-(2-methoxy-acetyl)-piperidin-4-yloxy]-7-(2-methoxy-ethoxy)-quinazoline or a pharmaceutically acceptable salt thereof.

15. The compound of claim 1 defined as 4-[(3-ethynyl-phenyl)amino]-6-{1-[(morpholin-4-yl)carbonyl]-piperidin-4-yloxy}-7-methoxy-quinazoline or a pharmaceutically acceptable salt thereof.

16. The compound of claim 1 defined as 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[trans-4-(N-methanesulphonyl-N-methyl-amino)-cyclohexan-1-yloxy]-7-methoxy-quinazoline or a pharmaceutically acceptable salt thereof.

17. The compound of claim 1 defined as 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(trans-4-{N-[(morpholin-4-yl)carbonyl]-N-methyl-amino}-cyclohexan-1-yloxy)-7-methoxy-quinazoline or a pharmaceutically acceptable salt thereof.

18. The compound of claim 1 defined as 4-{[3-methyl-4-(pyridin-3-yloxy)-phenyl]amino)-6-(1-methanesulphonyl-piperidin-4-yloxy)-7-methoxy-quinazoline-methanesulphonate or a pharmaceutically acceptable salt thereof.

19. The compound of claim 1 defined as 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(tetrahydropyran-4-yloxy)-7-(2-acetylamino-ethoxy)-quinazolin or a pharmaceutically acceptable salt thereof.

20. The compound of claim 1 defined as 4-[(3-chloro-4-fluoro-phenyl)amino]-6-(tetrahydropyran-4-yloxy)-7-(2-methanesulphonylamino-ethoxy)-quinazoline or a pharmaceutically acceptable salt thereof.