Spirocyclic Heterocycles Medicaments Containing Said Compounds, Use Thereof And Method For Their Production

• US 20110046148A1
• Filed: 02/05/2009
• Published: 02/24/2011
• Est. Priority Date: 02/07/2008
• Status: Active Grant

• Current Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Lotz, Ralf, Himmelsbach, Frank, Jung, Birgit
• Granted Patent: US 8,497,369 B2
• Time in Patent Office: Days
• US Class Current: 514/252.15
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 11/10 Expectorants
• 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: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links

Abstract

The present invention relates to spirocyclic heterocycles of general formula (I)

the tautomers, the stereoisomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids, which have valuable pharmacological properties, particularly an inhibitory effect on signal transduction mediated by tyrosine kinases, the use thereof for the treatment of diseases, particularly tumoral diseases as well as benign prostatic hyperplasia (BPH), diseases of the lungs and airways, and the preparation thereof.

Claims

1. A compound of the formula (I)

2. A compound Compounds according to claim 1, wherein,

R^a denotes a group selected from among 3-chloro-2-fluoro-phenyl, 3-chloro-4-fluoro-phenyl, 5-chloro-2-fluoro-phenyl, 2-fluoro-3-methyl-phenyl, 2-fluoro-5-methyl-phenyl, 4-fluoro-3-methyl-phenyl- and 3-chloro-2-methyl-phenyl group,

R^b and R^c which may be identical or different,

denote hydrogen or C_1-3-alkyl,

R^d denotes C_1-3-alkyl-O,

unless stated otherwise, the above-mentioned alkyl groups may be straight-chain or branched,

A denotes —

CH₂CH₂, while the —

CH₂CH₂—

group may be substituted by 1 or 2 methyl groups,

or a tautomer or pharmacologically acceptable salt thereof.

4. A method for treating inflammatory or allergic diseases of the airways which method comprises administering to a host suffering from an inflammatory or allergic disease of the airways a therapeutically effective amount of a compound according to claim 1 or 2.

5. The method of claim 4 wherein the disease to be treated is selected from the group consisting of chronic bronchitis, acute bronchitis, bronchitis caused by bacterial or viral infection or fungi or helminths, allergic bronchitis, toxic bronchitis, chronic obstructive bronchitis (COPD), asthma (intrinsic or allergic), paediatric asthma, bronchiectasis, allergic alveolitis, allergic or non-allergic rhinitis, chronic sinusitis, cystic fibrosis or mucoviscidosis, alpha-1-antitrypsin deficiency, cough, pulmonary emphysema, interstitial lung diseases, alveolitis, hyperreactive airways, nasal polyps, pulmonary oedema, pneumonitis of different origins, e.g. radiation-induced or caused by aspiration or infectious pneumonitis, collagenoses such as lupus erythematodes, systemic sclerodermy, sarcoidosis and Boeck'"'"'s disease.

6. The method of claim 4 wherein the disease to be treated is chronic obstructive bronchitis (COPD) or asthma.

8. A pharmaceutical composition comprising a compound according to claim 1 or 2 and a pharmaceutically acceptable carrier or diluent.

3. (canceled)

7. (canceled)

9-10. -10. (canceled)