Substituted oxazolidinones and their use in the field of blood coagulation

• US 8,129,378 B2
• Filed: 06/30/2009
• Issued: 03/06/2012
• Est. Priority Date: 12/24/1999
• Status: Expired due to Term

• Current Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Original Assignee: Bayer Pharma AG (Bayer AG)
• Inventors: Straub, Alexander, Lampe, Thomas, Pohlmann, Jens, Röhrig, Susanne, Perzborn, Elisabeth, Schlemmer, Karl-Heinz, Pernerstorfer, Joseph
• Primary Examiner(s): ANDERSON, REBECCA L
• Application Number:
  US12/494,879
• Publication Number:
  US 20100137274A1
• Time in Patent Office: 980 Days
• Field of Search: 514/376, 514/236.8, 544/139, 548/231
• US Class Current: 514/236.8
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 333/38 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/10 linked by a carbon chain containing aromatic 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 417/14 containing three or more hetero rings
• CPC Class Codes: C07D 495/04 Ortho-condensed systems
• CPC Class Codes: C07D 498/04 Ortho-condensed systems

Abstract

The invention relates to the field of blood coagulation. Novel oxazolidinone derivatives of the general formula (I)

processes for their preparation and their use as medicinally active compounds for the prophylaxis and/or treatment of disorders are described.

Claims

1. A compound of the formula (I)

2. The compound of the formula (I) according to claim 1,

characterized in that

R¹ represents thiophene which may optionally be mono- or polysubstituted by halogen, amino, aminomethyl or (C₁-C₈)-alkyl, where the (C₁-C₈)-alkyl radical for its part may optionally be mono- or polysubstituted by halogen,

R² represents

D-M-A-,

where

the radical “

A”

represents optionally substituted

3. The compound of the formula (I) according to claim 1,

characterized in that

R¹ represents thiophene which may optionally be mono- or polysubstituted by halogen or by (C₁-C₈)-alkyl, where the (C₁-C₈)-alkyl radical for its part may optionally be mono- or polysubstituted by halogen,

R² represents

D-M-A-,

where:

the radical “

A”

represents optionally substituted

4. The compound of the formula (I) according to claim 1,

characterized in that

R¹ represents 2-thiophene which may optionally be substituted in the 5-position by a radical selected from the group consisting of chlorine, bromine, methyl and trifluoromethyl,

R² represents

D-M-A-,

where:

the radical “

A”

represents optionally substituted

5. The compound of the formula (I) according to claim 1,

characterized in that

R¹ represents 2-thiophene which is substituted in the 5-position by a radical selected from the group consisting of chlorine, bromine, methyl and trifluoromethyl,

R² represents D-A-,

where:

the radical “

A”

represents

6. Process for preparing the substituted oxazolidinone of claim 1, where either according to a process alternative

(A) a compound of the formula (II)

7. A pharmaceutical composition comprising at least one compound of the formula (I) according to claim 1 and one or more pharmacologically acceptable auxiliaries or excipients.

8. A method for treatment of atherosclerosis comprising administering an effective amount of a compound of claim 1 to a patient in need thereof.

9. The compound of claim 1 wherein R¹ represents an optionally substituted 2-thiophene group, and wherein said halogen substituent is chlorine or bromine, and said (C₁-C₈)-alkyl substituent is methyl, where the methyl radical for its part optionally may be mono- or polysubstituted by fluorine.

10. The process of claim 6 wherein in process alternative “

A”

, the corresponding carbonyl halide of carboxylic acid (III) is a carbonyl chloride.

11. The process of claim 6 wherein in process alternative “

B”

, the phosgene equivalent employed in the cyclization of compound (VII) is carbonyldimidazole (CDI).

12. A method for treatment of a thromboembolic disorder comprising administering to a patient in need thereof an effective amount of a compound of claim 1, wherein the thromboembolic disorder is myocardial infarct, pulmonary embolism or deep venous thrombosis.

13. The compound of claim 1 that is purified and isolated.

14. A pharmaceutical composition comprising at least one compound of the formula (I) according to claim 2 and one or more pharmacologically acceptable auxiliaries or excipients.

15. A pharmaceutical composition comprising at least one compound of the formula (I) according to claim 3 and one or more pharmacologically acceptable auxiliaries or excipients.

16. A pharmaceutical composition comprising at least one compound of the formula (I) according to claim 4 and one or more pharmacologically acceptable auxiliaries or excipients.

17. A pharmaceutical composition comprising at least one compound of the formula (I) according to claim 5 and one or more pharmacologically acceptable auxiliaries or excipients.

18. A method for the treatment of atherosclerosis-comprising administering an effective amount of the composition of claim 14 to a patient in need thereof.

19. A method for the treatment of myocardial infarct, pulmonary embolism or deep venous thrombosis comprising administering an effective amount of the composition of claim 14 to a patient in need thereof.

20. A method for the treatment of atherosclerosis-comprising administering an effective amount of the composition of claim 15 to a patient in need thereof.

21. A method for the treatment of myocardial infarct, pulmonary embolism or deep venous thrombosis comprising administering an effective amount of the composition of claim 15 to a patient in need thereof.

22. A method for the treatment of atherosclerosis comprising administering an effective amount of the composition of claim 16 to a patient in need thereof.

23. A method for the treatment of myocardial infarct, pulmonary embolism or deep venous thrombosis comprising administering an effective amount of the composition of claim 16 to a patient in need thereof.

24. A method for the treatment of atherosclerosis comprising administering an effective amount of the composition of claim 17 to a patient in need thereof.

25. A method for the treatment of myocardial infarct, pulmonary embolism or deep venous thrombosis comprising administering an effective amount of the composition of claim 17 to a patient in need thereof.