Novel compounds inhibiting factor xa activity

• US 20030153510A1
• Filed: 02/19/2003
• Published: 08/14/2003
• Est. Priority Date: 08/23/2000
• Status: Active Grant

• Current Assignee: Michael W. Cappi, Robert Eckl, Silke Schabbert, Thilo Fuchs
• Original Assignee: Michael W. Cappi, Robert Eckl, Silke Schabbert, Thilo Fuchs
• Inventors: Eckl, Robert, Fuchs, Thilo, Schabbert, Silke, Cappi, Michael W
• Granted Patent: US 6,794,507 B2
• Time in Patent Office: Days
• US Class Current: 514/19
• 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 35/00 Antineoplastic agents
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• 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 211/32 by oxygen atoms
• CPC Class Codes: C07D 211/52 having an aryl radical as the second substituent in position 4
• CPC Class Codes: C07D 213/38 having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
• CPC Class Codes: C07D 213/74 Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• CPC Class Codes: C07D 217/06 with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates
• CPC Class Codes: C07D 295/185 from aliphatic carboxylic acids
• CPC Class Codes: C07D 295/24 Oxygen atoms
• CPC Class Codes: C07D 309/12 only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
• CPC Class Codes: C07D 401/12 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

Abstract

The present invention relates to compounds of formula (I):

or a pharmaceutically acceptable salt, solvate, hydrate or a pharmaceutically acceptable formulation thereof. Those compounds can be used for inhibiting factor Xa and for the prevention and/or treatment of thromboembolic conditions.

Claims

1. Compounds of formula (I):

2. Compounds according to claim 1 wherein X=R¹—

N═

C(—

NH₂)—

.

3. Compounds according to claim 1 or 2 wherein R¹=H, OH or C₁-C₄-alkoxy.

4. Compounds according to any one of claims 1 to 3 wherein Ar is a substituted or unsubstituted meta-phenylene.

5. Compounds according to any one of claims 1 to 4 wherein Ar is substituted in the para-position to X by an OH, NH₂, C₁-C₄-alkoxy, C₁-C₄-alkylamino or C₂-C₆-dialkylamino group or by a halogen atom.

6. Compounds according to any one of claims 1 to 5 wherein R³=H.

7. Compounds according to any one of claims 1 to 6 wherein the radicals R⁴ independently of one another are an OH, —

OCH₂COOH, —

COOH, C₁-C₄-alkoxy or glycosyloxy group or a halogen atom.

8. Compounds according to any one of claims 1 to 7 wherein n=0, 1 or 2.

9. Compounds according to any one of claims 1 to 8 wherein R⁵ is H, C₁-C₆-alkyl, C₁-C₆-heteroalkyl or the side chain of a natural amino acid.

10. Compounds according to any one of claims 1 to 9 wherein R⁶ and R⁷ together form part of an aryl-piperazinyl ring.

11. Compounds according to any one of claims 1 to 10 wherein R⁸=H or C₁-C₆-alkyl.

12. Pharmaceutical compositions comprising a compound according to claims 1 to 11 as active ingredient and optionally excipients and/or adjuvants.

13. Use of a compound or a pharmaceutical composition according to any one of claims 1 to 12 for inhibiting factor Xa.

14. Use of a compound or a pharmaceutical composition according to any one of claims 1 to 12 for the treatment and/or prevention of thromboembolic conditions, arterial restenosis, septicaemia, cancer, acute inflammation or other conditions mediated by factor Xa activity.

15. Use of a compound or a pharmaceutical composition according to any one of claims 1 to 12 for application in vascular surgery.