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US 7,745,443 B2Granted
Inhibitors of the GPIb-vWF interaction, their preparation and use
AssigneesSanofi-Aventis Deutschland GmbH, Ajinomoto Co., Inc.
InventorsOtmar Klingler, Melitta Just, Kuniya Sakurai, Naoyuki Fukuchi
Life of this patent
Estimating the term…
Abstract
The present invention relates to compounds of the formula I, in which R1, R2, A, B, D, E, n, m or o have the meanings indicated below. The compounds of the formula I are valuable pharmacologically active compounds. They are reversible inhibitors of the interaction between the plasma protein von Willebrand factor (vWF) and the blood platelet receptor glycoprotein Ib-IX-V complex (GPIb). They exhibit an antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of atherothrombotic diseases.
Claims7
A compound of the formula I,
- wherein
- n is the integer zero, 1, 2, 3 or 4;
- m is the integer zero, 1, 2, 3 or 4;
- o is the integer zero, 1, 2, 3 or 4;
- R1 is —(C1-C8)-alkyl;
- R2 is —NR4R5, wherein
- R4 and R5 are identical or different and are hydrogen atom or —(C1-C8)-alkyl;
- A is —CO—NH—;
- B is 1. a covalent bond,
- 2. a monocyclic or bicyclic 6- to 14-membered aryl, wherein aryl is unsubstituted or mono-, di-, tri- or tetrasubstituted independently of one another by R3,
- 3. (C3-C8)-cycloalkyl or
- 4. Het, wherein Het is unsubstituted or mono-, di-, tri- or tetrasubstituted independently of one another by R3,
- D is —NH—;
- E is Het, wherein Het is a saturated, partially unsaturated or aromatic monocyclic or bicyclic heterocyclic ring system containing 3 to 10 ring atoms of which 1, 2, 3 or 4 are identical or different heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur and wherein Het is unsubstituted or mono-, di-, tri- or tetrasubstituted independently of one another by R3;
- with the proviso that, when B is a covalent bond and Het is a bicyclic heterocyclic ring system, the ring of Het to which D-(CH2)o— is attached contains at least one hetero atom;
- R3 is 1. —(C1-C8)-alkyl,
- 2. (C1-C8)-alkoxy,
- 3. hydroxyl,
- 4. trifluoromethoxy,
- 5. trifluoromethyl,
- 6. halogen,
- 7. nitro,
- 8. —NR4R5, wherein R4 and R5 are as defined above,
- 9. —(C1-C8)-alkylcarbonyl,
- 10. —CN,
- 11. aminosulfonyl-,
- 12. amidino,
- 13. guanidino,
- 14. tri-((C1-C4)-alkyl)ammonio-,
- 15. di-((C1-C8)-alkyl)amino-,
- 16. (C1-C8)-alkylaminosulfonyl-,
- 17. di-((C1-C8)-alkyl)aminosulfonyl,
- 18. —O-Het, wherein Het is unsubstituted or mono-, di-, tri- or tetrasubstituted independently of one another by R3 and R3 is as defined above under 1. to 17., or
- 19. Het-, wherein Het is unsubstituted or mono-, di-, tri- or tetrasubstituted independently of one another by R3 and R3 is as defined above under 1. to 17.,
- in all their stereoisomeric forms and their physiologically tolerable salts.
32 more elements
A compound of the formula I,
- wherein
- n is the integer zero, 1, 2, 3 or 4;
- m is the integer zero, 1, 2, 3 or 4;
- o is the integer zero, 1, 2, 3 or 4;
- R1 is —(C1-C8)-alkyl;
- R2 is —NR4R5, wherein
- R4 and R5 are identical or different and are hydrogen atom or —(C1-C8)-alkyl;
- A is —CO—NH—;
- B is 1. a monocyclic or bicyclic 6- to 14-membered aryl, wherein aryl is unsubstituted or mono-, di-, tri- or tetrasubstituted independently of one another by R3,
- 2. (C3-C8)-cycloalkyl or
- 3. Het, wherein Het is unsubstituted or mono-, di-, tri- or tetrasubstituted independently of one another by R3,
- D is —NH—;
- E is Het, wherein Het is a saturated, partially unsaturated or aromatic monocyclic or bicyclic heterocyclic ring system containing 3 to 10 ring atoms of which 1, 2, 3 or 4 are identical or different heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur and wherein Het is unsubstituted or mono-, di-, tri- or tetrasubstituted independently of one another by R3;
- with the proviso that, when B is a covalent bond and Het is a bicyclic heterocyclic ring system, the ring of Het to which D-(CH2)o— is attached contains at least one hetero atom;
- R3 is 1. —(C1-C8)-alkyl,
- 2. (C1-C8)-alkoxy,
- 3. hydroxyl,
- 4. trifluoromethoxy,
- 5. trifluoromethyl,
- 6. halogen,
- 7. nitro,
- 8. —NR4R5, wherein R4 and R5 are as defined above,
- 9. —(C1-C8)-alkylcarbonyl,
- 10. —CN,
- 11. aminosulfonyl-,
- 12. amidino,
- 13. guanidino,
- 14. tri-((C1-C4)-alkyl)ammonio-,
- 15. di-((C1-C8)-alkyl)amino-,
- 16. (C1-C8)-alkylaminosulfonyl-,
- 17. di-((C1-C8)-alkyl)aminosulfonyl,
- 18. —O-Het, wherein Het is unsubstituted or mono-, di-, tri- or tetrasubstituted independently of one another by R3 and R3 is as defined above under 1. to 17., or
- 19. Het-, wherein Het is unsubstituted or mono-, di-, tri- or tetrasubstituted independently of one another by R3 and R3 is as defined above under 1. to 17.,
- in all their stereoisomeric forms and their physiologically tolerable salts.
31 more elements
Dependencies are inferred from the claim text.