2-iminoimidazole derivatives (2)

1. A compound having the structure:

or salt thereof;

wherein R 1 , R 2 and R 3 may be the same or different and each independently represents (1) hydrogen, (2) cyano, (3) halogen or (4) a group selected from Substituent Group A; and R 1 and R 2 may bond together to form a 5-membered ring;

R 6 represents (1) hydrogen, (2) C 1-6 alkyl, (3) acyl, (4) carbamoyl, (5) hydroxyl, (6) C 1-6 alkoxy, (7) C 1-6 alkyloxycarbonyloxy, (8) C 3-8 cycloalkyl, (9) C 1-6 alkyloxycarbonyl optionally substituted with acyloxy or (10) a C 6-14 aromatic hydrocarbon ring group; wherein each of the foregoing groups is optionally substituted with at least one group selected from Substituent Group E;

Y 1 represents —(CH 2 ) m —; wherein m represents an integer of 1 to 3;

Y 2 represents —CO— or —C(═N—OH)—; and

Ar represents:

(1) hydrogen,

(2) a group represented by the formula:

wherein R 10 , R 11 , R 12 , R 13 and R 14 are the same or different and each independently represents (1) hydrogen, (2) cyano, (3) halogen, (4) nitro or (5) a group selected from Substituent Group B; wherein

Substituent Group A is selected from the group consisting of C 1-6 alkyl, alkylidene, C 2-6 alkenyl, C 2-6 alkynyl, acyl, carboxyl, carbamoyl, C 1-6 alkoxycarbonyl, C 1-6 alkylaminocarbonyl, hydroxyl, C 1-6 alkoxy, C 3-8 cycloalkyloxy, amino, C 1-6 alkylamino, C 3-8 cycloalkylamino, acylamino, sulfonylamino, sulfonyl, sulfamoyl, C 3-8 cycloalkyl, a 5- or 6-membered non-aromatic heterocyclic group, a C 6-14 aromatic hydrocarbon ring group and a 5- or 6-membered aromatic heterocyclic group, wherein each of the foregoing groups is optionally substituted with at least one group selected from Substituent Group A′; wherein

Substituent Group A′ represents moieties selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, cyano, acyl, carboxyl, carbamoyl, C 1-6 alkoxycarbonyl, C 1-6 alkylaminocarbonyl, hydroxyl, C 1-6 alkoxy, C 3-8 cycloalkyloxy, amino, C 1-6 alkylamino, C 3-8 cycloalkylamino, acylamino, ureido, ureylene, sulfonylamino, sulfonyl, sulfamoyl, halogen, C 3-8 cycloalkyl, a heterocyclic alkyl group, a 5- or 6-membered non-aromatic heterocyclic group, a C 6-14 aromatic hydrocarbon ring group and a 5- or 6-membered aromatic heterocyclic group, wherein the C 6-14 aromatic hydrocarbon ring group and the 5- or 6-membered aromatic heterocyclic group may be substituted with at least one group selected from the group consisting of C 1-6 alkyl, cyano, acyl, carboxyl, carbamoyl, C 1-6 alkoxycarbonyl, C 1-6 alkylaminocarbonyl, hydroxyl, C 1-6 alkoxy, C 3-8 cycloalkyloxy, nitro, amino, C 1-6 alkylamino, C 3-8 cycloalkylamino, acylamino, ureido, ureylene, sulfonylamino, sulfonyl, sulfamoyl, halogen and C 3-8 cycloalkyl;

Substituent Group B is selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, acyl, carboxyl, carbamoyl, C 1-6 alkoxycarbonyl, C 1-6 alkylaminocarbonyl, hydroxyl, C 1-6 alkoxy, C 3-8 cycloalkyloxy, amino, C 1-6 aminoalkyl, C 1-6 alkylamino, C 3-8 cycloalkylamino, acylamino, ureido, sulfonylamino, sulfonyl, sulfamoyl, C 3-8 cycloalkyl, and a C 6-14 aromatic hydrocarbon ring group; wherein each of the foregoing groups is optionally substituted with at least one group selected from Substituent Group B′; wherein

Substituent Group B′ is selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, oxo, cyano, C 1-6 cyanoacyl, C 2-7 acyl, C 1-6 alkanoyl, benzoyl, aralkanoyl, C 1-6 alkoxyalkylcarbonyl, C 1-6 hydroxyalkylcarbonyl, carboxyl, C 1-6 carboxyalkyl, C 1-6 carboxyalkyloxy, carbamoyl, carbamoylalkyloxy, C 1-6 alkoxycarbonyl, C 1-10 alkoxycarbonyl-C 1-6 alkyl, C 1-10 alkoxycarbonyl-C 1-6 alkyloxy, C 1-6 monoalkylaminocarbonyl, C 2-6 dialkylaminocarbonyl, hydroxyl, C 1-6 alkoxy, C 1-10 alkoxyalkyl, C 1-10 aralkyloxyalkyl, C 1-6 hydroxyalkyl, C 3-8 cycloalkyloxy, amino, C 1-6 alkylamino, C 3-8 cycloalkylamino, acylamino, ureido, ureylene, C 1-6 alkylsulfonylamino, phenylsulfonylamino, C 1-6 alkylsulfonyl, phenylsulfonyl, C 1-6 monoalkylaminosulfonyl, C 2-6 dialkylaminosulfonyl, sulfamoyl, halogeno, C 3-8 cycloalkyl, a C 6-14 aromatic hydrocarbon ring group, wherein the C 6-14 aromatic hydrocarbon ring group, may be substituted with at least one group selected from the group consisting of C 1-6 alkyl, oxo, cyano, acyl, carboxyl, carbamoyl, C 1-6 alkoxycarbonyl, C 1-6 alkylaminocarbonyl, hydroxyl, C 1-6 alkoxy, C 3-8 cycloalkyloxy, nitro, amino, C 1-6 aminoalkyl, C 1-6 alkylamino, C 1-6 dialkylamino, C 3-8 cycloalkylamino, acylamino, ureido, ureylene, alkylsulfonylamino, alkylsulfonyl, sulfamoyl, halogeno and C 3-8 cycloalkyl; and

Substituent Group E selected from the group consisting of C 1-6 alkyl, cyano, acyl, carboxyl, carbamoyl, C 1-6 alkoxycarbonyl, C 1-6 alkylaminocarbonyl, hydroxyl, C 1-6 alkoxy, C 3-8 cycloalkyloxy, amino, C 1-6 alkylamino, C 3-8 cycloalkylamino, acylamino, ureido, ureylene, sulfonylamino, sulfonyl, sulfamoyl, halogen and C 3-8 cycloalkyl.

2. A compound of claim 1 , wherein R 1 , R 2 and R 3 may be the same or different and each independently represents C 1-6 alkyl, C 2-6 alkenyl or C 1-6 alkoxy; wherein each of the foregoing groups is optionally substituted with at least one group selected from Substituent Group A″; wherein

Substituent Group A″ represents moieties selected from the group consisting of C 1-6 alkyl, acyl, carboxyl, C 1-6 alkoxycarbonyl, C 1-6 alkylaminocarbonyl, hydroxyl, C 1-6 alkoxy, C 1-6 alkylamino, a C 6-14 aromatic hydrocarbon ring group and a 5- or 6-membered aromatic heterocyclic group, wherein the C 6-14 aromatic hydrocarbon ring group and the 5- or 6-membered aromatic heterocyclic group may be substituted with at least one group selected from the group consisting of C 1-6 alkyl, carboxyl, C 1-6 alkoxycarbonyl, C 1-6 alkylaminocarbonyl, hydroxyl, C 1-6 alkoxy, nitro, C 1-6 alkylamino, acylamino, sulfonylamino and halogen;

R 6 represents a group selected from the group consisting of hydrogen, C 1-6 alkyl and C 1-6 alkyloxycarbonyl optionally substituted with acyloxy;

Y 2 represents —CO—; and Ar represents hydrogen or a group represented by the formula:

wherein R 10 , R 11 , R 12 , R 13 and R 14 are the same or different and each independently represents a group selected from the group consisting of hydrogen, C 1-6 alkyl, hydroxyl, C 1-6 alkoxy, C 1-6 alkylamino, C 3-8 cycloalkylamino, acylamino, and C 1-6 alkyloxycarbonyloxy; wherein each of the foregoing groups ids optionally substituted with at least one group selected from Substituent Group F′; wherein

Substituent Group F″is selected from the group consisting of C 1-6 alkyl, oxo, cyano, acyl, carboxyl and C 1-6 alkoxy.

3. The compound according of claim 1 , wherein Y 1 is —CH 2 —.

4. The compound according of claim 1 , wherein Y 2 is —CO—.

5. The compound according to claim 1 , wherein Y 1 is —CH 2 — and Y 2 is —CO—.

6. The compound according to claim 1 , wherein Ar is a group having the structure:

wherein R 10 , R 11 , R 12 , R 13 and R 14 are as defined in claim 1 .

7. The compound according to claim 6 , wherein R 10 and R 14 are hydrogen.

8. The compound of claim 1 , wherein Ar is a group having the structure:

wherein R 11 and R 13 are as defined in claim 1 ; and

R 15 represents (1) hydrogen or (2) a group selected from Substituent Group H; wherein

Substituent Group H selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, acyl, C 1-6 alkoxycarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl, C 3-8 cycloalkyl, C 1-6 aminoalkyl, sulfonyl, C 3-8 cycloalkylamino, a C 6-14 aromatic hydrocarbon ring group; wherein each of the foregoing groups is optionally substituted with at least one group selected from Substituent Group H′; wherein

Substituent Group H′ is selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, oxo, cyano, C 1-6 cyanoalkyl, C 2-7 acyl, C 1-6 alkanoyl, benzoyl, aralkanoyl, C 1-6 alkoxyalkylcarbonyl, C 1-6 hydroxyalkylcarbonyl, carboxyl, C 1-6 carboxyalkyl, C 1-6 carboxyalkyloxy, carbamoyl, carbamoylalkyloxy, C 1-6 alkoxycarbonyl, C 1-10 alkoxycarbonyl-C 1-6 alkyl, C 1-10 alkoxycarbonyl-C 1-6 alkyloxy, C 1-6 monoalkylaminocarbonyl, C 2-6 dialkylaminocarbonyl, hydroxyl, C 1-6 alkoxy, C 1-10 alkoxyalkyl, C 1-10 aralkyloxyalkyl, C 1-6 hydroxyalkyl, C 3-8 cycloalkyloxy, amino, C 1-6 alkylamino, C 3-8 cycloalkylamino, acylamino, ureido, ureylene, C 1-6 alkylsulfonylamino, phenylsulfonylamino, C 1-6 alkylsulfonyl, phenylsulfonyl, C 1-6 monoalkylaminosulfonyl, C 2-6 dialkylaminosulfonyl, sulfamoyl, halogeno, C 3-8 cycloalkyl, and a C 6-14 aromatic hydrocarbon ring group, wherein the C 6-14 aromatic hydrocarbon ring group may be substituted with at least one group selected from the group consisting of C 1-6 alkyl, oxo, cyano, acyl, carboxyl, carbamoyl, C 1-6 alkoxycarbonyl, C 1-6 alkylaminocarbonyl, hydroxyl, C 1-6 alkoxy, C 3-8 cycloalkyloxy, nitro, amino, C 1-6 aminoalkyl, C 1-6 alkylamino, C 1-6 dialkylamino, C 3-8 cycloalkylamino, acylamino, ureido, ureylene, alkylsulfonylamino, alkylsulfonyl, sulfamoyl, halogeno and C 3-8 cycloalkyl.

9. A compound of claim 1 , wherein Ar is a group having the structure:

wherein R 11 and R 15 are as defined in claim 1 ; and

R 16 represents (1) hydrogen or (2) a group selected from Substituent Group H, wherein Substituent Group H is as defined in claim 1 .

10. The compound according of claim 1 , wherein Ar is a group having the structure:

wherein R 11 and R 15 are as defined in claim 1 , and

R 17 and R 18 are the same or different and each independently represents (1) hydrogen or (2) a group selected from Substituent Group I; wherein

Substituent Group I selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, acyl, carbamoyl, C 1-6 alkoxycarbonyl, C 1-6 alkylaminocarbonyl, C 1-6 aminoalkyl, sulfonyl, sulfamoyl, C 3-8 cycloalkyl, and a C 6-14 aromatic hydrocarbon ring group wherein each of the foregoing groups is optionally substituted with at least one group selected from Substituent Group I′; wherein

Substituent Group I′ is selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, oxo, cyano, C 1-6 cyanoalkyl, C 2-7 acyl, C 1-6 alkanoyl, benzoyl, aralkanoyl, C 1-6 alkoxyalkylcarbonyl, C 1-6 hydroxyalkylcarbonyl, carboxyl, C 1-6 carboxyalkyl, C 1-6 carboxyalkyloxy, carbamoyl, carbamoylalkyloxy, C 1-6 alkoxycarbonyl, C 1-10 alkoxycarbonyl-C 1-6 alkyl, C 1-10 alkoxycarbonyl-C 1-6 alkyloxy, C 1-6 monoalkylaminocarbonyl, C 2-6 dialkylaminocarbonyl, hydroxyl, C 1-6 alkoxy, C 1-10 alkoxyalkyl, C 1-10 aralkyloxyalkyl, C 1-6 hydroxyalkyl, C 3-8 cycloalkyloxy, amino, C 1-6 alkylamino, C 3-8 cycloalkylamino, acylamino, ureido, ureylene, C 1-6 alkylsulfonylamino, phenylsulfonylamino, C 1-6 alkylsulfonyl, phenylsulfonyl, C 1-6 monoalkylaminosulfonyl, C 2-6 dialkylaminosulfonyl, sulfamoyl, halogeno, C 3-8 cycloalkyl, a C 6-14 aromatic hydrocarbon ring group, wherein the C 6-14 aromatic hydrcarbon ring group, may be substituted with at least one group selected from the group consisting of C 1-6 alkyl, oxo, cyano, acyl, carboxyl, carbamoyl, C 1-6 alkoxycarbonyl, C 1-6 alkylaminocarbonyl, hydroxyl, C 1-6 alkoxy, C 3-8 cycloalkyloxy, nitro, amino, C 1-6 aminoalkyl, C 1-6 alkylamino, C 1-6 dialkylamino, C 3-8 cycloalkylamino, acylamino, ureido, ureylene, alkylsulfonylamino, alkylsulfonyl, sulfamoyl, halogeno and C 3-8 cycloalkyl.

11. The compound of claim 1 , having the structure:

12. The compound of claim 1 , having the structure:

13. The compound of claim 1 , having the structure:

14. The compound of claim 1 , having the structure:

15. The compound of claim 1 , having the structure:

16. The compound of claim 1 , having the structure:

17. The compound of claim 1 , having the structure:

18. The compound of claim 1 , having the structure:

19. The compound of claim 1 , having the structure:

20. The compound of claim 1 , having the structure:

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

22. A method for treating thrombosis, vascular restenosis and/or, deep venous thrombosis, in a patient compromising administering to the patient in need thereof an amount of a compound of claim 1 or a composition of claim 21 effective to antagonize a thrombin receptor.

23. The method of claim 22 wherein the thrombin receptor is a PAR1 thrombin receptor.