IP Library › Granted Patent US 7,423,176

Granted Patent B2

US 7,423,176 · App. 11/104,237 · Granted Sep 9, 2008

Bicyclic aromatic sulfinyl derivatives

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Quick Facts

Patent No.: US 7,423,176
App. No.: 11/104,237
Granted: Sep 9, 2008
Kind: B2

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Abstract

The present invention provides compounds of the structure: wherein the constituent members are defined herein, including pharmaceutical compositions thereof and methods of treating diseases therewith.

Claims (241)

1. A compound of formula (I):

wherein

Ar is

wherein X is a bond, CH 2 , O, S(O) y , or NR 10 ;

rings A, C, and D are optionally substituted with one to three groups selected from F, Cl, Br, I, OR 21 , OR 25 , NR 23 R 24 , NHOH, NO 2 , CN, CF 3 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5 or 6 membered heteroaryl, arylalkyl, C(═O)R 22 , CO 2 R 21 , OC(═O)R 22 , C(═O)NR 22 R 24 , NR 21 C(═O)R 22 , NR 21 CO 2 R 22 , OC(═O)NR 23 R 24 , NR 21 C(═S)R 22 , and S(O) y R 22 ;

ring B is optionally substituted with one to three groups selected from C 1 -C 6 alkyl, phenyl, and 5-6 membered heteroaryl;

Y is (C 1 -C 6 alkylene)-R 1 ; or (C 1 -C 4 alkylene) m -Z-(C 1 -C 4 alkylene) n -R 1 ;

wherein said alkylene groups are optionally substituted with one to three R 20 groups;

Z is O, NR 10A , S(O) y , CR 21 ═CR 21 , C═C(R 21 ) 2 , C≡C, C 6 -C 10 arylene, 5-10 membered heteroarylene, C 3 -C 6 cycloalkylene, or 3-6 membered heterocycloalkylene; wherein said arylene, heteroarylene, cycloalkylene, and heterocycloalkylene groups are optionally substituted with one to three R 20 groups;

R 1 is NR 12 R 13 , NR 21 C(═O)R 14 , C(═O)R 15 , COOH, CO 2 R 14 , OC(═O)R 11 , C(═O)NR 12 R 13 , C(═O)NR 21 OR 14 , C(═N)NR 12 R 13 , OC(═O)NR 12 R 13 , NR 21 S(O) 2 R 11 , S(O) 2 NR 12 R 13 , NR 21 C(═O)NR 12 R 13 , NR 21 S(O) 2 NR 12 R 13 , or PO(OR 21 ) 2 ;

R 10 and R 10A are each independently selected from H, C 1 -C 6 alkyl, C 6 -C 10 aryl, C(═O)R 15 , and S(O) y R 14 ; wherein said alkyl and aryl groups are optionally substituted with one to three R 20 groups;

R 11 at each occurrence is independently selected from H, C 1 -C 6 alkyl, and C 6 -C 10 aryl; wherein said alkyl and aryl groups are optionally substituted with one to three R 20 groups;

R 12 and R 13 at each occurrence are each independently selected from H, C 1 -C 6 alkyl, and C 6 -C 10 aryl, or R 12 and R 13 , together with the nitrogen to which they are attached, form a 3-7 membered heterocycloalkyl ring;

wherein said alkyl and aryl groups and heterocycloalkyl ring are optionally substituted with one to three R 20 groups;

R 14 at each occurrence is independently selected from C 1 -C 6 alkyl, C 6 -C 10 aryl, and arylalkyl; wherein said alkyl, aryl and arylalkyl groups are optionally substituted with one to three R 20 groups;

R 15 each occurrence is independently selected from C 1 -C 6 alkyl, C 6 -C 10 aryl, arylalkyl, and heteroaryl; wherein said alkyl, aryl, arylalkyl, and heteroaryl groups are optionally substituted with one to three R 20 groups;

R 20 at each occurrence is independently selected from F, Cl, Br, I, OR 21 , OR 25 , O(C 1 -C 4 alkylene)OR 21 , NR 23 R 24 , NHOH, NO 2 , CN, CF 3 , C 1 -C 6 alkyl, C 3 -C 6 spirocycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5 or 6 membered heteroaryl, arylalkyl, ═O, C(═O)R 22 , CO 2 R 21 , OC(═O)R 22 , C(═O)NR 23 R 24 , NR 21 C(═O)R 22 , NR 21 CO 2 R 22 , OC(═O)NR 23 R 24 , NR 21 C(═O)R 22 , NR 21 C(═S)R 22 , and S(O) y R 22 ;

R 21 at each occurrence is independently selected from H and C 1 -C 6 alkyl;

R 22 at each occurrence is independently selected from C 1 -C 6 alkyl, and C 6 -C 10 aryl;

R 23 and R 24 at each occurrence are each independently selected from H, C 1 -C 6 alkyl, and C 6 -C 10 aryl, or R 23 and R 24 , together with the nitrogen to which they are attached, form a 3-7 membered heterocycloalkyl ring;

R 25 at each occurrence is independently the residue of an amino acid after the hydroxyl group of the carboxyl group is removed;

m is 0 or 1;

n is 0 or 1;

q is 1 or 2;

y is 0, 1, or 2;

and the stereoisomeric forms, mixtures of stereoisomeric forms or pharmaceutically acceptable salts forms thereof.

2. A compound as defined in claim 1 , wherein q is 1.

3. A compound as defined in claim 1 , wherein X is a bond.

4. A compound as defined in claim 1 , wherein X is CH 2 , O or S(O) y .

5. A compound as defined in claim 1 , wherein Y is C 1 -C 6 alkylene-R 1 .

6. A compound as defined in claim 5 , wherein Y is CH 2 -R 1 .

7. A compound as defined in claim 1 , wherein R 1 is selected from NR 21 C(═O)R 14 , C(═O)NR 12 R 13 , C(═N)NR 12 R 13 , and NR 21 C(═O)NR 12 R 13 .

8. A compound as defined in claim 7 , wherein R 1 is C(═O)NR 12 R 13 .

9. A compound as defined in claim 8 , wherein R 12 and R 13 are each independently selected from H and C 1 -C 6 alkyl.

10. A compound as defined in claim 8 , wherein R 12 and R 13 together with the nitrogen to which they are attached, form a 5-6 membered heterocycloalkyl ring, wherein said heterocycloalkyl ring is optionally substituted with one R 20 group.

11. A compound as defined in claim 1 , wherein Y is C 1 -C 4 alkylene-Z-C 1 -C 4 alkylene-R 1 , wherein Z is CR 21 ═CR 21 , C═C(R 21 ) 2 , C≡C, or phenylene.

12. A compound as defined in claim 1 , wherein Y is C 1 -C 4 alkylene-Z-C 1 -C 4 alkylene-R 1 , wherein Z is O or NR 10A .

13. A compound as defined in claim 1 , wherein:

rings A, C, and D are optionally substituted with one to three groups selected from F, Cl, Br, I, OR 21 , OR 25 , NR 23 R 24 , NHOH, NO 2 , CN, C 1 -C 6 alkyl, and C(═O)R 22 ;

ring B is optionally substituted with one to three groups selected from C 1 -C 4 alkyl, and phenyl;

Y is (C 1 -C 6 alkylene)-R 1 ;

wherein said alkylene group is optionally substituted with one to three R 20 groups;

R 10 is independently selected from H, C 1 -C 6 alkyl, C(═O)R 15 , and S(O) y R 14 ; wherein said alkyl group is optionally substituted with one to three R 20 groups;

R 11 at each occurrence is independently selected from H, and C 1 -C 6 alkyl; wherein said alkyl and aryl groups are optionally substituted with one to three R 20 groups;

R 12 and R 13 at each occurrence are each independently selected from H and C 1 -C 6 alkyl, or R 12 and R 13 , together with the nitrogen to which they are attached, form a 5-6 membered heterocycloalkyl ring;

wherein said alkyl and heterocycloalkyl groups are optionally substituted with one to three R 20 groups;

R 20 at each occurrence is independently selected from F, Cl, Br, I, OR 21 , OR 25 , O(C 1 -C 4 alkylene)OR 21, NR 23 R 24 NHOH, NO 2 , CN, CF 3 , phenyl, benzyl, 5-6 membered heteroaryl, ═O, C(═O)R 22 , CO 2 R 21 , OC(═O)R 22 , C(═O)NR 23 R 24 , NR 21 C(═O)R 22 , NR 21 CO 2 R 22 , OC(═O)NR 23 R 24 , NR 21 C(═O)R 22 , NR 21 C(═S)R 22 , and S(O) y R 22 ;

R 22 at each occurrence is independently selected from C 1 -C 6 alkyl, and phenyl; and

R 23 and R 24 at each occurrence are each independently selected from H and C 1 -C 6 alkyl, or R 23 and R 24 , together with the nitrogen to which they are attached, form a 5-6 membered heterocycloalkyl ring.

14. A compound as defined in claim 13 , wherein q is 1.

15. A compound as defined in claim 13 , wherein X is a bond.

16. A compound as defined in claim 13 , wherein X is CH 2 , O, or S(O) y .

17. A compound as defined in claim 13 , wherein Y is CH 2 —R 1 or CH 2 CH 2 -R 1 .

18. A compound as defined in claim 17 , wherein R 1 is selected from NR 21 C(═O)R 14 , C(═O)NR 12 R 13 , C(═N)NR 12 R 13 , and NR 21 C(═O)NR 12 R 13 .

19. A compound as defined in claim 13 , wherein q is 1; and Y is C 1 -C 2 alkylene-C(═O)NR 12 R 13 .

20. A compound as defined in claim 19 , wherein X is a bond.

21. A compound as defined in claim 19 , wherein Ar is tetrahydronaphthyl.

22. A compound as defined in claim 19 , wherein Ar is chromanyl.

23. A compound as defined in claim 19 , wherein Ar is thiochromanyl or 1-oxo-thiochromanyl.

24. A compound as defined in claim 19 , wherein Y is CH 2 —R 1 .

25. A compound as defined in claim 24 , wherein R 12 and R 13 are each independently selected from H and C 1 -C 6 alkyl.

26. A compound as defined in claim 24 , wherein R 12 and R 13 together with the nitrogen to which they are attached, form a 5-6 membered heterocycloalkyl ring, wherein said heterocycloalkyl ring is optionally substituted with one group.

27. A compound of formula (IV):

wherein

Ar is

wherein X is a bond, CH 2 , O, S, or S(O);

rings A, C, and D are optionally substituted with one to three groups selected from F, Cl, Br, I, OR 21 , OR 25 , NR 23 R 24 , NHOH, NO 2 , CN, C 1 -C 6 alkyl, and C(═O)R 22 ;

ring B is optionally substituted with one to three groups selected from C 1 -C 4 alkyl, and phenyl;

Y′ is C 1 -C 4 alkylene, wherein said alkylene group is optionally substituted with an R 20 group;

R 12 and R 13 at each occurrence are each independently selected from H, and C 1 -C 6 alkyl, wherein said alkyl group can optionally be substituted with one or two CN, OR 21 , O(CH 2 ) 1-4 R 21 C(═O)N(R 21 ) 2 , or pyridyl groups, or R 12 and R 13 , together with the nitrogen to which they are attached, form a pyrrolidinyl, piperidinyl, or piperazinyl ring, optionally substituted with OR 21 , C(═O)N(R 21 ) 2 , or C(═O)R 21 ; provided that when Ar is naphthyl, R 12 and R 13 cannot both be H;

R 20 at each occurrence is independently selected from F, Cl, Br, I, OR 21 , OR 25 , NR 23 R 24 , NHOH, NO 2 , CN, and CF 3 ;

R 21 at each occurrence is independently selected from H and C 1 -C 6 alkyl;

R 22 at each occurrence is independently selected from C 1 -C 6 alkyl, and phenyl;

R 25 at each occurrence is independently the residue of an amino acid after the hydroxyl group of the carboxyl group is removed;

and the stereoisomeric forms, mixtures of stereoisomeric forms or pharmaceutically acceptable salts forms thereof.

28. A compound as defined in claim 27 , having the structure of formula (V)

wherein:

the phenylene ring is optionally substituted with one to three groups selected from F, Cl, Br, I, OR 21 , OR 25 , NR 23 R 24 , NHOH, NO 2 , CN, C 1 -C 6 alkyl, and C(═O)R 22 ;

X is a bond, CH 2 , O, S, or S(O);

Y′ is C 1 -C 4 alkylene, wherein said alkylene group is optionally substituted with an R 20 group;

R 12 and R 13 at each occurrence are each independently selected from H, C 1 -C 6 alkyl, wherein said alkyl group can optionally be substituted with one or two CN, OR 21 , O(CH 2 ) 1-4 OR 21 , C(═O)N(R 21 ) 2 , or pyridyl groups, or R 12 and R 13 , together with the nitrogen to which they are attached, form a pyrrolidinyl, piperidinyl, or piperazinyl ring, optionally substituted with OR 21 , C(═O)N(R 21 ) 2 , or C(═O)R 21 ;

R 20 at each occurrence is independently selected from F, Cl, Br, I, OR 21 , OR 25 , NR 23 R 24 , NHOH, NO 2 , CN, or CF 3 ;

R 21 at each occurrence is independently selected from H and C 1 -C 6 alkyl;

R 22 at each occurrence is independently selected from C 1 -C 6 alkyl, and phenyl;

R 25 at each occurrence is independently the residue of an amino acid after the hydroxyl group of the carboxyl group is removed;

and the stereoisomeric forms, mixtures of stereoisomeric forms or pharmaceutically acceptable salts forms thereof.

29. A compound as defined in claim 28 , wherein X is a bond, Y′ is CH 2 , or CH 2 CH 2 , and R 12 and R 13 is H, C 1 -C 4 alkyl, optionally substituted with a CN, OR 21 , or O(CH 2 ) 1-4 OR 21 group; or R 12 and R 13 , together with the nitrogen to which they are attached, form a pyrrolidinyl, piperidmyl, or piperazinyl ring, optionally substituted with OR 21 , C(═O)N(R 21 ) 2 , or C(═O)R 21 group.

30. A compound as defined in claim 28 , wherein X is CH 2 , Y′ is CH 2 , and R 12 and R 13 is H or C 1 -C 4 alkyl, or R 12 and R 13 , together with the nitrogen to which they are attached, form a pyrrolidinyl ring.

31. A compound as defined in claim 28 , wherein X is O, Y′ is CH 2 , and R 12 and R 13 is H or C 1 -C 4 alkyl, optionally substituted with a pyridyl group; or R 12 and R 13 , together with the nitrogen to which they are attached, form a pyrrolidinyl ring.

32. A compound as defined in claim 28 , wherein X is S or S═O, Y′ is CH 2 , and R 12 and R 13 is C 1 -C 4 alkyl.

33. A compound as defined in claim 27 , having the structure of formula (VI):

wherein:

the naphthyl ring is optionally substituted with one to three groups selected from F, Cl, Br, I, OR 21 , OR 25 , NR 23 R 24 , NHOH, NO 2 , CN, C 1 -C 6 alkyl, and C(═O)R 22 ;

Y′ is C 1 -C 4 alkylene, wherein said alkylene group is optionally substituted with an R 20 group;

R 12 and R 13 at each occurrence are each independently selected from H, C 1 -C 6 alkyl, wherein said alkyl group can optionally be substituted with one OR 21 or C(═O)N(R 21 ) 2 group, or R 12 and R 13 , together with the nitrogen to which they are attached, form a pyrrolidinyl, piperidinyl, or piperazinyl ring substituted with OR 21 , C(═O)N(R 21 ) 2 , or C(═O)R 21 ; provided that R 32 and R 13 cannot both be H;

R 20 at each occurrence is independently selected from F, Cl, Br, I, OR 21 , OR 25 , NR 23 R 24 , NHOH, NO 2 , CN, or CF 3 ;

R 21 at each occurrence is independently selected from H and C 1 -C 6 alkyl;

R 22 at each occurrence is independently selected from C 1 -C 6 alkyl, and phenyl;

R 25 at each occurrence is independently the residue of an amino acid after the hydroxyl group of the carboxyl group is removed;

and the stereoisomeric forms, mixtures of stereoisomeric forms or pharmaceutically acceptable salts forms thereof.

34. A compound as defined in claim 33 , having the structure of formula (VII):

35. A compound as defined in claim 33 , wherein Y′ is CH 2 , and R 12 and R 13 is C 1 -C 4 alkyl, optionally substituted with an OR 21 group, or one or two C(═O)N(R 21 ) 2 groups; or R 12 and R 13 , together with the nitrogen to which they are attached, form a pyrrolidinyl ring, optionally substituted with a C(═O)N(R 21 ) 2 group.

36. A compound selected from the following table:

Example

Structure

37. A pharmaceutical composition comprising a compound as defined in claim 1 , in admixture with one or more pharmaceutically acceptable excipients.

38. A compound of formula (I):

wherein

Ar is

wherein X is a bond, CH 2 , O, S(O), or NR 10 ;

rings A, C, and D are optionally substituted with one to three groups selected from F, Cl, Br, I, OR 21 , OR 25 , NR 23 R 24 , NHOH, NO 2 , CN, CF 3 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5 or 6 membered heteroaryl, arylalkyl, C(═O)R 22 , CO 2 R 21 , OC(═O)R 22 , C(═O)NR 23 R 24 , NR 21 C(═O)R 22 , NR 21 CO 2 R 22 , OC(═O)NR 23 R 24 , NR 21 C(═S)R 22 , and S(O) y R 22 ;

ring B is optionally substituted with one to three groups selected from C 1 -C 6 alkyl, phenyl, and 5-6 membered heteroaryl;

Y is (C 1 -C 6 alkylene)-R 1 , C 1 -C 4 alkylene:-Z 1 -R 1 , Z 1 -C 1 -C 4 alkylene-R 1 , C 1 -C 4 alkylene-Z 1 -C 1 -C 4 alkylene-R 1 , or (C 1 -C 4 alkylene) m -Z 2 -(C 1 -C 4 alkylene) n -R 1 ; wherein Z 1 is CR 21 ═CR 21 , C═C(R 22 ), C≡C 1 C 6 -C 10 arylene, 5-10 membered heteroarylene, C 3 -C 6 cycloalkylene, or 3-6 membered heterocycloalkylene; and Z 2 is O, NR 10A , or S(O) y ;

wherein said alkylene groups are optionally substituted with one to three R 20 groups;

R 1 is NR 21 C(═O)R 14 , C(═O)R 15 , COOH, CO 2 R 14 , OC(═O)R 11 , C(═O)NR 12 R 13 , C(═O)NR 21 OR 14 , C(═N)NR 12 R 13 , OC(═O)NR 12 R 13 , NR 21 S(O) 2 R 11 , S(O) 2 NR 12 R 13 , NR 21 C(═O)NR 12 R 13 , NR 21 S(O) 2 NR 12 R 13 , or PO(OR 21 ) 2 ;

R 11 at each occurrence is independently selected from H, C 1 -C 10 alkyl, and C 6 -C 10 aryl; wherein said alkyl and aryl groups are optionally substituted with one to three R 20 groups;

R 15 at each occurrence is independently selected from C 1 -C 6 alkyl, C 6 -C 10 aryl, arylalkyl, and heteroaryl; wherein said alkyl, aryl, arylalkyl, and heteroaryl groups are optionally substituted with one to three R 20 groups;

R 21 at each occurrence is independently selected from H and C 1 -C 6 alkyl;

R 22 at each occurrence is independently selected from C 1 -C 6 alkyl, and C 6 -C 10 aryl;

R 25 at each occurrence is independently the residue of an amino acid after the hydroxyl group of the carboxyl group is removed;

m is 0 or 1;

n is 0 or 1;

q is 1 or 2;

y is 0, 1, or 2;

with the following provisos:

I. when Ar is naphthyl, and Y is C 1 -C 6 alkyl-C(═O)NR 12 R 13 , then naphthyl cannot be substituted with phenyl or heteroaryl, and R 12 and R 13 cannot both be H; and

II. when Ar is indane, then Y cannot be -triazolyl-C(═O)NR 12 R 13 ;

and the stereoisomeric forms, mixtures of stereoisomeric forms or pharmaceutically acceptable salts forms thereof.

39. A compound as defined in claim 38 , wherein q is 1.

40. A compound as defined in claim 38 , wherein Ar is naphthyl.

41. A compound as defined in claim 38 , wherein Y is C 1 -C 6 alkylene-R 1 .

42. A compound as defined in claim 41 , wherein Y is CH 2 -R 1 .

43. A compound as defined in claim 38 , wherein R 1 is selected from NR 21 C(═O)R 14 , C(═O)NR 12 R 13 , C(═N)NR 12 R 13 , and NR 21 C(═O)NR 12 R 13 .

44. A compound as defined in claim 43 , wherein R 1 is C(═O)NR 12 R 13 .

45. A compound as defined in claim 44 , wherein R 12 and R 13 are each independently selected from H and C 1 -C 6 alkyl.

46. A compound as defined in claim 38 , wherein:

rings A, C, and D are optionally substituted with one to three groups selected from F, Cl, Br, I, OR 21 , OR 25 , NR 23 R 24 , NHOH, NO 2 , CN, C 1 -C 6 alkyl, and C(═O)R 22 ;

ring B is optionally substituted with one to three groups selected from C 1 -C 4 alkyl, and phenyl;

Y is (C 1 -C 6 alkylene)-R 1 ;

wherein said alkylene group is optionally substituted with one to three R 20 groups;

R 10 is independently selected from H, C 1 -C 6 alkyl, C(═O)R 15 , and S(O) y R 14 ; wherein said alkyl group is optionally substituted with one to three R 20 groups;

R 11 at each occurrence is independently selected from H, and C 1 -C 6 alkyl; wherein said alkyl and aryl groups are optionally substituted with one to three R 20 groups;

R 20 at each occurrence is independently selected from F, Cl, Br, I, OR 21 , OR 25 , O(C 1 -C 4 alkylene)OR 21 , NR 23 R 24 , NHOH, NO 2 , CN, CF 3 , phenyl, benzyl, 5-6 membered heteroaryl, ═O, C(═O)R 22 , CO 2 R 21 , OC(═O)R 22 , C(═O)NR 23 R 24, NR 21 C(═O)R 22 , NR 21 CO 2 R 22 , OC(═O)NR 23 R 24 , NR 21 C(═O)R 22 , NR 21 C(═S)R 22 , and S(O) y R 22 ;

R 22 at each occurrence is independently selected from C 1 -C 6 alkyl, and phenyl; and

R 23 and R 24 at each occurrence are each independently selected from H and C 1 -C 6 alkyl, or R 23 and R 24 together with the nitrogen to which they are attached, form a 5-6 membered heterocycloalkyl ring.

47. A compound of formula (I):

wherein

Ar is

wherein X is a bond, CH 2 , O, S(O) y , or NR 10 ;

rings A, C, and D are optionally substituted with one to three groups selected from F, Cl, Br, I, OR 21 , OR 25 , NR 23 R 24 , NHOH, NO 2 , CN, CF 3 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5 or 6 membered heteroaryl, arylalkyl, C(O)R 22 , CO 2 R 21 , OC(═O)R 22 , C(═O)NR 23 R 24 , NR 21 C(═O)R 22 , NR 21 CO 2 R 22 , OC(═O)NR 23 R 24 , NR 21 C(═S)R 22 , and S(O) y R 22 ;

ring B is optionally substituted with one to three groups selected from C 1 -C 6 alkyl, phenyl, and 5-6 membered heteroaryl;

Y is CH 2 -R 1 , C 1 -C 4 alkylene-Z 1 -R 1 , Z 1 -C 1 -C 4 alkylene-R 1 , C 1 -C 4 alkylene-Z 1 -C 1 -C 4 alkylene-R 1 , or (C 1 -C 4 alkylene) m -Z 2 -(C 1 -C 4 alkylene) n -R 1 ; wherein Z 1 is CR 21 ═CR 21 , C═C(R 22 ), C≡C, C 6 -C 10 arylene, 5-10 membered heteroarylene, C 3 -C 6 cycloalkylene, or 3-6 membered heterocycloalkylene; and Z 2 is O, NR 10A or S(O) y ;

wherein said alkylene groups are optionally substituted with one to three R 20 groups;

R 1 is R 12 R 13 , NR 21 C(═O)R 14 , C(═O)R 15 , COOH, CO 2 R 14 , OC(═O)R 11 , C(O)NR 12 R 13 , C(═O)NR 21 OR 14 , C(═N)NR 12 R 13 , OC(═O)NR 12 R 13 , NR 21 S(O) 2 R 11 , S(O) 2 NR 12 R 13 , NR 21 C(═O)NR 12 R 13 , NR 21 S(O) 2 NR 12 R 13 , or PO(OR 21 ) 2 ;

R 11 at each occurrence is independently selected from H, C 1 -C 6 alkyl, and C 6 -C 10 aryl; wherein said alkyl and aryl groups are optionally substituted with one to three R 20 groups;

wherein said alkyl and aryl groups and heterocycloalkyl ring are optionally substituted with one to three R 20 groups;

R 15 at each occurrence is independently selected from CrC 6 alkyl, C 6 -C 10 aryl, arylalkyl, and heteroaryl; wherein said alkyl, aryl, arylalkyl, and heteroaryl groups are optionally substituted with one to three R 20 groups;

R 20 at each occurrence is independently selected from F, Cl, Br, I, OR 21 , OR 25 O(C 1 -C 4 alkylene)OR 21 , NR 23 R 24 , NHOH, NO 2 , CN, CF 3 , C 1 -C 6 alkyl, C 3 -C 6 spirocycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5 or 6 membered heteroaryl, arylalkyl, ═O, C(═O)R 22 , CO 2 R 21 , OC(═O)R 22 C(═O)NR 23 R 24 , NR 21 C(═O)R 22 , NR 21 CO 2 R 22 , OC(═O)NR 23 R 24 , NR 21 C(═O)R 22 NR 21 C(═S)R 22 , and S(O) y R 22 ;

R 21 at each occurrence is independently selected from H and C 1 -C 6 alkyl;

R 22 at each occurrence is independently selected from C 1 -C 6 alkyl, and C 6 -C 10 aryl;

R 25 at each occurrence is independently the residue of an amino acid after the hydroxyl group of the carboxyl group is removed;

m is 0 or 1;

n is 0 or 1;

q is 1 or 2;

y is 0, 1, or 2;

with the following provisos:

1. when Ar is naphthyl, and Y is C 1 -C 6 alkyl-C(═O)NR 12 R 13 , then naphthyl cannot be substituted with phenyl or heteroaryl, and R 12 and R 13 cannot both be H; and

2. when Ar is indane, then Y cannot be -triazolyl-C(═O)NR 12 R 13 ;

and the stereoisomeric forms, mixtures of stereoisomeric forms or pharmaceutically acceptable salts forms thereof.

48. A compound as defined in claim 47 , wherein q is 1.

49. A compound as defined in claim 47 , wherein Ar is naphthyl.

50. A compound as defined in claim 47 , wherein Y is CH 2 -R 1 .

51. A compound as defined in claim 47 , wherein R 1 is selected from NR 21 C(═O)R 14 , C(═O)NR 12 R 13 , C(═N)NR 12 R 13 and NR 21 C(═O)NR 12 R 13 .

52. A compound as defined in claim 51 , wherein R 1 is C(═O)NR 12 R 13 .

53. A compound as defined in claim 52 , wherein R 12 and R 13 are each independently selected from H and C 1 -C 6 alkyl.

54. A compound as defined in claim 47 , wherein:

rings A, C, and D are optionally substituted with one to three groups selected from F, Cl, Br, I, OR 21 , OR 25 , NR 23 R 24 , NHOH, NO 2 , CN, C 1 -C 6 alkyl, and C(═O)R 22 ;

ring B is optionally substituted with one to three groups selected from C 1 -C 4 alkyl, and phenyl;

Y is CH 2 -R 1 ;

R 10 is independently selected from H, C 1 -C 6 alkyl, C(═O)R 15 , and S(O) y R 14 ; wherein said alkyl group is optionally substituted with one to three R 20 groups;

R 11 at each occurrence is independently selected from H, and C 1 -C 6 alkyl; wherein said alkyl and aryl groups are optionally substituted with one to three R 20 groups;

wherein said alkyl and heterocycloalkyl groups are optionally substituted with one to three R 20 groups;

R 20 at each occurrence is independently selected from F, Cl, Br, 1, OR 21 , OR 25 , O(C 1 -C 4 alkylene)OR 21 , NR 23 R 24 , NHOH, NO 2 , CN, CF 3 , phenyl, benzyl, 5-6 membered heteroaryl, O, C(═O)R 22 , CO 2 R 21 , OC(═O)R 22 , C(═O)NR 23 R 24 , NR 21 C(═O)R 22 , NR 21 CO 2 R 22 , OC(═O)NR 23 R 24 , NR 21 C(═O)R 22 , NR 21 C(═S)R 22 , and S(O) y R 22 ;

R 22 at each occurrence is independently selected from C 1 -C 6 alkyl, and phenyl; and

55. A pharmaceutical composition comprising a compound as defined in claim 13 , in admixture with one or more pharmaceutically acceptable excipients.

56. A pharmaceutical composition comprising a compound as defined in claim 38 , in admixture with one or more pharmaceutically acceptable excipients.

57. A pharmaceutical composition comprising a compound as defined in claim 46 , in admixture with one or more pharmaceutically acceptable excipients.

58. A pharmaceutical composition comprising a compound as defined in claim 47 , in admixture with one or more pharmaceutically acceptable excipients.

59. A pharmaceutical composition comprising a compound as defined in claim 54 , in admixture with one or more pharmaceutically acceptable excipients.

Assignments (2)

MERGER Recorded Jan 24, 2013

From: CEPHALON FRANCE

To: TEVA SANTE

Reel/Frame 029692/0457 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 29, 2005

From: BACON, EDWARD R.; CHATTERJEE, SANKAR; IQBAL, MOHAMED; LESUR, BRIGITTE; LOUVET, PHILIPPE

To: CEPHALON, INC.; CEPHALON FRANCE

Reel/Frame 016432/0786 →