Benzenesulfonyl-chromane, thiochromane, tetrahydronaphthalene and related gamma secretase inhibitors

1. A compound having the formula (IF):

or a pharmaceutically acceptable salt thereof,

wherein Q is a cyclohexyl ring unsubstituted or substituted with one or more independently selected L 3 groups;

X is —O—;

each L 3 is independently selected from the group consisting of: —CN, ═O, R 5 , —OR 5 ; ═N—R 5 and —N(R 5 ) 2 ;

R 4 is H or alkyl;

each R 5 is independently selected from the group consisting of: (1) H, (2) (C 1 -C 6 )alkyl, (3) hydroxyl substituted alkyl, (4) R 6 , (5) R 7 , (6) —C(O)—(C 1 -C 6 )alkyl, (7) —C(O)—(C 1 -C 6 )haloalkyl, (8) —C(O)—R 6 , (9) —C(O)—R 7 , (10) —C(O)NH—(C 1 -C 6 )alkyl, (11) —C(O)N((C 1 -C 6 )alkyl) 2 wherein each alkyl group is independently selected, (12) —S(O) 2 —(C 1 -C 6 )alkyl, (13) —S(O) 2 —(C 1 -C 6 )haloalkyl, (14) —S(O) 2 —R 6 , (15) —S(O) 2 —R 7 , (16) —S(O) 2 —R 8 , (17) -alkylene-C(O)—(C 1 -C 6 )alkyl, (18) -alkylene-C(O)—(C 1 -C 6 )haloalkyl, (19) -alkylene-C(O)—R 6 , (20) -alkylene-C(O)—R 7 , (21) -alkylene-S(O) 2 —(C 1 -C 6 )alkyl, (22) -alkylene-S(O) 2 —(C 1 -C 6 )haloalkyl, (23) -alkylene-S(O) 2 —R 6 , (24) -alkylene-S(O) 2 —R 7 , (25) -alkylene-S(O) 2 —R 8 , (26) -alkylene-NHC(O)—(C 1 -C 6 )alkyl, (27) -alkylene-NHC(O)—(C 1 -C 6 )haloalkyl, (28) -alkylene-NHC(O)—R 6 , (29) -alkylene-NHC(O)—R 7 , (30) -alkylene-NHS(O) 2 —(C 1 -C 6 )alkyl, (31) -alkylene-NHS(O) 2 —(C 1 -C 6 )haloalkyl, (32) -alkylene-NHS(O) 2 —R 6 , (33) -alkylene-NHS(O) 2 —R 7 , (34) -alkylene-N(alkyl)C(O)—(C 1 -C 6 )alkyl, (35) -alkylene-N(alkyl)C(O)—(C 1 -C 6 )haloalkyl, (36) -alkylene-N(alkyl)C(O)—R 6 , (37) -alkylene-N(alkyl)C(O)—R 7 , (38) -alkylene-N(alkyl)S(O) 2 —(C 1 -C 6 )alkyl, (39) -alkylene-N(alkyl)S(O) 2 —(C 1 -C 6 )haloalkyl, (40) -alkylene-N(alkyl)S(O) 2 —R 6 , (41) -alkylene-N(alkyl)S(O) 2 —R 7 , (42) -alkylene-C(O)—NH—(C 1 -C 6 )alkyl, (43) -alkylene-C(O)—NHR 6 , (44) -alkylene-C(O)—NHR 7 , (45) -alkylene-S(O) 2 NH—(C 1 -C 6 )alkyl, (46) -alkylene-S(O) 2 NH—R 6 , (47) -alkylene-S(O) 2 NH—R 7 , (48) -alkylene-C(O)—N((C 1 -C 6 )alkyl) 2 wherein each alkyl group is independently selected, (49) -alkylene-C(O)—N(alkyl)R 6 , (50) -alkylene-C(O)—N(alkyl)R 7 , (51) -alkylene-S(O) 2 N((C 1 -C 6 )alkyl) 2 wherein each alkyl group is independently selected, (52) -alkylene-S(O) 2 N(alkyl)-R 6 , (53) -alkylene-S(O) 2 N(alkyl)-R 7 , (54) -alkylene-OH, (55) -alkylene-OC(O)—NH-alkyl, (56) -alkylene-OC(O)NH—R 8 , (57) -alkylene-CN, (58) —R 8 , (59) -alkylene-SH, (60) -alkylene-S(O) 2 —NH—R 8 , (61) -alkylene-S(O) 2 -alkylene-R 6 , (62) halo substituted alkylene, (63) —C(O)OR 8 , (64) —C(O)O(C 1 -C 6 )alkyl, (65) —C(O)R 8 , (66) —C(O)-alkylene-β-(C 1 -C 6 )alkyl, (67) —C(O)NH 2 , (68) -alkylene-O—(C 1 -C 6 )alkyl, (69) -alkylene-R 8 , (70) —S(O) 2 -halo(C 1 -C 6 )alkyl, (71) hydroxy substituted halo(C 1 -C 6 )alkyl, (72) -alkylene-NH 2 , (73) -alkylene-NH—S(O) 2 —R 8 , (74) -alkylene-NH—C(O)—R 8 , (75) -alkylene-NH—C(O)O—(C 1 -C 6 )alkyl, (76) -alkylene-O—C(O)—(C 1 -C 6 )alkyl, (77) -alkylene-O—S(O) 2 —(C 1 -C 6 )alkyl, (78) -alkylene-R 6 , (79) -alkylene-R 7 , (80) -alkylene-NH—C(O)—NH—(C 1 -C 6 )alkyl, (81) -alkylene-N(S(O) 2 halo(C 1 -C 6 )alkyl) 2 wherein each —S(O) 2 halo(C 1 -C 6 )alkyl moiety is independently selected, (82) -alkylene-N((C 1 -C 6 )alkyl)S(O) 2 R 8 , (83) -alkylene-OC(O)—N(alkyl) 2 wherein each alkyl is independently selected, (84) -alkylene-NH—(C 1 -C 6 )alkyl, (85) —C(O)-alkylene-C(O)O—(C 1 -C 6 )alkyl, (86) —C(O)—C(O)—O—(C 1 -C 6 )alkyl, (87) —C(O)-alkylene-R 6 , (88) —C(O)—NH—R 8 , (89) —C(O)—NH—R 6 , (90) —C(O)—NH-alkylene-R 6 , (91) —C(O)-alkylene-NH—S(O) 2 -halo(C 1 -C 6 )alkyl, (92) —C(O)-alkylene-NH—C(O)—O—(C 1 -C 6 )alkyl, (93) —C(O)-alkylene-NH 2 , (94) —C(O)-alkylene-NH—S(O) 2 —R 8 , (95) —C(O)-alkylene-NH—S(O) 2 —(C 1 -C 6 )alkyl, (96) —C(O)-alkylene-NH—C(O)—(C 1 -C 6 )alkyl, (97) —C(O)-alkylene-N(S(O) 2 (C 1 -C 6 )alkyl) 2 wherein each —S(O) 2 (C 1 -C 6 )alkyl moiety is independently selected, (98) —C(O)-alkylene-NH—C(O)—NH—(C 1 -C 6 )alkyl, (99) -alkylene-O—R 6 , (100) -alkylene-R 7 , (101) —C(O)OH, (102) -alkylene-N(S(O) 2 (C 1 -C 6 )alkyl) 2 , (103) -alkylene-C(O)—O—(C 1 -C 6 )alkyl, (104) haloalkyl, (105) halo, (106) -alkylene —C(O)—NH 2 , (107) ═N—O—(C 1 -C 6 )alkyl, (108) ═N—O-alkylene-R 6 , (109) ═N—O-alkenyl, (110) ═N—O—R 6 , (111) ═N—NH—S(O) 2 —R 6 , (112) alkenyl, (113)=R 8 , (114) -alkylene-O-alkylene-SK(C 1 -C 6 )alkyl) 3 wherein each alkyl is independently selected, (115) -alkylene-S(O) 2 —N(alkylene-R 6 ) 2 wherein each alkylene-R 6 moiety is independently selected, (116) -alkylene-S(O) 2 —NH 2 , (117) —O—C(O)—R 9 , (118) —O—C(O)—(C 1 -C 6 )alkyl, (119) —S(O) 2 NH((C 1 -C 6 )alkyl), (120) —S(O) 2 N((C 1 -C 6 )alkyl) 2 wherein each alkyl is independently selected, (121) —S(O) 2 NHR 8 , (122) -alkylene-C(O)OH, (123) -alkylene-C(O)NH(halo(C 1 -C 6 )alkyl), (124) -alkylene-C(O)—NH-alkylene-R 8 , (125) -alkylene-C(O)—NH-alkylene-OH, (126) —C(O)O(haloC 1 -C 6 alkyl), (127) —C(O)OR 6 , (128) —C(O)OR 7 , (129) -alkylene-NHSO 2 N(alkyl) 2 wherein each alkyl is independently selected, (130) -alkylene-NHSO 2 NHalkyl, (131) -alkylene-N(alkyl)-SO 2 N(alkyl) 2 wherein each alkyl is independently selected, (132) -alkylene-N(alkyl)-SO 2 NHalkyl wherein each alkyl is independently selected, (133) -alkylene-O—SO 2 -alkyl, (134) -alkylene-NH—C(O)—N(alkyl) 2 wherein each alkyl is independently selected, (135) -alkylene-NH—C(O)—NHalkyl, (136) -alkylene-N(alkyl)-C(O)—N-(alkyl) 2 wherein each alkyl is independently selected, (137) -alkylene-N(alkyl)-C(O)—NHalkyl, (138) —CN, (139) -alkylene-P(O)(Oalkyl) 2 wherein each alkyl is independently selected, (140) -alkylene-CH(OH)—P(O)(Oalkyl) 2 wherein each alkyl is independently selected, (141) -alkylene-OC(O)N(C 1 -C 6 alkyl)-R 8 , (142) -alkylene-S(O) 2 —N(C 1 -C 6 alkyl)-R 8 , (143) -alkylene-N(C 1 -C 6 alkyl)-S(O) 2 —R 8 , (144) -alkylene-N(C 1 -C 6 alkyl)-C(O)—R 8 , (145) -alkylene-N(C 1 -C 6 alkyl)-C(O)O—(C 1 -C 6 )alkyl wherein each alkyl is independently selected, (146) -alkylene-N(C 1 -C 6 alkyl)-C(O)—NH—(C 1 -C 6 )alkyl wherein each alkyl is independently selected, (147) -alkylene-NH—C(O)—N(C 1 -C 6 alkyl) 2 wherein each alkyl is independently selected, (148) -alkylene-N(C 1 -C 6 alkyl)-C(O)—N(C 1 -C 6 alkyl) 2 wherein each alkyl is independently selected, (149) —C(O)—N(C 1 -C 6 alkyl)-R 8 , (150) —C(O)—N(C 1 -C 6 alkyl)-R 6 , (151) —C(O)—N(C 1 -C 6 alkyl)-alkylene-R 6 , (152) —C(O)-alkylene-N(C 1 -C 6 alkyl)-S(O) 2 -halo(C 1 -C 6 )alkyl wherein each alkyl is independently selected, (153) —C(O)-alkylene-N(C 1 -C 6 alkyl)-C(O)—O—(C 1 -C 6 )alkyl wherein each alkyl is independently selected, (154) —C(O)-alkylene-NH(C 1 -C 6 alkyl), (155) —C(O)-alkylene-N(C 1 -C 6 alkyl) 2 wherein each alkyl is independently selected, (156) —C(O)-alkylene-N(C 1 -C 6 alkyl)-S(O) 2 —R 8 , (157) —C(O)-alkylene-N(C 1 -C 6 alkyl)-S(O) 2 —(C 1 -C 6 )alkyl, (158) —C(O)-alkylene-N(C 1 -C 6 alkyl)-C(O)—(C 1 -C 6 )alkyl, (159) —C(O)-alkylene-N(C 1 -C 6 alkyl)-C(O)—NH—(C 1 -C 6 )alkyl wherein each alkyl is independently selected, (160) —C(O)-alkylene-NH—C(O)—N((C 1 -C 6 )alkyl) 2 wherein each alkyl is independently selected, (161) —C(O)-alkylene-N(C 1 -C 6 alkyl)-C(O)—N((C 1 -C 6 )alkyl) 2 wherein each alkyl is independently selected, (162) -alkylene-C(O)—N(C 1 -C 6 alkyl) 2 wherein each alkyl is independently selected, (163) ═N—N(C 1 -C 6 alkyl)-S(O) 2 —R 6 , (164) —S(O) 2 N(C 1 -C 6 alkyl)R 8 , (165) -alkylene-C(O)N(C 1 -C 6 alkyl)(halo(C 1 -C 6 )alkyl) wherein each alkyl group is independently selected, (166) -alkylene-C(O)N(halo(C 1 -C 6 )alkyl) 2 wherein each alkyl group is independently selected, (167) -alkylene-C(O)—N(C 1 -C 6 alkyl)-alkylene-R 8 , (168) -alkylene-C(O)—N(C 1 -C 6 alkyl)-alkylene-OH, and (169) —O—C(O)—R 7 ;

R 6 is selected from the group consisting of: unsubstituted (C 6 -C 14 )aryl, (C 6 -C 14 )aryl substituted with one or more L 1 groups, unsubstituted (C 5 -C 14 )heteroaryl, and (C 5 -C 14 )heteroaryl substituted with one or more L 1 groups;

R 7 is selected from the group consisting of unsubstituted heterocycloalkyl and heterocycloalkyl substituted with one or more L 2 groups;

R 8 is selected from the group consisting of unsubstituted cycloalkyl and cycloalkyl substituted with one or more L 3 groups;

Ar is unsubstituted phenyl or phenyl substituted with one or more L 1 groups;

R 9 is a bridged multicyclic heterocycloalkyl ring wherein said R 9 moiety is unsubstituted or said R 9 moiety is substituted with one or more L 2 groups;

each L 1 is independently selected from the group consisting of: halogen, alkyl, —CN, —CF 3 , —O—(C 1 -C 6 )alkyl, —O-(halo(C 1 -C 6 )alkyl), —C(O)—O—(C 1 -C 6 )alkyl, -alkylene-OH, halo(C 1 -C 6 )alkyl, hydroxyalkoxy-, and alkoxyalkoxy-;

each L 2 is independently selected from the group consisting of: (a) —OH, (b) alkyl, (c) alkyl substituted with one or more —OH groups, (d) halo, (e) haloalkyl, and (f) heterocycloalkyl;

n is 0, 1, 2 or 3; and

m is 1; and

provided that for the substituent —OR 5 , the R 5 moiety and the oxygen atom to which it is bound to does not form a —O—O— group; and

provided that for the substituents —OR 5 , ═N—R 5 and —NHR 5 , R 5 is not —CH 2 OH, —CH 2 NH 2 , —CH 2 NHalkyl, —CH 2 NHaryl or —C(O)OH.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein each L 3 is the same or different —NHR 5 group, and each R 5 is independently selected from the group consisting of: —S(O) 2 —(C 1 -C 6 )alkyl, —S(O) 2 —(C 1 -C 6 )haloalkyl, —S(O) 2 R 6 , —S(O) 2 R 7 and —S(O) 2 R 8 .

3. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein each L 3 is the same or different OR 5 group, and each R 5 is independently selected from the group consisting of: H, (C 1 -C 6 )alkyl, R 6 , R 7 , —C(O)—(C 1 -C 6 )alkyl, —C(O)—C 1 -C 6 )haloalkyl, —C(O)—R 6 , and —C(O)—R 7 .

4. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein each L 3 is the same or different R 5 group, and each R 5 is independently selected from the group consisting of: H, (C 1 -C 6 )alkyl, R 6 , R 7 , S(O) 2 —(C 1 -C 6 )alkyl, —S(O) 2 —(C 1 -C 6 )haloalkyl, —S(O) 2 R 6 , —S(O) 2 R 7 , —S(O) 2 R 8 , —C(O)—(C 1 -C 6 )alkyl, —C(O)—(C 1 -C 6 )haloalkyl, —C(O)—R 6 , and —C(O)—R 7 .

5. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 4 is H.

6. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein L 1 is halogen.

7. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein L 1 is halogen wherein each halogen is individually selected from the group consisting of: Cl and F.

8. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein substituent Ar is phenyl substituted with one or more L 1 groups.

9. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein substituent Ar is phenyl substituted with an L 1 group wherein said L 1 group is halogen or halo (C 1 -C 6 )alkyl.

10. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein substituent Ar is phenyl substituted with an L 1 group wherein said L 1 group is Cl or —CF 3 .

11. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein n is 1 or 2.

12. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein n is 1.

13. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein n is 2.

14. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein L 1 is halogen wherein each halogen is independently selected from the group consisting of Cl and Br, and n is 2.

15. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein L 1 is F and n is 2.

16. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein n is 2, and L 1 is selected from the group consisting of Cl and F.

17. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein n is 2, L 1 is selected from the group consisting of Cl and F, and Ar is phenyl substituted with Cl.

18. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein n is 2, and L 1 is F.

19. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein n is 2, L 1 is F, and Ar is phenyl substituted with Cl.

20. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound of formula (IF) is a compound of formula (IF.1):

21. The compound of claim 20 or a pharmaceutically acceptable salt thereof, wherein R 4 is H, L 1 is F, and Ar is phenyl substituted with Cl.

22. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Q is

23. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Q is:

wherein L 3 is selected from the group consisting of: ═O, —OR 5 , —NHR 5 , —SO 2 R 6 , —SO 2 R 7 , and —SO 2 R 8 , wherein R 5 is selected from the group consisting of: —SO 2 —(C 1 -C 6 )haloalkyl, —C(O)—(C 1 -C 6 )alkyl, —C(O)NH(C 1 -C 6 )alkyl, —SO 2 —(C 1 -C 6 )alkyl, and —(C 1 -C 6 )alkyl, and wherein R 6 is unsubstituted (C5-C 14 ) heteroaryl, and wherein R 7 is an unsubstituted heterocycloalkyl ring, and wherein R 8 is an unsubstituted cycloalkyl ring.

24. The compound of claim 23 or a pharmaceutically acceptable salt thereof, wherein L 3 is selected from the group consisting of: ═O, —OH, —NH 2 , —NHSO 2 CF 3 , —NHC(O)CH 3 , —NHC(O)NHCH 2 CH 3 , —NHSO 2 CH 3 , —NHSO 2 CH 2 CH 3 , —NHSO 2 CH 2 CH 2 CH 3 , —OCH 3 ,

25. The compound of claim 20 or a pharmaceutically acceptable salt thereof, wherein Q is

26. The compound of claim 20 or a pharmaceutically acceptable salt thereof, wherein Q is:

wherein L 3 is selected from the group consisting of: ═O, —OR 5 , —NHR 5 , —SO 2 R 6 , —SO 2 R 7 , and —SO 2 R 8 , wherein R 5 is selected from the group consisting of: —SO 2 —(C 1 -C 6 )haloalkyl, —C(O)—(C 1 -C 6 )alkyl, —C(O)NH(C 1 -C 6 )alkyl, —SO 2 —(C 1 -C 6 )alkyl, and —(C 1 -C 6 )alkyl, and wherein R 6 is unsubstituted (C 5 -C 14 ) heteroaryl, and wherein R 7 is an unsubstituted heterocycloalkyl ring, and wherein R 8 is an unsubstituted cycloalkyl ring.

27. The compound of claim 26 or a pharmaceutically acceptable salt thereof, wherein L 3 is selected from the group consisting of: ═O, —OH, —NH 2 , —NHSO 2 CF 3 , —NHC(O)CH 3 , —NHC(O)NHCH 2 CH 3 , —NHSO 2 CH 3 , —NHSO 2 CH 2 CH 3 , —NHSO 2 CH 2 CH 2 CH 3 , —OCH 3 ,

28. The compound of claim 21 or a pharmaceutically acceptable salt thereof, wherein Q is:

wherein L 3 is selected from the group consisting of: ═O, —OR 5 , —NHR 5 , —SO 2 R 6 , —SO 2 R 7 , and —SO 2 R 8 , wherein R 5 is selected from the group consisting of: —SO 2 —(C 1 -C 6 )haloalkyl, —C(O)—(C 1 -C 6 )alkyl, —C(O)NH(C 1 -C 6 )alkyl, —SO 2 —(C 1 -C 6 )alkyl, and —(C 1 -C 6 )alkyl, and wherein R 6 is unsubstituted (C 5 -C 14 ) heteroaryl, and wherein R 7 is an unsubstituted heterocycloalkyl ring, and wherein R 8 is an unsubstituted cycloalkyl ring.

29. The compound of claim 28 or a pharmaceutically acceptable salt thereof, wherein L 3 is selected from the group consisting of: ═O, —OH, —NH 2 , —NHSO 2 CF 3 , —NHC(O)CH 3 , —NHC(O)NHCH 2 CH 3 , —NHSO 2 CH 3 , —NHSO 2 CH 2 CH 3 , —NHSO 2 CH 2 CH 2 CH 3 , —OCH 3 ,

30. The compound of claim 1 or a pharmaceutically acceptable salt thereof, having formula (IF.1A):

wherein Q is an unsubstituted cyclohexyl ring or, cyclohexyl substituted with one or more independently selected L 3 groups, unsubstituted heterocycloalkyl, and heterocycloalkyl substituted with one or more independently selected L 3 groups, and wherein Y is bound to the carbon atom common to the two fused rings and Y is selected from the group consisting of: —NHR 5 , —OH, and —OR 5 .

31. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein ring Q is:

32. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein ring Q is:

33. The compound of claim 20 or a pharmaceutically acceptable salt thereof, wherein ring Q is:

34. The compound of claim 20 or a pharmaceutically acceptable salt thereof, wherein ring Q is:

35. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein ring Q is a substituted cyclohexyl ring:

wherein L 3 is selected from the group consisting of: -alkylene-C(O)NH(C 1 to C 6 )alkyl, alkylene-C(O)N((C 1 to C 6 )alkyl) 2 wherein each alkyl is independently selected, -alkylene-C(O)NH(C 1 to C 6 )haloalkyl, and -alkylene-C(O)N((C 1 to C 6 )haloalkyl) 2 wherein each alkyl is independently selected.

36. The compound of claim 35 or a pharmaceutically acceptable salt thereof, wherein L 3 is selected from the group consisting of: —CH 2 C(O)NHC 2 H 5 , —CH 2 C(O)NHCH 3 , and —CH 2 C(O)NHCH 2 CF 3 .

37. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Q is a substituted cyclohexyl ring:

wherein L 3 is selected from the group consisting of: -alkylene-NHS(O) 2 —(C 1 -C 6 )alkyl, and -alkylene-NHS(O) 2 —(C 1 -C 6 )haloalkyl.

38. The compound of claim 37 or a pharmaceutically acceptable salt thereof, wherein L 3 is selected from the group consisting of: —CH 2 NHS(O) 2 CH 2 CH 3 and —CH 2 NHS(O) 2 CF 3.

39. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Q is a substituted cyclohexyl ring:

wherein L 3 is hydroxyl substituted alkyls.

40. The compound of claim 39 or a pharmaceutically acceptable salt thereof, wherein L 3 is selected from the group consisting of: —CH 2 CH(OH)CH 2 CH 3 and —CH 2 CH 2 CH(OH)CH 2 OH).

41. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Q is a substituted cyclohexyl ring:

wherein L 3 is -alkylene-S(O) 2 —(C 1 -C 6 )alkyl.

42. The compound of claim 41 or a pharmaceutically acceptable salt thereof, wherein L 3 is —CH 2 CH 2 SO 2 CH 2 CH 3 or —CH 2 CH 2 SO 2 CH 3 .

43. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Q is a substituted cyclohexyl ring:

wherein L 3 is -alkylene-C(O)—(C 1 -C 6 )alkyl.

44. The compound of claim 43 or a pharmaceutically acceptable salt thereof, wherein L 3 is —CH 2 CH 2 —C(O)—CH 3 .

45. The compound of claim 20 or a pharmaceutically acceptable salt thereof, wherein ring Q is a substituted cyclohexyl ring:

wherein L 3 is selected from the group consisting of: -alkylene-C(O)NH(C 1 to C 6 )alkyl, alkylene-C(O)N((C 1 to C 6 )alkyl) 2 wherein each alkyl is independently selected, -alkylene-C(O)NH(C 1 to C 6 )haloalkyl, and -alkylene-C(O)N((C 1 to C 6 )haloalkyl) 2 wherein each alkyl is independently selected.

46. The compound of claim 45 or a pharmaceutically acceptable salt thereof, wherein L 3 is selected from the group consisting of: —CH 2 C(O)NHC 2 H 6 , —CH 2 C(O)NHCH 3 , and —CH 2 C(O)NHCH 2 CF 3 .

47. The compound of claim 20 or a pharmaceutically acceptable salt thereof, wherein Q is a substituted cyclohexyl ring:

wherein L 3 is selected from the group consisting of: -alkylene-NHS(O) 2 —(C 1 -C 6 )alkyl, and -alkylene-NHS(O) 2 —(C 1 -C 6 )haloalkyl.

48. The compound of claim 47 or a pharmaceutically acceptable salt thereof, wherein L 3 is selected from the group consisting of: —CH 2 NHS(O) 2 CH 2 CH 3 and —CH 2 NHS(O) 2 CF 3.

49. The compound of claim 20 or a pharmaceutically acceptable salt thereof, wherein Q is a substituted cyclohexyl ring:

wherein L 3 is hydroxyl substituted alkyls.

50. The compound of claim 49 or a pharmaceutically acceptable salt thereof, wherein L 3 is selected from the group consisting of: —CH 2 CH(OH)CH 2 CH 3 and —CH 2 CH 2 CH(OH)CH 2 OH).

51. The compound of claim 20 or a pharmaceutically acceptable salt thereof, wherein Q is a substituted cyclohexyl ring:

wherein L 3 is selected from the group consisting of: -alkylene-S(O) 2 —(C 1 -C 6 )alkyl.

52. The compound of claim 51 or a pharmaceutically acceptable salt thereof, wherein L 3 is —CH 2 CH 2 SO 2 CH 2 CH 3 or —CH 2 CH 2 SO 2 CH 3 .

53. The compound of claim 20 or a pharmaceutically acceptable salt thereof, wherein Q is a substituted cyclohexyl ring:

wherein L 3 is -alkylene-C(O)—(C 1 -C 6 )alkyl.

54. The compound of claim 53 or a pharmaceutically acceptable salt thereof, wherein L 3 is —CH 2 CH 2 —C(O)—CH 3 .

55. The compound of claim 45 or a pharmaceutically acceptable salt thereof, wherein R 4 is H, L 1 is F, and Ar is phenyl substituted with Cl.

56. The compound of claim 47 or a pharmaceutically acceptable salt thereof, wherein R 4 is H, L 1 is F, and Ar is phenyl substituted with Cl.

57. The compound of claim 49 or a pharmaceutically acceptable salt thereof, wherein R 4 is H, L 1 is F, and Ar is phenyl substituted with Cl.

58. The compound of claim 51 or a pharmaceutically acceptable salt thereof, R 4 is H, L 1 is F, and Ar is phenyl substituted with Cl.

59. The compound of claim 53 or a pharmaceutically acceptable salt thereof, wherein R 4 is H, L 1 is F, and Ar is phenyl substituted with Cl.

60. The compound of claim 58 or a pharmaceutically acceptable salt thereof, wherein L 3 is selected from the group consisting of: —CH 2 C(O)NHC 2 H 5 , —CH 2 C(O)NHCH 3 and —CH 2 C(O)NHCH 2 CF 3 .

61. The compound of claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of the compounds

62. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein said compound is selected from the group consisting of

63. The compound of claim 1 or a pharmaceutically acceptable salt thereof in purified form.

64. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.