IP Library › Granted Patent US 8,093,237

Granted Patent B2

US 8,093,237 · App. 12/047,858 · Granted Jan 10, 2012

Dibenzo[b,f][1,4]oxazapine compounds

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Quick Facts

Patent No.: US 8,093,237
App. No.: 12/047,858
Granted: Jan 10, 2012
Kind: B2

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Abstract

The present invention relates to 11-(piperazin-1-yl)dibenzo[b,f][1,4 ]oxazapine compounds of the formula: where the variables are as defined herein, their salts and pharmaceutically acceptable compositions thereof. Methods of preparing these compounds are also described. These compounds may be used in the treatment of disorders such as schizophrenia, treatment resistant schizophrenia, bipolar disorder, psychotic depression, treatment resistant depression, schizophrenia-associated depression, treatment resistant OCD, autism, senile psychosis, psychotic dementia, L-DOPA induced psychosis, psychogenic polydipsia, psychotic symptoms of neurological disorders, sleep disorders.

Claims (345)

1. A compound having the structure

or a pharmaceutically acceptable salt thereof,

wherein

R 1 and R 2 are independently —Cl, —F, —Br, —I or —H;

R 3 is —(C 0 -C 6 alk)C(O)OR e , —(C 0 -C 6 alk)C(O)NR a 2 , —(C 0 -C 6 alk)C(O)NR a R 19 ,—(C 0 -C 6 alk)C(O)NR 19 2 , —(C 0 -C 6 alk)-C(O)NR 20 , —(C 0 -C 6 alk)Ar, —(C 0 -C 6 alk)-O—(C 0 -C 6 alk)Ar, —(C 0 -C 6 alk)-OR, —(C 0 -C 6 alk)C(O)R k , or —(C 0 -C 6 alk)-NR a R 19 ;

R 4 is —H or —R;

each R 5 , R 6 and R 7 is independently —R, —(C 0 -C 6 alk)-OR, —(C 0 -C 6 alk)-NR a R 19 , —NO 2 , -halogen, —CN, —OH, —(C 0 -C 6 alk)COOR e , —(C 0 -C 6 alk)C(O)NR a R 19 , —(C 0 -C 6 alk)Ar, —(C 0 -C 6 alk)-O—(C 0 -C 6 alk)Ar, —(C 0 -C 6 alk)Het, —(C 0 -C 6 alk)-O—(C 0 -C 6 alk)Het, —(C 0 -C 6 alk)Hca, —(C 0 -C 6 alk)-O—(C 0 -C 6 alk)Hca, —(C 0 -C 6 alk)Cak, —(C 0 -C 6 alk)-O—(C 0 -C 6 alk)Cak, —(C 0 -C 6 alk)C(O)Hca, —(C 0 -C 6 alk)C(O)Ar, —(C 0 -C 6 alk)C(O)Het, or —(C 0 -C 6 alk)C(O)Cak;

w is 0, 1, 2 or 3;

x is 0, 1, 2 or 3; and

y is 0, 1, 2 or 3;

in which

each R e is independently —H, —R, —(C 1 -C 6 alk)C(O)Hca, —(C 1 -C 6 alk) C(O)Cak, —(C 1 -C 6 alk)C(O)Het, —(C 1 -C 6 alk)C(O)Ar, —(C 1 -C 6 alk)C(O)O—Hca, —(C 1 -C 6 alk)C(O)O-Cak, —(C 1 -C 6 alk)C(O)O—Het, —(C 1 -C 6 alk)C(O)O—Ar, —(C 0 -C 6 alk) Hca, —(C 0 -C 6 alk) Het, —(C 0 -C 6 alk)Ar, —(C 0 -C 6 alk)Cak, —(C 1 -C 6 alk)C(O)OR, —(C 1 -C 6 alk)C(O)NR 19 2 , —(C 0 -C 6 alk)-OR, or —(C 0 -C 6 alk)-OH;

each R a is independently —H, —R, —(C 1 -C 6 alk)-OR, —(C 1 -C 6 alk)-OH, —(C 0 —C 6 alk)C(O)OR, —(C 1 -C 6 alk)-NR 19 2 , —(C 0 -C 6 alk)Hca, —(C 0 -C 6 alk)Ar, —(C 0 -C 6 alk)Het, or —(C 0 -C 6 alk)Cak;

each R k is independently —H, —R, —(C 1 -C 6 alk)C(O)Hca, —(C 1 -C 6 alk)C(O)Cak, —(C 1 -C 6 alk)C(O)Het, —(C 1 -C 6 alk)C(O)Ar, —(C 1 -C 6 alk)Hca, —(C 0 -C 6 alk)Het, —(C 0 -C 6 alk)Ar, —(C 0 -C 6 alk)Cak, —(C 1 -C 6 alk)C(O)OR, or —(C 1 -C 6 alk)C(O)NR 19 2 ;

each Cak is a cycloalkyl or cycloalkenyl group, optionally substituted with 1, 2 or 3 substituents independently selected from —R, —(C 0 -C 6 alk)C(O)OR, ═O, —OH, —CN, —(C 0 -C 6 alk)OR, —OCH 2 CH 2 —O—, —OCH 2 —O—, —SO 2 —R, —SO 2 —(C 1 -C 6 haloalkyl), —(C 0 -C 6 alk)C(O)NR 19 2 , —(C 0 -C 6 alk)Het, —SO 2 (C 0 -C 6 alk)-Hca, —(C 0 -C 6 alk)Ar, —(C 0 -C 6 alk)Het, —(C 0 -C 6 alk)Hca, —(C 0 -C 6 alk)C(O)R, —SO 2 (C 0 -C 6 alk)Ar, —SO 2 (C 0 -C 6 alk)Het, and —SO 2 (C 0 -C 6 alk)cycloalk,

each Ar is an aryl group, optionally substituted with 1, 2 or 3 substituents independently selected from —R, —OR, —(C 0 -C 6 alk)NR 19 2 , —NO 2 , —Cl, —F, —Br, —I, —CN, —(C 0 -C 6 alk)OH, —(C 0 -C 6 alk)C(O)OR, —(C 0 -C 6 alk)C(O)OH, —(C 1 -C 6 haloalkyl), —O(C 1 -C 6 haloalkyl), —(C 0 -C 6 alkyl)heterocycloalk, —SO 2 R, —(C 0 -C 6 alk)-C)(O)-heterocycloalk, —(C 0 -C 6 alk)-C(O)-cycloalk, —(C 0 -C 6 alkyl)-C(O)-heteroaryl, —(C 0 -C 6 alk)-C(O)-aryl, —(C 0 -C 6 alkyl)-C(O)O-heterocycloalk, —(C 0 -C 6 alk)-C(O)O-cycloalk, —(C 0 -C 6 alkyl)-C(O)O-heteroaryl, —(C 0 -C 6 alk)-C(O)O-aryl, —(C 0 -C 6 alk)-heterocycloalkyl, —(C 0 -C 6 alk)-heteroaryl, —(C 0 -C 6 alk)-aryl, and -(C 0 -C 6 alk)-cycloalk;

each Het is a heteroaryl group, optionally substituted with 1, 2 or 3 groups independently selected from —R, —OR, —(C 0 -C 6 alk)NR 19 2 , —NO 2 , —Cl, —F, —Br, —I, —CN, —(C 0 -C 6 alk)OH, —(C 0 -C 6 alk)CO 2 R, —(C 0 -C 6 alk)C(O)OH, —(C 1 -C 6 haloalkyl), -O(C 1 -C 6 haloalkyl), -(C 0 -C 6 alkyl)heterocycloalk, —SO 2 R, —(C 0 -C 6 alk)-C(O)-heterocycloalk, —(C 0 -C 6 alk)-C(O)-cycloalk, —(C 0 -C 6 alk)-C(O)-heteroaryl, —(C 0 -C 6 alk)-C(O)-aryl, —(C 0 -C 6 alk)-C(O)O- heterocycloalk, —(C 0 -C 6 alk)-C(O)O-cycloalk, —(C 0 -C 6 alk)-C(O)O-heteroaryl, —(C 0 -C 6 alk)-C(O)O-aryl, —(C 0 -C 6 alk)-heterocycloalkyl, —(C 0 -C 6 alk)-heteroaryl, —(C 0 -C 6 alk)-aryl, and -(C 0 -C 6 alk)-cycloalk;

each Hca is a heterocycloalk group, optionally substituted with 1, 2 or 3substituents independently selected from —R, —(C 1 -C 6 haloalkyl), —O(C 1 -C 6 haloalkyl), —(C 0 -C 6 alk)-C(O)OR, —(C 0 -C 6 alk)-C(O)R, ═O, —OH, —CN, —(C 0 -C 6 alk)OR, —OCH 2 CH 2 —O—, —OCH 2 O—, —SO 2 R, —SO 2 —(C 1 -C 6 haloalkyl), —(C 0 -C 6 alk)C(O)NR 19 2 , —(C 0 -C 6 alk)-heterocycloalk, —(C 0 -C 6 alk)-aryl, —(C 0 -C 6 alk)-heterocycloalk, —(C 0 -C 6 alk)-cycloalk, —SO 2 (C 0 -C 6 alk)-heterocycloalk, —SO 2 (C 0 -C 6 alk)-aryl, —SO 2 (C 0 -C 6 alk)-heteroaryl —SO 2 (C 0 -C 6 alkyl)heteroaryl, and —SO 2 (C 0 -C 6 alk)-cycloalk;

each R 19 is independently selected from —H, —OH and —R, in which any (C 1 -C 8 alk) or —(C 1 -C 8 haloalkyl) groups are optionally substituted with 1, 2 or 3substituents independently selected from ═O, —(C 1 -C 6 alkoxy), —OH, and -halogen;

each R 20 is a Hca or Het ring wherein that N from the —(C 0 -C 6 alk)-C(O)NR 20 is a heteroatom in the Hca or Het ring, the ring optionally substituted with 1 or 2 substituents independently selected from ═O, —(C 1 -C 6 alkoxy), —OH, -halogen, —(C 1 -C 6 haloalkyl), —SO 2 —(C 1 -C 6 alk), and -C(O)—(C 1 -C 6 alk),

each R is independently -(C 1 -C 8 alk), —(C 3 -C 8 cycloalk), —(C 3 -C 12 heterocycloalk), —(C 1 -C 8 haloalkyl), or —(C 3 -C 8 halocycloalk), optionally substituted with 1, 2 or 3 substituents independently selected from —(C 1 -C 6 alkoxy), —(C 1 -C 6 hydroxyalkyoxy), —(C 1 -C 6 hydroxyalkyl), acetoxyalkyl, —C(O)O(C 1 -C 6 alkyl), —OH, ═O, —N(C 1 -C 6 alkyl) 2 ,-NH(C 1 -C 6 alk), —NH 2 , —OC(O)(C 0 -C 6 alk), —SO 2 —(C 1 -C 6 alk), and —CO—(C 0 -C 6 alk); and

each (C 0 -C 6 alk), (C 1 -C 6 alk), and —(C 1 -C 8 alk) is independently optionally substituted with 1, 2, 3 or 4 substituents selected independently from -(C 1 -C 4 alkyl), —(C 1 -C 4 alkoxy), —OH, ═O, -halogen, —C(O)O(C 1 -C 3 alkyl) and —C(O)(C 1 -C 3 alkyl).

2. A compound according to claim 1 , wherein R 3 is —(C 0 -C 6 alk)C(O)OR e , —(C 0 -C 6 alk)C(O)NR a 2 , —(C 0 -C 6 -alk)C(O)NR a R 19 , —(C 0 -C 6 alk)C(O)NR 19 2 , or —(C 0 -C 6 alk)-C(O)NR 20 .

3. A compound according to claim 2 , wherein R 3 is —(C 0 -C 6 alk)C(O)OR e .

4. A compound or salt according to claim 3 , wherein each alk group is an alkyl group.

5. A compound or salt according to claim 3 , wherein at least one of R 1 and R 2 is —F, —Cl, —Br or —I.

6. A compound or salt according to claim 3 , wherein both x and y are 0.

7. A compound or salt according to claim 3 , wherein all of w, x and y are 0.

8. A compound or salt according to claim 3 having S configuration at the carbon of attachment of the R 3 group.

9. A compound or salt according to claim 3 having R configuration at the carbon of attachment of the R 3 group.

10. The compound or salt according to claim 3 having a mixture of configurations at the carbon of attachment of the R 3 group.

11. A compound or salt according to claim 3 , wherein all of w, x and y are 0 and R 4 is —H.

12. A compound or salt according to claim 1 , wherein

R 1 and R 2 are independently —Cl, —F, —Br, —I or —H, with the proviso that at least one of R 1 and R 2 is —Cl, —F, —Br or —I;

R 3 is —(C 0 -C 6 alk)C(O)OR e , —(C 0 -C 6 alk)C(O)NR a 2 , or —(C 0 -C 6 -alk)C(O)NR a R 19 ;

R 4 is —H or —R;

each R 5 , R 6 , and R 7 is independently —R, —OR, —NR a R 19 , —NO 2 , —F, —Br, —I, —CN, —OH, —(C 0 -C 6 alkyl)C(O)OR e , —(C 0 -C 6 alkyl)C(O)NR a R 19 , or —(C 0 -C 6 alkyl)C(O)NR a R 19 ; and

w, x and y are independently 0, 1 or 2;

in which

each R e is independently —H or —R,

each R a is independently —H or —R,

each R 19 is independently —H or —R,

each Ar is independently phenyl optionally substituted with 1, 2 or 3 substituents selected from —R, —OR, —NR 2 , —NO 2 , —Cl, —F, —Br, —I, —CN, —OH, —C(O)OR, —(C 1 -C 6 haloalkyl) and —O(C 1 -C 6 haloalkyl),

each R is independently —(C 1 -C 8 alkyl), —(C 3 -C 8 cycloalkyl), —(C 3 -C 12 heterocycloalk), —(C 1 -C 8 fluoroalkyl), —(C 3 -C 8 fluorocycloalk), —(C 1 -C 8 chloroalkyl), or —(C 3 -C 8 chlorocycloalk), wherein the —(C 1 -C 6 fluoroalkyl), —(C 3 -C 8 fluorocycloalk), —(C 1 -C 6 chloroalkyl), or —(C 3 -C 8 chlorocycloalk) may be substituted with from 1 to 6 fluorines or chlorines, respectively, each R optionally substituted with 1, 2 or 3 substituents selected from —(C 1 -C 6 alkoxy), —(C 1 -C 6 hydroxyalkyl), acetoxyalkyl, and —C(O)O(C 1 -C 4 alkyl).

13. A compound or salt according to claim 12 , wherein each alk group is an alkyl group.

14. A compound or salt according to claim 12 , wherein R 3 is —(C 0 -C 6 alkyl)C(O)OR e .

15. A compound or salt according to claim 14 , wherein R e is —H, -Me, -Et, -Pr or -Bu.

16. A compound or salt according to claim 12 having S configuration at the carbon of attachment of the R 3 group.

17. A compound or salt according to claim 12 having R configuration at the carbon of attachment of the R 3 group.

18. A compound or salt according to claim 12 having a mixture of configurations at the carbon of attachment of the R 3 group.

19. A compound or salt according to claim 12 , wherein R 4 is —H.

20. A compound or salt according to claim 12 , wherein w, x and y are each 0.

21. A compound or salt according to claim 1 , having the structure:

wherein,

R 1 and R 2 are independently —Cl, —F, —Br, —I or —H, with the proviso that at least one of R 1 and R 2 is —Cl, —F, —Br or —I;

R 4 is —H or —R;

R 8 is —H, -Me, -Et or -Pr;

R 9 is —H, -Me, -Et or -Pr;

B is O or NH, and

R 12 is —H, -Me, -Et or -Pr.

22. A compound or salt according to claim 21 , wherein B is O.

23. A compound or salt according to claim 1 , wherein the compound is

(E)-ethyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

(E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-isobutylacetamide;

(E)-ethyl2-(4-(2-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate *(S) or (R) at stereocenter;

(R,E)-methyl4-((4-(2-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)methoxy)benzoate;

(E)-2-(4-(8-chlorodibenzo[b,j][1,4]oxazepin-11-yl)piperazin-2-yl)acetic acid;

(E)-ethyl4-(2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)ethyl)benzoate;

(E)-methyl4-((4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)methoxy)benzoate;

(E)-ethyl2-(4-(7-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

(E)-methyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

(E)-ethyl2-(4-(7-fluorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

(S,E)-ethyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

(E)-isopropyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

(E)-isopropyl2-(4-(7-fluorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

(S,E)-methyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

(R,E)-ethyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

(R,E)-methyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

(S,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetic acid;

(R)-2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)propanoic acid;

(S)-2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)propanoic acid;

(R)-2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)butanoic acid;

(S)-2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)butanoic acid;

(S,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-methylpropanoic acid;

(S,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-ethylbutanoic acid;

(R,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetic acid;

(R)-2-((R)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)propanoic acid;

(S)-2-((R)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)propanoic acid;

(R)-2-((R)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)butanoic acid;

(S)-2-((R)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)butanoic acid;

(R,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-methylpropanoic acid;

(R,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-ethylbutanoic acid;

(2R)-2-(4-((E)-2-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)propanoic acid;

(2S)-2-(4-((E)-2-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)propanoic acid;

(2R)-2-(4-((E)-2-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)butanoic acid;

(2S)-2-(4-((E)-2-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)butanoic acid;

(E)-2-(4-(2-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-methylpropanoic acid;

(E)-2-(4-(2-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-ethylbutanoic acid;

(E)-ethyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)propanoate;

(E)-ethyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)butanoate;

(E)-ethyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)pentanoate;

(E)-ethyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-methylpropanoate;

(E)-ethyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-ethylbutanoate;

(E)-ethyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-y)piperazin-2-yl)-2-methylbutanoate;

(2R)-ethyl2-(4-((E)-2-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)propanoate;

(2S)-ethyl2-(4-((E)-2-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)propanoate;

(2R)-ethyl2-(4-((E)-2-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)butanoate;

(2S)-ethyl2-(4-((E)-2-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)butanoate;

(E)-ethyl2-(4-(2-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-methylpropanoate;

(E)-ethyl2-(4-(2-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-ethylbutanoate;

(R)-ethyl2-((R)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)propanoate;

(S)-ethyl2-((R)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)propanoate;

(R)-ethyl2-((R)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)butanoate;

(S)-ethyl2-((R)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)butanoate;

(R,E)-ethyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-methylpropanoate;

(R,E)-ethyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-ethylbutanoate;

(S)-ethyl2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)propanoate;

(R)-ethyl2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)propanoate;

(S)-ethyl2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)butanoate;

(R)-ethyl2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)butanoate;

(S,E)-ethyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-methylpropanoate;

(S,E)-ethyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-ethylbutanoate;

(E)-methyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)propanoate;

(E)-methyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)butanoate;

(E)-methyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)pentanoate;

(E)-methyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-methylpropanoate;

(E)-methyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-ethylbutanoate;

(E)-methyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-methylbutano ate;

(E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)propanoic acid;

(E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)butanoic acid;

(E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)pentanoic acid;

(E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-methylpropanoic acid;

(E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-ethylbutanoic acid;

(E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-methylbutanoic acid;

(R)-methyl2-((R)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)propanoate;

(S)-methyl2-((R)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)propanoate;

(R)-methyl2-((R)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)butanoate;

(S)-methyl2-((R)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)butanoate;

(R,E)-methyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-methylpropanoate;

(R,E)-methyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-ethylbutanoate;

(S)-methyl2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)propanoate;

(R)-methyl2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)propanoate;

(R)-methyl2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)butanoate;

(S)-methyl2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)butanoate;

(S,E)-methyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-methylpropanoate;

(S,E)-methyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-ethylbutanoate;

(E)-methyl2-((4-(2-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-1-methylpiperazin-2-yl)methoxy)acetate;

(E)-ethyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-1-methylpiperazin-2-yl)acetate;

(E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-11-methylpiperazin-2-yl)acetic acid;

(E)-methyl2-(4-(8-(trifluoromethyl)dibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

(S,E)-cyclopentyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

(S)-quinuclidin-3-yl2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-1-methylpiperazin-2-yl)acetate;

(R)-quinuclidin-3-yl2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

(S)-quinuclidin-3-yl2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

(S,E)-tetrahydro-2H-pyran-4-yl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

(S,E)-methyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-1-methylpiperazin-2-yl)acetate;

(S,E)-cyclopentyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-1-methylpiperazin-2-yl)acetate;

sec-butyl2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-1-methylpiperazin-2-yl)acetate;

(S,E)-tetrahydro-2H-pyran-4-yl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-1-methylpiperazin-2-yl)acetate;

(S,E)-neopentyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

(S,E)-3-methoxy-3-methylbutyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

(S,E)-3-hydroxy-3-methylbutyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

(R)-4-hydroxy-4-methylpentan-2-yl2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

(S)-((R)-4-hydroxy-4-methylpentan-2-yl)2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)propanoate;

(R)(R)-4-hydroxy-4-methylpentan-2-yl)2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)propanoate;

(S)-((R)-4-hydroxy-4-methylpentan-2-yl)2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)butanoate;

(R)-((R)-4-hydroxy-4-methylpentan-2-yl)2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)butanoate;

(R)-4-hydroxy-4-methylpentan-2-yl2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-methylpropanoate;

(R)-4-hydroxy-4-methylpentan-2-yl2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-ethylbutanoate;

(2S,4S)-4-hydroxypentan-2-yl2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

sec-butyl2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

(S)-tetrahydrofuran-3-yl2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

(S,E)-ethyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-1-isopentylpiperazin-2-yl)acetate;

(R)-1-methylpyrrolidin-3-yl2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-1-methylpiperazin-2-yl)acetate;

(S,E)-methyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-1-(cyclopropylmethyl)piperazin-2-yl)acetate;

(S,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-1-methylpiperazin-2-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide;

(S,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-1-methylpiperazin-2-yl)-N-(1,3-difluoropropan-2-yl)acetamide;

(S,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-1-methylpiperazin-2-yl)-N,N-bis(2,2,2-trifluoroethypacetamide;

(S,E)-3-fluoropropyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-1-methylpiperazin-2-yl)acetate;

(S,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-(1-hydroxy-2-methylpropan-2-yl)acetamide;

(S,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-(2-hydroxyethyl)-N-propylacetamide;

(S,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-(2-hydroxyethyl)acetamide;

2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-((R)-2-hydroxypropyl)acetamide;

(S,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-(2-methoxyethypacetamide;

(R)-2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-(2-methoxyethyl)propanamide;

(S)-2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-(2-methoxyethyl)propanamide;

(R)-2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-(2-methoxyethyl)butanamide;

(S)-2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-2-methoxyethyl)butanamide;

(S,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-(2-methoxyethyl)-2-methylpropanamide;

(S,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-ethyl-N-(2-methoxyethyl)butanamide;

(S,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-(2-(2-hydroxyethoxy)ethyl)acetamide;

(S,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-(2-hydroxyethyl)-N-methylacetamide;

(S,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-(6-methoxypyridin-3-yl)acetamide;

(S,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-(2,2-difluoroethyl)acetamide;

2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-(((S)-tetrahydrofuran-2-yl)methypacetamide;

(S,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-(3-hydroxypropyl)acetamide;

(R)-2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-(3-hydroxypropyl)propanamide;

(S)-2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-(3-hydroxypropyl)propanamide;

(R)-2((S)-4((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-(3-hydroxypropyl)butanamide;

(S)-2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-(3-hydroxypropyl)butanamide;

(S,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-(3-hydroxypropyl)-2-methylpropanarnide;

(S,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-2-ethyl-N-(3-hydroxypropyl)butanamide;

(S,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-(3-methoxypropyl)acetamide;

2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-1-((R)-3-hydroxypyrrolidin-1-yl)ethanone;

2((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-N-(3,3,3-trifluoro-2-hydroxypropyl)acetamide;

(S,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-1-morpholinoethanone;

2-((S)-4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)-1-((S)-2-(trifluoromethyl)pyrrolidin-1-yl)ethanone; or (S,E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-1-(2-hydroxyethyl)piperazin-2-yl)-N-(2-methoxyethypacetamide.

24. A compound or salt according to claim 1 , wherein the compound is

(E)-ethyl2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetate;

(E)-2-(4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetic acid;