Substituted Sulfonamide Compounds

• US 20080249128A1
• Filed: 10/16/2007
• Published: 10/09/2008
• Est. Priority Date: 10/16/2006
• Status: Active Grant

• Current Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Original Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Inventors: Reich, Melanie, Schiene, Klaus, Jostock, Ruth, Schunk, Stefan, Engels, Michael, Christoph, Thomas, Germann, Tieno, Hees, Sabine, OBERBOERSCH, Stefan, Kless, Achim, Bijsterveld, Edward
• Granted Patent: US 8,580,965 B2
• Time in Patent Office: Days
• US Class Current: 514/309
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 211/38 Halogen atoms or nitro radicals
• CPC Class Codes: C07D 211/52 having an aryl radical as the second substituent in position 4
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links

Abstract

Substituted sulfonamide compounds with bradykinin receptor (B1R) modulating activity; processes for the preparation thereof, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat or inhibit pain and/or other disorders and/or disease states.

Claims

1. A substituted sulfonamide derivative of the general formula I

2. A compound according to claim 1, wherein said compound is in the form of a pure enantiomer or diastereomer.

3. A compound according to claim 1, wherein said compound is in the form of a racemic mixture.

4. A compound according to claim 1, wherein

m represents 0, 1, 2 or 3

n represents 1 or 2

p represents 0, 1 or 2,

R¹ represents aryl or heteroaryl, unsubstituted or mono- or poly-substituted, optionally linked via a C_1-3-alkyl chain,

R² represents OH, OC_1-6-alkyl or F,

R³ represents aryl or heteroaryl, in each case unsubstituted or mono- or poly-substituted;

R⁴ and R^4a independently of one another represent H, C_1-6-alkyl, in each case saturated or unsaturated, branched or unbranched, unsubstituted or mono- or poly-substituted;

F;

Cl;

aryl, in each case unsubstituted or mono- or poly-substituted;

or aryl linked via a C_1-3-alkyl chain and in each case unsubstituted or mono- or poly-substituted;

Z represents O, CH₂ or NR^N, wherein R^N denotes H;

C_1-6-alkyl;

phenyl or benzyl, in each case unsubstituted or mono- or poly-substituted;

R⁵ and R^5a independently of one another represent H;

or Cl_1-6-alkyl, in each case saturated or unsaturated, branched or unbranched, unsubstituted or mono- or poly-substituted;

OH, OC_1-6-alkyl, F, Cl, phenoxy or benzyloxy;

R⁶ represents H;

C_1-6-alkyl, in each case saturated or unsaturated, branched or unbranched, unsubstituted or mono- or poly-substituted;

C_3-8-cycloalkyl, saturated or unsaturated, unsubstituted or mono- or poly-substituted;

aryl or heteroaryl, unsubstituted or mono- or poly-substituted;

aryl or C_3-8-cycloalkyl linked via a C_1-3-alkyl chain;

or together with Q, including the adjacent nitrogen, forms a four-, five-, six- or seven-membered ring, which can be saturated or unsaturated and can contain a further heteroatom O, S or N, on to which a further five- or six-membered ring, saturated or unsaturated, can be fused;

wherein in the case of the common ring closure Q represents

5. A compound according to claim 1, wherein R¹ denotes thienyl, phenyl, benzyl, phenethyl, pyridyl, or pyridyl linked via a —

CH₂—

or —

CH₂—

CH₂—

chain, in each case unsubstituted or mono- or poly-substituted.

6. A compound according to claim 1, wherein R³ denotes phenyl, naphthyl, thienyl or benzothiophene, in each case unsubstituted or mono- or poly-substituted.

7. A compound according to claim 1, wherein

R⁶ denotes H, methyl, ethyl, n-propyl, isobutyl, cyclopropyl, cyclopropyl linked via a C_1-3-alkyl chain, or benzyl, and

Q represents a single bond.

8. A compound according to claim 1, wherein

9. A compound according to claim 1, wherein Q denotes

10. A compound according to claim 1, wherein Z represents O or CH.

11. A compound according to claim 1, wherein p represents 1.

12. A compound according to claim 1, wherein R⁴ and R^4a each represent H.

13. A compound according to claim 1, wherein R⁵ and R^5a each represent H.

14. A compound according to claim 1, wherein

m represents 1,

n represents 1 or 2

R⁴, R^4a, R⁵ and R^5a each represent H, and

Z represents O;

or

m represents 0,

Z represents O or CH₂,

n represents 1 or 2, and

R⁴ and R^4a each represent H;

or

m represents 2,

Z represents O,

n represents 1, and

R⁴, R^4a, R⁵ and R^5a each represent H,

or

m represents 1 or 2,

Z represents CH₂,

n represents 1, and

R⁴, R^4a, R⁵ and R^5a each represent H.

15. A compound according to claim 1, wherein R¹ is selected from the group consisting of 2-pyridinyl, 3-pyridinyl, 4-pyridinyl,

16. A compound according to claim 15, wherein

R¹ is 3-pyridinyl, 4-pyridinyl,

17. A compound according to claim 1, wherein R² denotes OH.

18. A compound according to claim 1, wherein R³ denotes 2,6-dimethyl-4-methoxyphenyl.

19. A compound according to claim 1, selected from the group consisting of:

1 N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxy]-ethyl}-N-ethyl-4-methoxy-2,3,6-trimethyl-phenylsulfonamide

2 2,4,6-trichloro-N-{2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[3,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-N-methyl-phenylsulfonamide

3 N-(2-(2-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide hydrochloride

4 N-{2-[2-(4′

-hydroxy-3,4′

,5′

,6-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-4-methoxy-2,6,N-trimethyl-phenylsulfonamide

5 2,4,6-trichloro-N-(2-(2-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N-methylphenylsulfonamide hydrochloride

6 2,4,6-trichloro-N-{2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-N-methyl-phenylsulfonamide

7 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-[1-(4-methoxy-2,3,6-trimethyl-phenylsulfonyl)-pyrrolidin-3-yloxy]-ethanone

8 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-[1-(4-methoxy-2,3,6-trimethyl-phenylsulfonyl)-piperidin-4-yloxy]-ethanone

9 N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxy]-ethyl}-2,4,6-trichloro-N-methyl-phenylsulfonamide

10 2,6-dichloro-N-{2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-N-methyl-phenylsulfonamide

11 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-[1-(4-methoxy-2,3,6-trimethyl-phenylsulfonyl)-piperidin-3-yloxy]-ethanone

12 2-[1-(3,4-dichloro-phenylsulfonyl)-piperidin-2-ylmethoxy]-1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[3,4′

]bipyridinyl-1′

-yl)-ethanone

13 N-benzyl-N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxy]-ethyl}-4-methoxy-2,3,6-trimethyl-phenylsulfonamide

14 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-{2-[1-(4-methoxy-2,3,6-trimethyl-phenylsulfonyl)-piperidin-4-yl]-ethoxy}-ethanone

15 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-[1-(4-fluoro-phenylsulfonyl)-pyrrolidin-3-yloxy]-ethanone

16 N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxy]-ethyl}-3,4-dimethoxy-N-methyl-phenylsulfonamide

17 2-[1-(2,4-dichloro-phenylsulfonyl)-pyrrolidin-3-yloxy]-1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-ethanone

18 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-{2-[4-(4-methoxy-2,3,6-trimethyl-phenylsulfonyl)-piperazin-1-yl]-ethoxy}-ethanone

19 2-[1-(3,4-dichloro-phenylsulfonyl)-pyrrolidin-2-ylmethoxy]-1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[3,4′

]bipyridinyl-1′

-yl)-ethanone

20 N-{2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-N-methyl-4-trifluoromethoxy-phenylsulfonamide

21 1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-[1-(4-methoxy-2,6-dimethyl-phenylsulfonyl)-pyrrolidin-3-yloxy]-ethanone

22 2-(1-phenylsulfonyl-pyrrolidin-3-yloxy)-1-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethanone

23 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-[2-(4-methoxy-phenylsulfonyl)-1,2,3,4-tetrahydro-isoquinolin-3-ylmethoxy]-ethanone

24 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-[1-(toluene-4-sulfonyl)-pyrrolidin-3-yloxy]-ethanone

25 2-[1-(3,4-dichloro-phenylsulfonyl)-piperidin-2-ylmethoxy]-1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-ethanone

26 1-(4-hydroxy-3,4,5,6-tetrahydro-2H-[4,4′

]bipyridinyl-1-yl)-2-[1-(4-methoxy-phenylsulfonyl)-pyrrolidin-2-ylmethoxy]-ethanone

27 2-(1-phenylsulfonyl-piperidin-3-yloxy)-1-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethanone

28 N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxy]-ethyl}-4-methoxy-N-methyl-phenylsulfonamide

29 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-{2-[1-(4-methoxy-phenylsulfonyl)-piperidin-2-yl]-ethoxy}-ethanone

30 1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-[1-(2,4,6-trimethyl-phenylsulfonyl)-pyrrolidin-3-yloxy]-ethanone

31 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-[1-(4-chloro-phenylsulfonyl)-pyrrolidin-3-yloxy]-ethanone

32 2-[2-(4-phenylsulfonyl-piperazin-1-yl)-ethoxy]-1-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethanone

33 N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxy]-phenyl}-3,4-dichloro-N-methyl-phenylsulfonamide

34 2-(1-phenylsulfonyl-pyrrolidin-3-yloxy)-1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-ethanone

35 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-[1-(4-methoxy-phenylsulfonyl)-piperidin-2-ylmethoxy]-ethanone

36 2-[1-(3,4-dichloro-phenylsulfonyl)-pyrrolidin-2-ylmethoxy]-1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-ethanone

37 2-(1-phenylsulfonyl-piperidin-4-yloxy)-1-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethanone

38 N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxy]-ethyl}-N-methyl-3-trifluoromethyl-phenylsulfonamide

39 N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxy]-ethyl}-N-methyl-phenylsulfonamide

40 1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-[1-(4-methoxy-phenylsulfonyl)-pyrrolidin-2-ylmethoxy]-ethanone

41 N-{2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-3,4-dimethoxy-N-methyl-phenylsulfonamide

42 N-{2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-4-methoxy-N-methyl-phenylsulfonamide

43 N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxy]-cyclohexyl}-3,4-dichloro-N-methyl-phenylsulfonamide

44 1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-{2-[1-(4-methoxy-phenylsulfonyl)-piperidin-2-yl]-ethoxy}-ethanone

45 1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-{2-[1-(4-methoxy-2,3,6-trimethyl-phenylsulfonyl)-piperidin-4-yl]-ethoxy}-ethanone

46 2-(1-phenylsulfonyl-piperidin-4-yloxy)-1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[3,4′

]bipyridinyl-1′

-yl)-ethanone

47 1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[3,4′

]bipyridinyl-1′

-yl)-2-{2-[4-(4-methoxy-2,3,6-trimethyl-phenylsulfonyl)-piperazin-1-yl]-ethoxy}-ethanone

48 1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-{2-[4-(4-methoxy-2,3,6-trimethyl-phenylsulfonyl)-piperazin-1-yl]-ethoxy}-ethanone

49 2-[2-(4-phenylsulfonyl-piperazin-1-yl)-ethoxy]-1-(4-hydroxy-3,4,5,6-tetrahydro-2H-[4,4′

]bipyridinyl-1-yl)-ethanone

50 1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-[2-(4-methoxy-phenylsulfonyl)-1,2,3,4-tetrahydro-isoquinolin-3-ylmethoxy]-ethanone

51 2-(1-phenylsulfonyl-piperidin-3-yloxy)-1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-ethanone

52 2-[1-(3,4-dimethoxy-phenylsulfonyl)-pyrrolidin-3-yloxy]-1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-ethanone

53 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-[1-(4-chloro-phenylsulfonyl)-piperidin-2-ylmethoxy]-ethanone

54 2-(1-phenylsulfonyl-piperidin-4-yloxy)-1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-ethanone

55 1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-[1-(4-methoxy-2,3,6-trimethyl-phenylsulfonyl)-piperidin-3-yloxy]-ethanone

56 4-fluoro-N-{2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-N-methyl-phenylsulfonamide

57 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-[1-(4-methoxy-phenylsulfonyl)-pyrrolidin-2-ylmethoxy]-ethanone

58 2-[1-(4-fluoro-phenylsulfonyl)-pyrrolidin-3-yloxy]-1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-ethanone

59 1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-[1-(3-trifluoromethyl-phenylsulfonyl)-pyrrolidin-3-yloxy]-ethanone

60 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-[1-(2,4-dimethoxy-phenylsulfonyl)-piperidin-2-ylmethoxy]-ethanone

61 N-(2-(2-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-5-fluoro-N,2-dimethylphenylsulfonamide

62 N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxy]-ethyl}-5-fluoro-2,N-dimethyl-phenylsulfonamide

63 1-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-((1-(naphthalen-1-ylsulfonyl)piperidin-2-yl)methoxy)ethanone

64 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-[1-(naphthalene-1-sulfonyl)-piperidin-2-ylmethoxy]-ethanone

65 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-[1-(3-trifluoromethyl-phenylsulfonyl)-piperidin-2-ylmethoxy]-ethanone

66 1-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-((1-(mesitylsulfonyl)piperidin-2-yl)methoxy)ethanone

67 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-[1-(2,4,6-trimethyl-phenylsulfonyl)-piperidin-2-ylmethoxy]-ethanone

68 1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[3,4′

]bipyridinyl-1′

-yl)-2-[1-(2,4,6-trimethyl-phenylsulfonyl)-piperidin-2-ylmethoxy]-ethanone

69 N-benzyl-N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxymethyl]-thiophen-3-yl}-3,4-dichloro-phenylsulfonamide

70 3,5-difluoro-N-{2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-N-methyl-phenylsulfonamide

71 2,5-difluoro-N-{2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-N-methyl-phenylsulfonamide

72 2-[2-(4-fluoro-phenylsulfonyl)-1,2,3,4-tetrahydro-isoquinolin-3-ylmethoxy]-1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-ethanone

73 2-(2-phenylsulfonyl-1,2,3,4-tetrahydro-isoquinolin-3-ylmethoxy)-1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-ethanone

74 1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-[1-(4-methoxy-phenylsulfonyl)-4-phenyl-piperidin-4-yloxy]-ethanone

75 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-[2-(4-fluoro-phenylsulfonyl)-1,2,3,4-tetrahydro-isoquinolin-3-ylmethoxy]-ethanone

76 2-((2-(3,4-dichlorophenylsulfonyl)-1,2,3,4-tetrahydroisoquinolin-3-yl)methoxy)-1-(4-hydroxy-4-phenylpiperidin-1-yl)ethanone

77 2-(2-phenylsulfonyl-1,2,3,4-tetrahydro-isoquinolin-3-ylmethoxy)-1-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethanone

78 2-((2-(3,4-dichlorophenylsulfonyl)-1,2,3,4-tetrahydroisoquinolin-3-yl)methoxy)-1-(4-hydroxy-4-phenylpiperidin-1-yl)ethanone

79 1-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-((2-(2,4-dichlorophenylsulfonyl)-1,2,3,4-tetrahydroisoquinolin-3-yl)methoxy)ethanone

80 2-((2-(2,4-dichlorophenylsulfonyl)-1,2,3,4-tetrahydroisoquinolin-3-yl)methoxy)-1-(4-hydroxy-4-phenylpiperidin-1-yl)ethanone

81 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-[2-(2,4-dichloro-phenylsulfonyl)-1,2,3,4-tetrahydro-isoquinolin-3-ylmethoxy]-ethanone

82 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-[1-(4-methoxy-phenylsulfonyl)-4-phenyl-piperidin-4-yloxy]-ethanone

83 N-benzyl-3,4-dichloro-N-(2-(2-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)cyclohexyl)phenylsulfonamide

84 N-benzyl-N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxy]-cyclohexyl}-3,4-dichloro-phenylsulfonamide

85 1-(4-hydroxy-4-thiophen-2-yl-piperidin-1-yl)-2-[1-(4-methoxy-2,6-dimethyl-phenylsulfonyl)-piperidin-2-ylmethoxy]-ethanone

86 N-{2-[2-(4-hydroxy-4-thiophen-2-yl-piperidin-1-yl)-2-oxo-ethoxy]-ethyl}-4-methoxy-2,6,N-trimethyl-phenylsulfonamide

87 1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[3,4′

]bipyridinyl-1′

-yl)-2-[1-(4-methoxy-2,6-dimethyl-phenylsulfonyl)-piperidin-2-ylmethoxy]-ethanone;

hydrochloride

88 N-{2-[2-(4-hydroxy-3,4,5,6-tetrahydro-2H-[4,4′

]bipyridinyl-1-yl)-2-oxo-ethoxy]-ethyl}-4-methoxy-2,6,N-trimethyl-phenylsulfonamide

89 1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[3,4′

]bipyridinyl-1′

-yl)-2-[1-(4-methoxy-2,6-dimethyl-phenylsulfonyl)-pyrrolidin-2-ylmethoxy]-ethanone;

hydrochloride

90 2-(2-phenylsulfonyl-1,2,3,4-tetrahydro-isoquinolin-3-ylmethoxy)-1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[3,4′

]bipyridinyl-1′

-yl)-ethanone

91 2-[2-(3,4-dichloro-phenylsulfonyl)-1,2,3,4-tetrahydro-isoquinolin-3-ylmethoxy]-1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[3,4′

]bipyridinyl-1′

-yl)-ethanone

92 2-[2-(2,4-dichloro-phenylsulfonyl)-1,2,3,4-tetrahydro-isoquinolin-3-ylmethoxy]-1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[3,4′

]bipyridinyl-1′

-yl)-ethanone

93 N-(2-(2-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-3,5-difluoro-N-methylphenylsulfonamide

94 1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-[1-(2,4,6-trimethyl-phenylsulfonyl)-piperidin-2-ylmethoxy]-ethanone

95 N-benzyl-3,4-dichloro-N-{2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-cyclohexyl}-phenylsulfonamide

96 1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-[1-(3-trifluoromethyl-phenylsulfonyl)-piperidin-2-ylmethoxy]-ethanone

97 5-fluoro-N-{2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-2,N-dimethyl-phenylsulfonamide

98 1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-[1-(2,4,6-trichloro-phenylsulfonyl)-pyrrolidin-3-yloxy]-ethanone

99 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-[1-(3,4-dichloro-phenylsulfonyl)-2,3-dihydro-1H-indol-2-ylmethoxy]-ethanone

100 2-[1-(3,4-dichloro-phenylsulfonyl)-2,3-dihydro-1H-indol-2-ylmethoxy]-1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[3,4′

]bipyridinyl-1′

-yl)-ethanone

101 1-(4-hydroxy-4-phenylpiperidin-1-yl)-2-((2-(mesitylsulfonyl)-1,2,3,4-tetrahydroisoquinolin-3-yl)methoxy)ethanone

102 5-chloro-thiophene-2-sulfonic acid {2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[3,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-methyl-amide

103 5-chloro-thiophene-2-sulfonic acid {2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-methyl-amide

104 2,4-dichloro-N-(2-(2-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N,6-dimethylphenylsulfonamide

105 2,4-dichloro-N-(2-(2-(4-hydroxy-4-phenylpiperidin-1-yl)-2-oxoethoxy)ethyl)-N,6-dimethylphenylsulfonamide

106 N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxy]-ethyl}-2,4-dichloro-6,N-dimethyl-phenylsulfonamide

107 1-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-(1-(2,4,6-trichlorophenylsulfonyl)pyrrolidin-3-yloxy)ethanone

108 1-(4-hydroxy-4-phenylpiperidin-1-yl)-2-(1-(2,4,6-trichlorophenylsulfonyl)pyrrolidin-3-yloxy)ethanone

109 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-[1-(2,4,6-trichloro-phenylsulfonyl)-pyrrolidin-3-yloxy]-ethanone

111 3-(1-(4-chloro-2,5-dimethylphenylsulfonyl)piperidin-2-yl)-1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)propan-1-one hydrochloride

112 1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-3-(1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)propan-1-one

113 4-chloro-N-(4-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-4-oxobutyl)-N,2,5-trimethylphenylsulfonamide hydrochloride

114 N-(4-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-4-oxobutyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

115 N-(4-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-4-oxobutyl)-N-methylnaphthalene-2-sulfonamide

116 2,4-dichloro-N-(4-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-4-oxobutyl)-N-methylphenylsulfonamide

117 1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-3-(1-(naphthalen-2-ylsulfonyl)piperidin-2-yl)propan-1-one

118 3-(1-(2,4-dichlorophenylsulfonyl)piperidin-2-yl)-1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)propan-1-one

119 3-(1-(4-chloro-2,5-dimethylphenylsulfonyl)piperidin-2-yl)-1-(4-hydroxy-4-(pyridin-2-yl)piperidin-1-yl)propan-1-one

120 3-(1-(4-chloro-2,5-dimethylphenylsulfonyl)piperidin-2-yl)-1-(4-(3-fluorophenyl)-4-hydroxypiperidin-1-yl)propan-1-one

121 N-(5-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-5-oxopentyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

122 3-(1-(4-chloro-2,5-dimethylphenylsulfonyl)piperidin-2-yl)-1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)propan-1-one

123 1-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-3-(1-(3-(trifluoromethyl)phenylsulfonyl)piperidin-2-yl)propan-1-one

124 3,4-dichloro-N-(2-(3-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-3-oxopropyl)phenyl)-N-methylphenylsulfonamide

125 3,4-dichloro-N-(2-(3-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-3-oxopropyl)phenyl)-N-methylphenylsulfonamide

127 1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)ethanone

128 (S)-1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-((2-(4-methoxy-2,6-dimethylphenylsulfonyl)-1,2,3,4-tetrahydroisoquinolin-3-yl)methoxy)ethanone

129 (S)-2-((2-(2,4-dichlorophenylsulfonyl)-1,2,3,4-tetrahydroisoquinolin-3-yl)methoxy)-1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)ethanone

130 N-benzyl-N-(2-(2-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-2,6-dimethylphenylsulfonamide

131 2-((2-(2,4-dichlorophenylsulfonyl)-1,2,3,4-tetrahydroisoquinolin-3-yl)methoxy)-1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)ethanone hydrochloride

132 N-(2-(2-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

133 N-(2-(3-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-3-oxopropoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

134 (S)-1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-((2-(4-methoxyphenylsulfonyl)-1,2,3,4-tetrahydroisoquinolin-3-yl)methoxy)ethanone

135 2-((1-(2,4-dichlorophenylsulfonyl)indolin-2-yl)methoxy)-1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)ethanone

136 N-(2-(2-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

137 N-(2-(2-(4-hydroxy-4-phenylpiperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

138 1-(4-hydroxy-4-(pyridin-2-yl)piperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)ethanone

139 N-cyclopropyl-N-(2-(2-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-2,6-dimethylphenylsulfonamide

140 N-(2-(2-(4-hydroxy-4-(2-(pyridin-3-yl)ethyl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

141 N-(2-(2-(4-(3-fluorophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

142 1-(4-(3-fluorophenyl)-4-hydroxypiperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)ethanone

143 N-(2-(2-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

144 1-(4-hydroxy-4-(pyridin-4-yl)piperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)ethanone

145 2-((1-(3,4-dichlorophenylsulfonyl)-1,2,3,4-tetrahydroquinolin-2-yl)methoxy)-1-(4-(3-fluorophenyl)-4-hydroxypiperidin-1-yl)ethanone

146 2-((1-(3,4-dichlorophenylsulfonyl)-1,2,3,4-tetrahydroquinolin-2-yl)methoxy)-1-(4-hydroxy-4-(pyridin-2-yl)piperidin-1-yl)ethanone

147 2-((1-(3,4-dichlorophenylsulfonyl)-1,2,3,4-tetrahydroquinolin-2-yl)methoxy)-1-(4-hydroxy-4-(pyridin-4-yl)piperidin-1-yl)ethanone

148 N-(2-(2-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N,2-dimethylnaphthalene-1-sulfonamide

149 4-chloro-N-(2-(2-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N,2,5-trimethylphenylsulfonamide

150 4-chloro-N-(2-(2-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N,2,5-trimethylphenylsulfonamide

151 N-(2-(2-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-4-chloro-N,2,5-trimethylphenylsulfonamide

152 4-chloro-N-(2-(2-(4-hydroxy-4-phenylpiperidin-1-yl)-2-oxoethoxy)ethyl)-N,2,5-trimethylphenylsulfonamide

153 N-(2-(2-(4-benzyl-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-4-chloro-N,2,5-trimethylphenylsulfonamide

154 4-chloro-N-(2-(2-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N,2,5-trimethylphenylsulfonamide

155 1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-((1-(4-(trifluoromethyl)phenylsulfonyl)piperidin-2-yl)methoxy)ethanone

156 1-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-((1-(4-(trifluoromethyl)phenylsulfonyl)piperidin-2-yl)methoxy)ethanone

157 2-((1-(4-chloro-2,5-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)-1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)ethanone

158 2-((1-(4-chloro-2,5-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)-1-(4-hydroxy-4-phenylpiperidin-1-yl)ethanone

159 1-(4-benzyl-4-hydroxypiperidin-1-yl)-2-((1-(4-chloro-2,5-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)ethanone

160 2-((1-(4-chloro-2,5-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)-1-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)ethanone

161 2-((1-(3-chloro-4-methylphenylsulfonyl)piperidin-2-yl)methoxy)-1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)ethanone

162 2-((1-(2,6-dichloro-4-(trifluoromethyl)phenylsulfonyl)piperidin-2-yl)methoxy)-1-(4-hydroxy-4-phenylpiperidin-1-yl)ethanone

163 1-(4-benzyl-4-hydroxypiperidin-1-yl)-2-((1-(2,6-dichloro-4-(trifluoromethyl)phenylsulfonyl)piperidin-2-yl)methoxy)ethanone

164 2-((1-(2,6-dichloro-4-(trifluoromethyl)phenylsulfonyl)piperidin-2-yl)methoxy)-1-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)ethanone

165 1-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-2-((1-(2,6-dichloro-4-(trifluoromethyl)phenylsulfonyl)piperidin-2-yl)methoxy)ethanone

166 1-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-((1-(2,6-dichloro-4-(trifluoromethyl)phenylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone

167 1-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-2-((1-(2,6-dichloro-4-(trifluoromethyl)phenylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone

168 2-((1-(2,6-dichloro-4-(trifluoromethyl)phenylsulfonyl)pyrrolidin-2-yl)methoxy)-1-(4-hydroxy-4-phenylpiperidin-1-yl)ethanone

169 1-(4-benzyl-4-hydroxypiperidin-1-yl)-2-((1-(2,6-dichloro-4-(trifluoromethyl)phenylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone

170 2-((1-(2,6-dichloro-4-(trifluoromethyl)phenylsulfonyl)pyrrolidin-2-yl)methoxy)-1-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)ethanone

171 1-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-2-((1-(2,6-dichloro-4-(trifluoromethyl)phenylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone

172 1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-((1-(2-(trifluoromethyl)phenylsulfonyl)piperidin-2-yl)methoxy)ethanone

173 1-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-((1-(2-(trifluoromethyl)phenylsulfonyl)piperidin-2-yl)methoxy)ethanone

174 1-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-2-((1-(2-(trifluoromethyl)phenylsulfonyl)piperidin-2-yl)methoxy)ethanone

175 1-(4-hydroxy-4-phenylpiperidin-1-yl)-2-((1-(2-(trifluoromethyl)phenylsulfonyl)piperidin-2-yl)methoxy)ethanone

176 1-(4-benzyl-4-hydroxypiperidin-1-yl)-2-((1-(2-(trifluoromethyl)phenylsulfonyl)piperidin-2-yl)methoxy)ethanone

177 1-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)-2-((1-(2-(trifluoromethyl)phenylsulfonyl)piperidin-2-yl)methoxy)ethanone

178 1-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-2-((1-(2-(trifluoromethyl)phenylsulfonyl)piperidin-2-yl)methoxy)ethanone

179 1-(4-benzyl-4-hydroxypiperidin-1-yl)-3-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)propan-1-one

180 1-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-3-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)propan-1-one

181 1-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-3-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)propan-1-one

182 1-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-3-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)propan-1-one

183 1-(4-hydroxy-4-phenylpiperidin-1-yl)-3-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)propan-1-one

184 1-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-3-(1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-3-yloxy)propan-1-one

185 1-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-3-(1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-3-yloxy)propan-1-one

186 1-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-3-(1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-3-yloxy)propan-1-one

187 1-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-3-(1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-3-yloxy)propan-1-one

188 1-(4-hydroxy-4-phenylpiperidin-1-yl)-3-(1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-3-yloxy)propan-1-one

189 1-(4-benzyl-4-hydroxypiperidin-1-yl)-3-(1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-3-yloxy)propan-1-one

190 1-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)-3-(1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-3-yloxy)propan-1-one

191 N-benzyl-N-(2-(2-(4-benzyl-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-2,3,6-trimethylphenylsulfonamide

192 1-(4-benzyl-4-hydroxypiperidin-1-yl)-2-(1-(4-methoxy-2,3,6-trimethylphenylsulfonyl)piperidin-3-yloxy)ethanone

193 1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone

194 1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-3-yl)methoxy)ethanone

195 1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-((2-(4-methoxy-2,3,6-trimethylphenylsulfonyl)-1,2,3,4-tetrahydroisoquinolin-3-yl)methoxy)ethanone

196 2-((1-(2,6-dichlorophenylsulfonyl)piperidin-2-yl)methoxy)-1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)ethanone

197 2-((1-(2,6-dichlorophenylsulfonyl)pyrrolidin-2-yl)methoxy)-1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)ethanone

198 2,4-dichloro-N-(2-(2-(4-hydroxy-4-(pyridin-2-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N,6-dimethylphenylsulfonamide

199 2,4-dichloro-N-(2-(2-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N,5-dimethylphenylsulfonamide

200 1-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-((2-(mesitylsulfonyl)-1,2,3,4-tetrahydroisoquinolin-3-yl)methoxy)ethanone

201 1-(4-benzyl-4-hydroxypiperidin-1-yl)-2-((2-(mesitylsulfonyl)-1,2,3,4-tetrahydroisoquinolin-3-yl)methoxy)ethanone

202 1-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-3-yl)methoxy)ethanone

203 2-((1-(2,5-dichlorothiophen-3-ylsulfonyl)pyrrolidin-2-yl)methoxy)-1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)ethanone

204 1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-((1-(2,4,6-trichlorophenylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone

205 N-(2-(2-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N-(cyclopropylmethyl)-4-methoxy-2,3,6-trimethylphenylsulfonamide

206 N-(cyclopropylmethyl)-N-(2-(2-(4-hydroxy-4-phenylpiperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-2,3,6-trimethylphenylsulfonamide

207 N-(2-(2-(4-benzyl-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N-(cyclopropylmethyl)-4-methoxy-2,3,6-trimethylphenylsulfonamide

208 N-(cyclopropylmethyl)-N-(2-(2-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)-piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-2,3,6-trimethylphenylsulfonamide

209 N-(2-(2-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N-isobutyl-4-methoxy-2,3,6-trimethylphenylsulfonamide

210 N-(2-(2-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N-isobutyl-4-methoxy-2,3,6-trimethylphenylsulfonamide

211 N-(2-(2-(4-benzyl-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N-isobutyl-4-methoxy-2,3,6-trimethylphenylsulfonamide

212 N-(2-(2-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N-isobutyl-4-methoxy-2,3,6-trimethylphenylsulfonamide

213 1-(4-(4-chloro-3-(trifluormethyl)phenyl)-4-hydroxypiperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone

214 1-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone

215 1-(4-hydroxy-4-phenylpiperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone

216 1-(4-benzyl-4-hydroxypiperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone

217 1-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone

218 1-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-2-((1-(2,6-dichlorophenylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone

219 1-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-2-((1-(2,6-dichlorophenylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone

220 2-((1-(2,6-dichlorophenylsulfonyl)pyrrolidin-2-yl)methoxy)-1-(4-hydroxy-4-phenylpiperidin-1-yl)ethanone

221 1-(4-benzyl-4-hydroxypiperidin-1-yl)-2-((1-(2,6-dichlorophenylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone

222 2-((1-(2,6-dichlorophenylsulfonyl)pyrrolidin-2-yl)methoxy)-1-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)ethanone

223 1-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-2-((1-(2,5-dichlorothiophen-3-ylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone

224 1-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-2-((1-(2,5-dichlorothiophen-3-ylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone

225 2-((1-(2,5-dichlorothiophen-3-ylsulfonyl)pyrrolidin-2-yl)methoxy)-1-(4-hydroxy-4-phenylpiperidin-1-yl)ethanone

226 1-(4-benzyl-4-hydroxypiperidin-1-yl)-2-((1-(2,5-dichlorothiophen-3-ylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone

227 2-((1-(2,5-dichlorothiophen-3-ylsulfonyl)pyrrolidin-2-yl)methoxy)-1-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)ethanone

228 1-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-3-yl)methoxy)ethanone

229 2-((1-(2,5-dichlorothiophen-3-ylsulfonyl)piperidin-2-yl)methoxy)-1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)ethanone

230 1-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-3-yl)methoxy)ethanone

231 1-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-3-yl)methoxy)ethanone

232 1-(4-benzyl-4-hydroxypiperidin-1-yl)-2-((2-(4-methoxy-2,3,6-trimethylphenylsulfonyl)-1,2,3,4-tetrahydroisoquinolin-3-yl)methoxy)ethanone

233 1-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)-2-((2-(4-methoxy-2,3,6-trimethylphenylsulfonyl)-1,2,3,4-tetrahydroisoquinolin-3-yl)methoxy)ethanone

234 1-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-2-((1-(2,6-dichlorophenylsulfonyl)piperidin-2-yl)methoxy)ethanone

235 2-((1-(2,6-dichlorophenylsulfonyl)piperidin-2-yl)methoxy)-1-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)ethanone

236 1-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-2-((1-(2,6-dichlorophenylsulfonyl)piperidin-2-yl)methoxy)ethanone

237 N-(2-(2-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N-(cyclopropylmethyl)-4-methoxy-2,3,6-trimethylphenyl-sulfonamide

238 N-(2-(2-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N-isobutyl-4-methoxy-2,3,6-trimethylphenylsulfonamide

239 1-(4-hydroxy-4-(thiophen-2-yl)piperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-2-yl)methoxy)ethanone

240 N-(cyclopropylmethyl)-N-(2-(2-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-2,3,6-trimethylphenylsulfonamide

241 N-(2-(2-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N-isobutyl-4-methoxy-2,3,6-trimethylphenylsulfonamide

242 1-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)ethanone

243 1-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)ethanone

244 1-(4-hydroxy-4-phenylpiperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)ethanone

245 1-(4-benzyl-4-hydroxypiperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)ethanone

246 1-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)ethanone

247 1-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-2-((1-(2,5-dichlorothiophen-3-ylsulfonyl)piperidin-2-yl)methoxy)ethanone

248 1-(4-benzyl-4-hydroxypiperidin-1-yl)-2-((1-(2,4,6-trichlorophenylsulfonyl)pyrrolidin-3-yl)methoxy)ethanone

249 1-(4-benzyl-4-hydroxypiperidin-1-yl)-2-(1-(2,4,6-trichlorophenylsulfonyl)piperidin-3-yloxy)ethanone

250 1-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-2-(1-(2,4,6-trichlorophenylsulfonyl)piperidin-3-yloxy)ethanone

251 1-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-3-yl)methoxy)ethanone

252 1-(4-benzyl-4-hydroxypiperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-3-yl)methoxy)ethanone

253 1-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-3-yl)methoxy)ethanone

254 1-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-((1-(2,4,6-trichlorophenylsulfonyl)piperidin-3-yl)methoxy)ethanone

255 1-(4-hydroxy-4-phenylpiperidin-1-yl)-2-((1-(2,4,6-trichlorophenylsulfonyl)piperidin-3-yl)methoxy)ethanone

256 N-(2-(2-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N,2,5-trimethylthiophene-3-sulfonamide

257 N-(2-(2-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N,2,5-trimethylthiophene-3-sulfonamide

258 N-(2-(2-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N,2,5-trimethylthiophene-3-sulfonamide

259 N-(2-(2-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N,2,5-trimethylthiophene-3-sulfonamide

260 2,5-dichloro-N-(2-(2-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N-methylthiophene-3-sulfonamide

261 N-(2-(2-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-2,5-dichloro-N-methylthiophene-3-sulfonamide

262 2,5-dichloro-N-(2-(2-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N-methylthiophene-3-sulfonamide

263 2,5-dichloro-N-(2-(2-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N-methylthiophene-3-sulfonamide

264 1-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-2-(1-(2-methoxy-4,6-dimethylphenylsulfonyl)pyrrolidin-3-yloxy)ethanone

265 1-(4-benzyl-4-hydroxypiperidin-1-yl)-2-(1-(2-methoxy-4,6-dimethylphenylsulfonyl)pyrrolidin-3-yloxy)ethanone

266 2-((1-(2,5-dichlorothiophen-3-ylsulfonyl)pyrrolidin-2-yl)methoxy)-1-(4-hydroxy-4-(thiophen-2-yl)piperidin-1-yl)ethanone

267 1-(4-hydroxy-4-(thiophen-2-yl)piperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-3-yl)methoxy)ethanone

268 N-(cyclopropylmethyl)-N-(2-(2-(4-hydroxy-4-(thiophen-2-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-2,3,6-trimethylphenylsulfonamide

269 N-(2-(2-(4-hydroxy-4-(thiophen-2-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N-isobutyl-4-methoxy-2,3,6-trimethylphenylsulfonamide

270 2-((1-(2,6-dichlorophenylsulfonyl)piperidin-2-yl)methoxy)-1-(4-hydroxy-4-(thiophen-2-yl)piperidin-1-yl)ethanone

271 2-((1-(2,5-dichlorothiophen-3-ylsulfonyl)piperidin-2-yl)methoxy)-1-(4-hydroxy-4-phenylpiperidin-1-yl)ethanone

272 1-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-((1-(2,4,6-trichlorophenylsulfonyl)pyrrolidin-3-yl)methoxy)ethanone

273 2-((1-(benzo[b]thiophen-3-ylsulfonyl)piperidin-2-yl)methoxy)-1-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)ethanone

274 2-((1-(benzo[b]thiophen-3-ylsulfonyl)piperidin-2-yl)methoxy)-1-(4-benzyl-4-hydroxypiperidin-1-yl)ethanone

275 N-(2-(3-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-3-oxopropoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

276 N-(2-(3-(4-hydroxy-4-phenylpiperidin-1-yl)-3-oxopropoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

277 N-(2-(3-(4-benzyl-4-hydroxypiperidin-1-yl)-3-oxopropoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

278 N-(2-(3-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-3-oxopropoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

279 N-(2-(2-(4-hydroxy-4-(pyridin-3-ylmethyl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide hydrochloride, and

280 N-(2-(2-(4-hydroxy-4-(pyridin-4-ylmethyl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide.

20. A process for preparing a substituted sulfonamide compound according to claim 1, said process comprising:

reacting a carboxylic acid corresponding to formula G with a primary or secondary amine corresponding to formula S;

21. A method according to claim 20, wherein the dehydrating agent is selected from the group consisting of sodium sulfate, magnesium sulfate and phosphorus oxide;

the coupling agent is CDI or polymer-bonded DCC, TBTU, EDCI, PyBOP or PFPTFA;

HOAt or HOBt is added;

the organic base is selected from the group consisting of DIPEA and pyridine, and the organic solvent is selected from the group consisting of THF, methylene chloride, diethyl ether, dioxane, DMF and acetonitrile.

22. A pharmaceutical composition comprising a compound according to claim 1 and at least one pharmaceutically acceptable carrier, additive or auxiliary substance.

23. A method of treating or inhibiting pain in a subject, said method comprising administering to said subject a pharmacologically effective amount of a compound according to claim 1.

24. A method according to claim 19, wherein said pain is selected from the group consisting of acute pain, visceral pain, neuropathic pain, chronic pain and inflammatory pain.

25. A method of treating or inhibiting a bradykinin receptor mediated disorder or disease state selected from the group consisting of migraine, diabetes, diseases of the respiratory tract, inflammatory bowel diseases, neurological diseases, inflammations of the skin, rheumatic diseases, septic shock, reperfusion syndrome and obesity, or of inhibiting angiogenesis, in a subject, said method comprising administering to said subject a pharmacologically effective amount of a compound according to claim 1.