Biphenyl sulfonamides as dual angiotensin endothelin receptor antagonists

• US 20020143024A1
• Filed: 12/14/2000
• Published: 10/03/2002
• Est. Priority Date: 07/06/1998
• Status: Active Grant

• Current Assignee: Pharmacopeia LLC (Ligand Pharmaceuticals, Inc.)
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Macor, Jhon E., Gu, Zhengxiang, Murugesan, Natesan, Tellew, John E.
• Granted Patent: US 6,638,937 B2
• Time in Patent Office: Days
• US Class Current: 514/258.1
• CPC Class Codes: C07D 261/16 Benzene-sulfonamido isoxazoles
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/14 containing three or more hetero rings
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

Novel biphenyl sulfonamide compounds which are combined angiotensin and endothelin receptor antagonists are claimed along with methods of using such compounds in the treatment of conditions such as hypertension and other diseases, as well as pharmaceutical compositions containing such compounds.

Claims

1. A compound of the following formula I, or an enantiomer, diastereomer, salt or metabolite thereof:

2. A compound of claim 1, wherein

3. A compound of claim 1, wherein

4. A compound of claim 1, wherein

5. A compound of claim 1, wherein R₃ is isoxazol-5-yl or isoxazol-3-yl independently substituted with two substituents selected from alkyl or halogen.

6. A compound of claim 5, wherein R₁ is

7. A compound of claim 6, wherein R₂ is alkyl, haloalkyl, alkoxyalkyl or haloalkoxyalkyl and R₁₀₁, R₁₀₂, R₁₀₃, R₁₀₄ are each independently hydrogen, halogen, or alkyl.

8. A compound of claim 6, wherein R₂ is —

CH₂Y.

9. A compound of claim 8, wherein Y is Q.

10. A compound of claim 5, wherein R₁ is

11. A compound of claim 10, wherein R₂ is alkyl, haloalkyl, alkoxyalkyl or haloalkoxyalkyl and R₁₀₁, R₁₀₂, R₁₀₃, R₁₀₄ are each independently hydrogen, halogen, or alkyl.

12. A compound of claim 10, wherein R₂ is —

CH₂Y.

13. A compound of claim 12, wherein Y is Q.

14. A compound of claim 5, wherein R₁ is

15. A compound of claim 14, wherein R₂ is alkyl, haloalkyl, alkoxyalkyl or haloalkoxyalkyl and R₁₀₁, R₁₀₂, R₁₀₃, R₁₀₄ are each independently hydrogen, halogen, or alkyl.

16. A compound of claim 14, wherein R₂ is —

CH₂Y.

17. A compound of claim 16, wherein Y is Q.

18. A compound of claim 1, wherein R₂ is alkoxyalkyl alkyl, haloalkyl or haloalkoxyalkyl

19. A compound of claim 18, wherein R₃ is isoxazol-5-yl or isoxazol-3-yl independently substituted with two substituents selected from alkyl or halogen.

20. A compound of claim 1, wherein R₂ is —

CH₂Y.

21. A compound of claim 20, wherein R₃ is isoxazol-5-yl or isoxazol-3-yl independently substituted with two substituents selected from alkyl or halogen.

22. A compound of claim 20, wherein Y is Q.

23. A compound of claim 22, wherein R₃ is isoxazol-5-yl or isoxazol-3-yl independently substituted with two substituents selected from alkyl or halogen.

24. A compound of claim 1, wherein said compound is selected from the group consisting of

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-[(methylamino)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-formyl-N-(3,4-dimethyl-5-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-[(3-methyl-2-oxo-1-imidazolidinyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-N-(2-pyrazinyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3-chloro-2-pyrazinyl)-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-[(2-oxo-1-pyrrolidinyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-N-(3,6-dimethyl-2-pyrazinyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-N-(3-methoxy-2-pyrazinyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-formyl-N-(4,5-dimethyl-3-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-[(2-oxo-1-pyrrolidinyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

(S)-N-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-[2-methyl-1-(3-methyl-1,2,4-oxadiazol-5-yl)propyl]pentanamide;

N-(3,4-Dimethyl-5-isoxazolyl)-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-4′

-[(2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[2-(2-methoxyethyl)-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[2-(ethoxymethyl)-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl]-2′

-[(2-oxo-1-pyrrolidinyl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl]-2′

-[(3-methyl-2-oxo-1-imidazolidinyl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

(S)-2-[N-[2′

-[[N-(3-Methyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-(1-oxopentyl)amino]-3,N-dimethylbutanamide;

(S)-2-[N-[2′

-[[N-(4-Bromo-3-methyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-(1-oxopentyl)amino]-3,N-dimethylbutanamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-propyl[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(7-Methoxycarbonyl-2-ethoxybenzimidazol-1-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(7-Carboxy-2-ethoxybenzimidazol-1-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(7-Methoxycarbonyl-2-ethylbenzimidazol-1-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(7-Carboxy-2-ethylbenzimidazol-1-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

2′

-[(3,3-Dimethyl-2-oxopyrrolidin-1-yl)methyl]-4′

-[(2-ethoxy-7-(methoxycarbonyl)benzimidazol-1-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

2′

-[(3,3-Dimethyl-2-oxopyrrolidin-1-yl)methyl]-4′

-[(2-ethoxy-7-(carboxy)benzimidazol-1-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

2′

-[(3,3-Dimethyl-2-oxopyrrolidin-1-yl)methyl]-4′

-[(2-ethoxy-7-(N-methylcarbamoyl)benzimidazol-1-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

2′

-[(3,3-Dimethyl-2-oxopyrrolidin-1-yl)methyl]-4′

-[(2-ethoxy-7-(N,N-dimethylcarbamoyl)benzimidazol-1-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Ethylquinolin-4-yl)oxymethyl]-N-(1,3,5-trimethylpyrazol-4-yl) [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Ethylquinolin-4-yl)oxymethyl]-N-(3-methylisoxazol-5-yl) [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(5-Acetyl-2-n-propyl-4-chloroimidazol-1-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(5-Methoxycarbonyl-2-n-propyl-4-chloroimidazol-1-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(5-(N,N-dimethylcarbamoyl)-2-n-propyl-4-chloroimidazol-1-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-hydroxymethyl[1,1′

-biphenyl]-2-sulfonamide

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-ethoxymethyl[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-propyl [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-N-(3-methoxy-5-methyl-2-pyrazinyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4-bromo-3-methyl-5-isoxazolyl)-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-[(formylmethylamino)-methyl][1,1′

-biphenyl]-2-sulfonamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methylpropanamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methylcyclopropanecarbox-amide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,2-dimethylpropanamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methylbutanamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-2-methoxy-N-methylacetamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methyl-4-pentynamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methylcyclobutanecarboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,3-dimethylbutanamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,2,2-trimethylpropanamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-3-methoxy-N-methylpropanamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-2-ethoxy-N-methylacetamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methyl-2-furancarboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,4-dimethylpentanamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methyl-3-thiophenecarboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methylcyclopentaneacetamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methylcyclohexanecarboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,3-dimethylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methylbenzeneacetamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-2-fluoro-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-3-fluoro-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-4-fluoro-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methylcyclohexaneacetamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-2-fluoro-N-methylbenzeneacetamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-3-fluoro-N-methylbenzeneacetamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-4-fluoro-N-methylbenzeneacetamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,N′

,N′

-trimethylurea;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N′

-(1,1-dimethylethyl)-N-methylurea;

[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]methylcarbamic acid ethyl ester;

[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]methylcarbamic acid 2-methylpropyl ester;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,3,3-trimethylbutanamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methyl-2-pyridinecarboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methyl-3-pyridinecarboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methyl-2-pyrazinecarboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,1-dimethyl-1H-pyrrole-2-carboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methyl-1,2,3-thiadiazole-4-carboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,5-dimethyl-2-pyrazinecarboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,3,5-trimethyl-4-isoxazolecarboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,3-dimethyl-2-thiophenecarboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,5-dimethyl-2-thiophenecarboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-3-cyano-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-4-cyano-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-2-methoxy-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-2-chloro-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-3-chloro-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-4-chloro-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-2,3-difluoro-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-3,4-difluoro-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-3,5-difluoro-N-methylbenzamide;

4-Acetyl-N-[[4-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-3-ethoxy-N-methyl-2-thiophenecarboxamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-[(propylsulfonyl)amino][1,1′

-biphenyl]-2-sulfonamide;

N-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-(1-oxopentyl)-L-valine methyl ester;

N-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-(1-oxopentyl)-L-valine;

N-(3,4-Dimethyl-5-isoxazolyl)-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-4′

-[(2-propyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl]-4-[(2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl][1,1′

-biphenyl]-2-yl]methyl]-N,3,3-trimethylbutanamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N2-(1-oxopentyl)-L-valinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopentyl)-L-valinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N,N-dimethyl-N2-(1-oxopentyl)-L-valinamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-[[(2,2,2-trifluoroethyl)amino]methyl][1,1′

-biphenyl]-2-sulfonamide;

4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-carboxylic acid;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-(trifluoromethyl)[1,1′

-biphenyl]-2-sulfonamide;

4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-carboxylic acid methyl ester;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-(methoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-fluoro[1,1′

-biphenyl]-2-sulfonamide;

2′

-(Cyanomethyl)-N-(3,4-dimethyl-5-isoxazolyl)-4′

-[(2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-(cyanomethyl)-N-(3,4-dimethyl-5-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-cyano-N-(3,4-dimethyl-5-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-methyl [1,1′

-biphenyl]-2-sulfonamide;

2′

-Cyano-N-(3,4-dimethyl-5-isoxazolyl)-4′

-[(2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl]-2-methyl[1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopentyl)-L-valinamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[(2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl]-2′

-[[(2,2,2-trifluoroethyl)amino]methyl][1,1′

-biphenyl]-2-sulfonamide;

N-[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]benzeneacetamide;

N-[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]-3,3-dimethylbutanamide;

2′

-Amino-4′

-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-nitro[1,1′

-biphenyl]-2-sulfonamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopropyl)-L-isoleucinamide;

N2-(Cyclopropylcarbonyl)-N2-[[2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-L-isoleucinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxo-3-phenylpropyl)-L-isoleucinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(3-methyl-1-oxobutyl)-L-isoleucinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxohexyl)-L-isoleucinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxobutyl)-L-isoleucinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopropyl)-L-leucinamide;

N2-(Cyclopropylcarbonyl)-N2-[[2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-L-leucinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxo-3-phenylpropyl)-L-leucinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(phenylacetyl)-L-leucinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(3-methyl-1-oxobutyl)-L-leucinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxohexyl)-L-leucinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxobutyl)-L-leucinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopropyl)-L-valinamide;

N2-(Cyclopropylcarbonyl)-N2-[[2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-L-valinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxo-3-phenylpropyl)-L-valinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(phenylacetyl)-L-valinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(3-methyl-1-oxobutyl)-L-valinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxohexyl)-L-valinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxobutyl)-L-valinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-ethyl-N2-(1-oxopentyl)-L-valinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-hexyl-N2-(1-oxopentyl)-L-valinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl]-2-cyano[1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopentyl)-L-valinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl]-2-hydroxymethyl[1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopentyl)-L-valinamide;

4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-carboxamide;

N,N-Dimethyl-4-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-carboxamide;

N-Methyl-4-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-carboxamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2′

-(methoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-methyl [1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2′

-methyl[1,1′

-biphenyl]-2-sulfonamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl]-2-(methoxymethyl)[1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopentyl)-L-valinamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2′

-(hydroxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

2′

-Chloro-N-(3,4-dimethyl-5-isoxazolyl)-4′

-[[(5,6,7,8-tetrahydro-2-ethyl-4-quinolinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl]-2-fluoro[1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopentyl)-L-valinamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-(phenoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl]-2-(1H-pyrazol-1-ylmethyl)[1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopentyl)-L-valinamide;

N2-(Cyclopropylcarbonyl)-N2-[[2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N,N-dimethyl-L-valinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N,N-dimethyl-N2-(1-oxobutyl)-L-valinamide;

N2-(Cyclopropylcarbonyl)-N2-[[2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl]-2-(methoxymethyl)[1,1′

-biphenyl]-4-yl]methyl]-N,N-dimethyl-L-valinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl]-2-(methoxymethyl)[1,1′

-biphenyl]-4-yl]methyl]-N,N-dimethyl-N2-(1-oxobutyl)-L-valinamide;

N2-[[2-Chloro-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopentyl)-L-valinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl]-2-(trifluoromethyl)[1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopentyl)-L-valinamide;

N2-(Cyclobutylcarbonyl)-N2-[[2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-L-valinamide;

1-[[2-Chloro-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-2-propyl-1H-imidazole-5-carboxylic acid;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-[(methylsulfonyl)amino][1,1′

-biphenyl]-2-sulfonamide;

(S)-N-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-[2-methyl-1-[(4-methyl-1-piperazinyl)carbonyl]propyl]pentanamide;

(S)-N-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-(1-piperidinyl)carbonyl]propyl]pentanamide;

N-(3,3-Dimethylbutyl)-N2-[[2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N2-(1-oxopentyl)-L-valinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-[(4-fluorophenyl)methyl]-N2-(1-oxopentyl)-L-valinamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-[(methylethoxy)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-(propoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

4-Chloro-1-[[2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-2-propyl-1H-imidazole-5-carboxamide;

N-(3,4-Dimethyl-5-isoxazolyl)-2′

-fluoro-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[(1,2-dihydro-2-oxo-1-pyridinyl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-(1H-pyrazol-1-ylmethyl)[1,1′

-biphenyl]-2-sulfonamide;

2-Butyl-4-chloro-1-[[2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-1H-imidazole-5-carboxamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(2-methyl-4-quinolinyl)oxy]methyl] [1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(2-ethyl-4-quinolinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(2-ethyl-5,6,7,8-tetrahydro-4-quinolinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(2-propyl-4-quinolinyl)oxy]methyl] [1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[(5,6,7,8-tetrahydro-2,4-dimethyl-7-oxopyrido[2,3-d]pyrimidin-8-yl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[[(2-Ethyl-4-quinolinyl)oxy]methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-4′

-[[(5,6,7,8-tetrahydro-2-ethyl-4-quinolinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

3-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-2-ethyl-N-methyl-3H-benzimidazole-4-carboxamide;

1-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-2-ethyl-1H-benzimidazole-7-carboxylic acid phenylmethyl ester;

1-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-2-ethyl-1H-benzimidazole-7-carboxylic acid 2-phenylethyl ester;

1-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-2-ethyl-1H-benzimidazole-7-carboxylic acid 2-(2-oxo-1-pyrrolidinyl)ethyl ester;

1-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-2-ethyl-1H-benzimidazole-7-carboxylic acid 3-(2-oxo-1-pyrrolidinyl)propyl ester;

2′

-Cyano-N-(3,4-dimethyl-5-isoxazolyl)-4′

-[[(2-ethyl-4-quinolinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

2′

-(Cyanomethyl)-N-(3,4-dimethyl-5-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

3-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-5-ethyl-N-methyl-2-propyl-3H-imidazole-4-carboxamide;

1-[[2-Chloro-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-2-propyl-1H-imidazole-5-carboxamide;

3-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-5-ethyl-2-propyl-3H-imidazole-4-carboxamide;

3-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-2-ethoxy-N-methyl-3H-benzimidazole-4-carboxamide;

3-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-2-ethoxy-N,N-dimethyl-3H-benzimidazole-4-carboxamide;

2-[[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]propylamino]-3-pyridinecarboxylic acid;

4′

-[(3,5-Dibutyl-1H-1,2,4-triazol-1-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2,7-Diethyl-5H-pyrazolo[1,5-b][1,2,4]triazol-5-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

N-[2-Butyl-3-[[2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-3,4-dihydro-4-oxo-6-quinazolinyl]-N′

-methyl-N′

-(1-methylethyl)urea;

2-[[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]propylamino]-N-methyl-3-pyridinecarboxamide;

4′

-[[(3-Methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-N-(3,4-dimethyl-5-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-(methoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

3-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-2-ethyl-5-methyl-3H-imidazole-4-carboxamide;

4′

-[(2-Butyl-3,4-dihydro-4-oxo-3-quinazolinyl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl]-2-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopentyl)-L-valinamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-[(4,4-dimethyl-2-oxo-1-pyrrolidinyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(3,5-Dibutyl-H-1,2,4-triazol-1-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-[2-[[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl]-4-[(2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl][1,1′

-biphenyl]-2-yl]methyl]methylamino]ethyl]acetamide;

4-[(2-Ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl]-2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-acetic acid ethyl ester;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N2-(1-oxopentyl)-N-propyl-L-valinamide;

N2-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N2-(1-oxopentyl)-N-[(tetrahydro-2-furanyl)methyl]-L-valinamide;

2′

-Chloro-N-(3,4-dimethyl-5-isoxazolyl)-4′

-[[(2-ethyl-4-quinolinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(2-ethyl-4-quinolinyl)oxy]methyl]-2′

-(trifluoromethyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-chloro-N-(3,4-dimethyl-5-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-[(2-methylpropoxy)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-[(ethylsulfonyl)amino][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-[(2,2,2-trifluoroethoxy)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-[(2-fluoroethoxy)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-ethoxymethyl [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(ethoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2′

-(ethoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethylisoxazol-5-yl)-2′

-(3,3,3-trifluoropropyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethylisoxazol-5-yl)-2′

-(3-fluoropropyl) [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-(1,1-difluoroethyl)-N-(3,4-dimethylisoxazol-5-yl) [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-(2,2,2-trifluoroethyl)-N-(3,4-dimethylisoxazol-5-yl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethylisoxazol-5-yl)-2′

-[(2-methyl)propoxy] [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethylisoxazol-5-yl)-2′

-(2-methoxyethoxy)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-butyl-N-(3,4-dimethylisoxazol-5-yl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3-methylisoxazol-5-yl)-2′

-trifluoromethyl[1,1′

-biphenyl]-2-sulfonamide;

N-(4-Bromo-3-methyl-5-isoxazolyl)-4′

-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-trifluoromethyl [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4-chloro-3-methyl-5-isoxazolyl)-2′

-trifluoromethyl [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-(N-methoxy-N-methylaminomethyl) [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-(2,2-difluoroethoxymethyl)-N-(3,4-dimethylisoxazol-5-yl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethylisoxazol-5-yl)-2′

-(2-fluoroethyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethylisoxazol-5-yl)-2′

-(2-hydroxyethyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethylisoxazol-5-yl)-2′

-(3-methylbutyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethylisoxazol-5-yl)-2′

-(2-methypropyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[[2-(3,3-Difluorobutyl)-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl]methyl]-N-(3,4-dimethylisoxazol-5-yl)-2′

-(ethoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-(3,3,3-trifluoropropyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethylisoxazol-5-yl)-2′

-[(1,1-dimethylethoxy)methyl][1,1′

-biphenyl]-2-sulfonamide;

1-[[2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl-2-methoxymethyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl-2-methoxymethyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-N-methyl-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl-2-methyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl-2-methyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-N-methyl-2-propyl-1H-imidazole-5-carboxamide;

N-(4,5-Dimethyl-3-isoxazolyl)-2′

-ethoxymethyl-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(2-fluoroethoxymethyl) [1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-2′

-[(2-fluoroethoxy)methyl]-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl] [1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-2′

-[(2-fluoroethoxy)methyl]-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl] [1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-2′

-ethoxymethyl-4′

-[[4-oxo-2-(3,3,3-trifluoropropyl)-1,3-diazaspiro[4.4]non-1-en-3-yl]methyl] [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-ethyl [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-(1-hydroxyethyl) [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-propyl [1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-propyl [1,1′

-biphenyl]-2-sulfonamide;

1-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl-2-(ethoxymethyl)][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl-2-(ethoxymethyl)][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-N-methyl-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl-2-methyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-N-methyl-2-propyl-1H-imidazole-5-carboxamide;

N,4-Diethyl-1-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl-2-methyl][1,1′

-biphenyl]-4-yl]methyl]-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl-2-ethyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl-2-methyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-N-(1-methylethyl)-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl-2-(2-fluoroethoxymethyl)][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-2-propyl-1H-imidazole-5-carboxamide;

N-(4,5-Dimethyl-3-isoxazolyl)-2′

-ethoxymethyl-4′

-[[(6-ethyl-3-methoxy-2-methyl-4-pyridinyl)oxy]methyl] [1,1′

-biphenyl]-2-sulfonamide;

N2-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxobutyl)-L-valinamide;

N2-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N,N-dimethyl-N2-(1-oxopentyl)-L-valinamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-ethyl[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(5-Acetyl-4-ethyl-2-propylimidazol-1-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-methyl[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-2′

-ethyl-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl] [1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(6-ethyl-3-methoxy-2-methyl-4-pyridinyl)oxy]methyl]-2′

-propyl [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-3′

-chloro-N-(4,5-dimethyl-3-isoxazolyl)-5-methoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-3′

-fluoro-4-methoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-5′

-chloro-N-(4,5-dimethyl-3-isoxazolyl)-2′

-fluoro-4-methoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-3′

-chloro-N-(4,5-dimethyl-3-isoxazolyl)-4-methoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-4-methoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(ethoxymethyl)-4-methoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-3′

-fluoro-5-methoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-5′

-chloro-N-(4,5-dimethyl-3-isoxazolyl)-2′

-fluoro-5-methoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-5-methoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(ethoxymethyl)-5-methoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-3′

-fluoro-4,5-dimethoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-5′

-chloro-N-(4,5-dimethyl-3-isoxazolyl)-2′

-fluoro-4,5-dimethoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-3′

-chloro-N-(4,5-dimethyl-3-isoxazolyl)-4,5-dimethoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-4,5-dimethoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(ethoxymethyl)-4,5-dimethoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-5′

-chloro-N-(4,5-dimethyl-3-isoxazolyl)-2′

-fluoro[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-3′

-chloro-N-(4,5-dimethyl-3-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-4-methoxy-3′

-methyl[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-3′

-fluoro-4-methoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-3′

-methyl[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-5-fluoro [1,1′

-biphenyl]-2-sulfonamide;

N²-(Cyclopropylcarbonyl)-N²-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-L-valinamide;

N²-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N,3-dimethyl-N²-(1-oxobutyl)-L-valinamide;

N²-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N²-(2-methyl-1-oxopropyl)-L-valinamide;

N²-(Cyclopentylcarbonyl)-N²-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-L-valinamide;

N²-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl]-3-fluoro[1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N²-(1-oxobutyl)-L-valinamide;

N²-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-(1-methylethyl)-N²-(1-oxobutyl)-L-valinamide;

N²-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-(2-methoxyethyl)-N²-(1-oxobutyl)-L-valinamide;

N-(Cyclopropylmethyl)-N²-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N²-(1-oxobutyl)-L-valinamide;

N²-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N²-(1-oxobutyl)-N-(3-pyridinyl)-L-valinamide;

N²-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N²-(1-oxopentyl)-L-valinamide;

N-Methyl-N²-[[2′

-[[(5-methyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N²-(1-oxopentyl)-L-valinamide;

N²-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-ethyl-N²-(1-oxobutyl)-L-valinamide;

N²-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl]-5′

-fluoro[1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N²-(1-oxobutyl)-L-valinamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(2,6-dimethyl-3-methoxy-4-pyridinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(2,6-dimethyl-3-methoxy-4-pyridinyl)oxy]methyl]-3′

-fluoro[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-3′

-fluoro-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-5-fluoro-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(hydroxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

N-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl]-2-(ethoxymethyl)[1,1′

-biphenyl]-4-yl]methyl]-1-[(1-oxopentyl)amino]cyclopentanamide;

and salts, enantiomers and diasteriomer thereof.

25. A compound of claim 1, wherein said compound is selected from the group consisting of

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-[(methylamino)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-formyl-N-(4,5-dimethyl-3-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-[(3-methyl-2-oxo-1-imidazolidinyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-[(2-oxo-1-pyrrolidinyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-formyl-N-(3,4-dimethyl-5-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-[(2-oxo-1-pyrrolidinyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

(S)-N-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-[2-methyl-1-(3-methyl-1,2,4-oxadiazol-5-yl)propyl]pentanamide;

N-(4,5-dimethyl-3-isoxazolyl)-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-4′

-[(2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-dimethyl-3-isoxazolyl)-4′

-[2-(2-methoxyethyl)-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(4, 5-dimethyl-3-isoxazolyl)-4′

-[2-(ethoxymethyl)-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl]-2′

-[(2-oxo-1-pyrrolidinyl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl]-2′

-[(3-methyl-2-oxo-1-imidazolidinyl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

(S)-2-[N-[2′

-[[N-(5-Methyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-(1-oxopentyl)amino]-3,N-dimethylbutanamide;

(S)-2-[N-[2′

-[[N-(4-Bromo-5-methyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-(1-oxopentyl)amino]-3,N-dimethylbutanamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-propyl [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(7-Methoxycarbonyl-2-ethoxybenzimidazol-1-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(7-Carboxy-2-ethoxybenzimidazol-1-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(7-Methoxycarbonyl-2-ethylbenzimidazol-1-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(7-Carboxy-2-ethylbenzimidazol-1-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

2′

-[(3,3-Dimethyl-2-oxopyrrolidin-1-yl)methyl]-4′

-[(2-ethoxy-7-(methoxycarbonyl)benzimidazol-1-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

2′

-[(3,3-Dimethyl-2-oxopyrrolidin-1-yl)methyl]-4′

-[(2-ethoxy-7-(carboxy)benzimidazol-1-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

2′

-[(3,3-Dimethyl-2-oxopyrrolidin-1-yl)methyl]-4′

-[(2-ethoxy-7-(N-methylcarbamoyl)benzimidazol-1-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

2′

-[(3,3-Dimethyl-2-oxopyrrolidin-1-yl)methyl]-4′

-[(2-ethoxy-7-(N,N-dimethylcarbamoyl)benzimidazol-1-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Ethylquinolin-4-yl)oxymethyl]-N-(5-methylisoxazol-3-yl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(5-Acetyl-2-n-propyl-4-chloroimidazol-1-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(5-Methoxycarbonyl-2-n-propyl-4-chloroimidazol-1-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(5-(N,N-dimethylcarbamoyl)-2-n-propyl-4-chloroimidazol-1-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-hydroxymethyl[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-ethoxymethyl[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-propyl[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4-bromo-5-methyl-3-isoxazolyl)-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-[(formylmethylamino)-methyl][1,1′

-biphenyl]-2-sulfonamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methylpropanamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methylcyclopropanecarbox-amide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,2-dimethylpropanamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methylbutanamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-2-methoxy-N-methylacetamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methyl-4-pentynamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methylcyclobutanecarboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,3-dimethylbutanamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,2,2-trimethylpropanamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-3-methoxy-N-methylpropanamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-2-ethoxy-N-methylacetamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methyl-2-furancarboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,4-dimethylpentanamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methyl-3-thiophenecarboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methylcyclopentaneacetamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methylcyclohexanecarboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,3-dimethylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methylbenzeneacetamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-2-fluoro-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-3-fluoro-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-4-fluoro-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methylcyclohexaneacetamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-2-fluoro-N-methylbenzeneacetamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-3-fluoro-N-methylbenzeneacetamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-4-fluoro-N-methylbenzeneacetamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,N′

,N′

-trimethylurea;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N′

-(1,1-dimethylethyl)-N-methylurea;

[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]methylcarbamic acid ethyl ester;

[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]methylcarbamic acid 2-methylpropyl ester;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,3,3-trimethylbutanamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methyl-2-pyridinecarboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methyl-3-pyridinecarboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methyl-2-pyrazinecarboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,1-dimethyl-1H-pyrrole-2-carboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methyl-1,2,3-thiadiazole-4-carboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,5-dimethyl-2-pyrazinecarboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,3,5-trimethyl-4-isoxazolecarboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,3-dimethyl-2-thiophenecarboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N,5-dimethyl-2-thiophenecarboxamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-3-cyano-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-4-cyano-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-2-methoxy-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-2-chloro-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-3-chloro-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-4-chloro-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-2,3-difluoro-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-3,4-difluoro-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4, 5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-3,5-difluoro-N-methylbenzamide;

4-Acetyl-N-[[4-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-N-methylbenzamide;

N-[[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]methyl]-3-ethoxy-N-methyl-2-thiophenecarboxamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-[(propylsulfonyl)amino][1,1′

-biphenyl]-2-sulfonamide;

N-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-(1-oxopentyl)-L-valine methyl ester;

N-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-(1-oxopentyl)-L-valine;

N-(4,5-dimethyl-3-isoxazolyl)-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-4′

-[(2-propyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-[(2-ethyl-5,7-dimethyl-3H-imidazo [4,5-b]pyridin-3-yl)methyl][1,1′

-biphenyl]-2-yl]methyl]-N,3,3-trimethylbutanamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N2-(1-oxopentyl)-L-valinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopentyl)-L-valinamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-[[(2,2,2-trifluoroethyl)amino]methyl][1,1′

-biphenyl]-2-sulfonamide;

4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-carboxylic acid;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(trifluoromethyl)[1,1′

-biphenyl]-2-sulfonamide;

4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-carboxylic acid methyl ester;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(methoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-fluoro[1,1′

-biphenyl]-2-sulfonamide;

2′

-(Cyanomethyl)-N-(4,5-dimethyl-3-isoxazolyl)-4′

-[(2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-(cyanomethyl)-N-(4,5-dimethyl-3-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-cyano-N-(4,5-dimethyl-3-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-methyl[1,1′

-biphenyl]-2-sulfonamide;

2′

-Cyano-N-(4,5-dimethyl-3-isoxazolyl)-4′

-[(2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-2-methyl[1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopentyl)-L-valinamide;

N-(4,5-dimethyl-3-isoxazolyl)-4′

-[(2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl]-2′

-[[(2,2,2-trifluoroethyl)amino]methyl][1,1′

-biphenyl]-2-sulfonamide;

N-[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]benzeneacetamide;

N-[4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-yl]-3,3-dimethylbutanamide;

2′

-Amino-4′

-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-nitro[1,1′

-biphenyl]-2-sulfonamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopropyl)-L-isoleucinamide;

N2-(Cyclopropylcarbonyl)-N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-L-isoleucinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxo-3-phenylpropyl)-L-isoleucinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(3-methyl-1-oxobutyl)-L-isoleucinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxohexyl)-L-isoleucinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxobutyl)-L-isoleucinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopropyl)-L-leucinamide;

N2-(Cyclopropylcarbonyl)-N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-L-leucinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxo-3-phenylpropyl)-L-leucinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(phenylacetyl)-L-leucinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(3-methyl-1-oxobutyl)-L-leucinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxohexyl)-L-leucinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxobutyl)-L-leucinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopropyl)-L-valinamide;

N2-(Cyclopropylcarbonyl)-N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-L-valinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxo-3-phenylpropyl)-L-valinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(phenylacetyl)-L-valinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(3-methyl-1-oxobutyl)-L-valinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxohexyl)-L-valinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxobutyl)-L-valinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-ethyl-N2-(1-oxopentyl)-L-valinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-hexyl-N2-(1-oxopentyl)-L-valinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-2-cyano[1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopentyl)-L-valinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-2-hydroxymethyl[1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopentyl)-L-valinamide;

4-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-carboxamide;

N,N-Dimethyl-4-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-carboxamide;

N-Methyl-4-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-carboxamide;

N-(4,5-dimethyl-3-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2′

-(methoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-dimethyl-3-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-methyl [1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-dimethyl-3-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2′

-methyl[1,1′

-biphenyl]-2-sulfonamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-2-(methoxymethyl)[1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopentyl)-L-valinamide;

N-(4,5-dimethyl-3-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2′

-(hydroxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

2′

-Chloro-N-(4,5-dimethyl-3-isoxazolyl)-4′

-[[(5,6,7,8-tetrahydro-2-ethyl-4-quinolinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-2-fluoro[1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopentyl)-L-valinamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(phenoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-2-(1H-pyrazol-1-ylmethyl)[1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopentyl)-L-valinamide;

N2-(Cyclopropylcarbonyl)-N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N,N-dimethyl-L-valinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N,N-dimethyl-N2-(1-oxobutyl)-L-valinamide;

N2-(Cyclopropylcarbonyl)-N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-2-(methoxymethyl)[1,1′

-biphenyl]-4-yl]methyl]-N,N-dimethyl-L-valinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-2-(methoxymethyl)[1,1′

-biphenyl]-4-yl]methyl]-N,N-dimethyl-N2-(1-oxobutyl)-L-valinamide;

N2-[[2-Chloro-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopentyl)-L-valinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-2-(trifluoromethyl)[1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopentyl)-L-valinamide;

N2-(Cyclobutylcarbonyl)-N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-L-valinamide;

1-[[2-Chloro-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-2-propyl-1H-imidazole-5-carboxylic acid;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-[(methylsulfonyl)amino][1,1′

-biphenyl]-2-sulfonamide;

(S)-N-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-[2-methyl-1-[(4-methyl-1-piperazinyl)carbonyl]propyl]pentanamide;

(S)-N-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-(1-piperidinyl)carbonyl]propyl]pentanamide;

N-(3,3-Dimethylbutyl)-N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N2-(1-oxopentyl)-L-valinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-[(4-fluorophenyl)methyl]-N2-(1-oxopentyl)-L-valinamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-[(methylethoxy)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(propoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

4-Chloro-1-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-2-propyl-1H-imidazole-5-carboxamide;

N-(4,5-dimethyl-3-isoxazolyl)-2′

-fluoro-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-[(1,2-dihydro-2-oxo-1-pyridinyl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(1H-pyrazol-1-ylmethyl)[1,1′

-biphenyl]-2-sulfonamide;

2-Butyl-4-chloro-1-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-1H-imidazole-5-carboxamide;

N-(4,5-dimethyl-3-isoxazolyl)-4′

-[[(2-methyl-4-quinolinyl)oxy]methyl] [1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-dimethyl-3-isoxazolyl)-4′

-[[(2-ethyl-4-quinolinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-dimethyl-3-isoxazolyl)-4′

-[[(2-ethyl-5,6,7,8-tetrahydro-4-quinolinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-dimethyl-3-isoxazolyl)-4′

-[[(2-propyl-4-quinolinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-dimethyl-3-isoxazolyl)-4′

-[(5,6,7,8-tetrahydro-2,4-dimethyl-7-oxopyrido[2,3-d]pyrimidin-8-yl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[[(2-Ethyl-4-quinolinyl)oxy]methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-dimethyl-3-isoxazolyl)-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-4′

-[[(5,6,7,8-tetrahydro-2-ethyl-4-quinolinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

3-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-2-ethyl-N-methyl-3H-benzimidazole-4-carboxamide;

1-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-2-ethyl-1H-benzimidazole-7-carboxylic acid phenylmethyl ester;

1-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-2-ethyl-1H-benzimidazole-7-carboxylic acid 2-phenylethyl ester;

1-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-2-ethyl-1H-benzimidazole-7-carboxylic acid 2-(2-oxo-1-pyrrolidinyl)ethyl ester;

1-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-2-ethyl-1H-benzimidazole-7-carboxylic acid 3-(2-oxo-1-pyrrolidinyl)propyl ester;

2′

-Cyano-N-(4,5-dimethyl-3-isoxazolyl)-4′

-[[(2-ethyl-4-quinolinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

2′

-(Cyanomethyl)-N-(4,5-dimethyl-3-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

3-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-5-ethyl-N-methyl-2-propyl-3H-imidazole-4-carboxamide;

1-[[2-Chloro-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-2-propyl-1H-imidazole-5-carboxamide;

3-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-5-ethyl-2-propyl-3H-imidazole-4-carboxamide;

3-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-2-ethoxy-N-methyl-3H-benzimidazole-4-carboxamide;

3-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-2-ethoxy-N,N-dimethyl-3H-benzimidazole-4-carboxamide;

2-[[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]propylamino]-3-pyridinecarboxylic acid;

4′

-[(3,5-Dibutyl-1H-1,2,4-triazol-1-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-dimethyl-3-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2,7-Diethyl-5H-pyrazolo[1,5-b][1,2,4]triazol-5-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

N-[2-Butyl-3-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-3,4-dihydro-4-oxo-6-quinazolinyl]-N′

-methyl-N′

-(1-methylethyl)urea;

2-[[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]propylamino]-N-methyl-3-pyridinecarboxamide;

4′

-[[(3-Methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-N-(4,5-dimethyl-3-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-dimethyl-3-isoxazolyl)-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-dimethyl-3-isoxazolyl)-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-dimethyl-3-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-(methoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

3-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-2-ethyl-5-methyl-3H-imidazole-4-carboxamide;

4′

-[(2-Butyl-3,4-dihydro-4-oxo-3-quinazolinyl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-2-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxopentyl)-L-valinamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-[(4,4-dimethyl-2-oxo-1-pyrrolidinyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(3,5-Dibutyl-1H-1,2,4-triazol-1-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-[2-[[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-[(2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl][1,1′

-biphenyl]-2-yl]methyl]methylamino]ethyl]acetamide;

4-[(2-Ethyl-5,7-dimethyl-3H-imidazo [4,5-b]pyridin-3-yl)methyl]-2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-2-acetic acid ethyl ester;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N2-(1-oxopentyl)-N-propyl-L-valinamide;

N2-[[2′

-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N2-(1-oxopentyl)-N-[(tetrahydro-2-furanyl)methyl]-L-valinamide;

2′

-Chloro-N-(4,5-dimethyl-3-isoxazolyl)-4′

-[[(2-ethyl-4-quinolinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-dimethyl-3-isoxazolyl)-4′

-[[(2-ethyl-4-quinolinyl)oxy]methyl]-2′

-(trifluoromethyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-chloro-N-(4,5-dimethyl-3-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-[(2-methylpropoxy)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-[(ethylsulfonyl)amino][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-[(2,2,2-trifluoroethoxy)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-[(2-fluoroethoxy)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-ethoxymethyl[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2′

-(ethoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(3,3,3-trifluoropropyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethylisoxazol-3-yl)-2′

-(3-fluoropropyl) [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-(1,1-difluoroethyl)-N-(4,5-dimethylisoxazol-3-yl) [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-(2,2,2-trifluoroethyl)-N-(4,5-dimethylisoxazol-3-yl) [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethylisoxazol-3-yl)-2′

-[(2-methyl)propoxy] [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethylisoxazol-3-yl)-2′

-(2-methoxyethoxy) [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-butyl-N-(4,5-dimethylisoxazol-3-yl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(N-methoxy-N-methylaminomethyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2′

-(2,2-difluoroethoxymethyl)-N-(4,5-dimethylisoxazol-3-yl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethylisoxazol-3-yl)-2′

-(2-fluoroethyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethylisoxazol-3-yl)-2′

-(2-hydroxyethyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethylisoxazol-3-yl)-2′

-(3-methylbutyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethylisoxazol-3-yl)-2′

-(2-methypropyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[[2-(3,3-Difluorobutyl)-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl]methyl]-N-(4,5-dimethylisoxazol-3-yl)-2′

-(ethoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-(3,3,3-trifluoropropyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethylisoxazol-3-yl)-2′

-[(1,1-dimethylethoxy)methyl][1,1′

-biphenyl]-2-sulfonamide;

1-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl-2-methoxymethyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl-2-methoxymethyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-N-methyl-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl-2-methyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl-2-methyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-N-methyl-2-propyl-1H-imidazole-5-carboxamide;

N,4-Diethyl-[[2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl-2-methyl][1,1′

-biphenyl]-4-yl]methyl]-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl-2-methyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-N-(1-methylethyl)-2-propyl-1H-imidazole-5-carboxamide;

N-(3,4-Dimethyl-5-isoxazolyl)-2′

-ethoxymethyl-4′

-[[(6-ethyl-3-methoxy-2-methyl-4-pyridinyl)oxy]methyl] [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(5-Acetyl-4-ethyl-2-propylimidazol-1-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-methyl [1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(6-ethyl-3-methoxy-2-methyl-4-pyridinyl)oxy]methyl]-2′

-propyl [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-3′

-chloro-N-(3,4-dimethyl-5-isoxazolyl)-5-methoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-3′

-fluoro-4-methoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-5′

-chloro-N-(3,4-dimethyl-5-isoxazolyl)-2′

-fluoro-4-methoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-3′

-chloro-N-(3,4-dimethyl-5-isoxazolyl)-4-methoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-4-methoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-(ethoxymethyl)-4-methoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-3′

-fluoro-5-methoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-5′

-chloro-N-(3,4-dimethyl-5-isoxazolyl)-2′

-fluoro-5-methoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-5-methoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-(ethoxymethyl)-5-methoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-3′

-fluoro-4,5-dimethoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-5′

-chloro-N-(3,4-dimethyl-5-isoxazolyl)-2′

-fluoro-4,5-dimethoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-3′

-chloro-N-(3,4-dimethyl-5-isoxazolyl)-4,5-dimethoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-4,5-dimethoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-(ethoxymethyl)-4,5-dimethoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-5′

-chloro-N-(3,4-dimethyl-5-isoxazolyl)-2′

-fluoro [1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-3′

-chloro-N-(3,4-dimethyl-5-isoxazolyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-4-methoxy-3′

-methyl[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-3′

-fluoro-4-methoxy[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-3′

-methyl[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-5-fluoro[1,1′

-biphenyl]-2-sulfonamide;

N²-(Cyclopropylcarbonyl)-N²-[[2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-L-valinamide;

N²-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N,3-dimethyl-N²-(1-oxobutyl)-L-valinamide;

N²-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N²-(2-methyl-1-oxopropyl)-L-valinamide;

N²-(Cyclopentylcarbonyl)-N²-[[2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-L-valinamide;

N²-[[2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl]-3-fluoro[1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N²-(1-oxobutyl)-L-valinamide;

N²-[[2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-(1-methylethyl)-N²-(1-oxobutyl)-L-valinamide;

N²-[[2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-(2-methoxyethyl)-N²-(1-oxobutyl)-L-valinamide;

N-(Cyclopropylmethyl)-N²-[[2′

-[[(3,4-dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N²-(1-oxobutyl)-L-valinamide;

N²-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N²-(1-oxobutyl)-N-(3-pyridinyl)-L-valinamide;

N²-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N²-(1-oxopentyl)-L-valinamide;

N-Methyl-N²-[[2′

-[[(3-methyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N²-(1-oxopentyl)-L-valinamide;

N²-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-ethyl-N²-(1-oxobutyl)-L-valinamide;

N²-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl]-5′

-fluoro[1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N²-(1-oxobutyl)-L-valinamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(2,6-dimethyl-3-methoxy-4-pyridinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(2,6-dimethyl-3-methoxy-4-pyridinyl)oxy]methyl]-3′

-fluoro [1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-3′

-fluoro-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-5-fluoro-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-(hydroxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

N-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl]-2-(ethoxymethyl)[1,1′

-biphenyl]-4-yl]methyl]-1-[(1-oxopentyl)amino]cyclopentanamide;

and salts, enantiomers and diasteriomer thereof.

26. A method for the treatment of an endothelin-dependent or angiotensin II-dependent disorder, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

27. A method for the treatment of hypertension, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

28. A method for the treatment of pulmonary hypertension, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

29. A method for the treatment of primary pulmonary hypertension, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

30. A method for the treatment of low renin hypertension, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

31. A method for the treatment of male erectile dysfunction, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

32. A method for the treatment of male or female sexual dysfunction, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

33. A method for the treatment of heart failure, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

34. A method for the treatment of atherosclerosis, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

35. A method for the treatment of restenosis, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

36. A method for the treatment of endotoxemia, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

37. A method for the inhibition of cell growth, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

38. A method for the treatment of cancer, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

39. A method for the treatment of migraine, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

40. A method for the treatment of asthma, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

41. A method for the treatment of ischemia, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

42. A method for the treatment of subarachnoid hemorrhage, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

43. A method for the treatment of benign prostatic hypertrophy, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

44. A method for the treatment of renal, glomerular or mesangial cell disorders, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

45. A method for the treatment of acute or chronic renal failure, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

46. A pharmaceutical composition for the treatment of an endothelin-dependent or angiotensin II-dependent disorder, comprising a pharmaceutically acceptable vehicle or diluent and at least one compound of claim 1 in an amount effective therefor.

47. A compound of the formula

48. The compound of claim 47, wherein R₅₁ is —

CH₂OCH₂CH₂OCH₃, —

CH₂OCH₂CH₂Si(CH₃)₃, —

CH₂OCH₃, or —

CH₂OCH₂-aryl.

49. A compound of the formula

50. The compound of claim 49, wherein R₅₁ is —

CH₂OCH₂CH₂OCH₃, —

CH₂OCH₂CH₂Si(CH₃)₃, —

CH₂OCH₃, or —

CH₂OCH₂-aryl.

51. A compound of the formula

52. A compound of claim 51

wherein

53. A process for the preparation of a compound of claim 1, comprising at least one of the following steps:

a) displacement of a leaving group R₅₀ via the anion of a compound R₁—

H from a compound of the formula

wherein R₁, R₂, R_3, R₁₀₁, R₁₀₂, R₁₀₃, and R₁₀₄ are as defined in claim 1, R₅₀ is hydroxy, chloro, bromo, iodo, —

OSO₂-alkyl or —

OSO₂-aryl, and R₅₁ is hydrogen or a suitable nitrogen protecting group, using a Mitsunobu reaction or S_n1 or S_n2 displacement reaction, with removal of said nitrogen protecting group as appropriate;

b) removal of the nitrogen protecting group R₅₁ from a compound of formula

wherein R₁, R₂, R_3, R₁₀₁, R₁₀₂, R₁₀₃, and R₁₀₄ are as defined in claim 1, and R₅₁ is a suitable nitrogen protecting group;

c) organometallic coupling of a compound of formula

with a compound of formula

wherein

R₁, R₂, R_3, R₁₀₁, R₁₀₂, R₁₀₃, and R₁₀₄ are as defined for a compound of formula I and R₅₁ is a suitable nitrogen protecting group;

R₅₂ is chloro, bromo, iodo or —

OSO₂CF₃ and R₅₄ is a boronic acid, boronic ester or stannane derivative;

or R₅₂ is a boronic acid, boronic ester or stannane derivative and R₅₄ is chloro, bromo, iodo or —

OSO₂CF₃;

d) acylation of a compound of the formula

wherein R₁, R_3, R₁₀₁, R₁₀₂, R₁₀₃, and R₁₀₄ are as defined in claim 1, and R₅₁ is hydrogen or a suitable nitrogen protecting group, with an acylating agent of the formula R₅₅—

(C═

O)R₂₂, R₁₉N═

C═

O, R₅₅—

CO₂R₁₈, R₅₅SO₂R₂₂, wherein R₁₈, R₁₉ and R₂₂ are as defined in claim 1 and R₅₅ is an activating group for an acid, or made using an acid activating agent, with removal of said nitrogen protecting group as appropriate;

or

e) reductive amination of a compound of formula

wherein R₁, R_3, R₁₀₁, R₁₀₂, R₁₀₃, and R₁₀₄ are as defined in claim 1, and R₅₁ is hydrogen or a suitable nitrogen protecting group, with an amine of the formula

wherein R₂₃, R₂₄, and x are as defined in claim 1, with removal of said nitrogen protecting group as appropriate.

54. A compound of claim 1, wherein said compound is selected from the group consisting of:

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-ethyl[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-(2,2-dimethylpropyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-(2-ethoxyethyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-ethyl[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(2,2-dimethylpropyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(2-ethoxyethyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-2′

-ethyl-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-2′

-(2,2-dimethylpropyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-2′

-(2-ethoxyethyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

2′

-[(1,1-Dimethylethoxy)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-2′

-ethyl-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-2′

-(2,2-dimethylpropyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl] [1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-2′

-(2-ethoxyethyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

2′

-[(1,1-Dimethylethoxy)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-4-isoxazolyl)-2′

-ethyl-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-2′

-(2,2-dimethylpropyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-2′

-(2-ethoxyethyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

2′

-[(1,1-Dimethylethoxy)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-2′

-ethyl-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-2′

-(2,2-dimethylpropyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-2′

-(2-ethoxyethyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl][1,1′

-biphenyl]-2-sulfonamide;

2′

-[(1,1-Dimethylethoxy)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl][1,1′

-biphenyl]-2-sulfonamide

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-(1-hydroxyethyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-(1-hydroxy-1-methylethyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-(1,2,3,4-tetrahydrofur-1-yl)[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-(1-hydroxyethyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-(1-hydroxy-1-methylethyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-(1,2,3,4-tetrahydrofur-1-yl)[1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2′

-(1-hydroxyethyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2′

-(1-hydroxy-1-methylethyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2′

-(1,2,3,4-tetrahydrofur-1-yl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(1-hydroxyethyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(1-hydroxy-1-methylethyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(1,2,3,4-tetrahydrofur-1-yl)[1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-(1-hydroxyethyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-(1-hydroxy-1-methylethyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-(1,2,3,4-tetrahydrofur-1-yl)[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2′

-(1-hydroxyethyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2′

-(1-hydroxy-1-methylethyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2′

-(1,2,3,4-tetrahydrofur-1-yl)[1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-(3,3,3-trifluoropropyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-(3,3,3-trifluoropropyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2′

-(3,3,3-trifluoropropyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2′

-(3,3,3-trifluoropropyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-propyl[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-propyl[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2′

-propyl[1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2′

-propyl[1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-(2-fluoroethoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-(2-fluoroethoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2′

-(2-fluoroethoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2′

-(2-fluoroethoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[[2-(2,2-Difluorobutyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl]methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-propyl[1,1′

-biphenyl]-2-sulfonamide;

4′

-[[2-(2,2-Difluorobutyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl]methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-propyl[1,1′

-biphenyl]-2-sulfonamide;

4′

-[[2-(3,3,3-Trifluorobutyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl]methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(ethoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[[2-(3,3,3-Trifluorobutyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl]methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-(ethoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[[2-(3,3,3-Trifluorobutyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl]methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-propyl[1,1′

-biphenyl]-2-sulfonamide;

4′

-[[2-(3,3,3-Trifluorobutyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl]methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-propyl[1,1′

-biphenyl]-2-sulfonamide;

4′

-[[2-(3,3,3-Trifluoropropyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl]methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(ethoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[[2-(3,3,3-Trifluoropropyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl]methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-(ethoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[[2-(3,3,3-Trifluoropropyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl]methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-propyl[1,1′

-biphenyl]-2-sulfonamide;

4′

-[[2-(3,3,3-Trifluoropropyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl]methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-propyl [1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-(1,1-difluoropropyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-(1,1-difluoropropyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2′

-(1,1-difluoropropyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2′

-(1,1-difluoropropyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(1,1-difluoropropyl)[1,1′

-biphenyl]-2-sulfonamide;

4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2′

-(1,1-difluoropropyl)[1,1′

-biphenyl]-2-sulfonamide;

1-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl-2-ethyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-N-methyl-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl-2-propyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-N-methyl-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl-2-(2-fluoroethoxymethyl)][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-N-methyl-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl-2-ethyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl-2-propyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl-2-(ethoxymethyl)][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl-2-ethyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-N-methyl-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl-2-propyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-N-methyl-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl-2-(2-fluoroethoxymethyl)][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-N-methyl-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl-2-(ethoxymethyl)][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-N-methyl-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl-2-ethyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl-2-propyl][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl-2-(2-fluoroethoxymethyl)][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-2-propyl-1H-imidazole-5-carboxamide;

1-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl-2-(ethoxymethyl)][1,1′

-biphenyl]-4-yl]methyl]-4-ethyl-2-propyl-1H-imidazole-5-carboxamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(6-ethyl-3-methoxy-2-methyl-4-pyridinyl)oxy]methyl]-2′

-ethyl [1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(6-ethyl-3-methoxy-2-methyl-4-pyridinyl)oxy]methyl]-2′

-ethyl [1,1′

-biphenyl]-2-sulfonamide;

N-(4, 5-Dimethyl-3-isoxazolyl)-4′

-[[(3-methoxy-2-methyl-6-propyl-4-pyridinyl)oxy]methyl]-2′

-ethyl [1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(3-methoxy-2-methyl-6-propyl-4-pyridinyl)oxy]methyl]-2′

-ethyl [1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(3-methoxy-2-methyl-6-propyl-4-pyridinyl)oxy]methyl]-2′

-(ethoxymethyl)[1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(3-methoxy-2-methyl-6-propyl-4-pyridinyl)oxy]methyl]-2′

-(ethoxymethyl) [1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(3-methoxy-2-methyl-6-propyl-4-pyridinyl)oxy]methyl]-2′

-propyl[1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(3-methoxy-2-methyl-6-propyl-4-pyridinyl)oxy]methyl]-2′

-propyl[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(3-ethoxy-6-ethyl-2-methyl-4-pyridinyl)oxy]methyl]-2′

-ethyl [1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(3-ethoxy-6-ethyl-2-methyl-4-pyridinyl)oxy]methyl]-2′

-ethyl[1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(3-ethoxy-6-ethyl-2-methyl-4-pyridinyl)oxy]methyl]-2′

-ethoxymethyl [1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(3-ethoxy-6-ethyl-2-methyl-4-pyridinyl)oxy]methyl]-2′

-ethoxymethyl [1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(3-ethoxy-6-ethyl-2-methyl-4-pyridinyl)oxy]methyl]-2′

-propyl [1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(3-ethoxy-6-ethyl-2-methyl-4-pyridinyl)oxy]methyl]-2′

-propyl [1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(3-ethoxy-2-methyl-6-propyl-4-pyridinyl)oxy]methyl]-2′

-ethyl [1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(3-ethoxy-2-methyl-6-propyl-4-pyridinyl)oxy]methyl]-2′

-ethyl [1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(3-ethoxy-2-methyl-6-propyl-4-pyridinyl)oxy]methyl]-2′

-ethoxymethyl [1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(3-ethoxy-2-methyl-6-propyl-4-pyridinyl)oxy]methyl]-2′

-ethoxymethyl [1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(3-ethoxy-2-methyl-6-propyl-4-pyridinyl)oxy]methyl]-2′

-propyl [1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(3-ethoxy-2-methyl-6-propyl-4-pyridinyl)oxy]methyl]-2′

-propyl [1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(2,6-dimethyl-3-ethoxy-4-pyridinyl)oxy]methyl]-2′

-ethyl [1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(2,6-dimethyl-3-ethoxy-4-pyridinyl)oxy]methyl]-2′

-ethyl [1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(2,6-dimethyl-3-ethoxy-4-pyridinyl)oxy]methyl]-2′

-ethoxymethyl [1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(2,6-dimethyl-3-ethoxy-4-pyridinyl)oxy]methyl]-2′

-ethoxymethyl [1,1′

-biphenyl]-2-sulfonamide;

N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(2,6-dimethyl-3-ethoxy-4-pyridinyl)oxy]methyl]-2′

-propyl [1,1′

-biphenyl]-2-sulfonamide;

N-(3,4-Dimethyl-5-isoxazolyl)-4′

-[[(2,6-dimethyl-3-ethoxy-4-pyridinyl)oxy]methyl]-2′

-propyl [1,1′

-biphenyl]-2-sulfonamide;

and salts, enantiomers and diasteriomers thereof.

55. A compound of formula LXX, or an enantiomer, diastereomer or salt thereof

56. A compound of claim 5, wherein R₁ is

57. A compound of claim 56, wherein R₂ is alkyl, haloalkyl, alkoxyalkyl or haloalkoxyalkyl and R₁₀₁, R₁₀₂, R₁₀₃, R₁₀₄ are each independently hydrogen, halogen, or alkyl.

58. A compound of claim 56, wherein R₂ is —

CH₂Y.

59. A compound of claim 58, wherein Y is Q.

68. A compound of claim 5, where in R₁ is

72. A method for the treatment of chronic obstructive pulmonary disease, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

73. A method for the alleviation of pain associated with prostate cancer, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

74. A method for preventing or reducing organ damage associated with the cell poliferative effects of endothelin, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

75. A method for reducing general morbidity and mortality associated with endothelin-dependent or angiotensin II-depedendent disorders, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

76. A method for the treatment of diabetic nephropathy, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

77. A method for the treatment of dementia, comprising the step of administering to a subject in need thereof an amount effective therefor of at least one compound of claim 1.

78. A compound of claim 1 wherein R₃ is other than pyridyl when R₁ is A.

79. The method of claim 26 wherein said compound of claim 1 is administered prior to, simultaneously with or following the administration of at least one ACE inhibitor.

80. The method of claim 79 wherein said ACE inhibitor is selected from captopril, zofenopril, fosinopril, ceranapril, alacepril, enalapril, delapril, pentopril, quinapril, ramipril, or lisinopril.

81. The method of claim 26 wherein said compound of claim 1 is administered prior to, simultaneously with or following the administration of at least one vasopepsidase inhibtor.

82. The method of claim 81 wherein said vasopepsidase inhibitor is selected from omapatrilat or gemopatrilat.

83. The method of claim 26 wherein said compound of claim 1 is administered prior to, simultaneously with or following the administration of at least one HMG CoA reductase inhibitor.

84. The method of claim 83 wherein said HMG CoA reductase inhibitor is selected from pravastatin, lovastatin, atorvastatin, simvastatin, NK-104 or ZD-4522.

85. The method of claim 26 wherein said compound of claim 1 is administered prior to, simultaneously with or following the administration of at least one anti-platelet agent.

86. The method of claim 85 wherein said anti-platelet agent is selected from clopidigrel, ticlopidine, CS-747 or aspirin.

87. The method of claim 26 wherein said compound of claim 1 is administered prior to, simultaneously with or following the administration of at least one anti-diabetic agent.

88. The method of claim 87 wherein said anti-diabetic agent is selected from biguanides or biguanide/glyburide combinations.

89. The method of claim 26 wherein said compound of claim 1 is administered prior to, simultaneously with or following the administration of at least one beta-adrenergic agent.

90. The method of claim 89 wherein said beta-adrenergic agent is selected from carvedilol or metoprolol.

91. The method of claim 26 wherein said compound of claim 1 is administered prior to, simultaneously with or following the administration of at least one mineralocorticoid receptor antagonist.

92. The method of claim 91 wherein said mineralocorticoid receptor antagonist is selected from spironolactone or eplerenone.

93. The pharmaceutical composition of claim 46 further comprising at least one ACE inhibitor.

94. The pharmaceutical composition of claim 93 wherein said ACE inhibitor is selected from captopril, zofenopril, fosinopril, ceranapril, alacepril, enalapril, delapril, pentopril, quinapril, ramipril, or lisinopril.

95. The pharmaceutical composition of claim 46 further comprising at least one vasopepsidase inhibitor.

96. The pharmaceutical composition of claim 95 wherein said vasopepsidase inhibitor is selected from omapatrilat or gemopatrilat.

97. The pharmaceutical composition of claim 46 further comprising at least one HMG CoA reductase inhibitor.

98. The pharmaceutical composition of claim 97 wherein said HMG CoA reductase inhibitor is selected from pravastatin, lovastatin, atorvastatin, simvastatin, NK-104 or ZD-4522.

99. The pharmaceutical composition of claim 46 further comprising at least one anti-platelet agent.

100. The pharmaceutical composition of claim 99 wherein said anti-platelet agent is selected from clopidigrel, ticlopidine, CS-747 or aspirin.

101. The pharmaceutical composition of claim 46 further comprising at least one anti-diabetic agent.

102. The pharmaceutical composition of claim 101 wherein said anti-diabetic agent is selected from biguanides or biguanide/glyburide combinations.

103. The pharmaceutical composition of claim 46 further comprising at least one beta-adrenergic agent.

104. The pharmaceutical composition of claim 103 wherein said beta-adrenergic agent is selected from carvedilol or metoprolol.

105. The pharmaceutical composition of claim 46 further comprising at least one mineralocorticoid receptor antagonist.

106. The pharmaceutical composition of claim 105 wherein said mineralocorticoid receptor antagonist is selected from spironolactone or eplerenone.

60. A crystalline form of 4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(ethoxymethyl) [1,1′

-biphenyl]-2-sulfonamide having a melting point of about 148°

C.

61. N2-[[2′

-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′

-biphenyl]-4-yl]methyl]-N-methyl-N2-(1-oxobutyl)-L-valinamide or a salt, enantiomer or diasteriomer thereof.

62. 4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(ethoxymethyl) [1,1′

-biphenyl]-2-sulfonamide or a salt, enantiomer or diasteriomer thereof.

107. The compound of claim 62 that is (+)-4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(ethoxymethyl) [1,1′

-biphenyl]-2-sulfonamide.

108. The compound of claim 62 that is (−

)-4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(ethoxymethyl) [1,1′

-biphenyl]-2-sulfonamide.

63. 4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-(2-fluoroethoxymethyl) [1,1′

-biphenyl]-2-sulfonamide or a salt, enantiomer or diasteriomer thereof.

64. 4′

-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′

-propyl [1,1′

-biphenyl]-2-sulfonamide or a salt, enantiomer or diasteriomer thereof.

65. N-(4,5-Dimethyl-3-isoxazolyl)-2′

-ethoxymethyl-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl] [1,1′

-biphenyl]-2-sulfonamide or a salt, enantiomer or diasteriomer thereof.

66. N-(4,5-Dimethyl-3-isoxazolyl)-2′

-[(2-fluoroethoxy)methyl]-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl][1,1′

-biphenyl]-2-sulfonamide or a salt, enantiomer or diasteriomer thereof.

69. A compound of claim 68, wherein R₂ is hydrogen, alkyl, haloalkyl, alkoxyalkyl or haloalkoxyalkyl and R₁₀₁, R₁₀₂, R₁₀₃, R₁₀₄ are each independently hydrogen, halogen, or alkyl.

70. A compound of claim 68 wherein R₂ is —

CH₂Y.

71. A compound of claim 70, wherein Y is Q.

67. N-(4,5-Dimethyl-3-isoxazolyl)-4′

-[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′

-propyl [1,1′

-biphenyl]-2-sulfonamide or a salt, enantiomer or diasteriomer thereof.