Biphenyl sulfonamides as dual angiotensin endothelin receptor antagonists
First Claim
Patent Images
1. A compound of the following formula I, or an enantiomer, diastereomer, salt or metabolite thereof:
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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.
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Citations
108 Claims
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1. A compound of the following formula I, or an enantiomer, diastereomer, salt or metabolite thereof:
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 68, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106)
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2. A compound of claim 1, wherein
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3. A compound of claim 1, wherein
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4. A compound of claim 1, wherein
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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.
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6. A compound of claim 5, wherein R1 is
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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.
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8. A compound of claim 6, wherein R2 is —
- CH2Y.
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9. A compound of claim 8, wherein Y is Q.
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10. A compound of claim 5, wherein R1 is
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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.
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12. A compound of claim 10, wherein R2 is —
- CH2Y.
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13. A compound of claim 12, wherein Y is Q.
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14. A compound of claim 5, wherein R1 is
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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.
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16. A compound of claim 14, wherein R2 is —
- CH2Y.
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17. A compound of claim 16, wherein Y is Q.
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18. A compound of claim 1, wherein R2 is alkoxyalkyl alkyl, haloalkyl or haloalkoxyalkyl
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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.
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20. A compound of claim 1, wherein R2 is —
- CH2Y.
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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.
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22. A compound of claim 20, wherein Y is Q.
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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.
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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-sulfonamide4′
-[(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.
- -[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)[1,1′
-
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.
- -[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)[1,1′
-
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.
- CH2OCH2CH2OCH3, —
-
49. A compound of the formula
-
50. The compound of claim 49, wherein R51 is —
- CH2OCH2CH2OCH3, —
CH2OCH2CH2Si(CH3)3, —
CH2OCH3, or —
CH2OCH2-aryl.
- CH2OCH2CH2OCH3, —
-
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 formulawherein R1, R2, R3, 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 Sn1 or Sn2 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, R3, 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, R3, 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, R3, 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;
ore) reductive amination of a compound of formula wherein R1, R3, 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-sulfonamide4′
-[(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.
-
2. A compound of claim 1, wherein
-
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.
- -[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′
-
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.
- -[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl][1,1′
-
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. - View Dependent Claims (107, 108)
-
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.
- -[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′
-
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.
- )-4′
-
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′
-
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.
- -[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′
-
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.
- -[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5-dimethyl-3-isoxazolyl)-2′
-
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.
- -ethoxymethyl-4′
-
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. - View Dependent Claims (69, 70, 71)
-
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.
-
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.
- -[(2-fluoroethoxy)methyl]-4′
-
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.
- -[[(3-methoxy-2,6-dimethyl-4-pyridinyl)oxy]methyl]-2′
Specification
- Resources
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Current AssigneePharmacopeia LLC (Ligand Pharmaceuticals, Inc.)
-
Original AssigneeBristol-Myers Squibb Company
-
InventorsMacor, Jhon E., Gu, Zhengxiang, Murugesan, Natesan, Tellew, John E.
-
Granted Patent
-
Time in Patent OfficeDays
-
Field of Search
-
US Class Current514/258.1
-
CPC Class CodesC07D 261/16 Benzene-sulfonamido isoxazolesC07D 401/12 linked by a chain containin...C07D 403/14 containing three or more he...C07D 413/12 linked by a chain containin...C07D 413/14 containing three or more he...C07D 417/14 containing three or more he...C07D 471/04 Ortho-condensed systemsC07D 487/04 Ortho-condensed systems