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US 8,796,280 B2Granted
2,3-disubstituted pyrazinesulfonamides as CRTH2 inhibitors
AssigneeMerck Serono SA
InventorsPatrick Page, Matthias Schwarz, Eric Sebille, Christophe Cleva, Cedric Merlot, Maurizio Maio
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Abstract
The present invention is related to the use of 2,3 substituted pyrazine sulfonamides of formula (I) for the treatment and/or prevention of allergic diseases, inflammatory dermatoses and other diseases with an inflammatory component. Specifically, the present invention is related to the use of 2,3 substituted pyrazine sulfonamides for the modulation, notably the inhibition, of CRTH2 activity.
Claims3
A pharmaceutical composition which inhibits chemoattractant receptor-homologous molecule expressed on T-helper 2 cell activity comprising a pharmaceutically acceptable carrier, diluent or excipient and a compound according to Formula (I),
- or stereoisomers, tautomers and pharmaceutically acceptable salts thereof, wherein:
- A is selected from the group consisting of:
- where n is 0, 1, 2, 3 or 4;
- m is 2;
- B is selected from the group consisting of phenyl or piperazinyl;
- R1 is hydrogen;
- R2 is phenyl, wherein R2 is optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, C1-C6-alkyl;
- R3 is selected from the group consisting of C1-C6-alkyl, aryl, heteroaryl, C1-C6-alkylaryl, C1-C6-alkylheteroaryl, C3-C8-cycloalkyl and C3-C8-heterocycloalkyl wherein each of said C1-C6-alkyl, aryl, heteroaryl, C1-C6-alkylaryl, C1-C6-alkylheteroaryl, C3-C8-cycloalkyl and C3-C8-heterocycloalkyl is optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, C1-C6-alkyl, C1-C6-alkoxy, heteroaryl, aryl, thioalkoxy and thioalkyl, or wherein said aryl, heteroaryl, C1-C6-alkylaryl, C1-C6-alkylheteroaryl, C3-C8-cycloalkyl or C3-C8-heterocycloalkyl may be fused to one or more aryl, heteroaryl, C3-C8-cycloalkyl or C3-C8-heterocycloalkyl groups and may be substituted with one or more substituents selected of the group consisting of C1-C6-alkyl, alkoxy, aryl, heteroaryl, carboxyl, cyano, halogen, hydroxy, amino, aminocarbonyl, nitro, sulfoxy, sulfonyl, sulfonamide and trihaloalkyl;
- R7 is selected from the group consisting of hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, aryl, heteroaryl, C3-C8-cycloalkyl, C3-C8-heterocycloalkyl, carboxy, cyano, amino and hydroxy;
- the aryl is selected from phenyl or naphthyl;
- and
- the heteroaryl is selected from pyridyl, indolyl, benzimidazolyl and quinolyl.
9 more elements
A compound selected from the group consisting of:
- N-{3-[4-(1H-indol-1-ylmethyl)phenyl]pyrazin-2-yl}-2-(trifluoromethyl)-benzenesulfonamide,
- 2-chloro-N-{3-[4-({methyl[4-(trifluoromethoxy)phenyl]amino}methyl)phenyl]-pyrazin-2-yl}benzenesulfonamide,
- N-(3-{4-[(2-ethyl-1H-benzimidazol-1-yl)methyl]phenyl}pyrazin-2-yl)-2-(trifluoromethyl)benzenesulfonamide,
- 2-chloro-N-[3-(4-{[methyl(phenyl)amino]methyl}phenyl)pyrazin-2-yl]-benzenesulfonamide,
- 2-chloro-N-(3-{4-[(2-naphthyloxy)methyl]phenyl}pyrazin-2-yl)benzene-sulfonamide,
- 2-chloro-N-{3-[4-(1H-indol-1-ylmethyl)phenyl]pyrazin-2-yl}benzenesulfonamide,
- 2-chloro-N-(3-{4-[(5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl]phenyl}-pyrazin2-yl)benzenesulfonamide,
- 2-chloro-N-(3-{4-[(2-ethyl-1H-benzimidazol-1-yl)methyl]phenyl}pyrazin-2-yl)-benzenesulfonamide,
- N-(3-{4-[(1,3-benzodioxol-5-ylamino)methyl]phenyl}pyrazin-2-yl)-2-(trifluoromethyl)benzenesulfonamide,
- N-[3-(4-{[(3-methoxybenzyl)oxy]methyl}phenyl)pyrazin-2-yl]-2-(trifluoromethyl)benzenesulfonamide,
- 3-chloro-N-{3-[4-({methyl [4-(trifluoromethoxy)phenyl]amino}methyl)phenyl]-pyrazin-2-yl}benzenesulfonamide,
- 4-phenoxy-N-{3-[4-(quinolin-2-ylmethyl)piperazin-1-yl]pyrazin-2-yl}-benzenesulfonamide,
- 4-methyl-N-{3-[4-({methyl [4-(trifluoromethoxy)phenyl]amino}methyl)phenyl]-pyrazin-2-yl}benzenesulfonamide,
- 4-chloro-N-[3-(4-{[methyl(phenyl)amino]methyl}phenyl)pyrazin-2-yl]-benzenesulfonamide,
- 4-cyano-N-{3-[4-({methyl[4-(trifluoromethoxy)phenyl]-amino}-methyl)phenyl]pyrazin-2-yl}benzenesulfonamide,
- N-[3-(4-{[(4-Fluoro-phenyl)-methyl-amino]-methyl}-phenyl)-pyrazin-2-yl]-2-trifluoromethyl-benzenesulfonamide,
- N-(3-{4-[(Methyl-phenyl-amino)-methyl]-phenyl}-pyrazin-2-yl)-2-trifluoromethyl-benzenesulfonamide,
- N-[3-(4-{[(4-Cyano-phenyl)-methyl-amino]-methyl}-phenyl)-pyrazin-2-yl]-2-trifluoromethyl-benzenesulfonamide,
- N-{3-[4-(4-Fluoro-phenoxymethyl)-phenyl]-pyrazin-2-yl}-2-trifluoromethyl-benzenesulfonamide,
- N-(3-{4-[(Ethyl-phenyl-amino)-methyl]-phenyl}-pyrazin-2-yl)-2-trifluoromethyl-benzenesulfonamide,
- N-{3-[4-(2,3-Dihydro-benzo[1,4]oxazin-4-ylmethyl)-phenyl]-pyrazin-2-yl}-2-trifluoromethyl-benzenesulfonamide,
- N-[3-(4-{[(3-Fluoro-phenyl)-methyl-amino]-methyl}-phenyl)-pyrazin-2-yl]-2-trifluoromethyl-benzenesulfonamide,
- N-{3-[4-(6-Chloro-pyridin-3-yloxymethyl)-phenyl]-pyrazin-2-yl}-2-trifluoromethyl-benzenesulfonamide,
- N-{3-[4-(2-Pyridin-2-yl-indol-1-ylmethyl)-phenyl]-pyrazin-2-yl}-2-trifluoromethyl-benzenesulfonamide,
- N-{3-[4-(5-Fluoro-indol-1-ylmethyl)-phenyl]-pyrazin-2-yl}-2-trifluoromethyl-benzenesulfonamide,
- N-[3-(4-Phenoxymethyl-phenyl)-pyrazin-2-yl]-2-trifluoromethyl-benzenesulfonamide,
- N-[3-(4-{[(4-Chloro-phenyl)-methyl-amino]-methyl}-phenyl)-pyrazin-2-yl]-2-trifluoromethyl-benzenesulfonamide,
- 2-Chloro-N-[3-(4-{[(4-cyano-phenyl)-methyl-amino]-methyl}-phenyl)-pyrazin-2-yl]-benzenesulfonamide,
- N-[3-(4-{[(3,4-Dichloro-phenyl)-methyl-amino]-methyl}-phenyl)-pyrazin-2-yl]-2-trifluoromethyl-benzenesulfonamide,
- N-{3-[4-(4-Cyano-phenoxymethyl)-phenyl]-pyrazin-2-yl}-2-trifluoromethyl-benzenesulfonamide,
- N-{3-[4-(6-Fluoro-indol-1-ylmethyl)-phenyl]-pyrazin-2-yl}-2-trifluoromethyl-benzenesulfonamide,
- 2-Chloro-N-{3-[4-(5-methoxy-2-methyl-indol-1-ylmethyl)-phenyl]-pyrazin-2-yl}-benzenesulfonamide,
- N-{3-[4-(4-Methoxy-phenoxymethyl)-phenyl]-pyrazin-2-yl}-2-trifluoromethyl-benzenesulfonamide,
- N-(3-{4-[(Benzyl-pyridin-2-yl-amino)-methyl]-phenyl}-pyrazin-2-yl)-2-chloro-benzenesulfonamide,
- N-{3-[4-(2,3-Dihydro-indol-1-ylmethyl)-phenyl]-pyrazin-2-yl}-2-trifluoromethyl-benzenesulfonamide,
- N-[3-(4-{[(2,4-Dichloro-phenyl)-methyl-amino]-methyl}-phenyl)-pyrazin-2-yl]-2-trifluoromethyl-benzenesulfonamide,
- N-{3-[4-(3-Chloro-phenoxymethyl)-phenyl]-pyrazin-2-yl}-2-trifluoromethyl-benzenesulfonamide,
- 2-Chloro-N-[3-(4-{[(2,4-difluoro-phenyl)-methyl-amino]-methyl}-phenyl)-pyrazin-2-yl]-benzenesulfonamide,
- N-{3-[4-(2-Methyl-indol-1-ylmethyl)-phenyl]-pyrazin-2-yl}-2-trifluoromethyl-benzenesulfonamide,
- 2-Chloro-N-{3-[4-(5-fluoro-indol-1-ylmethyl)-phenyl]-pyrazin-2-yl}-benzenesulfonamide,
- 2-Chloro-N-[3-(4-{[(2-fluoro-phenyl)-methyl-amino]-methyl}-phenyl)-pyrazin-2-yl]-benzenesulfonamide,
- 2-Chloro-N-{3-[4-(2-methyl-indol-1-ylmethyl)-phenyl]-pyrazin-2-yl}-benzenesulfonamide,
- N-(3-{4-[(Benzyl-pyridin-2-yl-amino)-methyl]-phenyl}-pyrazin-2-yl)-2-trifluoromethyl-benzenesulfonamide,
- 2-Chloro-N-(3-{4-[(ethyl-pyridin-2-yl-amino)-methyl]-phenyl}-pyrazin-2-yl)-benzenesulfonamide, and
- N-{3-[4-(5-Chloro-2-methyl-indol-1-ylmethyl)-phenyl]-pyrazin-2-yl}-2-trifluoromethyl-benzenesulfonamide.
42 more elements
Dependencies are inferred from the claim text.