Combination products for the treatment of RSV
The present invention is directed to the combination of the RSV inhibiting Compound A, i.e. 3-({5-chloro-1-[3-(methylsulfonyl)propyl]-1H-indol-2-yl}methyl)-1-(2,2,2-trifluoroethyl) 1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one, and one or more RSV inhibiting Compound B selected from from ribavirin, GS-5806, MDT-637, BTA-9881, BMS-433771, YM-543403, A-60444, TMC-353121, RFI-641, CL-387626, MBX-300, AZ-27, MEDI8897, CR9501, palivizumab, 3-({5-chloro-1-[3-(methylsulfonyl)propyl]-1H-benzimidazol-2-yl}methyl)-1 cyclopropyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one, 3-[[7-chloro-3-(2 ethyl-sulfonylethyl)imidazo[1,2-a]pyridin-2-yl]methyl]-1-cyclopropyl-imidazo[4,5-c]pyridin-2 one, N-(2-fluoro-6-methylphenyl)-6-(4-(5-methyl-2-(7-oxa-2-azaspiro[3.5]nonan-2 yl)nicotinamido)benzoyl)-5,6-dihydro-4H-benzo[b]thieno[2,3-d]azepine-2-carboxamide, and 4-amino-8-[3-[[2-(3,4-dimethoxyphenyl)ethyl]amino]propyl]-6,6-dimethyl-2-(4-methyl 3-nitrophenyl)-3H-imidazo[4,5-h]isoquinoline-7,9(6H,8H)-dione, for treating or ameliorating RSV infection. The invention further relates to the combination product of Compound A and one or more Compound B, a pharmaceutical product comprising Compound A and one or more Compound B, the use of the combination of Compound A and one or more of Compound B—or the pharmaceutical product comprising Compound A and one or more Compound B—for the treatment of RSV infection, and a method of treating or ameliorating RSV infection in a subject in need thereof comprising administering the combination of Compound A and one or more Compound B in an effective amount to said subject.
1. A combination comprising 3-({5-chloro-1-[3-(methylsulfonyl)propyl]-1H-indol-2-yl-(methyl)-1-(2,2,2-trifluoroethyl)-1.3-dihydro-2H-imidazo[4,5-c]pyridin-2-one, or a pharmaceutically acceptable salt thereof, as Compound A, and one or more Compound B selected from ribavirin, GS-5806, MDT-637, A-60444, AZ-27, CR9501, palivizumab, N-(2-fluoro-6-methylphenyl)-6-(4-(5-methyl-2-(7-oxa-2-azaspiro[3.5]nonan-2-yl)nicotinamido)-benzoyl)-5,6-dihydro-4H-benzo[b]thieno[2,3-d]azepine-2-carboxamide, and 4-amino-8-[3-[[2-(3,4-dimethoxyphenyl)ethyl]amino]propyl]-6,6-dimethyl-2-(4-methyl-3-nitrophenyl)-3H-imidazo[4,5h]isoquinoline-7,9(6H, 8H)-dione.
2. The combination according to claim 1 wherein Compound B is ribavirin.
3. The combination according to claim 1 wherein Compound B is GS-5806.
4. The combination according to claim 1 wherein Compound B is MDT-637.
5. The combination according to claim 1 wherein Compound B is A-60444.
6. The combination according to claim 1 wherein Compound B is a monoclonal antibody selected from CR9501, and palivizumab.
7. The combination according to claim 1 wherein Compound B is N-(2-fluoro-6-methylphenyl)-6-(4-(5-methyl-2-(7-oxa-2-azaspiro[3.5]nonan-2-yl)nicotinamido)benzoyl)-5,6-dihydro-4H-benzo[b]thieno[2,3-d]azepine-2-carboxamide.
8. The combination according to claim 1 wherein Compound B is 4-amino-8-[3-[[2-(3,4-dimethoxyphenyl)ethyl]amino]propyl]-6,6-dimethyl-2-(4-methyl-3-nitrophenyl)-3H-imidazo[4,5-h]isoquinoline-7,9(6H,8H)-dione.
9. The combination according to claim 1 wherein the amount of Compound A and the amount of Compound B is such that a synergistic antiviral effect against RSV is obtained.
10. The combination according to claim 8 wherein the amount of Compound A ranges from 10 mg to 2500 mg and the amount of Compound B ranges from 10 mg to 2500 mg.
11. A pharmaceutical composition comprising a combination as claimed in claim 1 , and a pharmaceutically acceptable carrier.
12. A method for treating or ameliorating RSV infection in a subject in need thereof comprising administering the combination of 3-({5-chloro-1-[3-(methylsulfonyl)propyl]-1 H-indol-2-yl}methyl)-1-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one, or a pharmaceutically acceptable salt thereof, as Compound A, and one or more Compound B selected from ribavirin, GS-5806, MDT-637, A-60444, AZ-27, CR9501, palivizumab, N-(2-fluoro-6-methylphenyl)-6-(4-(5-methyl-2-(7-oxa-2-azaspiro[3.5]nonan-2-yl)nicotinamido)-benzoyl)-5,6-dihydro-4H-benzo[b]thieno[2,3-d]azepine-2-carboxamide, and 4-amino-8-[3-[[2-(3,4-dimethoxyphenyl)ethyl]amino]propyl]-6,6-dimethyl-2-(4-methyl-3-nitrophenyl)-3H-imidazo[4,5-h]isoquinoline-7,9(6H,8H)-dione.
13. The method as claimed in claim 12 wherein the combination of Compound A and one or more Compound B is formulated in a single pharmaceutical composition.
14. The method as claimed in claim 12 wherein the combination of Compound A and one or more Compound B is formulated as a separate pharmaceutical composition comprising Compound A and a separate pharmaceutical composition comprising one or more Compound B whereby the pharmaceutical compositions are administered simultaneously or sequentially.