DERIVATIVES OF [1, 2, 4] TRIAZOLO [4, 3 - A] PYRIDINE AS P38 - MAP KINASE INHIBITORS

摘要

This invention relates to compounds selected in the group consisting of compounds of formula (Ia) to (Id) and compositions, that are p38 MAPK inhibitors, useful as anti-inflammatory agents in the treatment of, inter alia, diseases of the respiratory tract.;

主权项

1: A compound selected from the group consisting of:
1-[3-tert-Butyl-1′-(2-[1,4]oxazepan-4-yl-ethyl)-1′H[1,4′]bipyrazolyl-5-yl]-3-{(4-[3-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-{3-tert-Butyl-1′-[2-(4-methyl-piperazin-1-yl)-ethyl]-1′H-[1,4′]bipyrazolyl-5-yl}-3-{(4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-{3-tert-Butyl-1′-[2-(4-hydroxy-piperidin-1-yl)-ethyl]-1′H-[1,4′]bipyrazolyl-5-yl}-3-{4-[3-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-(3-tert-Butyl-1′-{2-[(2-methoxy-ethyl)-methyl-amino]-ethyl}-1′H-[1,4′]bipyrazolyl-5-yl)-3-4-[3-(-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1-[3-tert-Butyl-1′-(2-piperidin-1-yl-ethyl)-1′H-[1,4′]bipyrazolyl-5-yl]-3-{4-[3-2,6-dimethyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-[3-tert-Butyl-1′-(2-[1,4]oxazepan-4-yl-ethyl)-1′H-[1,4′]bipyrazolyl-5-yl]-3-{4-[3-2,6-dimethyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-[3-tert-Butyl-1′-(2-dimethylamino-ethyl)-1′H-[1,4′]bipyrazolyl-5-yl]-3-[4-(3-dimethylamino-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea formate salt; 1-[3-tert-Butyl-1′-(2-dimethylamino-ethyl)-1′H[1,4′]bipyrazolyl-5-yl]-3-{4-[3-(2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-[3-tert-Butyl-1′-(3-dimethylamino-propyl)-1′H-[1,4′]bipyrazolyl-5-yl]-3-{4-[3-(2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-{3-tert-Butyl-1′-[3-(4-methyl-piperazin-1-yl)-propyl]-1′H-[1,4′]bipyrazolyl-5-yl}-3-{4-[3-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-[3-tert-Butyl-1′-(2-dimethylamino-ethyl)-1′H-[1,3′]bipyrazolyl-5-yl]-3-{4-[3-(2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-[3-tert-Butyl-1′-(2-dimethylamino-ethyl)-1′H-[1,3′]bipyrazolyl-5-yl]-3-{4-[3-(2,6-dimethyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-[5-tert-Butyl-2-(2-dimethylamino-ethyl)-2H-pyrazol-3-yl]-3-{4-[3-(2,6-dimethyl-piperidin-1-yl)-[[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydronaphthalen-1-yl}-urea formate salt; 1-{5-tert-Butyl-2-[5-(2-dimethylamino-ethoxy)-pyridin-3-yl]-2H-pyrazol-3-yl}-3-{4-[3-((2S,6R)-2,6-dimethyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-{5-tert-Butyl-2-[5-(2-dimethylamino-ethoxy)-pyridin-3-yl]-2H-pyrazol-3-yl}-3-{4-[3-(2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-{5-tert-Butyl-2-[6-(2-dimethylamino-ethoxy)-pyridin-2-yl]-2H-pyrazol-3-yl}-3-{4-[3-(2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-[3-tert-Butyl-1′-(2-dimethylamino-ethyl)-1′H-[1,4′]bipyrazolyl-5-yl]-3-{-4-[3-(2,6-dichloro-phenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-[3-tert-Butyl-1′-(2-dimethylamino-ethyl)-1′H-[1,4′]bipyrazolyl-5-yl]-3[4-(3-isopropyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea formate salt; 1-[3-tert-Butyl-1′-(2-pyrrolidin-1-yl-ethyl)-1′H-[1,4′]bipyrazolyl-5-yl]-3-{4-[3-(2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-{3-tert-Butyl-1′-[2-(4-methoxy-piperidin-1-yl)-ethyl]-1′H-[1,4′]bipyrazolyl-5-yl}-3-{4-[3-(2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-(3-tert-Butyl-1′-{2-[(2-hydroxy-ethyl)-methyl-amino]-ethyl}-1′H-[1,4′]bipyrazolyl-5-yl)-3-{4-[3-(2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-{3-tert-Butyl-1′-[2-((S)-3-hydroxy-pyrrolidin-1-yl)-ethyl]-1′H-[1,4′]bipyrazolyl-5-yl}-3-{4-[3-(2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-{3-tert-Butyl-1′-[2-(3-methoxy-pyrrolidin-1-yl)-ethyl]-1′H-[1,4′]bipyrazolyl-5-yl}-3-{4-[3-(2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-{3-tert-Butyl-1′-[2-(ethyl-methyl-amino)-ethyl]-1′H-[1,4′]bipyrazolyl-5-yl}-3-{4-[3-(2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-{3-tert-Butyl-1′-[2-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-ethyl]-1′H-[1,4′]bipyrazolyl-5-yl}-3-{4-[3-(2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-{3-tert-Butyl-1′-[2-(5-methyl-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-ethyl]-1′H-[1,4′]bipyrazolyl-5-yl}-3-{4-[3-(2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-[3-tert-Butyl-1′-(2-dimethylamino-ethyl)-1′H-[1,4′]bipyrazolyl-5-yl]-3-{4-[3-(2-hydroxymethyl-pyrrolidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea 1-[3-tert-Butyl-1′-(2-hydroxy-ethyl)-1′H-[1,4′]bipyrazolyl-5-yl]-3-{4-[3-(1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; 1-[3-tert-Butyl-1′-(2-dimethylamino-ethyl)-1′H-[1,4′]bipyrazolyl-5-yl]-3-{4-[3-(1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt; and 1-{5-tert-Butyl-2-[6-(2-dimethylamino-ethoxy)-pyridazin-4-yl]-2H-pyrazol-3-yl}-3-{4-[3-(2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt, or a pharmaceutically acceptable of said compound.