Derivatives of [1, 2, 4] triazolo [4, 3 - a] pyridine as p38 - map kinase inhibitors

2:

• A compound or pharmaceutically acceptable salt according to claim 1 which is 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-{(1S,4R)-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-methyl-piperazin-1-yl)-ethyl]-1′H-[1,4′]bipyrazolyl-5-yl}-3-{(1S,4R)-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-{(1S,4R)-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-[(2-methoxy-ethyl)-methyl-amino]-ethyl}-1′H-[1,4′]bipyrazolyl-5-yl)-3-{(1S,4R)-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;
• 1-[3-tert-Butyl-1′-(2-piperidin-1-yl-ethyl)-1′H-[1,4′]bipyrazolyl-5-yl]-3-{(1S,4R)-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-[3-tert-Butyl-1′-(2-[1,4]oxazepan-4-yl-ethyl)-1′H-[1,4′]bipyrazolyl-5-yl]-3-{(1S,4R)-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-[3-tert-Butyl-1′-(2-dimethylamino-ethyl)-1′H-[1,4′]bipyrazolyl-5-yl]-3-[(1S,4R)-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-{(1S,4R)-4-[3-((R)-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-{(1S,4R)-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′-[3-(4-methyl-piperazin-1-yl)-propyl]-1′H-[1,4′]bipyrazolyl-5-yl}-3-{((1S,4R)-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-dimethylamino-ethyl)-1′H-[1,3′]bipyrazolyl-5-yl]-3-{((1S,4R)-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-dimethylamino-ethyl)-1′H-[1,3′]bipyrazolyl-5-yl]-3-{(1S,4R)-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-(2-dimethylamino-ethyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-((2S,6R)-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-{(1S,4R)-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-{(1S,4R)-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-{5-tert-Butyl-2-[6-(2-dimethylamino-ethoxy)-pyridin-2-yl]-2H-pyrazol-3-yl}-3-{(1S,4R)-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-dimethylamino-ethyl)-1′H-[1,4′]bipyrazolyl-5-yl]-3-{(1S,4R)-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 [(1S,4R)-4-(3-isopropyl-[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-pyrrolidin-1-yl-ethyl)-1′H-[1,4′]bipyrazolyl-5-yl]-3-{(1S,4R)-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-methoxy-piperidin-1-yl)-ethyl]-1′H-[1,4′]bipyrazolyl-5-yl}-3-{(1S,4R)-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-[(2-hydroxy-ethyl)-methyl-amino]-ethyl}-1′H-[1,4′]bipyrazolyl-5-yl)-3-{(1S,4R)-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-((S)-3-hydroxy-pyrrolidin-1-yl)-ethyl]-1′H-[1,4′]bipyrazolyl-5-yl}-3-{(1S,4R)-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-(3-methoxy-pyrrolidin-1-yl)-ethyl]-1′H-[1,4′]bipyrazolyl-5-yl}-3-{(1S,4R)-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-(ethyl-methyl-amino)-ethyl]-1′H-[1,4′]bipyrazolyl-5-yl}-3-{(1S,4R)-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-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-ethyl]-1′H-[1,4′]bipyrazolyl-5-yl}-3-{(1S,4R)-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-((1S,4S)-5-methyl-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-ethyl]-1′H-[1,4′]bipyrazolyl-5-yl}-3-{(1S,4R)-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-dimethylamino-ethyl)-1′H-[1,4′]bipyrazolyl-5-yl]-3-{(1S,4R)-4-[3-((S)-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-{(1S,4R)-4-[3-((S)-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-{(1S,4R)-4-[3-((S)-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-{(1S,4R)-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;
• or a pharmaceutically acceptable salt of said compound.

3:

• A compound or pharmaceutically acceptable salt according to claim 1, which is a compound of formula (Ia):
• wherein R2 is selected from the group consisting of:
• 1′-(2-[1,4]oxazepan-4-yl-ethyl);
• 2-[1,4]oxazepan-4-yl-ethyl;
• 2-(4-hydroxy-piperidin-1-yl)-ethyl;
• {2-[(2-methoxy-ethyl)-methyl-amino]-ethyl};
• 1′-(2-dimethylamino-ethyl);
• 1′-(3-dimethylamino-propyl);
• 1′-[3-(4-methyl-piperazin-1-yl)-propyl];
• 1′-(2-dimethylamino-ethyl);
• 1′-(2-pyrrolidin-1-yl-ethyl);
• 1′-[2-(4-methoxy-piperidin-1-yl)-ethyl];
• 1′-{2-[(2-hydroxy-ethyl)-methyl-amino]-ethyl};
• 1′-[2-((S)-3-hydroxy-pyrrolidin-1-yl)-ethyl];
• 1′-[2-(3-methoxy-pyrrolidin-1-yl)-ethyl];
• 1′-[2-(ethyl-methyl-amino)-ethyl];
• 1′-[2-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-ethyl];
• 1′-[2-((1S,4S)-5-methyl-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-ethyl];
• and
• 2-[6-(2-dimethylamino-ethoxy)-pyridazin-4-yl],
• or a pharmaceutically acceptable salt of said compound of formula (Ia).

4:

• A compound or pharmaceutically acceptable salt according to claim 1, which is a compound of formula (Ib):
• wherein R2 is selected from the group consisting of:
• 1′-(2-piperidin-1-yl-ethyl);
• 1′-(2-[1,4]oxazepan-4-yl-ethyl);
• and
• 1′-(2-dimethylamino-ethyl),
• or a pharmaceutically acceptable salt of said compound of formula (Ib).

5:

• A compound or pharmaceutically acceptable salt according to claim 1, which is a compound of formula (Ic):
• wherein R3 is selected from the group consisting of:
• 2-[5-(2-dimethylamino-ethoxy)-pyridin-3-yl];
• 2-[6-(2-dimethylamino-ethoxy)-pyridin-2-yl];
• and
• 2-[6-(2-dimethylamino-ethoxy)-pyridazin-4-yl],
• or a pharmaceutically acceptable salt of said compound of formula (Ic).

6:

• A compound or pharmaceutically acceptable salt according to claim 1, which is a compound of formula (Id):
• wherein R4 is selected from the group consisting of:
• 2-(2-dimethylamino-ethyl);
• and
• 2-[5-(2-dimethylamino-ethoxy)-pyridin-3-yl],
• or a pharmaceutically acceptable salt of said compound of formula (Id).