Kinase inhibitors
Compounds of formulae (I), (II), and (III), defined herein, are p38 MAPK inhibitors and are useful as anti-inflammatory agents in the treatment of, inter alia, diseases of the respiratory tract.
1. A compound of formula (I):
wherein
R 1 is a group of one of the following formulae:
or a pharmaceutically acceptable salt thereof.
2. A compound or pharmaceutically acceptable salt according to claim 1 , which is:
1-(3-tert-Butyl-1′-methyl-1′H-[1,4′]bipyrazolyl-5-yl)-3-{(1S,4R)-4-[3-(1-dimethylamino-1-methyl-ethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalenyl}-urea hydrochloride salt;
1-(3-tert-Butyl-1′-methyl-1′H-[1,4′]bipyrazolyl-5-yl)-3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalenyl}-urea hydrochloride salt;
1-(3-tert-Butyl-1′-methyl-1′H-[1,4′]bipyrazolyl-5-yl)-3-{(1S,4R)-4-[3-((S)-1-isopropyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalenyl}-urea hydrochloride salt; or
1-(3-tert-Butyl-1′-methyl-1′H-[1,4′]bipyrazolyl-5-yl)-3-{(1S,4R)-4-[3-((S)-1-isopropyl-piperidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea hydrochloride salt.
3. A compound of formula (II):
wherein
R 1 is a group of one of the following formulae:
or a pharmaceutically acceptable salt thereof.
4. A compound or pharmaceutically acceptable salt according to claim 3 , which is:
1-(5-tert-Butyl-2-methyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea hydrochloride salt; or
1-(5-tert-Butyl-2-methyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-(1-dimethylamino-1-methyl-ethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea hydrochloride salt.
5. A compound of formula (III):
wherein
R 1 is a group of one of the following formulae:
or a pharmaceutically acceptable salt thereof.
6. A compound or pharmaceutically acceptable salt according to claim 5 , which is:
1-(5-tert Butyl-isoxazol-3-yl)-3-{(1S,4R)-4-[3-((S)-1-isopropyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridine-6-yloxy]-1,2,3,4-tetrahydronaphthalen-1-yl)}-urea hydrochloride salt; or
1-(5-tert Butyl-isoxazol-3-yl)-3-{(1S,4R)-4-[3-((S)-1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridine-6-yloxy]-1,2,3,4-tetrahydronaphthalen-1-yl}-urea hydrochloride salt.
7. A pharmaceutical composition, comprising a compound or a pharmaceutically acceptable salt according to claim 1 and one or more pharmaceutically acceptable carriers.