Benzolactam compounds as protein kinase inhibitors
The invention provides a compound of formula (0): or a pharmaceutically acceptable salt, N-oxide or tautomer thereof; wherein: n is 1 or 2; X is CH or N; Y is selected from CH and C—F; Z is selected from C—R z and N; R 1 is selected from: -(Alk 1 ) t -Cyc 1 ; wherein t is 0 or 1; Optionally substituted C 1-6 acyclic hydrocarbon groups R 2 is selected from hydrogen; halogen; and C 1-8 hydrocarbon groups optionally substituted with one or more fluorine atoms; R 3 is hydrogen or a group L 1 -R 7 ; R 4 is selected from hydrogen; methoxy; and optionally substituted C 1-3 alkyl; and R 4a is selected from hydrogen and a C 1-3 alkyl group; wherein R z , Alk 1 , Cyc 1 , L 1 and R 7 are defined herein; provided that the compound is other than 6-benzyl-3-{2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl}-7,8-dihydro-1,6-naphthyridin-5(6H)-one and 3-{2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl}-7,8-dihydro-1,6-naphthyridin-5(6H)-one and salts and tautomers thereof. The compounds are inhibitors of ERK1/2 kinases and will be useful in the treatment of ERK1/2-mediated conditions. The compounds are therefore useful in therapy, in particular in the treatment of cancer.
1 . A compound which is
or a pharmaceutically acceptable salt or tautomer thereof.
2 . A compound according to claim 1 , which is
or a pharmaceutically acceptable salt or tautomer thereof.
3 . A compound according to claim 2 , which is
4 . A compound according to claim 2 , which is a pharmaceutically acceptable salt of
5 . A compound according to claim 1 , which is
or a pharmaceutically acceptable salt or tautomer thereof.
6 . A compound according to claim 5 , which is
7 . A compound according to claim 5 , which is a pharmaceutically acceptable salt of
8 . A combination of a compound according to claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, and another therapeutic agent.
9 . A combination according to claim 8 , wherein the compound is
or a pharmaceutically acceptable salt or tautomer thereof.
10 . A combination according to claim 8 , wherein the compound is
or a pharmaceutically acceptable salt or tautomer thereof.
11 . A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt or tautomer thereof, and a pharmaceutically acceptable excipient.
12 . A pharmaceutical composition according to claim 11 , wherein the compound is
or a pharmaceutically acceptable salt or tautomer thereof.
13 . A pharmaceutical composition according to claim 11 , wherein the compound is
or a pharmaceutically acceptable salt or tautomer thereof.