Azaquinazoline inhibitors of atypical protein kinase C
The present application provides a compound of formula (I) or a salt thereof, wherein R 7 , R 8 , R 9 , G, and X are as defined herein. This application further describes compositions comprising the same. Compounds of formula (I) and their salts have aPKC inhibitory activity, and may be used to treat proliferative diseases.
1. A compound selected from the group consisting of:
(5-Cyclobutyl-3-fluoro-pyridin-2-yl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;
{5-Cyclopropyl-2-[2-(3,5,6-trifluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-piperidin-4-yl-amine;
(4-Chloro-1-ethyl-1H-pyrazol-3-yl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;
[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-amine;
{4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-[1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-amine; and
{4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(1-isopropyl-1H-pyrazol-3-yl)-amine;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein the compound is (5-(Cyclobutyl-3-fluoro-pyridin-2-yl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine or a pharmaceutically acceptable salt thereof.
3. The compound of claim 1 , wherein the compound is {5-Cyclopropyl-2-[2-(3,5,6-trifluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-piperidin-4-yl-amine or a pharmaceutically acceptable salt thereof.
4. The compound of claim 1 , wherein the compound is (4-Chloro-1-ethyl-1H-pyrazol-3-yl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine or a pharmaceutically acceptable salt thereof.
5. The compound of claim 1 , wherein the compound is [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-amine or a pharmaceutically acceptable salt thereof.
6. The compound of claim 1 , wherein the compound is {4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-[1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-amine or a pharmaceutically acceptable salt thereof.
7. The compound of claim 1 , wherein the compound is {4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(1-isopropyl-1H-pyrazol-3-yl)-amine or a pharmaceutically acceptable salt thereof.
8. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.
9. The pharmaceutical composition of claim 8 , wherein the compound of claim 1 is (5-Cyclobutyl-3-fluoro-pyridin-2-yl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine or a pharmaceutically acceptable salt thereof.
10. The pharmaceutical composition of claim 8 , wherein the compound of claim 1 is {5-Cyclopropyl-2-[2-(3,5,6-trifluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-piperidin-4-yl-amine or a pharmaceutically acceptable salt thereof.
11. The pharmaceutical composition of claim 8 , wherein the compound of claim 1 is (4-Chloro-1-ethyl-1H-pyrazol-3-yl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine or a pharmaceutically acceptable salt thereof.
12. The pharmaceutical composition of claim 8 , wherein the compound of claim 1 is [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-amine or a pharmaceutically acceptable salt thereof.
13. The pharmaceutical composition of claim 8 , wherein the compound of claim 1 is {4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-[1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-amine or a pharmaceutically acceptable salt thereof.
14. The pharmaceutical composition of claim 8 , wherein the compound of claim 1 is {4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(1-isopropyl-1H-pyrazol-3-yl)-amine or a pharmaceutically acceptable salt thereof.