Azaquinazoline inhibitors of Atypical protein Kinase C
The present application provides azaquinazoline compounds as defined herein. This application further describes compositions comprising the same. These azaquinazoline compounds and their salts have atypical protein kinase C (“aPKC”) inhibitory activity, and may be used to treat proliferative disorders.
1. A compound of formula I:
wherein R 7 is an optionally substituted C 3 -C 6 cycloalkyl;
R 8 is hydrogen;
R 9 is hydrogen;
X is a 5-10 membered heterocycloalkyl containing 1 or 2 nitrogen atoms, wherein said heterocycloalkyl is optionally substituted with 1-4 hydroxyl or C 1 -C 3 alkyl;
G is
R 14 is hydrogen;
R 15 is hydrogen; and
R 12 and R 13 are independently hydrogen or an optionally substituted amino group; or
R 12 and R 13 , together with the atoms to which they are attached, form an optionally substituted 5 to 15 membered heteroaryl or an optionally substituted 3 to 15 membered heterocycloalkyl,
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein R 7 is cyclopropyl or cyclobutyl, or a pharmaceutically acceptable salt thereof.
3. The compound of claim 1 , wherein X is an optionally substituted piperazinyl, or a pharmaceutically acceptable salt thereof.
4. The compound of claim 1 , wherein X is an optionally substituted piperazinyl, wherein the piperazinyl is attached to the:
ring via a nitrogen atom, or a pharmaceutically acceptable salt thereof.
5. The compound of claim 1 , wherein X is an optionally substituted piperidinyl, or a pharmaceutically acceptable salt thereof.
6. The compound of claim 1 , wherein X is an optionally substituted piperidinyl, wherein the piperidinyl is attached to the:
ring via a nitrogen atom, or a pharmaceutically acceptable salt thereof.
7. The compound of claim 1 , wherein R 12 and R 13 , together with the atoms to which they are attached, form an optionally substituted 5 to 15 membered heteroaryl, or a pharmaceutically acceptable salt thereof.
8. The compound of claim 7 , wherein said optionally substituted 5 to 15 membered heteroaryl contains at least one nitrogen atom, or a pharmaceutically acceptable salt thereof.
9. The compound of claim 1 , wherein R 12 and R 13 , together with the atoms to which they are attached, form an optionally substituted 3 to 10 membered heterocycloalkyl, or a pharmaceutically acceptable salt thereof.
10. The compound of claim 9 , wherein said optionally substituted 3 to 10 membered heterocycloalkyl contains at least one nitrogen atom, or a pharmaceutically acceptable salt thereof.
11. A compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
12. A pharmaceutical composition comprising one or more compounds according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
13. A pharmaceutical composition comprising one or more compounds according to claim 11 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.