Lactam kinase inhibitors
Compounds useful as kinase inhibitors are provided herein, as well as salts, pharmaceutical compositions, methods of medical treatment and methods of synthesis thereof.
1. A compound of formula (Q):
or a pharmaceutically acceptable salt thereof;
wherein
R 26 is H;
each R 31 is independently aryl, alkyl, or cycloalkyl, wherein two R 31 s on adjacent ring atoms or on the same ring atom together with the ring atom(s) to which they are attached optionally form a 3-8-membered cycle;
yy is 2;
ZZ is —(CH 2 ) xx —wherein xx is 1, 2, 3, or 4;
R 55 is NHR A , wherein R A is unsubstituted C 1 -C 8 alkyl, cycloalkylalkyl, -TT-RR, C 1 -C 8 cycloalkyl, or heterocycloalkyl containing atoms selected from N, O, or S;
TT is C 1 -C 8 alkyl or C 3 -C 8 cycloalkyl linker;
RR is a hydroxyl, C 1 -C 6 alkoxy, amino, C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, C 6 -C 10 aryl, heteroaryl comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O, or S, C 3 -C 10 carbocycle, or heterocycle comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O or S;
R 27 is -(alkylene) m -C 3 -C 8 cycloalkyl, -(alkylene) m -heterocyclo, or C 1 -C 3 alkyl; and
m is 0 or 1.
2. The compound of claim 1 , wherein two R 31 s on adjacent ring atoms or on the same ring atom together with the ring atom(s) to which they are attached form a 3-8-membered cycle.
3. The compound of claim 1 , wherein two R 31 s on the same ring atom together with the ring atom to which they are attached form a 3-8 membered cycle.
4. The compound of claim 3 , wherein the 3-8 membered cycle is a 5 membered cycle.
5. The compound of claim 3 , wherein the 3-8 membered cycle is a 6 membered cycle.
6. The compound of claim 1 , having the formula:
or a pharmaceutically acceptable salt thereof.
7. The compound of claim 6 , wherein two R 31 s on adjacent ring atoms or on the same ring atom together with the ring atom(s) to which they are attached form a 3-8-membered cycle.
8. The compound of claim 6 , wherein two R 31 s on the same ring atom together with the ring atom to which they are attached form a 3-8 membered cycle.
9. The compound of claim 1 , wherein ZZ is selected from the group consisting of —CH 2 — and —CH 2 CH 2 —.
10. The compound of claim 1 , wherein R 31 is selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.
11. The compound of claim 1 , wherein R 55 is selected from the group consisting of cis 4-hydroxycyclohexylamino, trans 4-hydroxycyclohexylamino, cyclohexylamino, cyclopentylamino, and straight chain C 1 -C 8 alkylamino.
12. The compound of claim 11 , wherein xx is 2.
13. The compound of claim 12 , wherein two R 31 s on adjacent ring atoms or on the same ring atom together with the ring atom(s) to which they are attached form a 3-8-membered cycle.
14. The compound of claim 12 , wherein R 31 is selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.
15. A pharmaceutical composition comprising an effective amount of the compound of claim 1 , and a pharmaceutically acceptable carrier.
16. A pharmaceutical composition comprising an effective amount of the compound of claim 6 , and a pharmaceutically acceptable carrier.