Lactam kinase inhibitors
View Patent ↗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 (QQ):
wherein
R 26 is H or C 1 -C 6 alkyl;
R 27 is -(alkylene) m -C 3 -C 8 cycloalkyl or -(alkylene) m -aryl; any of which may be optionally independently substituted with one or more R x groups as allowed by valance;
each R 31 is alkyl or 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 0, 1, 2, 3, or 4;
ZZ is —(CH 2 ) xx —, wherein xx is 1 or 2;
R 77 is -(alkylene) m -heterocyclo or —(alkylene) m -NR 3 R 4 , any of which may be optionally independently substituted with one or more R x groups as allowed by valance;
R 3 and R 4 at each occurrence are independently selected from:
(i) hydrogen, or
(ii) alkyl, heterocyclo, or heteroaryl;
R x at each occurrence is independently selected from halo, cyano, nitro, oxo, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclo, aryl, heteroaryl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkyl, and
m is 0 or 1.
2. The compound of claim 1 , having the formula:
or a pharmaceutically acceptable salt thereof.
3. The compound of claim 1 , having the formula:
or a pharmaceutically acceptable salt thereof.
4. The compound of claim 1 , wherein R 26 is selected from the group consisting of H, methyl, ethyl, n-propyl, and sec-butyl.
5. The compound of claim 1 , wherein R 31 is selected from the group consisting of methyl, ethyl, n-propyl, and iso-propyl.
6. The compound of claim 1 , wherein R 27 is selected from the group consisting of phenyl, ortho-methylphenyl, ortho, ortho-dimethylphenyl, para-ethylphenyl and ortho, para-dichlorophenyl.
7. The compound of claim 1 , wherein yy is 0, 1 or 2.
8. The compound of claim 1 , wherein R 3 and R 4 are independently selected from the group consisting of H, methyl, and ethyl.
9. The compound of claim 1 , wherein R x is selected from the group consisting of chloro, methyl, ethyl, and cyclopentyl.
10. The compound of claim 1 , wherein R 77 is selected from the group consisting of 1-morpholino, 2-methyl-1-morpholino, and 2,6-dimethyl-1-morpholino.
11. A pharmaceutical composition comprising an effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
12. The compound of claim 1 , wherein R 27 is C 3 -C 8 cycloalkyl or phenyl.
13. The compound of claim 12 , wherein R 77 is heterocyclo.
14. The compound of claim 13 , wherein heterocyclo is piperazine.
15. The compound of claim 12 , wherein m is 0 and R 77 is heterocyclo substituted with one R x group.
16. The compound of claim 15 , wherein heterocyclo is piperazine and R x is alkyl.
17. The compound of claim 16 , wherein yy is 2 and xx is 2.
18. The compound of claim 17 , 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.
19. The compound of claim 18 , wherein the 3-8-membered cycle is a 6 membered cycle.
20. The compound of claim 19 , wherein R 26 is H.