Lactam kinase inhibitors

Patent metadata

Field	Value
Publication number	US-10464940-B2
Application number	US-201815860483-A
Country	US
Kind code	B2
Filing date	Jan 2, 2018
Priority date	Mar 29, 2012
Publication date	Nov 5, 2019
Grant date	Nov 5, 2019

Abstract

Compounds useful as kinase inhibitors are provided herein, as well as salts, pharmaceutical compositions, methods of medical treatment and methods of synthesis thereof.

First claim

What is claimed is:

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.

Assignees

• G1 Therapeutics Inc
• Gi Therapeutics Inc

Inventors

• Tavares Francis Xavier

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• C07D498/14

  Ortho-condensed systems · CPC title

• C07D487/14 Primary

  Ortho-condensed systems · CPC title

• C07D487/20

  Spiro-condensed systems · CPC title