Lactam kinase inhibitors

Patent metadata

Field	Value
Publication number	US-9745316-B2
Application number	US-201514982443-A
Country	US
Kind code	B2
Filing date	Dec 29, 2015
Priority date	Mar 29, 2012
Publication date	Aug 29, 2017
Grant date	Aug 29, 2017

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 (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.

Assignees

• G1 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

• C07D487/20

  Spiro-condensed systems · CPC title

• C07D487/14 Primary

  Ortho-condensed systems · CPC title