Substituted aromatic sulfur compounds and methods of their use

Patent metadata

Field	Value
Publication number	US-9475766-B2
Application number	US-201313975483-A
Country	US
Kind code	B2
Filing date	Aug 26, 2013
Priority date	Feb 24, 2011
Publication date	Oct 25, 2016
Grant date	Oct 25, 2016

Abstract

Compounds of formula II are described:

wherein D, n, R a , R b , and R c are as herein defined, along with pharmaceutical compositions and methods of using compounds of formula II for treating or reducing the risk of peritoneal carcinomatosis in a patient.

First claim

What is claimed is:

1. A compound of formula I, or a pharmaceutically acceptable salt form thereof,

wherein A is at the 3- or 4-position of the phenyl ring; and
A is

R 1 and R 2 are each independently substituted or unsubstituted alkyl or R 1 and R 2 , together with the carbon atom to which they are attached, form a three- to seven-membered substituted or unsubstituted cycloalkyl ring;
R 3 is —OH, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkalkyl, or —NR 4 R 5 ;
R 4 and R 5 are each independently H, substituted or unsubstituted alkyl, substituted or unsubstituted alkyene oxide, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroaralkyl, —COOalkyl, —COalkyl, —COcycloalkyl, —NHCOalkyl, —NHCOaryl, or —NHCOcycloalkyl; or R 4 and R 5 , together with the atoms through which they are attached, form a substituted or unsubstituted heterocycloalkyl ring; and
R 6 is substituted or unsubstituted heteroaryl.

2. The compound of claim 1 , wherein A is at the 4-position of the phenyl ring.

3. The compound of claim 1 , wherein A is

4. The compound of claim 1 , wherein R 1 and R 2 are each —CH 3 .

5. The compound of claim 3 , wherein R 3 is —OH.

6. The compound of claim 3 , wherein R 3 is substituted or unsubstituted heterocycloalkyl.

7. The compound of claim 3 , wherein R 3 is —NR 4 R 5 .

8. The compound of claim 7 , wherein R 4 is H.

9. The compound of claim 8 , wherein R 5 is substituted or unsubstituted alkyl.

10. The compound of claim 8 , wherein R 5 is substituted or unsubstituted aryl.

11. The compound of claim 8 , wherein R 5 is substituted or unsubstituted aralkyl.

12. The compound of claim 8 , wherein R 5 is substituted or unsubstituted heteroaryl.

13. The compound of claim 8 , wherein R 5 is substituted or unsubstituted heteroaralkyl.

14. The compound of claim 8 , wherein R 5 is substituted or unsubstituted cycloalkyl.

15. The compound of claim 8 , wherein R 5 is substituted or unsubstituted heterocycloalkyl.

16. The compound of claim 8 , wherein R 5 is substituted or unsubstituted alkyene oxide.

17. The compound of claim 8 , wherein R 5 is —NHCOcycloalkyl.

18. The compound of claim 8 , wherein R 4 and R 5 , together with the atoms through which they are attached, form a substituted or unsubstituted heterocycloalkyl ring.

19. The compound of claim 3 , wherein R 3 is —CH 3 .

20. The compound of claim 19 , wherein R 5 is substituted or unsubstituted alkyl.

21. The compound of claim 19 , wherein R 5 is substituted or unsubstituted aryl.

22. The compound of claim 19 , wherein R 5 is substituted or unsubstituted aralkyl.

23. The compound of claim 19 , wherein R 5 is substituted or unsubstituted heteroaryl.

24. The compound of claim 19 , wherein R 5 is substituted or unsubstituted heteroaralkyl.

25. The compound of claim 19 , wherein R 5 is substituted or unsubstituted cycloalkyl.

26. The compound of claim 19 , wherein R 5 is substituted or unsubstituted heterocycloalkyl.

27. The compound of claim 19 , wherein R 5 is substituted or unsubstituted alkyene oxide.

28. The compound of claim 19 , wherein R 5 is —NHCOcycloalkyl.

29. The compound of claim 19 , wherein R 4 and R 5 , together with the atoms through which they are attached, form a substituted or unsubstituted heterocycloalkyl ring.

30. The compound of claim 1 , wherein A is

31. The compound of claim 30 , wherein R 1 and R 2 are each —CH 3 .

32. The compound of claim 30 , wherein R 6 is substituted or unsubstituted oxadiazolyl.

33. The compound of claim 30 , wherein R 6 is substituted or unsubstituted benzoimidazolyl.

34. The compound of claim 30 , wherein R 6 is substituted or unsubstituted benzooxazolyl.

35. The compound of claim 30 , wherein R 6 is substituted or unsubstituted oxazolyl.

36. A compound according to claim 1 which is:
2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-2-methyl-propionic acid;
2-[3-((E)-2-Cyano-ethenesulfonyl)-phenyl]-2-methyl-propionic acid;
(E)-3-[4-(1,1-Dimethyl-2-morpholin-4-yl-2-oxo-ethyl)-benzene sulfonyl]-acrylonitrile;
2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-N-(2-hydroxy-ethyl)-isobutyramide;
2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-N-phenyl-isobutyramide;
N-Benzyl-2-[4-((E)-2-cyano-ethenesulfonyl)-phenyl]-isobutyramide;
2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-N-pyridin-2-ylmethyl-isobutyramide;
2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-N-isobutyl-isobutyramide;
(E)-3-{4-[1,1-Dimethyl-2-(4-methyl-piperazin-1-yl)-2-oxo-ethyl]-benzenesulfonyl}-acrylonitrile;
2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-N-cyclopropylmethyl-isobutyramide;
2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-N-(2,2-difluoro-ethyl)-isobutyramide;
2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-N-cyclohexyl-isobutyramide;
2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-N(tetrahydro-pyran-4-yl)-isobutyramide;
N-(4-Chloro-benzyl)-2-[4-((E)-2-cyano-ethenesulfonyl)-phenyl]-isobutyramide;
2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-N-thiophen-2-ylmethyl-isobutyramide;
2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-N—((S)-1-phenyl-ethyl)-isobutyramide;
2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-N—((R)-1-phenyl-ethyl)-isobutyramide;
2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-N-(4-fluoro-benzyl)-isobutyramide;
2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-N-prop-2-ynyl-isobutyramide;
(E)-3-{4-[2-(3,4-Dihydro-1H-isoquinolin-2-yl)-1, 1-dimethyl-2-oxo-ethyl]-benzenesulfonyl}-acrylonitrile;
2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl-N-(4-pyrazol-1-yl-benzyl)-isobutyramide;
N-Benzyl-2-[4-((E)-2-cyano-ethenesulfonyl)-phenyl]-N-methyl-isobutyramide;
2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-N-(4-methoxy-phenyl)-isobutyramide;
2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-N-phenethyl-isobutyramide;
2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-N-(3-methoxy-phenyl)-isobutyramide;
2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-N-(4-sulfamoyl-benzyl)-isobutyramide;
(E)-3-[4-(1,1-Dimethyl-2-oxo-2-piperidin-1-yl-ethyl)-benzenesulfonyl]-acrylonitrile;
2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-N—((S)-2-hydroxy-1-phenyl-ethyl)-isobutyramide;
2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-N—((S)-2-oxo-azepan-3-yl)-isobytyramide;
2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-N-[4-(2-methoxy-ethoxymethyl)-phenyl]-isobutyramide;
(2-{2-[4-((E)-2-Cyano-ethenesulfonyl)-phenyl]-2-methyl-propionylamino}-ethyl)-carbamic acid tert

Assignees

• Cephalon Inc
• Univ Hawaii
• Univ Utah Res Found

Inventors

• Dorsey Bruce D
• Kuwada Scott K
• Theroff Jay P
• Zificsak Craig A

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/04

  specific for metastasis · CPC title

• C07D309/14

  Nitrogen atoms not forming part of a nitro radical · CPC title

• C07D213/57

  Nitriles · CPC title

• C07D215/36

  Sulfur atoms (C07D215/24 takes precedence) · CPC title