Prenylated hydroxystilbenes

Patent metadata

Field	Value
Publication number	US-10196335-B2
Application number	US-201214115574-A
Country	US
Kind code	B2
Filing date	May 4, 2012
Priority date	May 4, 2011
Publication date	Feb 5, 2019
Grant date	Feb 5, 2019

Abstract

Prenylated stilbene compounds and the use of such compounds in the treatment of diseases and medical disorders, for example cancer, skin ageing, inflammation, bacterial or fungal infection and immunosuppression.

First claim

The invention claimed is:

1. A method for treating cancer comprising administering a therapeutically effective amount of a compound of formula (Ia),

wherein:
R 1a and R 1c are each independently selected from H or CH 2 CH═C(CH 3 ) 2 ; R 1b is selected from OH, OCH 3 or OCH 2 CH═C(CH 3 ) 2 ; R 1d is OH; wherein at least one of R 1a or R 1c is CH 2 CH═C(CH 3 ) 2 and/or R 1b is OCH 2 CH═C(CH 3 ) 2 ; R 2 is selected from OH or OCH 3 ; R 3 is selected from H, OH or OCH 3 ;
and A----B is CH═CH; provided that:
(i) when R 2 is OH, R 3 is H or OH, R 1a is H, R 1c is CH═CHCH(CH 3 ) 2 , then R 1b is not OH;

or pharmaceutically acceptable salts, solvates, or a pharmaceutical composition including said compounds, to a patient in need thereof.

2. A method according to claim 1 , wherein the compound is:

or pharmaceutically acceptable salts or solvates thereof.

3. A method according to claim 1 , wherein the cancer is leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer or breast cancer.

4. A method according to claim 1 , wherein the cancer is leukemia.

5. A method according to claim 1 , wherein the cancer is melanoma.

6. A method for treating cancer comprising administering a therapeutically effective amount of a compound of formula (Ia),

wherein:
R 1a and R 1c are each independently selected from H or CH 2 CH═C(CH 3 ) 2 ; R 1b is selected from OH, OCH 3 or OCH 2 CH═C(CH 3 ) 2 ; R 1d is OH; wherein at least one of R 1a or R 1c is CH 2 CH═C(CH 3 ) 2 and/or R 1b is OCH 2 CH═C(CH 3 ) 2 ; R 2 is selected from OH or OCH 3 ; R 3 is selected from OH or OCH 3 ;
and A----B is CH═CH;
or pharmaceutically acceptable salts, solvates, or a pharmaceutical composition including said compounds, to a patient in need thereof.

7. A method according to claim 6 , wherein the compound is:

or pharmaceutically acceptable salts or solvates thereof.

8. A method according to claim 6 , wherein the cancer is leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer or breast cancer.

9. A method according to claim 8 wherein the cancer is leukemia.

10. A method according to claim 8 wherein the cancer is melanoma.

11. A compound of formula (Ia)

or pharmaceutically acceptable salts or solvates thereof, wherein:
R 1a is selected from, CH 2 CH═C(CH 3 ) 2 , OCH 2 CH═C(CH 3 ) 2 , CH═CHCH(CH3) 2 , CH═CHC(CH 3 )═CH 2 , OCH═CHCH(CH 3 ) 2 , or OCH═CHC(CH 3 )═CH 2 ;
R 1b is selected from, H, OH, OR 4 , CH 2 CH═C(CH 3 ) 2 , OCH 2 CH═C(CH 3 ) 2 , CH═CHCH(CH3) 2 , CH═CHC(CH 3 )═CH 2 , OCH═CHCH(CH 3 ) 2 , or OCH═CHC(CH 3 )═CH 2 ;
R 1c is selected from H, OH, OR 4a , CH 2 CH═C(CH 3 ) 2 , OCH 2 CH═C(CH 3 ) 2 , CH═CHCH(CH3) 2 , CH═CHC(CH 3 )═CH 2 , OCH═CHCH(CH 3 ) 2 , or OCH═CHC(CH 3 )═CH 2 ;
R 1d is selected from H, OH, OR 4 , CH 2 CH═C(CH 3 ) 2 , OCH 2 CH═C(CH 3 ) 2 , CH═CHCH(CH3) 2 , CH═CHC(CH 3 )═CH 2 , OCH═CHCH(CH 3 ) 2 , or OCH═CHC(CH 3 )═CH 2 ;
wherein at least one of R 1b-1d is OH and at least one of R 1a-1d is CH 2 CH═C(CH 3 ) 2 , OCH 2 CH═C(CH 3 ) 2 , CH═CHCH(CH3) 2 , CH═CHC(CH 3 )═CH 2 , OCH═CHCH(CH 3 ) 2 , or OCH═CHC(CH 3 )═CH 2 ;
R 2 is selected from OH, OR 4a , OCH 2 CH═C(CH 3 ) 2 , CH═CHC(CH 3 )═CH 2 , OCH═CHCH(CH 3 ) 2 , or OCH═CHC(CH 3 )═CH 2 ;
R 3 is selected from OH, OR 4 , OCH 2 CH═C(CH 3 ) 2 , CH═CHC(CH 3 )═CH 2 , OCH═CHCH(CH 3 ) 2 , or OCH═CHC(CH 3 )═CH 2 ;
R 4 is selected from, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl or benzyl;
R 4a is selected from, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl or benzyl; and
A----B is selected from CH═CH, CH═CH(CH 2 )pCH 2 , or CH 2 —CH 2 (CH 2 )pCH 2 , where p is an integer selected from the group consisting of 1 or 2.

12. A compound according to claim 11 , wherein two of R 1b-1d are H.

13. A compound according to claim 11 , wherein one of R 1b-1d is H.

14. A compound according to claim 11 , wherein none of R 1b-1d are H.

15. A compound according to claim 11 , wherein at least one of R 1a-1d is CH 2 CH═C(CH 3 ) 2 .

16. A compound according to claim 11 , wherein at least one of R 1a-1d is OCH 2 CH═C(CH 3 ) 2 .

17. A compound according to claim 11 , wherein at least two of R 1b-1d are OH.

18. A compound according to claim 11 , wherein R 1b is OR 4 and R 4 is methyl.

19. A compound according to claim 11 , wherein at least one of R 1b-1d is OR 4 or OR 4a and R 4 or R 4a is benzyl.

20. A compound according to claim 11 , wherein at least one of R 2 or R 3 is OH.

21. A compound according to claim 11 , wherein R 3 is OR 4 and R 4 is methyl.

22. A compound according to claim 11 , wherein both R 2 and R 3 are OH.

23. A compound according to claim 11 , wherein R 3 is OR 4 and R 4 is benzyl.

24. A compound according to claim 11 , wherein A----B is CH═CH or CH═CH(CH 2 )pCH 2 , where p is an integer selected from the group consisting of 1 or 2.

25. A compound according to claim 11 , wherein A----B is CH 2 —CH 2 (CH 2 )pCH 2 , and where p is an integer selected from the group consisting of 1 or 2.

26. A compound according to claim 11 , wherein the compound of formula (Ia) is formula (Ie)

wherein, R 8 and R 9 are each independently selected from the group consisting of OH, OMe, OEt, OPr, O i Pr, O i Bu, O i Bu, and O t Bu, and R 10 is OH.

27. A compound according to claim 11 , wherein the compound is:

or pharmaceutically acceptable salts or solvates thereof.

28. A compound according to claim 11 , wherein the compound is chemically synthesised.

29. A method for treating immunosuppression, comprising administering a therapeutically effective amount of a compound according to claim 11 to a patient in need thereof.

30. A method for treating inflammation comprising administering a therapeutically effective amount of a compound according to claim 11 to a patient in need thereof.

31. A method for treating a bacterial or fungal infection comprising administering a therapeutically effective amount of a compound according to claim 11 to a patient in need thereof.

32. A method for treating skin aging comprising administering a therapeutically effective amount of a compound according to claim 11 to a patient in need thereof.

3

Assignees

• Duke Colin Charles
• Tran Van Hoan
• Duke Rujee Kyokajee
• Univ Sydney

Inventors

• Duke Colin Charles
• Tran Van Hoan
• Duke Rujee Kyokajee

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/10

  Antimycotics · CPC title