Prenylated hydroxystilbenes

Patent metadata

Field	Value
Publication number	US-10696615-B2
Application number	US-201816221666-A
Country	US
Kind code	B2
Filing date	Dec 17, 2018
Priority date	May 4, 2011
Publication date	Jun 30, 2020
Grant date	Jun 30, 2020

Abstract

A method for treating cancer can include administering a therapeutically effective amount of a compound of formula (Ia):

or pharmaceutically acceptable salts or solvates thereof, wherein R 1a , R 1b , R 1c , R 1d , R 2 , and R 3 are as defined, and A----B is selected from CH═CH, CH═CH(CH 2 ) p CH 2 , or CH 2 —CH 2 (CH 2 )pCH 2 , and where p is 1 or 2.

First claim

What is claimed is:

1. A method for treating cancer, comprising administering a therapeutically effective amount of 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(CH 3 ) 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(CH 3 ) 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(CH 3 ) 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(CH 3 ) 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(CH 3 ) 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 and 2.

2. 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.

3. A method according to claim 2 wherein the cancer is leukemia.

4. A method according to claim 2 wherein the cancer is melanoma.

5. A method according to claim 1 , wherein two of R 1b-1d are H.

6. A method according to claim 1 , wherein one of R 1b-1d is H.

7. A method according to claim 1 , wherein none of R 1b-1d are H.

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

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

10. A method according to claim 1 , wherein at least two of R 1b-1d are OH.

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

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

13. A method according to claim 1 , wherein at least one of R 2 or R 3 is OH.

14. A method according to claim 1 , wherein R 3 is OR 4 and R 4 is methyl.

15. A method according to claim 1 , wherein both R 2 and R 3 are OH.

16. A method according to claim 1 , wherein R 3 is OR 4 and R 4 is benzyl.

17. A method according to claim 1 , 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 and 2.

18. A method according to claim 1 , 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 and 2.

19. A method according to claim 1 , 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, Oft, OPr, O i Pr, OBu, O i Bu, and O t Bu, and wherein R 10 is OH.

20. A method according to claim 1 , wherein the compound is chemically synthesised.

21. A method according to claim 1 , wherein the compound originates from propolis, and wherein the propolis originates from plants of the Lepidosperma genus.

22. A method according to claim 1 , wherein the compound originates from the resin, gum, or exudate of the Lepidosperma genus.

23. A method of claim 1 , wherein the compound or pharmaceutically acceptable salt or solvate thereof is administered as a pharmaceutical composition which also comprises one or more pharmaceutically acceptable carriers, diluents, or excipients.

24. A method of claim 23 , wherein the pharmaceutical composition includes one or more further therapeutic agents.

25. A method of claim 23 , wherein the pharmaceutical composition is in the form of a parenteral solution, emulsion, or suspension.

Assignees

• Univ Sydney

Inventors

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

Classifications

• C07C39/215

  containing [IMAGE cpc-sch-C07C-0957.gif], e.g. diethylstilbestrol · CPC title

• C07C39/205 Primary

  polycyclic, containing only six-membered aromatic rings as cyclic parts with unsaturation outside the rings · CPC title

• A61K31/03

  aromatic · CPC title

• A61P17/00 Primary

  Drugs for dermatological disorders · CPC title

• C07C67/297

  by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups · CPC title