Small molecule Bcl-xL/Bcl-2 binding inhibitors
View Patent ↗Bcl-xL/Bcl-2 binding inhibitors useful in the treatment of unwanted proliferating cells, including cancers and precancers, in subjects in need of such treatment. Also provided are methods of treating a subject having unwanted proliferating cells comprising administering a therapeutically effective amount of a Bcl-xL/Bcl-2 binding inhibitor described herein to a subject in need of such treatment. Also provided are methods of preventing the proliferation of unwanted proliferating cells, such as cancers and precancers, in a subject comprising the step of administering a therapeutically effective amount of a Bcl-xL/Bcl-2 binding inhibitor described herein to a subject at risk of developing a condition characterized by unwanted proliferating cells.
1. A method of treating prostate cancer in a subject
previously identified as having an unwanted cell proliferation of the prostate,
the process comprising administering to the subject a therapeutically effective amount of at least one compound of the following formula II, formula III, formula VIII, formula IX or formula X:
wherein X 1 is selected from H, alkyl, alkoxy, halo, nitro and combinations thereof, and X 2 is selected from H, alkyl, alkoxy, halo and combinations thereof,
wherein X 1 is selected from H, alkyl, alkoxy, halo, nitro, haloalkylaryl, haloaryl, alkylaryl and combinations thereof, and X 2 is selected from H, methyl, methoxy, and bromo,
wherein W is selected from O, S and combinations thereof; Y is selected from straight chain alkenyl, branched alkenyl and combinations thereof, and Z′ is H,
wherein Y is selected from straight chain alkenyl, branched alkenyl and combinations thereof,
wherein Y is selected from straight chain alkenyl, branched alkenyl and combinations thereof, and Z′ is H,
and pharmaceutically acceptable salts thereof.
2. The method according to claim 1 , wherein the compound is administered orally, intravenously, intramuscularly, subcutaneously, or intraperitoneally.
3. The method according to claim 2 , wherein the therapeutically effective amount administered is in the range of about 0.1-2000 mg.
4. The method according to claim 2 , wherein the therapeutically effective amount administered is in the range of about 1-200 mg per kg of body weight of the subject.
5. The method of claim 1 , wherein a compound of formula II is administered.
6. The method of claim 5 , wherein X 1 in formula II is selected from H, Br, CH 3 , OCH 3 , OCH 2 CH 3 , NO 2 and Cl, and further wherein X 2 in formula II is selected from H, CH 3 , OCH 3 and Br.
7. The method of claim 1 , wherein a compound of formula III is administered.
8. The method of claim 7 , wherein X 1 in formula III is selected from bromo, nitro, trifluoromethylphenyl, fluorophenyl and ethylphenyl, and further wherein X 2 in formula III is selected from H, methyl, methoxy and bromo.
9. The method of claim 7 , wherein X 1 in formula III is bromo and X 2 in formula III is H.
10. The method of claim 1 , wherein a compound of formula VIII is administered.
11. The method of claim 10 , wherein Y in formula VIII is selected from the group consisting of
12. The method of claim 11 , wherein W in formula VIII is O.
13. The method of claim 11 , wherein W in formula VIII is S.
14. The method of claim 1 , wherein a compound of formula IX is administered.
15. The method of claim 14 , wherein Y in formula IX is selected from the group consisting of
16. The method of claim 1 , wherein a compound of formula X is administered.
17. The method of claim 16 , wherein Y in formula X is selected from the group consisting of