Sesquiterpenoid STAT3 inhibitors
The present disclosure provides a method of purifying pharmaceutical compositions consisting essentially of STAT3 inhibitors from a mixture of compounds, pharmaceutical compositions comprising STAT3 inhibitors used to inhibit STAT3 in tumor cells, and certain pharmaceutically acceptable salts thereof, and methods of use.
1. A compound represented by Formula I:
wherein
R 1 is selected from the group consisting of methyl (CH 3 ), 4-hydroxytigloyl, tigloyl, 2-methylacryloyl, acryloyl, proponoyl, butanoyl, pentanoyl, hexanoyl, isodecenoyl, isopentenoyl, cinnamoyl, 3-(4-(trifluoromethyl)phenyl) acryl, 3-(4-fluorophenyl)acryl, 3,7-dimethylocta-2,6-dienoyl, 3-methylbut-2-enoyl, 3,7-dimethyloct-6-enoyl, ethylbut-2-enoyl, 2-methylbut-2-enoyl, and stilbenoyl;
R 2 is selected from the group consisting of H, 4-hydroxytigloyl, acryloyl, cinnamoyl, 3-(4-(trifluoromethyl)phenyl) acryl, 3-(4-fluorophenyl)acryl, 3,7-dimethylocta-2,6-dienoyl, 3-methylbut-2-enoyl, 3,7-dimethyloct-6-enoyl, 2-methylbut-2-enoyl, 2-methylbut-2-enoyl, acetyl, proponoyl, butanoyl, pentanoyl, hexanoyl, isodecenoyl, isopentenoyl, stilbenoyl, and oleoyl;
R 3 is selected from the group consisting of H, methyl (CH 3 ), and acetyl;
or pharmaceutically acceptable solvates, or pharmaceutically acceptable salts, thereof,
with the proviso that when R 2 and R 3 are both H, R 1 is not tigloyl.
2. The compound of claim 1 , where R 1 is selected from the group consisting of tigloyl, 4-hydroxytigloyl, 2-methylacryloyl, acryloyl, benzoyl, stilbenoyl, substituted stilbenoyl, oleoyl, cinnamoyl, 3-(4-(trifluoromethyl)phenyl) acryl, 3-(4-fluorophenyl)acryl, 3,7-dimethylocta-2,6-dienoyl, 3-methylbut-2-enoyl, 3,7-dimethyloct-6-enoyl, 2-methylbut-2-enoyl, 2-methylbut-2-enoyl, and R 3 is H.
3. The compound of any of claims 1 or 2 , wherein the compound is the compound in Formula I, or a pharmaceutically acceptable salt, thereof.
4. A pharmaceutical composition for treating cancer comprising a therapeutically effective amount of a substantially pure isolated compound of the following formula:
wherein
R 1 is selected from the group consisting or methyl (CH 3 ), 4-hydroxytigloyl, tigloyl, 2-methylacryloyl, acryloyl, proponoyl, butanoyl, pentanoyl, hexanoyl, isodecenoyl, isopentenoyl, cinnamoyl, 3-(4-(trifluoromethyl)phenyl) acryl, 3-(4-fluorophenyl)acryl, 3,7-dimethylocta-2,6-dienoyl, 3-methylbut-2-enoyl, 3,7-dimethyloct-6-enoyl, 2-methylbut-2-enoyl, 2-methylbut-2-enoyl, stilbenoyl, and oleoyl;
R 2 is selected from the group consisting of H, 4-hydroxytigloyl, acryloyl, cinnamoyl, 3-(4-(trifluoromethyl)phenyl) acryl, 3-(4-fluorophenyl)acryl, 3,7-dimethylocta-2,6-dienoyl, 3-methylbut-2-enoyl, 3,7-dimethyloct-6-enoyl, 2-methylbut-2-enoyl, 2-methylbut-2-enoyl, acetyl, proponoyl, butanoyl, pentanoyl, hexanoyl, isodecenoyl, isopentenoyl, stilbenoyl, and oleoyl;
R 3 is selected from the group consisting of H or methyl (CH 3 ) or acetyl;
with the proviso that when R 2 and R 3 are both H, R 1 is not tigloyl, or pharmaceutically acceptable salts thereof;
and a pharmaceutically acceptable excipient.
5. A compound selected from: