Compositions, methods of use and preparation of 2,6-diisopropyl phenol and analogs for ischemic injury

1. A method of treating or ischemic injury in a human, wherein the method comprises administering to the human an amount of a 2,6-diisopropyl phenol analog selected from the group consisting of: (4-fluorophenyl)-(4-hydroxy-3,5-diisopropylphenyl)methanone, (4-(trifluoromethyl)phenyl)-(4-hydroxy-3,5-diisopropylphenyl)methanone, (4-3,5diisopropylphenyl(4-nitrophenyl)methanone, (3-fluoro-4-(trifluoromethyl)phenyl)-(4-hydroxy-3,5-diisopropylphenyl)methanone, (3-(trifluoromethyl)phenyl)-(4-hydroxy-3,5-diisopropylphenyl)methanone, (3-fluoro-5-(trifluoromethyl) phenyl)-4-hydroxy-3,5-diisopropylphenyl)methanone, (4-hydroxy-3,5-diisopropylphenyl)naphthalene-2-yl)methanone, (3,5-bis(trifluoromethyl)phenyl)-(4-hydroxy-3,5-diisopropylphenyl)methanone, (4-tert-butylphenyl)-(4-hydroxy-3,5-diisopropylphenyl)methanone, (4-hydroxy-3,5-diisopropylphenyl)-(4-isobutylphenyl)methanone, (4-hydroxy-3,5-diisopropylphenyl)-(4-iodophenyl)methanone, (4-hydroxy-3,5-diisopropylphenyl)-(4-methoxyphenyl)methanone, (4-cyanophenyl)-4-hydroxy-3,5-diisopropylphenyl)methanone, (6-(trifluoromethyl)pyridin-3-yl)-(4-hydroxy-3,5-diisopropylphenyl)methanone, (4-bromophenyl)-(4-hydroxy-3,5-diisopropylphenyl)methanone, (4-hydroxy-3,5-diisopropylphenyl)-(4-propylphenyl)methanone, (4-chlorophenyl)-(4-hydroxy-3,5-diisopropylphenyl)methanone, 4-((4-(trifluoromethyl)phenyl)-(methoxyimino)methyl)-2,6-diisopropylphenyl, 4-(4-(trifluoromethyl)benzyl)-2,6-diisopropylphenyl, 4-((4-(trifluoromethyl)phenyl)-(hydroxy)methyl)-2,6-diisopropylphenyl, 4-hydroxy-3,5-diisopropylphenyl)-(4-(methylsulfonyl)phenyl)methanone, and combinations thereof.

2. The method of claim 1 wherein the 2,6-diisopropyl phenol analog is included in a pharmaceutical composition.

3. The method of claim 2 , wherein the 2,6-diisopropyl phenol analog is administered by a method selected from the group consisting of oral administration, nasal respiratory administration, aerosol administration, bolus injection, intravenous administration, continuous infusion, intra-arterial administration, rectal administration, vaginal administration, sublingual administration, parenteral administration and cutaneous administration.

4. The method of claim 3 , wherein the pharmaceutical composition is for parenteral administration.

5. The method of claim 2 , wherein the pharmaceutical composition comprises nanoparticles of the 2,6-diisopropyl phenol analog.

6. The method of claim 5 , wherein the pharmaceutical composition is for parenteral administration.

7. The method of claim 2 , wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier.

8. The method of claim 1 , wherein the ischemic injury is induced by stroke, hemorrhage or trauma.

9. The method of claim 1 , wherein the 2,6-diisopropyl phenol analog is 4-(trifluoromethyl)phenyl)-(4-hydroxy-3,5-diisopropylphenyl)methanone.

10. The method of claim 9 , wherein the composition is administered continuously.

11. The method of claim 9 , wherein the composition is administered one or more times a day.

12. A method of treating or ischemic injury in a human with a pharmaceutical composition comprising:

a) 0.5-5 wt % 2,6-diisopropyl phenol or an analog thereof, and

b) 0.1-5 wt % oil,

wherein, the composition is administered to a human in an amount effective to treat ischemia.

13. The method of claim 12 , wherein the composition further comprises 0.1 to 3 wt % human serum albumin.

14. The method of claim 12 , wherein the composition further comprises 0.05 to 1 wt % lecithin.

15. The method of claim 12 , wherein the composition further comprises 0.1 to 2 wt % vitamin E-TPGS.

16. The method of claim 12 , wherein the composition further comprises about 2.25% glycerol.

17. The method of claim 12 , wherein the pharmaceutical composition has a pH of about 5 to about 8.

18. A method for treating ischemia in a human comprising administering to a human a low oil composition comprising 2,6-diisopropyl phenol or an analog thereof in an amount effective to treat ischemia.

19. The method of claim 18 , wherein the composition contains less than 5 wt % oil.

20. The method of claim 19 , wherein the composition contains less than 3 wt % oil.

21. The method of claim 20 , wherein the 2,6-diisopropyl phenol analog is 4-(trifluoromethyl)phenyl)-(4-hydroxy-3,5-diisopropylphenyl)methanone.

22. The method of claim 19 , wherein the analog is selected from the group consisting of:

(4-fluorophenyl)-(4-hydroxy-3,5-diisopropylphenyl)methanone,

(4-(trifluoromethyl)phenyl)-(4-hydroxy-3,5-diisopropylphenyl)methanone,

(4-hydroxy-3,5-diisopropylphenyl)-(4-nitrophenyl)methanone,

(3-fluoro-4-(trifluoromethyl)phenyl)-(4-hydroxy-3,5-diisopropylphenyl)methanone,

(3-(trifluoromethyl)phenyl)-(4-hydroxy-3,5-diisopropylphenyl)methanone,

(3-fluoro-5-(trifluoromethyl)phenyl)-(4-hydroxy-3,5-diisopropylphenyl)methanone,

(4-hydroxy-3,5-diisopropylphenyl)-(naphthalen-2-yl)methanone,

(3,5-bis(trifluoromethyl)phenyl)-(4-hydroxy-3,5-diisopropylphenyl)methanone,

(4-tert-butylphenyl)-(4-hydroxy-3,5-diisopropylphenyl)methanone,

(4-hydroxy-3,5-diisopropylphenyl)-(4-isobutylphenyl)methanone,

(4-hydroxy-3,5-diisopropyIphenyl)-(4-iodophenyl)methanone,

(4-hydroxy-3,5-diisopropylphenyl)-(4-methoxyphenyl)methanone,

(4-cyanophenyl)-(4-hydroxy-3,5-diisopropylphenyl)methanone,

(6-(trifluoromethyl)pyridin-3-yl)-(4-hydroxy-3,5-diisopropylphenyl)methanone,

(4-bromophenyl)-(4-hydroxy-3,5-diisopropylphenyl)methanone,

(4-hydroxy-3,5-diisopropylphenyl)-(4-propylphenyl)methanone,

(4-chlorophenyl)-(4-hydroxy-3,5-diisopropylphenyl)methanone,

4-((4-(trifluoromethyl)phenyl)-(methoxyimino)methyl)-2,6-diisopropylphenol,

4-(4-(trifluoromethyl)benzyl)-2,6-diisopropylphenol,

4-((4-(trifluoromethyl)phenyl)-(hydroxy)methyl)-2,6-diisopropylphenol,

4-hydroxy-3,5-diisopropylphenyl)-(4-(methylsulfonyl)phenyl)methanone, and combinations thereof.

23. The method of claim 18 , wherein the composition contains less than 2 wt % oil.