Prodrugs of urolithins and uses thereof
The invention provides compounds of formula (I) or salts thereof: wherein: A, B, C, D, W, X, Y and Z are as defined in the specification, and at least one of A, B, C, D, W, X, Y and Z is OR 1 ; each R 1 being independently H or C(═O)R 2 , and at least one R 1 group being C(═O)R 2 ; where each R 2 is selected from: CHR 3 NHR 4 , where R 4 is H and R 3 is a group selected from CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , CH 2 Ph, CH 2 -3-(1H-indole), CH 2 CH 2 SCH 3 , CH 2 OH, CHOHCH 3 , CH 2 SH, CH 2 SeH and CH 2 PhpOH, wherein said R 3 group can optionally be substituted by one or more groups selected from halogen, cyano, nitro, OR A or C 1 -C 4 alkyl; or R 3 and R 4 together with the C and N atoms to which they are attached form a 5-membered heteroalkyl ring, wherein said heteroalkyl ring can optionally be substituted by one or more groups selected from halogen, cyano, nitro, OR A or C 1 -C 3 alkyl, wherein R A is C 1 -C 4 alkyl optionally substituted with one or more halogen, cyano or nitro groups. The compounds are effective pro-drugs for urolithins and they enable the ready delivery of urolithins to the site in the digestive tract where they can be absorbed into the body.
1. A method of: treating a disease or condition selected from the group consisting of metabolic syndrome, reduced metabolic rate, metabolic stress, obesity, type II diabetes mellitus, multiple sclerosis, anxiety disorder, stress, and mood disorder; or managing body weight; or increasing muscle performance or mental performance, comprising:
administering to a subject in need thereof an effective amount of a compound of formula (I) or a salt thereof;
wherein:
A, B, and C are H,
D is selected from H and OR 1 ,
W, X and Y are each independently selected from H and OR 1 ,
Z is selected from H and OR 1 ;
provided that at least one of D, W, X, Y and Z is OR 1 ;
each R 1 is independently H or C(═O)R 2 , and at least one R 1 is C(═O)R 2 ;
each R 2 is selected from: CHR 3 NHR 4 , wherein R 4 is H and R 3 is a group selected from CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )CH 2 CH 3 , CH 2 Ph, CH 2 -3-(1H-indole), CH 2 CH 2 SCH 3 , CH 2 OH, CHOHCH 3 , CH 2 SH, CH 2 SeH and CH 2 PhpOH,
wherein said R 3 group can optionally be substituted by one or more groups selected from halogen, cyano, nitro, OR A or C 1 -C 4 alkyl; or R 3 and R 4 together with the C and N atoms to which they are attached form a 5-membered heteroalkyl ring, wherein said heteroalkyl ring can optionally be substituted by one or more groups selected from halogen, cyano, nitro, OR A or C 1 -C 3 alkyl, wherein R A is C 1 -C 4 alkyl optionally substituted with one or more halogen, cyano or nitro groups.
2. The method of claim 1 , wherein D is OR 1 .
3. The method of claim 1 , wherein Z is OR 1 .
4. The method of claim 1 , wherein D and Z are OR 1 .
5. The method of claim 1 , wherein W is H, X is H, Y is H; and Z is OR 1 .
6. The method of claim 1 , wherein R 2 is CHR 3 NHR 4 wherein R 4 is H, and R 3 is selected from CH 3 , CH 2 CH(CH 3 ) 2 , and CH(CH 3 )CH 2 CH 3 , or R 3 and R 4 together with the C and N atoms to which they are attached form an unsubstituted 5-membered heteroalkyl ring.
7. The method of claim 4 , wherein R 3 is CH 3 , CH 2 CH(CH 3 ) 2 , or CH(CH 3 )CH 2 CH 3 ; or R 3 and R 4 taken together with the C and N atoms to which they are attached form an unsubstituted 5-membered heteroalkyl ring.
8. The compound of claim 1 , wherein R 3 is CH 3 , CH 2 CH(CH 3 ) 2 , or CH(CH 3 )CH 2 CH 3 .
9. The compound of claim 4 , wherein R 3 is CH 3 , CH 2 CH(CH 3 ) 2 , or CH(CH 3 )CH 2 CH 3 .
10. The method of claim 1 , wherein the compound is selected from:
11. The method of claim 1 , wherein muscle performance is increased.
12. The method of claim 10 , wherein muscle performance is increased.
13. The method of claim 1 , wherein mental performance is increased.
14. The method of claim 10 , wherein mental performance is increased.
15. The method of claim 1 , wherein metabolic syndrome is treated.
16. The method of claim 1 , wherein reduced metabolic rate is treated.
17. The method of claim 1 , wherein metabolic stress is treated.
18. The method of claim 1 , wherein obesity is treated.
19. The method of claim 1 , wherein type II diabetes mellitus is treated.
20. The method of claim 1 , wherein multiple sclerosis is treated.
21. The method of claim 1 , wherein anxiety disorder is treated.
22. The method of claim 1 , wherein stress is treated.
23. The method of claim 1 , wherein mood disorder is treated.
24. The method of claim 1 , wherein body weight is managed.