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 compound of formula (I) or a salt thereof:
wherein:
A, B, C, W, X and Y are H,
D and Z are independently OR 1 ;
each R 1 is independently C(═O)R 2 ;
each R 2 is independently 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.
2. The compound of claim 1 , wherein R 2 is CHR 3 NHR 4 , where R 4 is H and R 3 is 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.
3. The compound of claim 1 , wherein R 2 is CHR 3 NHR 4 , where 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.
4. The compound of claim 3 which is selected from:
5. A method for treating aging of the skin, comprising topically administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I) or a salt thereof of claim 1 .
6. A composition, comprising a compound of formula (I) or a salt thereof of claim 1 ; and a carrier.
7. The composition of claim 6 , in the form of a solution or suspension.
8. The composition of claim 6 , in the form of a powder or granules suitable for dissolution or suspension in an aqueous medium.
9. The composition of claim 6 , further comprising a further active ingredient, wherein the further active ingredient is selected from rapamycin, resveratrol, metformin, and spermidine.
10. A food, beverage or dietary supplement comprising a compound of formula (I) or a salt thereof of claim 1 .