Substituted aromatic compounds and pharmaceutical compositions for tissue self-repair and regeneration
Described herein are compounds of Formula I, or pharmaceutically acceptable salts thereof, or combinations thereof, as well as uses thereof. Such uses include promoting tissue self-repair or tissue regeneration of an organ, stimulating the generation of tissue growth, modulating (e.g., increasing) the level of a tissue-repair marker, treating physical injury in an organ, tissue or cell, promoting wound healing, as well as anti-aging applications. Corresponding compositions, methods, kits, and uses are also described. Formula I wherein A is C 5 alkyl, C 6 alkyl, C 5 alkenyl, C 6 alkenyl, C(O)—(CH 2 ) n —CH 3 or CH(OH)—(CH 2 ) n —CH 3 wherein n is 3 or 4; R 1 is H, F of OH; R 2 is H, F, OH, C 5 alkyl, C 6 alkyl, C 5 alkenyl, C 6 alkenyl, C(O)—(CH 2 ) n —CH 3 or CH(OH)—(CH 2 ) n —CH 3 wherein n is 3 or 4; R 3 is H, F, OH, or CH 2 Ph; R 4 is H, F or OH; Q is 1) (CH 2 ), C(O)OH wherein m is 1 or 2 2) CH(CH 3 )C(O)OH, 3) C(CH 3 ) 2 C(O)OH, 4) CH(F)—C(O)OH, 5) CF 2 —C(O)OH or 6) C(O)—C(O)OH.
1. A method for renal tissue regeneration or for stimulating the generation of renal tissue growth in a subject in need of renal tissue growth or regeneration, the method comprising;
administering to the subject in need of renal tissue growth or regeneration a compound represented by Formula I or a pharmaceutically acceptable salt thereof, or a combination thereof:
wherein
A is C 5 alkyl, C 6 alkyl, C 5 alkenyl, C 6 alkenyl, C(O)—(CH 2 ) n —CH 3 or CH(OH)—(CH 2 ) n —CH 3 wherein n is 3 or 4;
R 1 is H, F or OH;
R 2 is H, F, OH, C 5 alkyl, C 6 alkyl, C 5 alkenyl, C 6 alkenyl, C(O)—(CH 2 ) n —CH 3 or CH(OH)—(CH 2 ) n —CH 3 wherein n is 3 or 4;
R 3 is H, F, OH or CH 2 Ph;
R 4 is H, F or OH;
Q is
1) (CH 2 ) m C(O)OH wherein m is 1 or 2,
2) CH(CH 3 )C(O)OH,
3) C(CH 3 ) 2 C(O)OH,
4) CH(F)—C(O)OH,
5) CF 2 —C(O)OH, or
6) C(O)—C(O)OH;
wherein the subject does not have renal fibrosis.
2. The method of claim 1 , wherein A is C 5 alkyl or C 6 alkyl.
3. The method of claim 1 , wherein R 2 is H, F, OH, C 5 alkyl or C 6 alkyl.
4. The method of claim 1 , wherein R 3 is H, OH or CH 2 Ph.
5. The method of claim 1 , wherein Q is (CH 2 ) m C(O)OH where m is 1 or 2.
6. The method of claim 1 , wherein A is C 5 alkyl or C 6 alkyl; R 1 is H, F or OH; R 2 is H, F, OH, C 5 alkyl or C 6 alkyl; R 3 is H, OH or CH 2 Ph; R 4 is H, F or OH; and Q is (CH 2 ) m C(O)OH where m is 1 or 2.
7. The method of claim 1 , wherein A is C 5 alkyl; R 1 is H; R 2 is H or C 5 alkyl; R 3 is H; R 4 is H; and Q is (CH 2 ) m C(O)OH where m is 1.
8. The method of claim 1 , wherein said compound is selected from the group consisting of the compounds represented by the following structures:
and pharmaceutically acceptable salts thereof.
9. The method of claim 1 , wherein said compound is represented by the following structure:
or pharmaceutically acceptable salt thereof.
10. The method of claim 1 , wherein said compound is represented by the following structure:
or pharmaceutically acceptable salt thereof.
11. The method of claim 1 , wherein the pharmaceutically acceptable salt is a base addition salt comprising a metal counterion selected from the group consisting of sodium, potassium, calcium, magnesium, lithium, ammonium, manganese, zinc, iron, or copper.
12. The method of claim 1 , wherein the pharmaceutically acceptable salt is sodium.
13. A method for modulating the expression of a tissue regeneration marker in renal tissue of a subject, the method comprising the step of administering to a subject in need of renal tissue regeneration a compound represented by Formula I or a pharmaceutically acceptable salt thereof, or a combination thereof:
wherein
A is C 5 alkyl, C 6 alkyl, C 5 alkenyl, C 6 alkenyl, C(O)—(CH 2 ) n —CH 3 or CH(OH)—(CH 2 ) n —CH 3 wherein n is 3 or 4;
R 1 is H, F or OH;
R 2 is H, F, OH, C 5 alkyl, C 6 alkyl, C 5 alkenyl, C 6 alkenyl, C(O)—(CH 2 ) n —CH 3 or CH(OH)—(CH 2 ) n —CH 3 wherein n is 3 or 4;
R 3 is H, F, OH or CH 2 Ph;
R 4 is H, F or OH;
Q is
1) (CH 2 ) m C(O)OH wherein m is 1 or 2,
2) CH(CH 3 )C(O)OH,
3) C(CH 3 ) 2 C(O)OH,
4) CH(F)—C(O)OH,
5) CF 2 —C(O)OH, or
6) C(O)—C(O)OH;
wherein the tissue regeneration marker is expressed in renal tissue; and
wherein the renal tissue is not fibrotic.
14. The method of claim 13 , wherein the marker is a metalloproteinase or a growth factor.
15. The method of claim 13 , wherein the marker is hepatocyte growth factor (HGF) or Serpin A1 (AAT).