Immunoregulatory compounds and derivatives and methods of treating diseases therewith
View Patent ↗Compounds are disclosed having the structure of Formula I: where R 1 , R 3 , and R 4 are independently hydrogen or C 1 to C 4 alkyl, and R 2 is: where R 5 is selected from the group consisting of hydrogen and C 1 to C 4 alkyl, or where R 6 , R 7 and R 8 are independently hydrogen or C 1 to C 4 alkyl; or the esters or pharmacologically acceptable salts thereof. Such compounds may be utilized for the prophylaxis or treatment of various diseases, particularly inflammatory conditions of the GI tract. Methods of treating inflammatory conditions of the GI tract such as inflammatory bowel disease using compounds having the following formula are also disclosed: where R 9 , R 10 and R 11 are independently selected from the group consisting of hydrogen and C 1 to C 4 alkyl, and R 12 is selected from the group consisting of hydrogen and —C(O)R 13 , where R 13 is a C 1 to C 6 alkyl or an aryl group.
1. A method of treating an inflammatory condition of the GI tract in a subject comprising administering to a subject in need of such treatment an effective amount of an active pharmaceutical ingredient comprising a compound of Formula II:
where R 9 , R 10 and R 11 are independently selected from the group consisting of hydrogen and C 1 to C 4 alkyl; and R 12 is selected from the group consisting of hydrogen and —C(O)R 13 , where R 13 is a C 1 to C 6 alkyl or an aryl group; or an ester or a pharmaceutically acceptable salt of such compound, in admixture with pharmaceutical diluent or carrier.
2. The method according to claim 1 , wherein the active pharmaceutical ingredient further comprises a compound of Formula (III):
or an ester or a pharmaceutically acceptable salt thereof.
3. The method according to claim 1 , wherein the compound of Formula II is from about 10 to 90 weight percent of the active pharmaceutical ingredient.
4. The method according to claim 1 , wherein the molar ratio of the compound of Formula II to the compound of Formula III is between about 1:10 and 10:1.
5. The method according to claim 1 , wherein R 9 , R 10 , and R 11 are independently selected from the group consisting of H, CH 3 , CH 2 CH3, and CH(CH 3 ) 2 .
6. The method according to claim 1 , wherein R 9 , R 10 , and R 11 are independently selected from the group consisting of H, and CH 3 .
7. The method according to claim 1 , wherein R 12 is hydrogen.
8. An in vivo method of generating active metabolites for the treatment of an inflammatory condition of the GI tract, the method comprising orally administering to a subject having intestinal bacterial a compound having the structure:
5-(4-carboxymethylphenylazo)-2-hydroxy-benzoic acid or an ester or a pharmaceutically acceptable salt thereof, wherein the active metabolites comprise at least one compound selected from the group consisting of 5-aminosalicylic acid (5-ASA) and 4-aminophenyl acetic acid (4-APAA).
9. The in vivo method of claim 8 , wherein the active metabolite further includes acetylated 5-ASA and acetylated 4-APAA.
10. The in vivo method of claim 8 , wherein the 5-(4-carboxymethylphenylazo)-2-hydroxy-benzoic acid or an ester or a pharmaceutically acceptable salt thereof is in a liquid solution comprising a biocompatible carrier.
11. The in vivo method of claim 8 , wherein the 5-(4-carboxymethylphenylazo)-2-hydroxy-benzoic acid or an ester or a pharmaceutically acceptable salt thereof is in a powder form.
12. The in vivo method of claim 8 , wherein the inflammatory condition of the GI tract is ulcerative colitis.
13. The in vivo method of claim 8 , wherein the inflammatory condition of the GI tract is Crohn's disease.
14. The in vivo method of claim 8 , wherein the active metabolites were generated within 24 hours of administration.
15. The in vivo method of claim 14 , wherein the active metabolites were located in urine or feces matter of subject.
16. A liquid solution comprising: 5-(4-carboxymethylphenylazo)-2-hydroxy-benzoic acid, 5-aminosalicylic acid (5-ASA) and 4-aminophenyl acetic acid (4-APAA).
17. The liquid solution of claim 16 further comprising 4-aminophenyl acetic acid (4-APAA), acetylated 5-ASA and acetylated 4-APAA.
18. A method for generating active metabolites; the method comprising contacting intestinal bacteria with 5-(4-carboxymethylphenylazo)-2-hydroxy-benzoic acid or an pharmaceutically acceptable salt thereof under conditions for metabolism thereof by the bacteria.
19. The method of claim 18 , wherein the active metabolites comprises at least one metabolite selected from the group consisting of 5-aminosalicylic acid (5-ASA) and 4-aminophenyl acetic acid (4-APAA).
20. The method of claim 19 , further comprising 4-aminophenyl acetic acid (4-APAA), acetylated 5-ASA and acetylated 4-APAA.