Derivatives of 4- or 5-aminosalicylic acid
The present invention provides new derivatives of 4- or 5-aminosalicylic acid, and a pharmaceutical composition containing these derivatives of 4- or 5-aminosalicylic acid as active ingredients, useful for the treatment of intestinal diseases such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) and for the prevention/treatment of colon cancer. More particularly, these derivatives comprise a hydrogen sulfide releasing moiety linked via an azo, an ester, an anhydride, a thioester or an amide linkage to a molecule of 4- or 5-aminosalicylic acid. Furthermore, the present invention provides a process for preparing these compounds and their use for treating IBD and IBS and the prevention/treatment of colon cancer.
1. A method of treating an inflammatory condition of the gastrointestinal tract selected from the group consisting of Crohn's disease, ulcerative colitis and irritable bowel syndrome in a subject in need of such treatment, said method comprising administering to the subject an amount effective to treat the inflammatory condition of the gastrointestinal tract of a compound of the general formula:
A-L-R (I)
where:
A is
where —N=is either at position 4 or 5,
where —NH is either at position 4 or 5,
where —NH 2 is either at position 4 or 5,
or
where —NH 2 is either at position 4 or 5;
L is either O, O—C=O, S, N or a covalent bond, to form an ester linkage, an anhydride linkage, a thioester linkage, an amide linkage or an azo linkage; and
R is a hydrogen sulfide releasing moiety selected from the group consisting of:
or a pharmacologically acceptable salt thereof.
2. The method according to claim 1 wherein the compound is 4- or 5- amino-2-hydroxy-benzoic acid anhydride with N-acetyl cysteine, or a pharmacologically acceptable salt thereof.
3. The method according to claim 1 wherein the inflammatory condition of the gastrointestinal tract is Crohn's disease.
4. The method according to claim 1 wherein the inflammatory condition of the gastrointestinal tract is ulcerative colitis.
5. The method according to claim 1 wherein the inflammatory condition of the gastrointestinal tract is irritable bowel syndrome.