Use of dipeptidyl peptidase IV inhibitors in the treatment of multiple sclerosis
The present invention provides a new use of DP IV-inhibitors. The compounds of the present invention, and their corresponding pharmaceutically acceptable acid addition salt forms, are useful in treating conditions mediated by DP IV or DP IV-like enzymes, such as immune, autoimmune or central nervous system disorder selected from the group consisting of strokes, tumors, ischemia, Parkinson's disease and migraines. In a more preferred embodiment, the compounds of the present invention are useful for the treatment of multiple sclerosis.
1. A method for treating multiple sclerosis, the method comprising administering to a subject in need thereof, a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a therapeutically effective amount of at least one inhibitor of dipeptidyl peptidase IV of formula
or a stereoisomer or pharmaceutically acceptable salt thereof,
wherein
A is glutamic acid;
B is Gly n , wherein n is from 1 to 6, and B is covalently bound to at least one functional group in the side chain of A; and
C is a thiazolidine, pyrrolidine, cyanopyrrolidine, hydroxyproline, dehydroproline or piperidine group amide-bonded to A.
2. The method of claim 1 , wherein C is thiazolidine or pyrrolidine.
3. The method of claim 2 , wherein C is thiazolidine.
4. The method of claim 2 , wherein C is pyrrolidine.
5. The method of claim 1 , wherein n is 3.
6. The method of claim 1 , wherein n is 5.
7. The method of claim 1 wherein the at least one inhibitor of dipeptidyl peptidase IV is capable of inhibiting activity of dipeptidyl peptidase IV by at least 10%.
8. The method of claim 7 wherein the at least one inhibitor of dipeptidyl peptidase IV is capable of inhibiting activity of dipeptidyl peptidase IV by at least 40%.
9. The method of claim 8 wherein the at least one inhibitor of dipeptidyl peptidase IV is capable of inhibiting activity of dipeptidyl peptidase IV by at least 60%.
10. The method of claim 9 wherein the at least one inhibitor of dipeptidyl peptidase IV is capable of inhibiting activity of dipeptidyl peptidase IV by at least 70%.
11. The method of claim 1 wherein the at least one inhibitor of dipeptidyl peptidase IV is substantially incapable of being transported by the peptide transporter PepT1.
12. A method for treating multiple sclerosis, the method comprising administering to a subject in need thereof, a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a therapeutically effective amount of at least one inhibitor of dipeptidyl peptidase IV, or a stereoisomer or pharmaceutically acceptable salt thereof, wherein the at least one inhibitor of dipeptidyl peptidase IV is selected from the group consisting of Glu(Gly 3 )-Thia, Glu(Gly 5 )-Thia and Glu(PEG)-Thia.
13. A method for treating multiple sclerosis, the method comprising administering to a subject in need thereof, a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a therapeutically effective amount of at least one inhibitor of dipeptidyl peptidase IV of formula
or a stereoisomer or pharmaceutically acceptable salt thereof,
wherein
A is an amino acid having a side chain with at least one functional group;
B comprises Gly n , wherein n is from 1 to 6, and B is covalently bound to at least one functional group in the side chain of A; and
C is a thiazolidine, pyrrolidine, cyanopyrrolidine, hydroxyproline, dehydroproline or piperidine group amide-bonded to A.