Inhibitors of dipeptidyl peptidase I

1. A pharmaceutically acceptable salt of a compound of the general formula (I)

wherein

R is H or a peptide or a branched or unbranched C 1 –C 9 alkyl chain, a branched or unbranched C 2 –C 9 alkenyl chain, a branched or unbranched C 2 –C 9 alkynyl chain, a C 3 –C 9 cycloalkyl, C 4 –C 9 carbocyclic, C 5 –C 14 aryl, C 3 –C 9 heteroaryl, or C 3 –C 9 heterocyclic, all of the above residues optionally being substituted, the residue AS—AS is a dipeptide or a mimetic thereof, with the proviso that AS—AS may not be Ala-Pro, Ala-Pro mimetic, Ile-Pro or Tyr-Gly,

E is O or S, and

R′ is a branched or unbranched C 1 –C 9 alkyl chain, a branched or unbranched C 2 –C 9 alkenyl chain, a branched or unbranched C 2 –C 9 alkynyl chain, a C 3 –C 9 cycloalkyl, C 4 –C 9 cycloalkenyl, C 2 –C 9 heterocycloalkyl, C 3 –C 9 heterocycloalkenyl, C 5 –C 14 aryl, C 3 –C 9 heteroaryl, or C 3 –C 9 heterocyclic, wherein the heterocycloalkyl, heterocycloalkenyl, heteroaryl, heterocyclic residue can have up to 6 hetero atoms in the ring, or R′ is an amino acid or a peptide or a mimetic thereof, all of the above residues optionally being substituted, or R′ is H or alkoxy, alkenyloxy, alkynyloxy, carbocyclicoxy, heteroaryloxy, heterocyclicoxy, thioether or a substituted residue thereof, with the proviso, that the compound H-Gly-Phe-NHO—BZ including all pharmaceutically acceptable salts thereof are excluded.

2. The pharmaceutically acceptable salt according to claim 1 , wherein R is phenyl or naphthyl optionally mono-, di-, or poly-substituted by C 1 –C 6 alkoxy, C 1 –C 6 alkyl, C 2 –C 6 alkenyloxy, C 2 –C 6 alkynyloxy, C 3 –C 9 heteroaryloxy, C 3 –C 9 heterocyclicoxy, C 1 –C 6 thioether or a substituted residue thereof, NO 2 , NH 2 , F, Cl, Br, 1 atoms or groups.

3. The pharmaceutically acceptable salt according to claim 1 , wherein R′ is a phenyl or naphthyl.

4. The pharmaceutically acceptable salt according to claim 1 , wherein R′ is

wherein V is N or CH and n=1–6.

5. The pharmaceutically acceptable salt according to claim 1 , wherein R′ is

wherein T 1 is CH or N,

W 1 , X 1 , Y 1 and Z 1 are independently from each other selected from CH 2 , NR 2 , N + (R 3 ) 2 , O, S, SO, S(R 4 ) 2 , SO 2 , with the proviso that at least two of W 1 , X 1 , Y 1 and Z 1 are CH 2 -groups, R 2 , R 3 and R 4 are independently from each other a branched or unbranched C 2 –C 9 alkyl chain, a branched or unbranched C 2 –C 9 alkenyl chain, a branched or unbranched C 2 –C 9 alkynyl chain, C 3 –C 9 cycloalkyl, C 4 –C 9 cycloalkenyl or H.

6. The pharmaceutically acceptable salt according to claim 1 , wherein R′ is

wherein T 2 is C or N + ,

W 2 , X 2 , Y 2 and Z 2 are independently from each other selected from CH, N + , N + R 5 or S + R 6 , R 5 and R 6 are independently from each other a branched or unbranched C 1 –C 9 alkyl chain, a branched or unbranched C 2 –C 9 alkenyl chain, a branched or unbranched C 2 –C 9 alkynyl chain, C 3 –C 9 cycloalkyl, C 4 –C 9 cycloalkenyl or H.

7. The pharmaceutically acceptable salt according to claim 1 , wherein R′ is

wherein T 3 , W 3 , X 3 , Y 3 and Z 3 are independently from each other are selected from CH, N + N + R 7 or S + R 8 , R 7 and R 8 are independently from each other a branched or unbranched C 1 –C 9 alkyl chain, a branched or unbranched C 2 –C 9 alkenyl chain, a branched or unbranched C 1 –C 9 alkynyl chain, C 1 –C 9 cycloalkyl, C 4 –C 9 cycloalkenyl or H.

8. The pharmaceutically acceptable salt according to claim 1 , wherein R′ is

wherein T 4 is C or N.

9. The pharmaceutically acceptable salt according to claim 1 , wherein R′ is an amino acid, a peptide, a dipeptide or a mimetic thereof.

10. The pharmaceutically acceptable salt according to claim 1 , wherein the residue R′ may be mono-, di-, or poly-substituted by C 1 –C 6 alkoxy, C 1 –C 6 alkyl, C 1 –C 6 thioether, NO 2 , NH 2 , F, Cl, Br, I atoms or groups, except when R′ is H.

11. The pharmaceutically acceptable salt according to claim 1 , wherein said compound is in the form of prodrugs.

12. A pharmaceutical composition comprising the pharmaceutically acceptable salt according to claim 1 and at least one pharmaceutically acceptable carrier and/or adjunct.

13. A method of treatment of a disease of a mammal comprising the step of administering to said mammal a therapeutically effective amount of the pharmaceutically acceptable salt according to claim 1 causing a modulation of the activity of DPI and/or DP I-like enzymes of said mammal.

14. A method of treatment of a disease of a mammal comprising the step of administering to said mammal a therapeutically effective amount of said pharmaceutical composition according to claim 12 causing a modulation of the activity of DPI and/or DP I-like enzymes of said mammal.

15. The method according to claim 13 , wherein said modulation comprises the inhibition of DP I and/or DP I-like enzymes.

16. The method according to claim 13 , wherein said disease is selected from the group consisting of malignant cell degeneration, immune diseases and metabolic diseases of humans.

17. The method according to claim 13 , wherein said disease is impaired wound-healing in humans.

18. The method according to claim 14 , wherein said modulation comprises the inhibition of DP I and/or DP I-like enzymes.

19. The method according to claim 18 , wherein said disease is selected from the group consisting of malignant cell degeneration, immune diseases and metabolic diseases of humans.

20. The method according to claim 18 , wherein said disease is impaired wound-healing in humans.