Pyrrolo[2,3-d]pyrimidine compounds

1. A method for the inhibition of Janus kinase 3 (JAK 3) in a mammal, comprising administering to said mammal an effective amount of a compound of the formula

or a pharmaceutically acceptable salt thereof; wherein

R 1 is a group of the formula

wherein y is 0, 1 or 2;

R 4 selected from the group consisting of hydrogen, (C 1 –C 6 )alkyl, (C 1 –C 6 )alkylsulfonyl, (C 2 –C 6 )alkenyl, (C 2 –C 6 )alkynyl wherein the alkyl, alkenyl and alkynyl groups are optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C 1 –C 4 )alkoxy, (C 1 –C 6 )acyloxy, (C 1 –C 6 )alkylamino, ((C 1 –C 6 )alkyl) 2 amino, cyano, nitro, (C 2 –C 6 )alkenyl, (C 2 –C 6 alkynyl or (C 1 –C 6 )acylamino; or R 4 is (C 3 –C 10 )cycloalkyl wherein the cycloalkyl group is optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C 1 –C 6 )acyloxy, (C 1 –C 6 )acylamino, (C 1 –C 6 )alkylamino, ((C 1 –C 6 )alkyl) 2 amino, cyano, cyano(C 1 –C 6 )alkyl, trifluoromethyl(C 1 –C 6 )alkyl, nitro, nitro(C 1 –C 6 )alkyl or (C 1 –C 6 )acylamino;

R 5 is (C 2 –C 9 )heterocycloalkyl wherein the heterocycloalkyl groups must be substituted by one to five groups consisting of carboxy, cyano, amino, deuterium, hydroxy, (C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy, halo, (C 6 C 6 )acyl, (C 1 –C 6 )alkylamino, amino(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy-CO—NH, (C 1 –C 6 )alkylamino-CO—, (C 2 –C 6 )alkenyl, (C 2 –C 6 ) alkynyl, (C 1 –C 6 ) alkylkylamino, amino(C 1 –C 6 )alkyl, hydroxy(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy(C 1 –C 6 )alkyl, (C 1 –C 6 )acyloxy(C 1 –C 6 )alkyl, nitro, cyano(C 1 –C 6 )alkyl, halo(C 1 –C 6 )alkyl, nitro(C 1 –C 6 )alkyl, trifluoromethyl, trifluoromethyl(C 1 –C 6 )alkyl, (C 1 –C 6 )acylamino, (C 1 –C 6 )acylamino(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy(C 1 –C 6 )acyl amino, amino(C 1 –C 6 )acyl, amino(C 1 –C 6 )acyl(C 1 –C 6 )alkyl, (C 1 –C 6 )alkylamino(C 1 –C 6 )acyl, ((C 1 –C 6 )acyl) 2 amino(C 1 –C 6 )acyl, R 15 R 16 N—CO—O—, R 15 R 16 N—CO—(C 1 C 6 )alkyl, (C 1 –C 6 )alkyl-S (O) m , R 15 R 16 NS(O) m , R 15 R 16 NS(O) m (C 1 –C 6 )alkyl, R 15 S(O) m R 16 N, R 15 S(O) m R 16 N(C 1 –C 6 )alkyl, and a group of the formula II

wherein:

m is 0, 1 or 2;

R 15 and R 16 are each independently selected from hydrogen or (C 1 –C 6 )alkyl;

a is 0, 1,2,3or 4;

b, c, e, f and g are each independently 0 or 1;

d is 0, 1, 2, or 3;

X is S(O) n wherein n is 0, 1 or 2; oxygen, carbonyl or —C(═N-cyano)-;

Y is S(O) n wherein n is 0, 1 or 2; or carbonyl; and

Z is carbonyl, C(O)O—, C(O)NR— wherein R is hydrogen or (C 1 –C 6 )alkyl; or Z is S(O) n wherein n is 0, 1 or 2;

R 6 , R 7 , R 8 , R 9 , R 10 and R 11 are each independently selected from the group consisting of hydrogen or (C 1 –C 6 )alkyl optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C 1 –C 6 )acyloxy, (C 1 –C 6 )acylamino, (C 1 –C 6 )alkyiamino, ((C 1 –C 6 )alkyl) 2 amino, cyano, cyano(C 1 –C 6 )alkyl, trifluoromethyl(C 1 –C 6 )alkyl, nitro, nitro(C 1 –C 6 )alkyl or (C 1 –C 6 )acylamino;

R 12 is (C 6 –C 10 )aryl, (C 2 –C 9 )heteroaryl, tetrazolyl, or (C 2 –C 9 )heterocycloalkyl, wherein the aryl, heteroaryl, terrazolyl, and heterocycloalkyl groups are optionally substituted by one to four groups consisting of hydrogen, deuterium, amino, halo, oxo, hydroxy, nitro, carboxy, (C 2 –C 6 )alkenyl, (C 2 –C 6 )alkynyl, trifluoromahyl, trifluoromethoxy, (C 1 –C 6 )alkyl, (C 1 –C6)alkoxy, (C 3 –C 10 )cycloalkyl, (C 1 –C 6 )alkyl-CO—NH—, (C 1 –C 6 )alkoxy-CO—NH—, (C 1 –C 6 )alkyl-C O—NH—(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy-CO—NH—(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy-CO—NH—(C 1 –C 6 )alkoxy, carboxy, carboxy(C 1 –C 6 alkyi, carboxy(C 1 –C 6 )alkoxy, benzyloxycarbonyl(C 1 –C 6 )alkoxy, (C 1 –C 6 )alkoxycarbonyl(C 1 –C 6 )alkoxy, (C 6 –C 10 )aryl, amino, amino(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxycarbonylamino, (C 6 –C 10 )aryl(C 1 –C 6 )alkoxycarbonylamino, (C 1 –C 6 )alkylamino, ((C 1 –C 6 )alkyl) 2 amino, (C 1 –C 6 ) alkylamino(C 1 –C 6 )alkyl, ((C 1 –C 6 )alkyl) 2 amino(C 1 –C 6 )alkyl, hydroxy, (C 1 –C 6 )alkoxy, carboxy, (C 1 )alkyl, (C 1 –C 6 )alkoxycarbonyl, (C 12 –C 6 )alkoxycarbonyl(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy -CO—NH—, (C 1 –C 6 )alkyl -CO—NH—, cyano, (C 5 –C 9 )heterocycloalkyl, amino-CO—NH—, (C 1 –C 6 )alkylamino-CO—NH—, ((C 1 –C 6 )alkyl) 2 amino-CO—NH—, (C 6 –C 10 )arylamino-CO—NH—, (C 5 –C 9 )heteroarylamino-CO—NH—, (C 1 –C 6 )alkylamino-CO—NH—(C 1 –C 6 )alkyl, ((C 1 –C 6 )alkyl) 2 amino-CO—NH—(C 1 –C 6 )alkyl, (C 6 –C 10 )arylamino-CO—NH—(C 1 –C 6 )alkyl, (C 5 –C 9 )heteroarylamino-CO—NH—(C 1 –C 6 ) alkyl, cyano(C 1 –C 6 )alkyl, carboxy(C 1 –C 6 )alkyl(C 1 –C 6 )alkoxy, carboxy(C 1 –C 6 )alkyl, sulfonylamino, aminosulfonyl, sulfonylamino(C 1 –C 6 )alkyl, sulfonylaminocarboxy(C 1 –C 6 )alkyl, (C 1 –C 6 )alkylsulfonyl, (C 1 –C 6 )alkylsulfonylamino, (C 1 –C 6 )alkylsulfonylamino(C 1 –C 6 )alkyl, (C 6 –C 10 )arylsulfonyl, (C 6 –C 10 )arylsulfonylamino, (C 6 C 10 )arylsulfonylamino(C 1 –C 6 )alkyl, (C 1 –C 6 )alkylsulfonylamino, (C 1 –C 6 )alkylsulfonylamino(C 1 –C 6 )alkyl, (C 3 –C 10 )cycloalkyl, (C 3 –C 10 )cycloalkoxy, (C 1 –C 6 )alkylamino, ((C 1 –C 6 )alkyl) 2 amino, (C 6 –C 6 )arylamino, (C 1 –C 6 )alkylthio, (C 6 –C 10 ) arylthio, (C 1 –C 6 )alkylsulfinyl, (C 6 –C 10 )arylsulfinyl, (C 1 –C 6 )alkylsulfonyl, (C 6 –C 10 )arylsulfonyl, (C 1 –C 6 ) acyl, (C 1 –C 6 )alkoxy-CO—NH—, (C 1 –C 6 )alkylamino-CO—, (C 5 –C 9 )heteroaryl, (C 2 –C 9 )heterocycloalkyl or (C 6 –C 10 )aryl wherein the heteroaryl, tetrazolyl, heterocycloalkyl and aryl groups which are optionally substituted on R 12 may be further substituted by one to three groups consisting of halo, (C 1 –C 6 )alkyl, (C 1 –C 6 )alkyl-CO—NH—, (C 1 –C 6 )alkoxy-CO—NH—, (C 1 –C 6 )alkyl-CO—NH—(C 1 –C 6 )alkyl, C 1 –C 6 )alkoxy-CO—NH—(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy-CO—NH—(C 1 –C 6 )alkoxy, carboxy, carboxy(C 1 –C 6 )alkyl, carboxy(C 1 –C6)alkoxy, benzyloxycarbonyl(C 1 –C 6 )alkoxy, (C 1 –C 6 )alkoxycarbonyl(C 1 –C 6 )alkoxy, (C 6 –C 10 )aryl, amino, amino(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxycarbonylamino, (C 6 –C 10 )aryl(C 1 –C 6 ) alkoxycarbonylaniino, (C 1 –C 3 alkylamino, ((C 1 –C 6 )alkyl ) 2 amino, (C 1 –C 6 )alkylamino(C 1 –C 6 )alkyl, ((C 1 –C 6 ) 2 amino(C 1 –C 6 )alkyl, hydroxy, (C 1 –C 6 )alkoxy, carboxy, carboxy(C 1 –C 6 )alkyl, (C 1 –C 6 ) alkoxycarbonyl, (C 1 –C 6 )alkoxycarbonyl(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy-CO—NH—, (C 1 –C 6 )alkyl-CO—NH —, cyano, (C 5 –C 9 )heterocycloalkyl, amino-CO—NH—, (C 1 –C 6 )alkylamino-CO—NH—, ((C 1 –C 6 )alkyl) 2 amino-CO—NH—, (C 6 –C 10 )arylamino-CO—NH—, (C 5 –C 9 )heteroarylamino-CO—NH—, (C 1 –C 6 )alkylamino-CO—NH—(C 1 –C 6 )alkyl, ((C 1 –C 6 )alkyl) 2 amino-CO—NH—(C 1 –C 6 )alkyl, (C 6 –C 10 )arylamino-C O—NH—(C 1 –C 6 )alkyl, (C 5 –C 9 )heteroarylamino-CO—NH—(C 1 –C 6 )alkyl, (C 1 –C 6 )alkylsulfonyl, (C 1 –C 6 ) alkylsulfonylamino, (C 1 –C 6 )alkylsulfonylamino(C 1 –C 6 )alkyl, (C 6 –C 10 )arylsulfonyl, (C 6 –C 10 )arylsulfonylamino, (C 6 –C 10 )arylsulfonylamino(C 1 –C 6 )alkyl, (C 1 –C 6 )alkylsulfonylamino, (C 1 –C 6 ) alkylsulfonylamino(C 1 –C 6 )alkyl, (C 5 –C 9 )heteroaryl and (C 2 –C 9 )heterocycloalkyl;

R 2 and R 3 are each independently selected from the group consisting of hydrogen, deuterium, amino, halo, hydroxy, nitro, carboxy, (C 2 –C 6 )alkenyl, (C 2 –C 6 )alkynyl, trifluoromethyl, trifluoromethoxy, (C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy, (C 3 –C 10 )cycloalkyl wherein the alkyl, alkoxy or cycloalkyl groups are optionally substituted by one to three groups selected from halo, hydroxy, carboxy, amino (C 1 –C 6 )alkylthio, (C 1 –C 6 )alkylamino, ((C 1 –C 6 )alkyl) 2 amino, (C 5 –C 9 )heteroaryl, (C 2 –C 9 )heterocycloalkyl, (C 3 –C 9 )cycloalkyl or (C 6 –C 10 )aryl; or R 2 and R 3 are each independently (C 3 –C 10 )cycloalkyl, (C 3 –C 10 )cycloalkoxy, (C 1 –C 6 )alkylamino, ((C 1 –C 6 )alkyl) 2 amino, (C 6 –C 10 )arylamino, (C 1 –C 6 )alkylthio, (C 6 –C 10 )arylthio, (C 1 –C 6 )alkylsulfinyl, (C 6 –C 10 ) arylsulfinyl, (C 1 –C 6 )alkylsulfonyl, (C 6 –C 10 )arylsulfony, (C 1 –C 6 )acyl, (C 1 –C 6 )alkoxy-CO—NH—, (C 1 –C 6 ) alkylamino-CO—, (C 5 –C 9 )heteroaryl, (C 2 –C 9 )heterocycloalkyl or (C 6 –C 10 )aryl wherein the heteroaryl, heterocycloalkyl and aryl groups are optionally substituted by one to three halo, (C 1 –C 6 )alkyl, (C 1 –C 6 )alkyl-CO—NH—, (C 1 –C 6 )alkoxy-CO—NH—, (C 1 –C 6 )alkyl-CO—NH—(C 12 –C 6 )alkyl, (C 1 C 6 )alkoxy-CO—NH—(C 1 –C 6 )alkyl, (C 1 –C 9 )alkoxy-CO—NH—(C 1 –C 6 )alkoxy, carboxy, carboxy(C 1 –C 6 )alkyl, carboxy(C 1 C 6 )alkoxy, benzyloxycarbonyl(C 1 –C 6 )alkoxy, (C 1 –C 6 )alkoxycarbonyl(C 1 –C 6 )alkoxy, (C 6 –C 10 aryl, amino, amino(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxycarbonylamino, (C 6 –C 10 )aryl(C 1 –C 6 ) alkoxycarbonylamino, (C 1 –C 6 )alkylamino, ((C 1 –C 6 )alkyl) 2 amino, (C 1 –C 6 )alkylamino(C 1 –C 6 )alkyl, ((C 1 C6)alkyl) 2 amino(C 1 –C 6 )alkyl, hydroxy, (C 1 –C 6 )alkoxy, carboxy, carboxy(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxycarbonyl, (C 1 –C 6 )alkoxycarbonyl(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy-CO—NH—, (C 1 –C 6 )alkyl-CO—NH—, cyano, (C 5 –C 9 )heterocycloalkyl, amino-CO—NH—, (C 1 –C 6 )alkylamino-CO—NH—, ((C 1 –C 6 )alkyl) 2 amino-CO—NH—, (C 6 –C 10 )arylamino-CO—NH—, (C 5 –C 9 )heteroarylamino-CO—NH—, (C 1 –C 6 )alkylamino-CO—NH—(C 1 –C 6 )alkyl, ((C 1 –C 6 )alkyl) 2 amino-CO—NH—(C 1 –C 6 )alkyl, (C 6 –C 10 ) arylarnino-CO—NH—(C 1 –C 6 )alkyl, (C 5 –C 9 )heteroarylamino-CO—NH—(C 1 –C 6 )alkyl, (C 1 –C 6 )alkylsulfonyl, (C 1 –C 6 ) alkylsulfonylamino, (C 1 –C 6 )alkylsulfonylamino(C 1 –C 6 )alkyl, (C 6 –C 10 )arylsulfonyl, (C 6 –C 10 )arylsulfonylamino, (C 6 –C 10 )arylsulfonyiamino(C 1 –C 6 )alkyl, (C 1 –C 6 )alkylsulfonylamino, (C 1 –C 6 )alkylsulfonylamino, (C 1 –C 6 )alkyl, (C 5 –C 9 )heteroaryl or (C 2 –C 9 )heterocycloalkyl;

with the proviso that R 5 must be substituted by the group of formula II;

alone or in combination with one or more additional agents which modulate a mammalian immune system or with anti-inflammatory agents.

2. The method according to claim 1 , wherein R 5 is (C 2 –C 9 )heterocycioalkyl optionally substituted by one to three groups selected from deuterium, hydroxy, (C 1 –C 6 )alkyl, halo, (C 1 –C 6 )alkoxy and a group of formula II.

3. The method according to claim 1 , wherein a is 0; b is 1; X is carbonyl; c is 0; d is 0; e is 0; f is 0; and g is 0.

4. The method according to claim 1 , wherein a is 0; b is 1; X is carbonyl; c is 0; d is 1; e is 0; f is 0, and g is 0.

5. The method according to claim 1 , wherein a is 0; b is 1; X is carbonyl; c is 1; d is 0; e is 0; f is 0; and g is 0.

6. The method according to claim 1 , wherein a is 0; b is 1; X is C(═N═cyano)-; c is 1; d is 0; e is 0; f is 0; and g is 0.

7. The method according to claim 1 , wherein a is 0; b is 0; c is 0; d is 0; e is 0; f is 0; g is 1; and Z is —C(O)—O—.

8. The method according to claim 1 , wherein a is 0; b is 1; X is S(O) n : n is 2; c is 0; d is 0; e is 0; f is 0; and g is 0.

9. The method according to claim 1 , wherein a is 0; b is 1; X is S(O) n ; n is 2; c is 0; d is 2; e is 0; f is 1;g is 1; and Z is carbonyl.

10. The method according to claim 1 , wherein a is 0; b is 1; X is S(O) n ; n is 2; c is 0; d is 2; e is 0; f is 1; and g is 0.

11. The method according to claim 1 , wherein a is 0; b is 1; X is carbonyl; c is 1; d is 0; e is 1; Y is S(O) n ; H is 2; f is 0; and g is 0.

12. The method according to claim 1 , wherein a is 0; b is 1; X is S(O) n ; n is 2; c is 1; d is 0; c is 0; f is 0; and g is 0.

13. The method according to claim 1 , wherein a is 1; b is 1; X is carbonyl; c is 1; d is 0; c is 0; f is 0; and g is 0.

14. The method according to claim 1 , wherein a is 0; b is 1; X is S(O) n ; c is 0; d is 1; e is 1; Y is S(O) n ; n is 2; f is 0; and g is 0.

15. The method according to claim 1 , wherein a is 0; b is 1; X is S(O) n ; c is 0; d is 1; e is 1; Y is S(O) n ; n is 2; f is 1; and g is 0.

16. The method according to claim 1 , wherein a is 0; b is 1; X is oxygen; c is 0; d is 1; e is 1; Y is S(O) n ; n is 2; f is 1; and g is 0.

17. The method according to claim 1 , wherein a is 0; h is 1; X is oxygen; c is 0; d is 1; e is 1; Y is S(O) n ; n is 2; f is 0; and g is 0.

18. The method according to claim 1 , wherein a is 0; h is 1; X is carbonyl; c is 1; d is 1; e is 1; Y is S(O) n ; f is 0; and g is 0.

19. The method according to claim 1 , wherein a is 0; b is 1; X is carbonyl; c is 1; d is 1; e is 1; Y is S(O) n ; n is 2; f is 1; and g is 0.

20. The method according to claim 1 , wherein R 12 is (C 6 –C 10 )aryl or (C 2 –C 9 )heteroaryl or tetrazolyl wherein the aryl or heteroaryl or tetrazolyl group is optionally substituted by one to four groups consisting of hydrogen, halo, hydroxy, carboxy, trifluoromethyl, (C 6 )alkyl, (C 1 –C 6 )alkoxy, (C 1 –C 6 )alkyl-CO—NH—, amino, amino(C 1 –C 6 )alkyl, (C 1 –C 6 )alkylamino, ((C 1 –C 6 )alkyl) 2 amino, cyano, amino-CO—NH—, (C 1 –C 6 )alkylamino-CO—NH—, ((C 1 –C 6 )alkyl) 2 amino-CONH—, (C 5 –C 9 )heteroarylamino-CO—NH—, (C 1 –C 6 )alkylsulfonyl, (C 1 –C 6 )alkylsuifonylamino, (C 6 –C 10 )arylsulfonylamino, (C 1 –C 6 )alkylsulfonylamino, and C 1 –C 6 )alkoxy-CO—NH—.

21. A method for the inhibition of Janus Kinase 3 (JAK3) in a mammal comprising administering to said mammal an effective amount of a compound selected from the group consisting of:

4-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-ylmethyl}-benzenesulfonamide;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylic acid (4-sulfamoyl-phenyl )-amide;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylic acid (4-nitro-phenyl)-amide;

1-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1yl}-2-tetrazol-1-yl-ethanone;

4-Methyl -3[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylic acid (4-methylsulfamoyl-phenyl)-amide;

(3-Hydroxy-pyrrolidin-1-yl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl }-methanone;

[2-({4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-amino)-thiazol-4-yl]-acetic acid;

5-(2-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]piperidin-1-yl}-2-oxo-ethyl)-thiazolidine-2,4-dione;

{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1yl}-thiazolidin-3-yl-methanone;

Methyl-[4-methyl-1-(5-nitro-thiazol-2-yl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine;

[2-({4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-amino)-thiazol-4-yl]-acetic acid ethyl ester;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylic acid thiazol-2-ylamide;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylic acid (4-cyano-phenyl)-amide;

{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-pyrrolidin-1-yl-methanone;

Furan-2-carboxylic acid (2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-amide;

{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}(tetrahydro-furan-3-yl)-methanone;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylic acid isoxazol-3-ylamide;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl )-amino]-piperidine-1-carboxylic acid (6-cyano-pyridin-3-yl)-amide;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylic acid (4-methyl-thiazol-2-yl)-amide;

2-Cyclopropyl-1-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4yl)-amino]-piperidin-1-yl}-ethanone;

Cyclopentyl-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-Methanone;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylic acid (3-methyl-isoxazol-4-yl)-amide;

[4-({4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-amino)-phenyl]-acetic acid;

[1-(5-Amino-thiazol-2-yl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4yl)-amine;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1carboxylic acid (3-methyl-isothiazol-5-yl)-amide;

3-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}cyclopentanone; and

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylic acid benzyl-methyl-amide; or a pharmaceutically acceptable salt thereof.

22. A method for treating organ transplant rejection comprising administering to a mammal an effective amount of a compound of the formula

or a pharmaceutically acceptable salt thereof; wherein

R 1 is a group of the formula

wherein y is 0, 1 or 2;

R 4 is selected from the group consisting of hydrogen, (C 1 –C 6 )alkyl, (C 1 –C 6 )alkylsulfonyl, (C 2 –C 6 )alkenyl, (C 2 –C 6 )alkynyl wherein the alkyl, alkenyl and alkynyl groups are optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C 1 –C 4 )alkoxy, (C 1 –C 6 )acyloxy, (C 1 –C 6 )alkylamino, ((C 1 –C 6 )alkyl) 2 amino, cyano, nitro, (C 2 –C 6 )alkenyl, (C 2 –C 6 )alkynyl or (C 1 –C 6 )acylamino; or R 4 is (C 3 –C 10 )cycloalkyl wherein the cycloalkyl group is optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C 1 –C 6 )acyloxy, (C 1 –C 6 )acylamino, (C 1 –C 6 )alkylamino, ((C 1 –C 6 )alkyl) 2 amino, cyano, cyano(C 1 –C 6 )alkyl, trifluoromethyl(C 1 –C 6 )alkyl, nitro, nitro(C 1 –C 6 )alkyl or (C 1 –C 6 )acylamino;

R 5 is (C 2 –C 9 )heterocycloalkyl wherein the heterocycloalkyl groups must be substituted by one to five groups consisting of carboxy, cyano, amino, deuterium, hydroxy, (C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy, halo, (C 1 –C 6 )acyl, (C 1 –C 6 )alkylamino, amino(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy-CO—NH, (C 1 –C 6 )alkylamino-CO—, (C 2 –C 6 )alkenyl, (C 2 –C 6 )alkynyl, (C 1 –C 6 )alkylamino, amino(C 1 –C 6 )alkyl, hydroxy(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy(C 1 –C 6 )alkyl, (C 1 –C 6 )acyloxy(C 1 –C 6 )alkyl, nitro, cyano(C 1 –C 6 )alkyl, halo(C 1 –C 6 )alkyl, nitro(C 1 –C 6 )alkyl, trifluoromethyl, trifluoromethyl(C 1 –C 6 )alkyl, (C 1 –C 6 )acylamino, (C 1 –C 6 )acylamino(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy(C 1 –C 6 )acylamino, amino(C 1 –C 6 )acyl, amino(C 1 –C 6 )acyl(C 1 –C 6 )alkyl, (C 1 –C 6 )alkylamino(C 1 –C 6 )acyl, ((C 1 –C 6 )alkyl) 2 amino(C 1 –C 6 )acyl, R 15 R 16 N—CO—O—, R 15 R 16 N—CO—(C 1 –C 6 )alkyl, (C 1 –C 6 )alkyl-S(O) m , R 15 R 16 NS(O) m , R 15 R 16 NS(O) m (C 1 –C 6 )alkyl, R 15 S(O) m R 16 N, R 15 S(O) m R 16 N(C 1 –C 6 )alkyl, and a group of the formula II

wherein:

m is 0, 1 or 2;

R 15 and R 16 are each independently selected from hydrogen or (C 1 –C 6 )alkyl;

a is 0, 1, 2, 3or 4;

b, c, e, f and g are each independently 0 or 1;

d is 0, 1, 2, or 3;

X is S(O) n wherein n is 0, 1 or 2; oxygen, carbonyl or C(═N-cyano)-;

Y is S(O) n wherein n is 0, 1 or 2; or carbonyl; and

Z is carbonyl, C(O)O—, C(O)NR— wherein R is hydrogen or (C 1 –C 6 )alkyl; or Z is S(O) n wherein n is 0, 1 or 2;

R 6 , R 7 , R 8 , R 9 , R 10 and R 11 are each independently selected from the group consisting of hydrogen or (C 1 –C 6 )alkyl optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C 1 –C 6 )acyloxy, (C 1 –C 6 )acylamino, (C 1 –C 6 )alkylamino, ((C 1 –C 6 ) 2 amino, cyano, cyano(C 1 –C 6 )alkyl, trifluorometbyl(C 1 –C 6 )alkyl, nitro, nitro(C 1 –C 6 )alkyl or (C 1 –C 6 )acylamino;

R 12 is (C 6 –C 10 )aryl, (C 2 –C 9 )heteroaryl, tetrazolyl, or (C 2 –C 9 ) heterocyeloalkyl, wherein the aryl, heteroaryl, tetrazolyl, and heterocycloalkyl groups are optionally substituted by one to four groups consisting of hydrogen, deuterium, amino, halo, oxo, hydroxy, nitro, carboxy, (C 2 –C 6 )alkenyl, (C 2 –C 6 )alkynyl, trifluoromethyl, trifluoromethoxy, (C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy, (C 3 –C 10 )cycloalkyl, (C 1 –C 6 )alkyl-CO—NH—, (C 1 –C 6 )alkoxy-CO—NH—, (C 1 –C 6 )alkyl -CO—NH—(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy-CO—NH—(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy-CO—NH-(C 1 –C 6 )alkoxy, carboxy, carboxy(C 1 –C 6 )alkyl, carboxy(C 1 –C 6 )alkoxy, benzyloxycarbonyl(C 1 –C 6 )alkoxy, (C 1 –C 6 ) alkoxycarbonyl(C 1 –C 6 )alkoxy, (C 6 –C 10 )aryl, amino, amino(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxycarbonylamino, (C 6 –C 10 )aryl(C 1 –C 6 )alkoxycarbonylamino, (C 1 –C 6 )alkylamino, ((C 1 –C 6 )alkyl) 2 amino, (C 1 –C 6 ) alkylamino(C 1 –C 6 )alkyl, ((C 1 –C 6 )alkyl) 2 amino(C 1 –C 6 )alkyl, hydroxy, (C 1 –C 6 )alkoxy, carboxy, carboxy(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxycarbonyl, (C 1 –C 6 )alkoxycarbonyl(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy-CO—NH—, (C 1 –C 6 )alkyl-CO—NH—, cyano, (C 5 –C 9 )heterocycloalkyl, amino-CO—NH—, (C 1 –C 6 )alkylamino-CO—NH—, ((C 1 –C 6 )alkyl) 2 amino-CO—NH—, (C 6 –C 10 )arylamino-CO—NH—, (C 5 –C 9 )heteroarylamino-CO—NH—, (C 1 –C 6 )alkylamino-CO—NH—(C 1 –C 6 )alkyl, ((C 1 –C 6 )alkyl) 2 amino-CO—NH—(C 1 –C 6 alkyl, (C 6 –C 10 )arylamino-CO—NH—(C 1 –C 6 )alkyl, (C 5 –C 9 )heteroarylamino-CO—NH—(C 1 –C 6 ), cyano(C 1 –C 6 )alkyl, carboxy(C 1 –C 6 )alkyl(C 1 –C 6 )alkoxy, carboxy(C 1 –C 6 )alkyl, sulfonylamino, aminosulfonyl, sulfonylamino(C 1 –C 6 )alkyl, sulfonylaminocarboxy(C 1 –C 6 )alkyl, (C 1 –C 6 )alkylsulfonyl, (C 1 –C 6 )alkylsulfonylamino, (C 1 –C 6 )alkylsulfonylamino(C 1 –C 6 )alkyl, (C 6 –C 10 )arylsulfonyl, (C 6 –C 10 )arylsulfonylamino, (C 6 –C 10 )arylsulfonylamino(C 1 –C 6 )alkyl, (C 1 –C 6 ) alkylsulfonylamino, C 1 –C 6 )alkylsulfonylamino(C 1 –C 6 )alkyl, (C 3 –C 10 )cycloalkyl, (C 3 –C 10 )cycloalkoxy, (C 1 –C 6 )alkylamino, ((C 1 –C 6 )alkyl) 2 amino, (C 6 –C 10 )arylamino, (C 1 –C 6 )alkylthio, (C 6 –C 10 )arylthio, (C 1 –C 6 )alkylsulfinyl, (C 6 –C 10 )arylsulfinyl, (C 1 –C 6 )alkylsulfonyl, (C 6 –C 10 )arylsulfonyl, (C 1 –C 6 )acyl, (C 1 –C 6 )alkoxy-CO—NH—, (C 1 –C 6 )alkylamino-CO—, (C 5 –C 9 )heteroaryl, (C 2 –C 9 )heterocycloalkyl or (C 6 –C 10 )aryl wherein the heteroaryl, tetrazolyl, hererocycloalkyl and aryl groups which are optionally substituted on R 12 may be further substituted by one to three groups consisting of halo, (C 1 –C 6 )alkyl, (C 1 –C 6 )alkyl-CO—NH—, C 1 –C 6 )alkoxy-CO—NH—, (C 1 –C 6 )alkyl-CO—NH—(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy-CO—NH—(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy-CO—NH—(C 1 –C 6 )alkoxy, carboxy, carboxy(C 1 –C 6 )alkyl, carboxy(C 1 –C 6 )alkoxy, benzyloxycarbonyl(C 1 –C 6 )alkoxy, (C 1 –C 6 )alkoxycarbonyl(C 1 –C 6 )alkoxy, (C 6 –C 10 )aryl, amino, amino(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxycarbonylamino, (C 6 –C 10)aryl(C 1 –C 6 )alkoxycarbonylamino, (C 1 –C 6 )alkylamino, ((C 1 –C 6 )alkyl ) 2 amino, (C 1 –C 6 )alkylamino(C 1 –C 6 ) alkyl, ((C 1 –C 6 )alkyl) 2 amino(C 1 –C 6 )alkyl, hydroxy, (C 1 –C 6 )alkoxy, carboxy, carboxy(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxycarbonyl, (C 1 –C 6 )alkoxycarbonyl(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy-CO—NH—, (C 1 –C 6 )alkyl-CO—NH—, cyano, (C 5 –C 9 )heterocycloaikyl, amino-CO—NH—, (C 1 –C 6 )alkylamino-CO—NH—, ((C 1 –C 6 ) 2 amino-CO—NH—, (C 1 –C 10 )arylamino-CO—NH—, (C 5 –C 9 )heteroarylamino-CO—NH—, (C 1 –C 6 )alkylamino-CO—NH—(C 1 –C 6 )alkyl, ((C 1 –C 6 )alkyl) 2 amino-CO—NH—(C 1 –C 6 )alkyl, (C 6 –C 10 )arylamino-CO —NH—(C 1 –C 6 )alkyl, (C 5 –C 9 )heteroarylamino-CO—NH—(C 1 –C 6 )alkyl, (C 1 –C 6 )alkylsulfonyl, (C 1 –C 6 ) alkylsulfonylamino, (C 1 –C 6 )alkylsulfonylamino(C 1 –C 6 )alkyl, (C 6 –C 10 )arylsulfonyl, (C 6 –C 10 )arylsulfonylamino, (C 6 –C 10 )arylsulfonylamino(C 1 –C 6 )alkyl, (C 1 –C 6 )alkylsulfonylamino, (C 1 –C 6 ) alkylsulfonylamino(C 1 –C 6 )alkyl, (C 5 –C 9 )heteroaryl and (C 2 –C 9 )heterocycloalkyl;

R 2 and R 3 are each independently selected from the group consisting of hydrogen, deuterium, amino, halo, hydroxy, nitro, carboxy, (C 2 –C 6 )alkenyl, (C 2 –C 6 )alkynyl, trifluoromethyl, trifluoromethoxy, (C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy, (C 3 –C 10 )cycloalkyl wherein the alkyl, alkoxy or cycloalkyl groups are optionally substituted by one to three groups selected from halo, hydroxy, carboxy, amino (C 1 –C 6 )alkylthio, (C 1 –C 6 )alkylamino, ((C 1 –C 6 )alkyl) 2 amino, (C 5 –C 9 )heteroaryl, (C 2 –C 9 )heterocycloalkyl, (C 3 –C 9 )cycloalkyl or (C 6 –C 10 )aryl; or R 2 and R 3 are each independently (C 3 –C 10 )cycloalkyl, (C 3 –C 10 )cycloalkoxy, (C 1 –C 6 )alkylamino, ((C 1 –C 6 )alkyl) 2 amino, (C 6 –C 10 )arylamino, (C 1 –C 6 )alkylthio, (C 6 –C 10 )arylthio, (C 1 –C 6 )alkylsulfinyl, (C 6 –C 10 ) arylsulfinyl, (C 1 –C 6 )alkylsulfonyl, (C 6 –C 10 )arylsulfonyl, (C 1 –C 6 )acyl, (C 1 –C 6 )alkoxy-CO—NH—, (C 1 –C 6 ) alkylamino-CO—, (C 5 –C 9 )heteroaryl, (C 2 –C 9 )heterocycloalkyl or (C 6 –C 10 )aryl wherein the heteroaryl, heterocycloalkyl and aryl groups are optionally substituted by one to three halo, (C 1 –C 6 )alkyl, (C 1 –C 6 )alkyl-CO —NH—, (C 1 –C 6 )alkoxy-CO—NH—, (C 1 –C 6 )alkyl -CO—NH—(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy-CO—NH—(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy-CO—NH—(C 1 –C 6 )alkoxy, carboxy, carboxy(C 1 –C 6 )alkyl, carboxy(C 1 –C 6 )alkoxy, benzyloxycarbonyl(C 1 –C 6 )alkoxy, (C 1 –C 6 )alkoxycarbonyl(C 1 –C 6 )alkoxy, (C 6 –C 10 )aryl, amino, amino(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxycarbonylamino, (C 6 –C 10 )aryl (C 1 –C 6 )alkoxycarbonylamino, (C 1 –C 6 )alkylamino, ((C 1 –C 6 )alkyl) 2 amino, (C 1 –C 6 )alkylamino(C 1 –C 6 )alkyl, ((C 1 –C 6 )alkyl) 2 amino(C 1 –C 6 )alkyl, hydroxy, (C 1 –C 6 )alkoxy, carboxy, carboxy(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxycarbonyl, (C 1 –C 6 )alkoxycarbonyl(C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy-CO—NH—, (C 1 –C 6 )alkyl-CO—NH—, cyano, (C 5 –C 9 )heterocycloalkyl, amino-CO—NH—, (C 1 –C 6 )alkylamino-CO—NH—, ((C 1 –C 6 )alkyl) 2 amino-C—NH—, (C 6 –C 10 )arylamino-CO—NH—, (C 5 –C 9 )heteroarylamino-CO—NH—, (C 1 –C 6 )alkylamino-CO—NH—(C 1 –C 6 )alkyl, ((C 1 –C 6 )alkyl) 2 amino-CO—NH—(C 1 –C 6 )alkyl, (C 6 –C 10 )arylamino-CO—NH—(C 1 –C 6 )alkyl, (C 5 –C 9 )heteroarylamino-CO—NH—(C 1 –C 6 )alkyl, (C 1 –C 6 )alkylsulfonyl, (C 1 –C 6 ) alkylsulfonylamino. (C 1 –C 6 )alkylsulfonylamino(C 1 –C 6 )al kyl, (C 6 –C 10 )arylsulfonyl, (C 6 –C 10 )arylsulfonylamino, (C 6 –C 10 )arylsulfonylamino(C 1 –C 6 )alkyl, (C 1 –C 6 )alkylsulfonylamino, (C 1 –C 6 )alkylsulfonylamino(C 1 –C 6 )alkyl, (C 5 –C 9 )heteroaryl or (C 2 –C 9 )heterocycloalkyl;

with the proviso that R 5 must be substituted by the group of formula II;

alone or in combination with one or more additional agents which modulate a mammalian immune system or with anti-inflammatory agents.

23. The method according to claim 22 , wherein R 5 is (C 2 –C 9 )heterocycloalkyl optionally substituted by one to three groups selected from deuterium, hydroxy, (C 1 –C 6 )alkyl, halo, (C 1 –C 6 )alkoxy and a group of formula II.

24. The method according to claim 22 , wherein a is 0; b is 1; X is carbonyl; e is 0; d is 0; e is 0; f is 0; and g is 0.

25. The method according to claim 22 , wherein a is 0; b is 1; X is carbonyl; c is 0; d is 1; e is 0; f is 0, and g is 0.

26. The method according to claim 22 , wherein a is 0; b is 1; X is carbonyl; c is 1; d is 0; e is 0; f is 0; and g is 0.

27. The method according to claim 22 , wherein a is 0; b is 1; X is —C(═N═cyano); c is 1; d is 0; e is 0; f is 0; and g is 0.

28. The method according to claim 22 , wherein a is 0; b is 0; c is 0; d is 0; e is 0; f is 0; g is 1; and Z is —C(O)—O—.

29. The method according to claim 22 , wherein a is 0; b is 1; X is S(O) n ; n is 2; c is 0; d is 0; e is 0; f is 0; and g is 0.

30. The method according to claim 22 , wherein a is 0; b is 1; X is S(O) n ; n is 2; c is 0; d is 2; e is 0; f is 1; g is 1; and Z is carbonyl.

31. The method according to claim 22 , wherein a is 0; b is 1; X is S(O) n ; n is 2; c is 0; d is 2; e is 0; f is 1; and g is 0.

32. The method according to claim 22 , wherein a is 0; b is 1; X is carbonyl; c is 1; d is 0; e is 1; Y is S(O) n ; n is 2; f is 0; and g is 0.

33. The method according to claim 22 , wherein a is 0; b is 1; X is S(O) n ; n is 2; c is 1; d is 0; e is 0; f is 0; and g is 0.

34. The method according to claim 22 , wherein a is 1; b is 1; X is carbonyl; c is 1; d is 0; e is 0; f is 0; and g is 0.

35. The method according to claim 22 , wherein a is 0; b is 1; X is S(O) n ; c is 0; d is 1; e is 1; Y is S(O) n ; n is 2; f is 0; and g is 0.

36. The method according to claim 22 , wherein a is 0; b is 1; X is S(O) n ; c is 0; d is 1; e is 1; Y is S(O) n ; n is 2; f is 1; and g is 0.

37. The method according to claim 22 , wherein a is 0; b is 1; X is oxygen; c is 0; d is 1; e is 1; Y is S(O) n ; n is 2; f is 1; and g is 0.

38. The method according to claim 22 , wherein a is 0; b is 1; X is oxygen; c is 0; d is 1; e is 1; Y is S(O) n ; n is 2; f is 0; and g is 0.

39. The method according to claim 22 , wherein a is 0; b is 1; X is carbonyl; c is 1; d is 1; e is 1; Y is S(O) n ; f is 0; and g is 0.

40. The method according to claim 22 , wherein a is 0; b is 1; X is carbonyl; c is 1; d is 1; e is 1; Y is S(O) n ; n is 2; f is 1; and g is 0.

41. The method according to claim 22 , wherein R 12 is (C 6 –C 10 )aryl or (C 2 –C 9 )heteroaryl or tetrazolyl wherein the aryl or heteroaryl or tetrazolyl group is optionally substituted by one to four groups consisting of hydrogen, halo, hydroxy, carboxy, trifluoromethyl, C 1 –C 6 )alkyl, (C 1 –C 6 )alkoxy, C 1 –C 6 )alkyl-CO—NH—, amino, amino(C 1 –C 6 )alkyl, (C 1 –C 6 )alkylamino, ((C 1 –C 6 )alkyl) 2 amino, cyano, amino-CO—NH—, (C 1 –C 6 )alkylamino-CO—NH—, ((C 1 –C 6 )alkyl) 2 amino-CO—NH—, (C 5 –C 9 )heteroarylamino-CO—NH—, (C 1 –C 6 )alkylsulfonyl, C 1 –C 6 )alkylsulfonylamino, (C 6 –C 10 )arylsulfonylamino, (C 1 –C 6 )alkylsulfonylamino, and (C 1 –C 6 )alkoxy-CO—NH—.

42. A method for treating organ transplant rejection, comprising administering to a mammal an effective amount of a compound selected from the group consisting of

4-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-ylmethyl}-benzenesulfonamide;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylic acid (4-sulfamoyl-phenyl)-amide;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4yl)-amino]-piperidine-1-carboxylic acid (4-nitro-phenyl)-amide;

1-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-aminol]-piperidin-1-yl}-2-tetrazol-1-yl-ethanone;

4-Methy1-3-methyl-(7H-pyrrolo[2,3-d[pyrimidin-4-yl)-amino]-piperidine-1-carboxylic acid (4-methylsulfamoyl-phenyl)-amide;

(3-Hydroxy-pyrrolidin-1-yl)-{4-methyl-3-[methyl-(7H-pyrrololo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl }-methanone;

[2-{4-Methyl-3-[methyl -(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-amino)-thiazol-4-yl]-acetic acid;

5-(2-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl }-2-oxo-ethyl)-thiazolidine-2,4-dione;

{4-Methyl-3-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-thiazolidin-3-yl-methanone;

Methyl-[4-methyl-1-(5-nitro-thiazol-2-yl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine;

[2-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-amino)-thiazol-4-y]-acetic acid ethyl ester;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylic acid thiazol-2-ylamide;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylic acid (4-cyano-phenyl)-amide;

{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1yl)}-pyrrolidin-1-yl-methanone;

Furan-2-carboxylic acid (2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-sulfonyl}-ethyl)-amide;

{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl }(tetrahydro-furan3-yl)-methanone;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylic acid isoxazol-3-ylamide;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylic acid (6-cyano-pyridin-3-yl)-amide;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylic acid (4-methyl-thiazol-2-yl)-amide;

2-Cyclopropyl-1-{4-methyl-3[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-ethanone;

Cyclopentyl-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl }-Methanone;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylic acid (3-methyl-isoxazol-4-yl)-amide;

[4-({4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-amino)-phenyl]4-acetic acid;

[1-(5-Amino-thiazol-2-yl)-4-methyl-piperidin-3-yl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine;

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylic acid (3-methyl-isothiazol-5-yl)-amide;

3-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carbonyl}-cyclopentanone; and

4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-carboxylic acid benzyl-methyl-amide;

or a pharmaceutically acceptable salt thereof.

43. The method according to claim 1 , wherein said one or more additional agents is selected from the group consisting of cyclosporin A, rapamycin, tacrolimus, leflunomide, deoxyspergualin, mycophenolate, azathioprine, daclizumab, muromonab-CD3, antithymocyre globulin, aspirin, acetaminophen, ibuprofen, naproxen, piroxicam, prednisolone and dexamethasone.

44. The method according to claim 22 , wherein said one or more additional agents is selected from the group consisting of cyciosporin A, rapamycin, tacrolimus, leflunomide, deoxyspergualin, mycophenol ate, azathioprine, daclizumab, muromonab-CD3, antithymocyte globulin, aspirin, acetaminophen, ibuprofen, naproxen, piroxicam, prednisolone and dexamethasone.

45. The method according to claim 21 further comprising administering one or more additional agents which modulate a mammalian immune system or with antiinflamatory agents.

46. The method according to claim 45 , wherein said one or more additional agents is selected from the group consisting of cyclosporin A, rapamycin, tacrolimus, leflunomide, deoxyspergualin, mycophenolate, azathioprine, daclizumab, muromonab-CD3, antithymocyte globulin, aspirin, acetaminophen, ibuprofen, naproxen, piroxicam, prednisolone and dexamethasone.

47. The method according to claim 42 further comprising administering one or more additional agents which modulate a mammalian immune system or with antiinflamatory agents.

48. The method according to claim 47 , wherein said one or more additional agents is selected from the group consisting of cyclosporin A, rapamycin, tacrolimus, leflunomide, deoxyspergualin, mycophenolate, azathioprine, daclizumab, muromonab-CD3, antithymocyte globulin, aspirin, acetaminophen, ibuprofen, naproxen, piroxicam, prednisolone and dexamethasone.