Claims for Patent: 7,192,963

Summary for Patent: 7,192,963

Title:	Pyrrolo[2,3-d]pyrimidine compounds
Abstract:	A compound of the formula ##STR00001## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined above, useful as inhibitors of protein kinases, such as the enzyme Janus Kinase 3.
Inventor(s):	Blumenkopf; Todd A. (Old Lyme, CT), Flanagan; Mark E. (Gales Ferry, CT), Munchhof; Michael J. (Salem, CT)
Assignee:	Pfizer Inc (New York, NY)
Application Number:	11/112,307
Patent Claims:	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 ##STR00011## or a pharmaceutically acceptable salt thereof; wherein R.sup.1 is a group of the formula ##STR00012## wherein y is 0, 1 or 2; R.sup.4 selected from the group consisting of hydrogen, (C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkylsulfonyl, (C.sub.2 C.sub.6)alkenyl, (C.sub.2 C.sub.6)alkynyl wherein the alkyl, alkenyl and alkynyl groups are optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C.sub.1 C.sub.4)alkoxy, (C.sub.1 C.sub.6)acyloxy, (C.sub.1 C.sub.6)alkylamino, ((C.sub.1 C.sub.6)alkyl).sub.2amino, cyano, nitro, (C.sub.2 C.sub.6)alkenyl, (C.sub.2 C.sub.6alkynyl or (C.sub.1 C.sub.6)acylamino; or R.sup.4 is (C.sub.3 C.sub.10)cycloalkyl wherein the cycloalkyl group is optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C.sub.1 C.sub.6)acyloxy, (C.sub.1 C.sub.6)acylamino, (C.sub.1 C.sub.6)alkylamino, ((C.sub.1 C.sub.6)alkyl).sub.2amino, cyano, cyano(C.sub.1 C.sub.6)alkyl, trifluoromethyl(C.sub.1 C.sub.6)alkyl, nitro, nitro(C.sub.1 C.sub.6)alkyl or (C.sub.1 C.sub.6)acylamino; R.sup.5 is (C.sub.2 C.sub.9)heterocycloalkyl wherein the heterocycloalkyl groups must be substituted by one to five groups consisting of carboxy, cyano, amino, deuterium, hydroxy, (C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy, halo, (C.sub.6C.sub.6)acyl, (C.sub.1 C.sub.6)alkylamino, amino(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy-CO--NH, (C.sub.1 C.sub.6)alkylamino-CO--, (C.sub.2 C.sub.6)alkenyl, (C.sub.2 C.sub.6) alkynyl, (C.sub.1 C.sub.6) alkylkylamino, amino(C.sub.1 C.sub.6)alkyl, hydroxy(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)acyloxy(C.sub.1 C.sub.6)alkyl, nitro, cyano(C.sub.1 C.sub.6)alkyl, halo(C.sub.1 C.sub.6)alkyl, nitro(C.sub.1 C.sub.6)alkyl, trifluoromethyl, trifluoromethyl(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)acylamino, (C.sub.1 C.sub.6)acylamino(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy(C.sub.1 C.sub.6)acyl amino, amino(C.sub.1 C.sub.6)acyl, amino(C.sub.1 C.sub.6)acyl(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkylamino(C.sub.1 C.sub.6)acyl, ((C.sub.1 C.sub.6)acyl).sub.2amino(C.sub.1 C.sub.6)acyl, R.sup.15R.sup.16N--CO--O--, R.sup.15R.sup.16N--CO--(C.sub.1C.sub.6)alkyl, (C.sub.1 C.sub.6)alkyl-S (O).sub.m, R.sup.15R.sup.16NS(O).sub.m, R.sup.15R.sup.16NS(O).sub.m (C.sub.1 C.sub.6)alkyl, R.sup.15S(O).sub.m R.sup.16N, R.sup.15S(O).sub.mR.sup.16N(C.sub.1 C.sub.6)alkyl, and a group of the formula II ##STR00013## wherein: m is 0, 1 or 2; R.sup.15 and R.sup.16 are each independently selected from hydrogen or (C.sub.1 C.sub.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).sub.n wherein n is 0, 1 or 2; oxygen, carbonyl or --C(.dbd.N-cyano)-; Y is S(O).sub.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.sub.1 C.sub.6)alkyl; or Z is S(O).sub.n wherein n is 0, 1 or 2; R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10 and R.sup.11 are each independently selected from the group consisting of hydrogen or (C.sub.1 C.sub.6)alkyl optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C.sub.1 C.sub.6)acyloxy, (C.sub.1 C.sub.6)acylamino, (C.sub.1 C.sub.6)alkyiamino, ((C.sub.1 C.sub.6)alkyl).sub.2amino, cyano, cyano(C.sub.1 C.sub.6)alkyl, trifluoromethyl(C.sub.1 C.sub.6)alkyl, nitro, nitro(C.sub.1 C.sub.6)alkyl or (C.sub.1 C.sub.6)acylamino; R.sup.12 is (C.sub.6 C.sub.10)aryl, (C.sub.2 C.sub.9)heteroaryl, tetrazolyl, or (C.sub.2 C.sub.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.sub.2 C.sub.6)alkenyl, (C.sub.2 C.sub.6)alkynyl, trifluoromahyl, trifluoromethoxy, (C.sub.1 C.sub.6)alkyl, (C.sub.1 C6)alkoxy, (C.sub.3 C.sub.10)cycloalkyl, (C.sub.1 C.sub.6)alkyl-CO--NH--, (C.sub.1 C.sub.6)alkoxy-CO--NH--, (C.sub.1 C.sub.6)alkyl-C O--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy-CO--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy-CO--NH--(C.sub.1 C.sub.6)alkoxy, carboxy, carboxy(C.sub.1 C.sub.6alkyi, carboxy(C.sub.1 C.sub.6)alkoxy, benzyloxycarbonyl(C.sub.1 C.sub.6)alkoxy, (C.sub.1 C.sub.6)alkoxycarbonyl(C.sub.1 C.sub.6)alkoxy, (C.sub.6 C.sub.10)aryl, amino, amino(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxycarbonylamino, (C.sub.6 C.sub.10)aryl(C.sub.1 C.sub.6)alkoxycarbonylamino, (C.sub.1 C.sub.6)alkylamino, ((C.sub.1 C.sub.6)alkyl).sub.2amino, (C.sub.1 C.sub.6) alkylamino(C.sub.1 C.sub.6)alkyl, ((C.sub.1 C.sub.6)alkyl).sub.2amino(C.sub.1 C.sub.6)alkyl, hydroxy, (C.sub.1 C.sub.6)alkoxy, carboxy, (C.sub.1)alkyl, (C.sub.1 C.sub.6)alkoxycarbonyl, (C.sub.12 C.sub.6)alkoxycarbonyl(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy -CO--NH--, (C.sub.1 C.sub.6)alkyl -CO--NH--, cyano, (C.sub.5 C.sub.9)heterocycloalkyl, amino-CO--NH--, (C.sub.1 C.sub.6)alkylamino-CO--NH--, ((C.sub.1 C.sub.6)alkyl).sub.2amino-CO--NH--, (C.sub.6 C.sub.10)arylamino-CO--NH--, (C.sub.5 C.sub.9)heteroarylamino-CO--NH--, (C.sub.1 C.sub.6)alkylamino-CO--NH--(C.sub.1 C.sub.6)alkyl, ((C.sub.1 C.sub.6)alkyl).sub.2amino-CO--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.6 C.sub.10)arylamino-CO--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.5 C.sub.9)heteroarylamino-CO--NH--(C.sub.1 C.sub.6) alkyl, cyano(C.sub.1 C.sub.6)alkyl, carboxy(C.sub.1 C.sub.6)alkyl(C.sub.1 C.sub.6)alkoxy, carboxy(C.sub.1 C.sub.6)alkyl, sulfonylamino, aminosulfonyl, sulfonylamino(C.sub.1 C.sub.6)alkyl, sulfonylaminocarboxy(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkylsulfonyl, (C.sub.1 C.sub.6)alkylsulfonylamino, (C.sub.1 C.sub.6)alkylsulfonylamino(C.sub.1 C.sub.6)alkyl, (C.sub.6 C.sub.10)arylsulfonyl, (C.sub.6 C.sub.10)arylsulfonylamino, (C.sub.6C.sub.10)arylsulfonylamino(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkylsulfonylamino, (C.sub.1 C.sub.6)alkylsulfonylamino(C.sub.1 C.sub.6)alkyl, (C.sub.3 C.sub.10)cycloalkyl, (C.sub.3 C.sub.10)cycloalkoxy, (C.sub.1 C.sub.6)alkylamino, ((C.sub.1 C.sub.6)alkyl).sub.2amino, (C.sub.6 C.sub.6)arylamino, (C.sub.1 C.sub.6)alkylthio, (C.sub.6 C.sub.10) arylthio, (C.sub.1 C.sub.6)alkylsulfinyl, (C.sub.6 C.sub.10)arylsulfinyl, (C.sub.1 C.sub.6)alkylsulfonyl, (C.sub.6 C.sub.10)arylsulfonyl, (C.sub.1 C.sub.6) acyl, (C.sub.1 C.sub.6)alkoxy-CO--NH--, (C.sub.1 C.sub.6)alkylamino-CO--, (C.sub.5 C.sub.9)heteroaryl, (C.sub.2 C.sub.9)heterocycloalkyl or (C.sub.6 C.sub.10)aryl wherein the heteroaryl, tetrazolyl, heterocycloalkyl and aryl groups which are optionally substituted on R.sup.12 may be further substituted by one to three groups consisting of halo, (C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkyl-CO--NH--, (C.sub.1 C.sub.6)alkoxy-CO--NH--, (C.sub.1 C.sub.6)alkyl-CO--NH--(C.sub.1 C.sub.6)alkyl, C.sub.1 C.sub.6)alkoxy-CO--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy-CO--NH--(C.sub.1 C.sub.6)alkoxy, carboxy, carboxy(C.sub.1 C.sub.6)alkyl, carboxy(C.sub.1 C6)alkoxy, benzyloxycarbonyl(C.sub.1 C.sub.6)alkoxy, (C.sub.1 C.sub.6)alkoxycarbonyl(C.sub.1 C.sub.6)alkoxy, (C.sub.6 C.sub.10)aryl, amino, amino(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxycarbonylamino, (C.sub.6 C.sub.10)aryl(C.sub.1 C.sub.6) alkoxycarbonylaniino, (C.sub.1 C.sub.3alkylamino, ((C.sub.1 C.sub.6)alkyl ).sub.2amino, (C.sub.1 C.sub.6)alkylamino(C.sub.1 C.sub.6)alkyl, ((C.sub.1 C.sub.6).sub.2amino(C.sub.1 C.sub.6)alkyl, hydroxy, (C.sub.1 C.sub.6)alkoxy, carboxy, carboxy(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6) alkoxycarbonyl, (C.sub.1 C.sub.6)alkoxycarbonyl(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy-CO--NH--, (C.sub.1 C.sub.6)alkyl-CO--NH --, cyano, (C.sub.5 C.sub.9)heterocycloalkyl, amino-CO--NH--, (C.sub.1 C.sub.6)alkylamino-CO--NH--, ((C.sub.1 C.sub.6)alkyl).sub.2amino-CO--NH--, (C.sub.6 C.sub.10)arylamino-CO--NH--, (C.sub.5 C.sub.9)heteroarylamino-CO--NH--, (C.sub.1 C.sub.6)alkylamino-CO--NH--(C.sub.1 C.sub.6)alkyl, ((C.sub.1 C.sub.6)alkyl).sub.2amino-CO--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.6 C.sub.10)arylamino-C O--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.5 C.sub.9)heteroarylamino-CO--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkylsulfonyl, (C.sub.1 C.sub.6) alkylsulfonylamino, (C.sub.1 C.sub.6)alkylsulfonylamino(C.sub.1 C.sub.6)alkyl, (C.sub.6 C.sub.10)arylsulfonyl, (C.sub.6 C.sub.10)arylsulfonylamino, (C.sub.6 C.sub.10)arylsulfonylamino(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkylsulfonylamino, (C.sub.1 C.sub.6) alkylsulfonylamino(C.sub.1 C.sub.6)alkyl, (C.sub.5 C.sub.9)heteroaryl and (C.sub.2 C.sub.9)heterocycloalkyl; R.sup.2 and R.sup.3 are each independently selected from the group consisting of hydrogen, deuterium, amino, halo, hydroxy, nitro, carboxy, (C.sub.2 C.sub.6)alkenyl, (C.sub.2 C.sub.6)alkynyl, trifluoromethyl, trifluoromethoxy, (C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy, (C.sub.3 C.sub.10)cycloalkyl wherein the alkyl, alkoxy or cycloalkyl groups are optionally substituted by one to three groups selected from halo, hydroxy, carboxy, amino (C.sub.1 C.sub.6)alkylthio, (C.sub.1 C.sub.6)alkylamino, ((C.sub.1 C.sub.6)alkyl).sub.2amino, (C.sub.5 C.sub.9)heteroaryl, (C.sub.2 C.sub.9)heterocycloalkyl, (C.sub.3 C.sub.9)cycloalkyl or (C.sub.6 C.sub.10)aryl; or R.sup.2 and R.sup.3 are each independently (C.sub.3 C.sub.10)cycloalkyl, (C.sub.3 C.sub.10)cycloalkoxy, (C.sub.1 C.sub.6)alkylamino, ((C.sub.1 C.sub.6)alkyl).sub.2amino, (C.sub.6 C.sub.10)arylamino, (C.sub.1 C.sub.6)alkylthio, (C.sub.6 C.sub.10)arylthio, (C.sub.1 C.sub.6)alkylsulfinyl, (C.sub.6 C.sub.10) arylsulfinyl, (C.sub.1 C.sub.6)alkylsulfonyl, (C.sub.6 C.sub.10)arylsulfony, (C.sub.1 C.sub.6)acyl, (C.sub.1 C.sub.6)alkoxy-CO--NH--, (C.sub.1 C.sub.6) alkylamino-CO--, (C.sub.5 C.sub.9)heteroaryl, (C.sub.2 C.sub.9)heterocycloalkyl or (C.sub.6 C.sub.10)aryl wherein the heteroaryl, heterocycloalkyl and aryl groups are optionally substituted by one to three halo, (C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkyl-CO--NH--, (C.sub.1 C.sub.6)alkoxy-CO--NH--, (C.sub.1 C.sub.6)alkyl-CO--NH--(C.sub.12 C.sub.6)alkyl, (C.sub.1C.sub.6)alkoxy-CO--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.9)alkoxy-CO--NH--(C.sub.1 C.sub.6)alkoxy, carboxy, carboxy(C.sub.1 C.sub.6)alkyl, carboxy(C.sub.1C.sub.6)alkoxy, benzyloxycarbonyl(C.sub.1 C.sub.6)alkoxy, (C.sub.1 C.sub.6)alkoxycarbonyl(C.sub.1 C.sub.6)alkoxy, (C.sub.6 C.sub.10aryl, amino, amino(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxycarbonylamino, (C.sub.6 C.sub.10)aryl(C.sub.1 C.sub.6) alkoxycarbonylamino, (C.sub.1 C.sub.6)alkylamino, ((C.sub.1 C.sub.6)alkyl).sub.2amino, (C.sub.1 C.sub.6)alkylamino(C.sub.1 C.sub.6)alkyl, ((C.sub.1C6)alkyl).sub.2amino(C.sub.1 C.sub.6)alkyl, hydroxy, (C.sub.1 C.sub.6)alkoxy, carboxy, carboxy(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxycarbonyl, (C.sub.1 C.sub.6)alkoxycarbonyl(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy-CO--NH--, (C.sub.1 C.sub.6)alkyl-CO--NH--, cyano, (C.sub.5 C.sub.9)heterocycloalkyl, amino-CO--NH--, (C.sub.1 C.sub.6)alkylamino-CO--NH--, ((C.sub.1 C.sub.6)alkyl).sub.2amino-CO--NH--, (C.sub.6 C.sub.10)arylamino-CO--NH--, (C.sub.5 C.sub.9)heteroarylamino-CO--NH--, (C.sub.1 C.sub.6)alkylamino-CO--NH--(C.sub.1 C.sub.6)alkyl, ((C.sub.1 C.sub.6)alkyl).sub.2amino-CO--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.6 C.sub.10) arylarnino-CO--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.5 C.sub.9)heteroarylamino-CO--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkylsulfonyl, (C.sub.1 C.sub.6) alkylsulfonylamino, (C.sub.1 C.sub.6)alkylsulfonylamino(C.sub.1 C.sub.6)alkyl, (C.sub.6 C.sub.10)arylsulfonyl, (C.sub.6 C.sub.10)arylsulfonylamino, (C.sub.6 C.sub.10)arylsulfonyiamino(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkylsulfonylamino, (C.sub.1 C.sub.6)alkylsulfonylamino, (C.sub.1 C.sub.6)alkyl, (C.sub.5 C.sub.9)heteroaryl or (C.sub.2 C.sub.9)heterocycloalkyl; with the proviso that R.sup.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.sup.5 is (C.sub.2 C.sub.9)heterocycioalkyl optionally substituted by one to three groups selected from deuterium, hydroxy, (C.sub.1 C.sub.6)alkyl, halo, (C.sub.1 C.sub.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(.dbd.N.dbd.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).sub.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).sub.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).sub.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).sub.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).sub.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).sub.n; c is 0; d is 1; e is 1; Y is S(O).sub.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).sub.n; c is 0; d is 1; e is 1; Y is S(O).sub.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).sub.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).sub.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).sub.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).sub.n; n is 2; f is 1; and g is 0. 20. The method according to claim 1, wherein R.sup.12 is (C.sub.6 C.sub.10)aryl or (C.sub.2 C.sub.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.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy, (C.sub.1 C.sub.6)alkyl-CO--NH--, amino, amino(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkylamino, ((C.sub.1 C.sub.6)alkyl).sub.2 amino, cyano, amino-CO--NH--, (C.sub.1 C.sub.6)alkylamino-CO--NH--, ((C.sub.1 C.sub.6)alkyl).sub.2amino-CONH--, (C.sub.5 C.sub.9)heteroarylamino-CO--NH--, (C.sub.1 C.sub.6)alkylsulfonyl, (C.sub.1 C.sub.6)alkylsuifonylamino, (C.sub.6 C.sub.10)arylsulfonylamino, (C.sub.1 C.sub.6)alkylsulfonylamino, and C.sub.1 C.sub.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-carboxyli- c acid (4-methylsulfamoyl-phenyl)-amide; (3-Hydroxy-pyrrolidin-1-yl)-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimid- in-4-yl)-amino]-piperidin-1-yl }-methanone; [2-({4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidi- ne-1-carbonyl}-amino)-thiazol-4-yl]-acetic acid; 5-(2-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]piperidi- n-1-yl}-2-oxo-ethyl)-thiazolidine-2,4-dione; {4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1y- l}-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]-piperidi- ne-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]-piperidin- e-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)-amin- o]-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]-piperidi- ne-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-1c- arboxylic 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 ##STR00014## or a pharmaceutically acceptable salt thereof; wherein R.sup.1 is a group of the formula ##STR00015## wherein y is 0, 1 or 2; R.sup.4 is selected from the group consisting of hydrogen, (C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkylsulfonyl, (C.sub.2 C.sub.6)alkenyl, (C.sub.2 C.sub.6)alkynyl wherein the alkyl, alkenyl and alkynyl groups are optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C.sub.1 C.sub.4)alkoxy, (C.sub.1 C.sub.6)acyloxy, (C.sub.1 C.sub.6)alkylamino, ((C.sub.1 C.sub.6)alkyl).sub.2amino, cyano, nitro, (C.sub.2 C.sub.6)alkenyl, (C.sub.2 C.sub.6)alkynyl or (C.sub.1 C.sub.6)acylamino; or R.sup.4 is (C.sub.3 C.sub.10)cycloalkyl wherein the cycloalkyl group is optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C.sub.1 C.sub.6)acyloxy, (C.sub.1 C.sub.6)acylamino, (C.sub.1 C.sub.6)alkylamino, ((C.sub.1 C.sub.6)alkyl).sub.2amino, cyano, cyano(C.sub.1 C.sub.6)alkyl, trifluoromethyl(C.sub.1 C.sub.6)alkyl, nitro, nitro(C.sub.1 C.sub.6)alkyl or (C.sub.1 C.sub.6)acylamino; R.sup.5 is (C.sub.2 C.sub.9)heterocycloalkyl wherein the heterocycloalkyl groups must be substituted by one to five groups consisting of carboxy, cyano, amino, deuterium, hydroxy, (C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy, halo, (C.sub.1 C.sub.6)acyl, (C.sub.1 C.sub.6)alkylamino, amino(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy-CO--NH, (C.sub.1 C.sub.6)alkylamino-CO--, (C.sub.2 C.sub.6)alkenyl, (C.sub.2 C.sub.6)alkynyl, (C.sub.1 C.sub.6)alkylamino, amino(C.sub.1 C.sub.6)alkyl, hydroxy(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)acyloxy(C.sub.1 C.sub.6)alkyl, nitro, cyano(C.sub.1 C.sub.6)alkyl, halo(C.sub.1 C.sub.6)alkyl, nitro(C.sub.1 C.sub.6)alkyl, trifluoromethyl, trifluoromethyl(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)acylamino, (C.sub.1 C.sub.6)acylamino(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy(C.sub.1 C.sub.6)acylamino, amino(C.sub.1 C.sub.6)acyl, amino(C.sub.1 C.sub.6)acyl(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkylamino(C.sub.1 C.sub.6)acyl, ((C.sub.1 C.sub.6)alkyl).sub.2amino(C.sub.1 C.sub.6)acyl, R.sup.15R.sup.16N--CO--O--, R.sup.15R.sup.16N--CO--(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkyl-S(O).sub.m, R.sup.15R.sup.16NS(O).sub.m, R.sup.15R.sup.16NS(O).sub.m(C.sub.1 C.sub.6)alkyl, R.sup.15S(O).sub.mR.sup.16N, R.sup.15S(O).sub.mR.sup.16N(C.sub.1 C.sub.6)alkyl, and a group of the formula II ##STR00016## wherein: m is 0, 1 or 2; R.sup.15 and R.sup.16 are each independently selected from hydrogen or (C.sub.1 C.sub.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).sub.n wherein n is 0, 1 or 2; oxygen, carbonyl or C(.dbd.N-cyano)-; Y is S(O).sub.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.sub.1 C.sub.6)alkyl; or Z is S(O).sub.n wherein n is 0, 1 or 2; R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10 and R.sup.11 are each independently selected from the group consisting of hydrogen or (C.sub.1 C.sub.6)alkyl optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C.sub.1 C.sub.6)acyloxy, (C.sub.1 C.sub.6)acylamino, (C.sub.1 C.sub.6)alkylamino, ((C.sub.1 C.sub.6).sub.2amino, cyano, cyano(C.sub.1 C.sub.6)alkyl, trifluorometbyl(C.sub.1 C.sub.6)alkyl, nitro, nitro(C.sub.1 C.sub.6)alkyl or (C.sub.1 C.sub.6)acylamino; R.sup.12 is (C.sub.6 C.sub.10)aryl, (C.sub.2 C.sub.9)heteroaryl, tetrazolyl, or (C.sub.2 C.sub.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.sub.2 C.sub.6)alkenyl, (C.sub.2 C.sub.6)alkynyl, trifluoromethyl, trifluoromethoxy, (C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy, (C.sub.3 C.sub.10)cycloalkyl, (C.sub.1 C.sub.6)alkyl-CO--NH--, (C.sub.1 C.sub.6)alkoxy-CO--NH--, (C.sub.1 C.sub.6)alkyl -CO--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy-CO--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy-CO--NH-(C.sub.1 C.sub.6)alkoxy, carboxy, carboxy(C.sub.1 C.sub.6)alkyl, carboxy(C.sub.1 C.sub.6)alkoxy, benzyloxycarbonyl(C.sub.1 C.sub.6)alkoxy, (C.sub.1 C.sub.6) alkoxycarbonyl(C.sub.1 C.sub.6)alkoxy, (C.sub.6 C.sub.10)aryl, amino, amino(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxycarbonylamino, (C.sub.6 C.sub.10)aryl(C.sub.1 C.sub.6)alkoxycarbonylamino, (C.sub.1 C.sub.6)alkylamino, ((C.sub.1 C.sub.6)alkyl).sub.2amino, (C.sub.1 C.sub.6) alkylamino(C.sub.1 C.sub.6)alkyl, ((C.sub.1 C.sub.6)alkyl).sub.2amino(C.sub.1 C.sub.6)alkyl, hydroxy, (C.sub.1 C.sub.6)alkoxy, carboxy, carboxy(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxycarbonyl, (C.sub.1 C.sub.6)alkoxycarbonyl(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy-CO--NH--, (C.sub.1 C.sub.6)alkyl-CO--NH--, cyano, (C.sub.5 C.sub.9)heterocycloalkyl, amino-CO--NH--, (C.sub.1 C.sub.6)alkylamino-CO--NH--, ((C.sub.1 C.sub.6)alkyl).sub.2amino-CO--NH--, (C.sub.6 C.sub.10)arylamino-CO--NH--, (C.sub.5 C.sub.9)heteroarylamino-CO--NH--, (C.sub.1 C.sub.6)alkylamino-CO--NH--(C.sub.1 C.sub.6)alkyl, ((C.sub.1 C.sub.6)alkyl).sub.2amino-CO--NH--(C.sub.1 C.sub.6alkyl, (C.sub.6 C.sub.10)arylamino-CO--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.5 C.sub.9)heteroarylamino-CO--NH--(C.sub.1 C.sub.6), cyano(C.sub.1 C.sub.6)alkyl, carboxy(C.sub.1 C.sub.6)alkyl(C.sub.1 C.sub.6)alkoxy, carboxy(C.sub.1 C.sub.6)alkyl, sulfonylamino, aminosulfonyl, sulfonylamino(C.sub.1 C.sub.6)alkyl, sulfonylaminocarboxy(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkylsulfonyl, (C.sub.1 C.sub.6)alkylsulfonylamino, (C.sub.1 C.sub.6)alkylsulfonylamino(C.sub.1 C.sub.6)alkyl, (C.sub.6 C.sub.10)arylsulfonyl, (C.sub.6 C.sub.10)arylsulfonylamino, (C.sub.6 C.sub.10)arylsulfonylamino(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6) alkylsulfonylamino, C.sub.1 C.sub.6)alkylsulfonylamino(C.sub.1 C.sub.6)alkyl, (C.sub.3 C.sub.10)cycloalkyl, (C.sub.3 C.sub.10)cycloalkoxy, (C.sub.1 C.sub.6)alkylamino, ((C.sub.1 C.sub.6)alkyl).sub.2amino, (C.sub.6 C.sub.10)arylamino, (C.sub.1 C.sub.6)alkylthio, (C.sub.6 C.sub.10)arylthio, (C.sub.1 C.sub.6)alkylsulfinyl, (C.sub.6 C.sub.10)arylsulfinyl, (C.sub.1 C.sub.6)alkylsulfonyl, (C.sub.6 C.sub.10)arylsulfonyl, (C.sub.1 C.sub.6)acyl, (C.sub.1 C.sub.6)alkoxy-CO--NH--, (C.sub.1 C.sub.6)alkylamino-CO--, (C.sub.5 C.sub.9)heteroaryl, (C.sub.2 C.sub.9)heterocycloalkyl or (C.sub.6 C.sub.10)aryl wherein the heteroaryl, tetrazolyl, hererocycloalkyl and aryl groups which are optionally substituted on R.sup.12 may be further substituted by one to three groups consisting of halo, (C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkyl-CO--NH--, C.sub.1 C.sub.6)alkoxy-CO--NH--, (C.sub.1 C.sub.6)alkyl-CO--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy-CO--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy-CO--NH--(C.sub.1 C.sub.6)alkoxy, carboxy, carboxy(C.sub.1 C.sub.6)alkyl, carboxy(C.sub.1 C.sub.6)alkoxy, benzyloxycarbonyl(C.sub.1 C.sub.6)alkoxy, (C.sub.1 C.sub.6)alkoxycarbonyl(C.sub.1 C.sub.6)alkoxy, (C.sub.6 C.sub.10)aryl, amino, amino(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxycarbonylamino, (C.sub.6 C 10)aryl(C.sub.1 C.sub.6)alkoxycarbonylamino, (C.sub.1 C.sub.6)alkylamino, ((C.sub.1 C.sub.6)alkyl ).sub.2amino, (C.sub.1 C.sub.6)alkylamino(C.sub.1 C.sub.6) alkyl, ((C.sub.1 C.sub.6)alkyl).sub.2amino(C.sub.1 C.sub.6)alkyl, hydroxy, (C.sub.1 C.sub.6)alkoxy, carboxy, carboxy(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxycarbonyl, (C.sub.1 C.sub.6)alkoxycarbonyl(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy-CO--NH--, (C.sub.1 C.sub.6)alkyl-CO--NH--, cyano, (C.sub.5 C.sub.9)heterocycloaikyl, amino-CO--NH--, (C.sub.1 C.sub.6)alkylamino-CO--NH--, ((C.sub.1 C.sub.6).sub.2amino-CO--NH--, (C.sub.1 C.sub.10)arylamino-CO--NH--, (C.sub.5 C.sub.9)heteroarylamino-CO--NH--, (C.sub.1 C.sub.6)alkylamino-CO--NH--(C.sub.1 C.sub.6)alkyl, ((C.sub.1 C.sub.6)alkyl).sub.2amino-CO--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.6 C.sub.10)arylamino-CO --NH--(C.sub.1 C.sub.6)alkyl, (C.sub.5 C.sub.9)heteroarylamino-CO--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkylsulfonyl, (C.sub.1 C.sub.6) alkylsulfonylamino, (C.sub.1 C.sub.6)alkylsulfonylamino(C.sub.1 C.sub.6)alkyl, (C.sub.6 C.sub.10)arylsulfonyl, (C.sub.6 C.sub.10)arylsulfonylamino, (C.sub.6 C.sub.10)arylsulfonylamino(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkylsulfonylamino, (C.sub.1 C.sub.6) alkylsulfonylamino(C.sub.1 C.sub.6)alkyl, (C.sub.5 C.sub.9)heteroaryl and (C.sub.2 C.sub.9)heterocycloalkyl; R.sup.2 and R.sup.3 are each independently selected from the group consisting of hydrogen, deuterium, amino, halo, hydroxy, nitro, carboxy, (C.sub.2 C.sub.6)alkenyl, (C.sub.2 C.sub.6)alkynyl, trifluoromethyl, trifluoromethoxy, (C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy, (C.sub.3 C.sub.10)cycloalkyl wherein the alkyl, alkoxy or cycloalkyl groups are optionally substituted by one to three groups selected from halo, hydroxy, carboxy, amino (C.sub.1 C.sub.6)alkylthio, (C.sub.1 C.sub.6)alkylamino, ((C.sub.1 C.sub.6)alkyl).sub.2amino, (C.sub.5 C.sub.9)heteroaryl, (C.sub.2 C.sub.9)heterocycloalkyl, (C.sub.3 C.sub.9)cycloalkyl or (C.sub.6 C.sub.10)aryl; or R.sup.2 and R.sup.3 are each independently (C.sub.3 C.sub.10)cycloalkyl, (C.sub.3 C.sub.10)cycloalkoxy, (C.sub.1 C.sub.6)alkylamino, ((C.sub.1 C.sub.6)alkyl).sub.2amino, (C.sub.6 C.sub.10)arylamino, (C.sub.1 C.sub.6)alkylthio, (C.sub.6 C.sub.10)arylthio, (C.sub.1 C.sub.6)alkylsulfinyl, (C.sub.6 C.sub.10) arylsulfinyl, (C.sub.1 C.sub.6)alkylsulfonyl, (C.sub.6 C.sub.10)arylsulfonyl, (C.sub.1 C.sub.6)acyl, (C.sub.1 C.sub.6)alkoxy-CO--NH--, (C.sub.1 C.sub.6) alkylamino-CO--, (C.sub.5 C.sub.9)heteroaryl, (C.sub.2 C.sub.9)heterocycloalkyl or (C.sub.6 C.sub.10)aryl wherein the heteroaryl, heterocycloalkyl and aryl groups are optionally substituted by one to three halo, (C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkyl-CO --NH--, (C.sub.1 C.sub.6)alkoxy-CO--NH--, (C.sub.1 C.sub.6)alkyl -CO--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy-CO--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy-CO--NH--(C.sub.1 C.sub.6)alkoxy, carboxy, carboxy(C.sub.1 C.sub.6)alkyl, carboxy(C.sub.1 C.sub.6)alkoxy, benzyloxycarbonyl(C.sub.1 C.sub.6)alkoxy, (C.sub.1 C.sub.6)alkoxycarbonyl(C.sub.1 C.sub.6)alkoxy, (C.sub.6 C.sub.10)aryl, amino, amino(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxycarbonylamino, (C.sub.6 C.sub.10)aryl (C.sub.1 C.sub.6)alkoxycarbonylamino, (C.sub.1 C.sub.6)alkylamino, ((C.sub.1 C.sub.6)alkyl).sub.2amino, (C.sub.1 C.sub.6)alkylamino(C.sub.1 C.sub.6)alkyl, ((C.sub.1 C.sub.6)alkyl).sub.2amino(C.sub.1 C.sub.6)alkyl, hydroxy, (C.sub.1 C.sub.6)alkoxy, carboxy, carboxy(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxycarbonyl, (C.sub.1 C.sub.6)alkoxycarbonyl(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy-CO--NH--, (C.sub.1 C.sub.6)alkyl-CO--NH--, cyano, (C.sub.5 C.sub.9)heterocycloalkyl, amino-CO--NH--, (C.sub.1 C.sub.6)alkylamino-CO--NH--, ((C.sub.1 C.sub.6)alkyl).sub.2amino-C--NH--, (C.sub.6 C.sub.10)arylamino-CO--NH--, (C.sub.5 C.sub.9)heteroarylamino-CO--NH--, (C.sub.1 C.sub.6)alkylamino-CO--NH--(C.sub.1 C.sub.6)alkyl, ((C.sub.1 C.sub.6)alkyl).sub.2amino-CO--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.6 C.sub.10)arylamino-CO--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.5 C.sub.9)heteroarylamino-CO--NH--(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkylsulfonyl, (C.sub.1 C.sub.6) alkylsulfonylamino. (C.sub.1 C.sub.6)alkylsulfonylamino(C.sub.1 C.sub.6)al kyl, (C.sub.6 C.sub.10)arylsulfonyl, (C.sub.6 C.sub.10)arylsulfonylamino, (C.sub.6 C.sub.10)arylsulfonylamino(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkylsulfonylamino, (C.sub.1 C.sub.6)alkylsulfonylamino(C.sub.1 C.sub.6)alkyl, (C.sub.5 C.sub.9)heteroaryl or (C.sub.2 C.sub.9)heterocycloalkyl; with the proviso that R.sup.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.sup.5 is (C.sub.2 C.sub.9)heterocycloalkyl optionally substituted by one to three groups selected from deuterium, hydroxy, (C.sub.1 C.sub.6)alkyl, halo, (C.sub.1 C.sub.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(.dbd.N.dbd.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).sub.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).sub.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).sub.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).sub.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).sub.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).sub.n; c is 0; d is 1; e is 1; Y is S(O).sub.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).sub.n; c is 0; d is 1; e is 1; Y is S(O).sub.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).sub.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).sub.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).sub.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).sub.n; n is 2; f is 1; and g is 0. 41. The method according to claim 22, wherein R.sup.12 is (C.sub.6 C.sub.10)aryl or (C.sub.2 C.sub.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.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkoxy, C.sub.1 C.sub.6)alkyl-CO--NH--, amino, amino(C.sub.1 C.sub.6)alkyl, (C.sub.1 C.sub.6)alkylamino, ((C.sub.1 C.sub.6)alkyl).sub.2amino, cyano, amino-CO--NH--, (C.sub.1 C.sub.6)alkylamino-CO--NH--, ((C.sub.1 C.sub.6)alkyl).sub.2amino-CO--NH--, (C.sub.5 C.sub.9)heteroarylamino-CO--NH--, (C.sub.1 C.sub.6)alkylsulfonyl, C.sub.1 C.sub.6)alkylsulfonylamino, (C.sub.6 C.sub.10)arylsulfonylamino, (C.sub.1 C.sub.6)alkylsulfonylamino, and (C.sub.1 C.sub.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-c- arboxylic 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-c- arboxylic acid (4-methylsulfamoyl-phenyl)-amide; (3-Hydroxy-pyrrolidin-1-yl)-{4-methyl-3-[methyl-(7H-pyrrololo[2,3-d]pyrim- idin-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)-t- hiazol-4-yl]-acetic acid; 5-(2-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperid- in-1-yl }-2-oxo-ethyl)-thiazolidine-2,4-dione; {4-Methyl-3-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-y- l}-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]-piperidin- e-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-1y- l)}-pyrrolidin-1-yl-methanone; Furan-2-carboxylic acid (2-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin- e-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)-amin- o]-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]-piperidi- ne-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.

Details for Patent 7,192,963

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Centocor Ortho Biotech Products, L.p.	ORTHOCLONE OKT3	muromanab-cd3	Injection	103463	09/14/1992		2020-06-26
Hoffmann-la Roche Inc.	ZENAPAX	daclizumab	Injection	103749	12/10/1997		2020-06-26
Biogen Inc.	ZINBRYTA	daclizumab	Injection	761029	05/27/2016		2020-06-26
Biogen Inc.	ZINBRYTA	daclizumab	Injection	761029	05/26/2017		2020-06-26