| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | September 30, 2003 |
| PATENT TITLE |
Pyrrolo[2,3-d]pyrimidine compounds |
| PATENT ABSTRACT | A compound of the formula ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined above, which are inhibitors of the enzyme protein kinases such as Janus Kinase 3 and as such are useful therapy as immunosuppressive agents for organ transplants, xeno transplation, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia and other autoimmune diseases |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | December 8, 2000 |
| PATENT REFERENCES CITED |
Traxler, P. Exp. Opin. Ther. Patents 7(6) 571-588, 1997.* Traxler, P. M., et al., 4-(Phenylamino)pyrrolopyrimidines: Potent and Selective, ATP Site Directed Inhibitors of the EGF-Receptor Protein Tyrosine Kinase; J. Med. Chem.; (1996), 39, p. 2285-2292. J. J. O'Shea, et al., Phosphorylation and activation of the Jak-3 Janus Kinase in response to Interleukin-2, Nature, 370, 151, (1994). S. M. Russell, et al., Interaction of IL-2R.beta. and .gamma.c Chains with Jak1 and Jak3: Implications for XSCID and XCID, Science, 266, 1042 (1994). J. N. Ihle, The Janus Protein Tyrosine Kinase Family and Its Role in Cytokine Signaling, Adv. Immunology, 60, 1, (1995). J. N. Ihle, The Janus Protein Tyrosine Kinases in hematopoietic cytokine signaling, Semin. Immunology, 7, 247, (1995). T. Musso, et al., Regulation of JAK3 Expression in Human Monocytes: Phosphorylation In Response to Interleukings 2, 4, and 7, J. Exp. Med., 181, 1425 (1995). R. A. Kirken, et al., Activation of JAK3, but not JAK1, is critical for IL-2-induced proliferation and STAT5 Recruitment by a COOH-terminal region of the IL-2 receptor .beta.-chain, Cytokine, 7 689, (1995). M. G. Malabarba, et al., Activation of JAK3, but not JAK1, is Critical to Interleukin-4 (IL4) Stimulated Proliferation and Requires a Membrane-proximal Region of IL4 Receptor .alpha.*, J. Biol. Chem., 270, 9630, (1995). J. H. Hanke, B. A. Pollok, and P. S. Changelian, Role of tyrosine kinases in lymphocyte activation: Targets for drug intervention, Inflamm. Res., 44, 357, (1995). E.E. Eynon, et al., Disruption of Cytokine Signaling in Lymphoid Development: Unique Contributions of the Common Cytokine Gamma Chain and the JAK3 Kinase, J. Interferon Cytokine Res., 16, 677, (1996). S. A. Oakes, et al., Signaling via IL-2 and IL-4 in JAK#-Deficient Severe Combined Immunodeficiency Lymphocytes: JAK3-Dependent and Independent Pathways, Immunity, 5, 605 (1996). L. D. Norangelo, et al, Severe Combined Immune Deficiency due to Defects of the JAK3 Tyrosine Kinase, Prog. Immunodeficiency, 6, 61, (1996). D. C. Thomis, et al., Peripheral Expression of JAK3 is Required to Maintain T Lymphocyte Function, J. Exp. Med., 185, 197, (1997). B. H. Nelson, et al., Requirement for an initial signal from the membrane-proximal region of the interleukin 2 receptor .gamma.c chain for Janus kinase activation leading to T cell proliferation, Proc. Natl. Acad. Sci. USA, 94, 1878, (1997). A. M. Baird, et al., T Cell development and activation in Jak3-deficient mice, J. Leukocyte Biol., 63, 669, (1998). K. D. Liu, et al., JAK/STAT signaling by cytokine receptors, Curr. Opin. Immunol. W. J. Leonard and J. J. O'Shea, JAKS and STATS: Biological Implications, Annu. Rev. Immunol., 16, 293, (1998). F. Candotti, et al., Severe combined immune deficiencies due to defects in the common .gamma. chain-JAK3 signaling pathway, Springer Semin. Immunopathol., 19, 401, (1998). R. Malaviya, et al., Targeting Janus Kinase 3 in Mast Cells Prevents Immediate Hypersensitivity Reactions and Anaphylaxis, J. Biol. Chem., 274, 27028 (1999). D. C. Thomis, et al., The Jak Family Tyrosine Kinase Jak3 is Required for IL-2 Synthesis by Naive/Resting CD4+ T Cells, J. Immunol., 163, 5411 (1999). E. Chen, et al., Advances in Cytokine Signaling: The Role of Jaks and STATs, Transplantation Proc., 31, 1482, (1999). R. Moriggi, et al., Stat5 Activation is Uniquely Associated with Cytokine Signaling in Peripheral T Cells, Immunity, 11, 225 (1995). L. H. Wang, et al., JAK3, STAT, and MAPK Signaling Pathways as Novel Molecular Targets for the Tyrphostin AG-490 Regulation of IL-2-Mediated T Cell Response, J. Immunol., 162, 3897, (1999). E. A. Sudbeck, et al., Structure-based Design of Specific Inhibitors of Janus Kinase 3 as Apoptosis-inducing Antileukemic Agents, Clin. Cancer Res., 5, 1569, (1999). F. M. Uckun, et al., In Vivo Toxicity and Pharmacokinetic Features of the Janus Kinase 3 Inhibitor WHI-P131 [40(4'-Hydroxyphenyl)-Amino-6,7-Dimethosyquinazoline], Clin. Cancer Research, 5, 2954, (1999). E. A. Sudbeck and F. M. Uckun, Recent Advances in JAK3 kinase inhibitors, IDrugs, 2, 1026, (1999). R. Malaviya, et al., Genetic and Biochemical Evidence for a Critical Role of Janus Kinase (JAK)-3 in Mast Cell-Mediated Type I Hypersensitivity Reactions, Biochem. Biophys., Res. Commun., 257, 807, (1999). V. N. Trieu, et al., A Specific Inhibitor of Janus Kinase-3 Increases Survival In a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis, Biochem. Biophys. Res. Commun., 267, 22, (2000). X. C. Li, et. al., Blocking the Common .gamma.-Chain of Cytokine Receptors Induces T Cell Apoptosis and Long-Term Islet Allograft Survival, J. Immunol., 164, 1193 (2000)/. R. Malaviya, et. al., Treatment of allergic asthma by targeting Janus kinase 3-dependent leukotriene synthesis in mast cells with 4-(3',5'-Dibromo-4'hydroxyphenyl)amino-6,7-dimethoxyquinazoline (WHI-P97), J. Pharmacol. Exp. Ther., 295, 912 (2000). S. Ghosh, et. al., 4[(3-Bromo-4-hydroxyphenyl)amino]6,7-dimethoxyquinazolin-1-ium chloride methanol solvate and 4-(3-hydroxyphenyl)amino0-6,7-dimethoxy-1-quinazolinium chloride. Acta Crystallogr,. C: Cryst. Struct. Commun., C57, 76 (2001). E. A. Skudbeck, et. al. An inhibitor of janus kinase 3: 4-(4-hydroxyphenylamino)-6,7-dimethoxyquinazolin-1-ium chloride, Acta Crystallogr., SectC: Cryst. Struct. Commun., C56, 1282 (2000). |
| PATENT PARENT CASE TEXT | This data is not available for free |
| PATENT CLAIMS |
What is claimed is: 1. A compound of the formula ##STR10## or the pharmaceutically acceptable salt thereof; wherein R.sup.1 is a group of the formula ##STR11## 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.2 amino, 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.2 amino, 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 a piperidinyl substituted by one to five 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.2 amino(C.sub.1 -C.sub.6)acyl, R.sup.15 R.sup.16 N--CO--O--, R.sup.15 R.sup.16 N--CO--(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkyl-S(O).sub.m, R.sup.15 R.sup.16 NS(O).sub.m, R.sup.15 R.sup.16 NS(O).sub.m (C.sub.1 -C.sub.6)alkyl, R.sup.15 S(O).sub.m R.sup.16 N, R.sup.15 S(O).sub.m R.sup.16 N(C.sub.1 -C.sub.6)alkyl wherein m is 0, 1 or 2 and R.sup.15 and R.sup.16 are each independently selected from hydrogen or (C.sub.1 -C.sub.6)alkyl; or a group of the formula ##STR12## wherein a is 0, 1, 2, 3 or 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-- or 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)alkyl).sub.2 amino, 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 carboxy, cyano, amino, oxo, deuterium, hydroxy, trifluoromethyl, (C.sub.1 -C.sub.6)alkyl, trifluoromethyl(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, ((C.sub.1 -C.sub.6)alkyl).sub.2 amino, 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, 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.2 amino(C.sub.1 -C.sub.6)acyl, R.sup.15 R.sup.16 N--CO--O--, R.sup.15 R.sup.16 N--CO--(C.sub.1 -C.sub.6)alkyl, R.sup.15 C(O)NH, R.sup.15 OC(O)NH, R.sup.15 NHC(O)NH, (C.sub.1 -C.sub.6)alkyl-S(O).sub.m, (C.sub.1 -C.sub.6)alkyl-S(O).sub.m --(C.sub.1 -C.sub.6)alkyl, R.sup.15 R.sup.16 NS(O).sub.m, R.sup.15 R.sup.16 NS(O).sub.m (C.sub.1 -C.sub.6)alkyl, R.sup.15 S(O).sub.m R.sup.16 N, R.sup.15 S(O).sub.m R.sup.16 N(C.sub.1 -C.sub.6)alkyl wherein m is 0, 1 or 2 and R.sup.15 and R.sup.16 are each independently selected from hydrogen or (C.sub.1 -C.sub.6)alkyl; R.sup.2 and R.sup.3 are each hydrogen. 2. A compound of the formula ##STR13## or the pharmaceutically acceptable salt thereof wherein R.sup.1 is a group of the formula ##STR14## wherein y is 0; R.sup.4 is (C.sub.1 -C.sub.6)alkyl; R.sup.5 is piperidinyl substituted by one to five 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.2 amino(C.sub.1 -C.sub.6)acyl, R.sub.15 R.sub.16 N--CO--O--, R.sub.15 R.sub.16 N--CO--(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkyl-S(O).sub.m, R.sub.15 R.sub.16 NS(O).sub.m, R.sub.15 R.sub.16 NS(O).sub.m ((C.sub.1 -C.sub.6)alkyl, R.sub.15 S(O).sub.m R.sub.16 N, R.sub.15 S(O).sub.m R.sub.16 N(C.sub.1 -C.sub.6)alkyl, or a group of the formula ##STR15## wherein: m is 0,1 or 2; R.sub.15 and R.sub.16 are each independently selected from hydrogen or (C.sub.1 -C.sub.6)alkyl; d is 1; R.sup.9 and R.sup.10 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)alkyl).sub.2 amino, 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 cyano, trifluoromethyl, (C.sub.1 -C.sub.6)alkyl, trifluoromethyl(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkylamino, ((C.sub.1 -C.sub.6)alkyl).sub.2 amino, (C.sub.2 -C.sub.6)alkynyl, cyano(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkyl-S(O).sub.m wherein m is 0, 1 or 2; and R.sup.2 and R.sup.3 are each H. 3. A compound selected from the group consisting of: Methyl-[4-methyl-1-(propane-1-sulfonyl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]p yrimidin-4-yl)-amine; 4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-ca rboxylic acid methyl ester; 3,3,3-Trifluoro-1-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-ami no]-piperidin-1-yl}-propan-1-one; 4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-ca rboxylic acid dimethylamide; 3-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1- yl}-3-oxo-propionitrile; 3,3,3-Trifluoro-1-{4-methyl-3-[methyl-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin- 4-yl)-amino]-piperidin-1-yl}-propan-1-one; 1-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1- yl}-but-3-yn-1-one; 1-{3-[(5-Chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-methyl-amino]-4-methyl-pip eridin-1-yl}-propan-1-one; and 1-{3-[(5-Fluoro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-methyl-amino]-4-methyl-pip eridin-1-yl}-propan-1-one. 4. A compound of claim 3, wherein said compound is 3-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1 -yl}-3-oxo-propionitrile, or pharmaceutically acceptable salt thereof. -------------------------------------------------------------------------------- |
| PATENT DESCRIPTION |
BACKGROUND OF THE INVENTION The present invention relates to pyrrolo[2,3-d]pyrimidine compounds which are inhibitors of protein kinases, such as the enzyme Janus Kinase 3 (hereinafter also referred to as JAK3) and as such are useful therapy as immunosuppressive agents for organ transplants, xeno transplation, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia and other indications where immunosuppression would be desirable. This invention also relates to a method of using such compounds in the treatment of the above indications in mammals, especially humans, and the phamaceutical compositions useful therefor. JAK3 is a member of the Janus family of protein kinases. Although the other members of this family are expressed by essentially all tissues, JAK3 expression is limited to hematopoetic cells. This is consistent with its essential role in signaling through the receptors for IL-2, IL-4, IL-7, IL-9 and IL-15 by non-covalent association of JAK3 with the gamma chain common to these multichain receptors. XSCID patient populations have been identified with severely reduced levels of JAK3 protein or with genetic defects to the common gamma chain, suggesting that immunosuppression should result from blocking signaling through the JAK3 pathway. Animal studies have suggested that JAK3 not only plays a critical role in B and T lymphocyte maturation, but that JAK3 is constitutively required to maintain T cell function. Modulation of immune activity through this novel mechanism can prove useful in the treatment of T cell proliferative disorders such as transplant rejection and autoimmune diseases. SUMMARY OF THE INVENTION The present invention relates to a compound of the formula ##STR2## or the pharmaceutically acceptable salt thereof; wherein R.sup.1 is a group of the formula ##STR3## 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, and (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.2 amino, 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.2 amino, 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)alkylamino; R.sup.5 is (C.sub.2 -C.sub.9)heterocycloalkyl wherein the heterocycloalkyl groups must be substituted by one to five 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.2 amino(C.sub.1 -C.sub.6)acyl, R.sup.15 R.sup.16 N--CO--O--, R.sup.15 R.sup.16 N--CO--(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkyl-S(O).sub.m, R.sup.5 R.sup.16 NS(O).sub.m, R.sup.15 R.sup.16 NS(O).sub.m (C.sub.1 -C.sub.6)alkyl, R.sup.15 S(O).sub.m R.sup.16 N, R.sup.15 S(O).sub.m R.sup.16 N(C.sub.1 -C.sub.6)alkyl, wherein m is 0, 1 or 2 and R.sup.15 and R.sup.16 are each independently selected from hydrogen or (C.sub.1 -C.sub.6)alkyl, or a group of the formula ##STR4## wherein a is 0, 1, 2, 3 or 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--, or 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 and (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)alkyl).sub.2 amino, 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 carboxy, cyano, amino, oxo, deuterium, hydroxy, trifluoromethyl, (C.sub.1 -C.sub.6)alkyl, trifluoromethyl(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, ((C.sub.1 -C.sub.6)alkyl).sub.2 amino, 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, 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(CH.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.2 amino((C.sub.1 -C.sub.6)acyl, R.sup.15 R.sup.16 N--CO--O--, R.sup.15 R.sup.16 N--CO--(C.sub.1 -C.sub.6)alkyl, R.sup.15 C(O)NH, R.sup.15 OC(O)NH, R.sup.15 NHC(O)NH, (C.sub.1 -C.sub.6)alkyl-S(O).sub.m, (C.sub.1 -C.sub.6)alkyl-S(O).sub.m -(C.sub.1 -C.sub.6)alkyl, R.sup.15 R.sup.16 NS(O).sub.m, R.sup.15 R.sup.16 NS(O).sub.m (C.sub.1 -C.sub.6)alkyl, R.sup.15 S(O).sub.m R.sup.16 N, or R.sup.15 S(O).sub.m R.sup.16 N(C.sub.1 -C.sub.6)alkyl, wherein m is 0, 1 or 2 and R.sup.15 and R.sup.16 are each independently selected from hydrogen or (C.sub.1 -C.sub.6)alkyl; 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, and (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.2 amino, (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.2 amino, (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)alkyamino-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.2 amino, (C.sub.1 -C.sub.6)alkylamino(C.sub.1 -C.sub.6)alkyl, C.sub.1 -C.sub.6)alkyl).sub.2 amino((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.2 amino-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.2 amino-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 or (C.sub.2 -C.sub.9)heterocycloalkyl. The present invention also relates to the pharmaceutically acceptable acid addition salts of compounds of the formula I. The acids which are used to prepare the pharmaceutically acceptable acid addition salts of the aforementioned base compounds of this invention are those which form non-toxic acid addition salts, i.e., salts containing pharmacologically acceptable anions, such as the hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, acetate, lactate, citrate, acid citrate, tartrate, bitartrate, succinate, maleate, fumarate, gluconate, saccharate, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate and pamoate [i.e., 1,1'-methylene-bis-(2-hydroxy-3-naphthoate)]salts. The invention also relates to base addition salts of formula I. The chemical bases that may be used as reagents to prepare pharmaceutically acceptable base salts of those compounds of formula I that are acidic in nature are those that form non-toxic base salts with such compounds. Such non-toxic base salts include, but are not limited to those derived from such pharmacologically acceptable cations such as alkali metal cations (e.g., potassium and sodium) and alkaline earth metal cations (e.g., calcium and magnesium), ammonium or water-soluble amine addition salts such as N-methylglucamine-(meglumine), and the lower alkanolammonium and other base salts of pharmaceutically acceptable organic amines. The term "alkyl", as used herein, unless otherwise indicated, includes saturated monovalent hydrocarbon radicals having straight or branched moieties or combinations thereof. The term "alkoxy", as used herein, includes O-alkyl groups wherein "alkyl" is defined above. The term "halo", as used herein, unless otherwise indicated, includes fluoro, chloro, bromo or iodo. The compounds of this invention may contain double bonds. When such bonds are present, the compounds of the invention exist as cis and trans configurations and as mixtures thereof. Unless otherwise indicated, the alkyl and alkenyl groups referred to herein, as well as the alkyl moieties of other groups referred to herein (e.g., alkoxy), may be linear or branched, and they may also be cyclic (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl) or be linear or branched and contain cyclic moieties. Unless otherwise indicated, halogen includes fluorine, chlorine, bromine, and iodine. (C.sub.2 -C.sub.9) Heterocycloalkyl when used herein refers to pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, pyranyl, thiopyranyl, aziridinyl, oxiranyl, methylenedioxyl, chromenyl, isoxazolidinyl, 1,3-oxazolidin-3-yl, isothiazolidinyl, 1,3-thiazolidin-3-yl, 1,2-pyrazolidin-2-yl, 1,3-pyrazolidin-1-yl, piperidinyl, thiomorpholinyl, 1,2-tetrahydrothiazin-2-yl, 1,3-tetrahydrothiazin-3-yl, tetrahydrothiadiazinyl, morpholinyl, 1,2-tetrahydrodiazin-2-yl, 1,3-tetrahydrodiazin-1-yl, tetrahydroazepinyl, piperazinyl, chromanyl, etc. One of ordinary skill in the art will understand that the connection of said (C.sub.2 -C.sub.9) heterocycloalkyl rings is through a carbon or a sp.sup.3 hybridized nitrogen heteroatom. (C.sub.2 -C.sub.9) Heteroaryl when used herein refers to furyl, thienyl, thiazolyl, pyrazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrrolyl, triazolyl, tetrazolyl, imidazolyl, 1,3,5-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,3-oxadiazolyl, 1,3,5-thiadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, 1,2,4-triazinyl, 1,2,3-triazinyl, 1,3,5-triazinyl, pyrazolo[3,4-b]pyridinyl, cinnolinyl, pteridinyl, purinyl, 6,7-dihydro-5H-[1]pyrindinyl, benzo[b]thiophenyl, 5,6,7,8-tetrahydro-quinolin-3-yl, benzoxazolyl, benzothiazolyl, benzisothiazolyl, benzisoxazolyl, benzimidazolyl, thianaphthenyl, isothianaphthenyl, benzofuranyl, isobenzofuranyl, isoindolyl, indolyl, indolizinyl, indazolyl, isoquinolyl, quinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, benzoxazinyl, etc. One of ordinary skill in the art will understand that the connection of said (C.sub.2 -C.sub.9)heteroaryl rings is through a carbon atom or a sp.sup.3 hybridized nitrogen heteroatom. (C.sub.6 -C.sub.10)aryl when used herein refers to phenyl or naphthyl. Compounds of formula (I) may be administered in a pharmaceutically acceptable form either alone or in combination with one or more additional agents which modulate a mammalian immune system or with antiinflammatory agents. These agents may include but are not limited to cyclosporin A (e.g. Sandimmune.RTM. or Neoral.RTM., rapamycin, FK-506 (tacrolimus), leflunomide, deoxyspergualin, mycophenolate (e.g. Cellcept.RTM.), azathioprine (e.g. Imuran.RTM.), daclizumab (e.g. Zenapax.RTM.. OKT3 (e.g. Orthoclone.RTM.), AtGam, aspirin, acetaminophen, ibuprofen, naproxen, piroxicam, and antiinflammatory steroids (e.g. prednisolone or dexamethasone). These agents may be administered as part of the same or separate dosage forms, via the same or different routes of administration, and on the same or different administration schedules according to standard pharmaceutical practice. The compounds of this invention include all conformational isomers (e.g., cis and trans isomers. The compounds of the present invention have asymmetric centers and therefore exist in different enantiomeric and diastereomeric forms. This invention relates to the use of all optical isomers and stereoisomers of the compounds of the present invention, and mixtures thereof, and to all pharmaceutical compositions and methods of treatment that may employ or contain them. In this regard, the invention includes both the E and Z configurations. The compounds of formula I may also exist as tautomers. This invention relates to the use of all such tautomers and mixtures thereof. This invention also encompasses pharmaceutical compositions containing prodrugs of compounds of the formula I. This invention also encompasses methods of treating or preventing disorders that can be treated or prevented by the inhibition of protein kinases, such as the enzyme Janus Kinase 3 comprising administering prodrugs of compounds of the formula I. Compounds of formula I having free amino, amido, hydroxy or carboxylic groups can be converted into prodrugs. Prodrugs include compounds wherein an amino acid residue, or a polypeptide chain of two or more (e.g., two, three or four) amino acid residues which are covalently joined through peptide bonds to free amino, hydroxy or carboxylic acid groups of compounds of formula I. The amino acid residues include the 20 naturally occurring amino acids commonly designated by three letter symbols and also include, 4-hydroxyproline, hydroxylysine, demosine, isodemosine, 3-methylhistidine, norvlin, beta-alanine, gamma-aminobutyric acid, citrulline, homocysteine, homoserine, ornithine and methioine sulfone. Prodrugs also include compounds wherein carbonates, carbamates, amides and alkyl esters which are covalently bonded to the above substituents of formula I through the carbonyl carbon prodrug sidechain. Preferred compounds of formula I include those 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. Other preferred compounds of formula I include those 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. Other preferred compounds of formula I include those 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. Other preferred compounds of formula I include those 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. Other preferred compounds of formula I include those 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--. Other preferred compounds of formula I include those 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. Other preferred compounds of formula I include those 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. Other preferred compounds of formula I include those 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. Other preferred compounds of formula I include those 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. Other preferred compounds of formula I include those 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. Other preferred compounds of formula I include those 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. Other preferred compounds of formula I include those 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. Other preferred compounds of formula I include those 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. Other preferred compounds of formula I include those 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. Other preferred compounds of formula I include those 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. Other preferred compounds of formula I include those 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. Other preferred compounds of formula I include those 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. Other preferred compounds of formula I include those wherein R.sup.12 is cyano, trifluoromethyl, (C.sub.1 -C.sub.6)alkyl, trifluoromethyl(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkylamino, ((C.sub.1 -C.sub.6)alkyl).sub.2 amino, (C.sub.2 -C.sub.6)alkynyl, cyano(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkyl-S(O).sub.m wherein m is 0, 1 or 2. Specific preferred compounds of formula I include those wherein said compound is selected from the group consisting of: Methyl-[4-methyl-1-(propane-1-sulfonyl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d]p yrimidin-4-yl)-amine; 4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-ca rboxylic acid methyl ester; 3,3,3-Trifluoro-1-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-ami no]-piperidin-1-yl}-propan-1-one; 4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-ca rboxylic acid dimethylamide; ({4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1- carbonyl}-amino)-acetic acid ethyl ester; 3-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1- yl}-3-oxo-propionitrile; 3,3,3-Trifluoro-1-{4-methyl-3-[methyl-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin- 4-yl)-amino]-piperidin-1-yl}-propan-1-one; 1-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1- yl}-but-3-yn-1-one; 1-{3-[(5-Chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-methyl-amino]-4-methylpipe ridin-1-yl}-propan-1-one; 1-{3-[(5-Fluoro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-methyl-amino]-4-methylpipe ridin-1-yl}-propan-1-one; N-cyano-4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-N'-prop yl-piperidine-1-carboxamidine; and N-cyano-4,N',N'-Trimethyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino ]-piperidine-1-carboxamidine. The present invention also relates to a pharmaceutical composition for (a) treating or preventing a disorder or condition selected from organ transplant rejection, xeno transplation, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia, and other autoimmune diseases or (b) the inhibition of protein kinases or Janus Kinase 3 (JAK3) in a mammal, including a human, comprising an amount of a compound of formula I or a pharmaceutically acceptable salt thereof, effective in such disorders or conditions and a pharmaceutically acceptable carrier. The present invention also relates to a method for the inhibition of protein typrosine kinases or Janus Kinase 3 (JAK3) in a mammal, including a human, comprising administering to said mammal an effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof. The present invention also relates to a method for treating or preventing a disorder or condition selected from organ transplant rejection, xeno transplation, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia, and other autoimmune diseases in a mammal, including a human, comprising administering to said mammal an amount of a compound of formula I or a pharmaceutically acceptable salt thereof, effective in treating such a condition. |
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