Details for Patent: RE41783

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, 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.
Inventor(s):	Blumenkopf; Todd A. (Old Lyme, CT), Flanagan; Mark E. (Gales Ferry, CT), Munchhof; Michael J. (Salem, CT)
Assignee:	Pfizer Inc. (Madison, NJ)
Filing Date:	Oct 13, 2009
Application Number:	12/577,790
Claims:	1. A compound of the formula ##STR00010## or a pharmaceutically acceptable salt thereof; wherein R.sup.1 is a group of the formula ##STR00011## 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 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.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 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 ##STR00012## 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.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 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.2amino, 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.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, R.sup.15C(O)NH, R.sup.15OC(O)NH, R.sup.15NHC(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.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 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 ##STR00013## or a pharmaceutically acceptable salt thereof wherein R.sup.1 is a group of the formula ##STR00014## 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.2amino(C.sub.1-C.sub.6)acyl, R.sub.15R.sub.16N--CO--O--, R.sub.15R.sub.16N--CO--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkyl-S(O).sub.m, R.sub.15R.sub.16NS(O).sub.m, R.sub.15R.sub.16NS(O).sub.m.[.(.]. (C.sub.1-C.sub.6)alkyl, R.sub.15S(O).sub.mR.sub.16N, R.sub.15S(O).sub.mR.sub.16N(C.sub.1-C.sub.6)alkyl, or a group of the formula ##STR00015## 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.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 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.2amino, (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- ]pyrimidin-4-yl)-amine; 4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-- carboxylic acid methyl ester; 3,3,3-Trifluoro-1-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-a- mino]-piperidin-1-yl}-propan-1-one; 4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-- carboxylic 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]pyrimidi- n-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-p- iperidin-1-yl}-propan-1-one; and 1-{3-[(5-Fluoro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-methyl-amino]-4-methyl-p- iperidin-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 a pharmaceutically acceptable salt thereof.