Protein kinase inhibitors and uses thereof
First Claim
1. A compound of formula I:
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or a pharmaceutically acceptable salt thereof, wherein;
A-B is N—
O or O—
N;
Ar is an optionally substituted C5-10 aryl group;
T is a C1-4 alkylidene chain wherein one or two methylene units of T are optionally and independently replaced by O, NR, S, C(O), C(O)NR, NRC(O)NR, SO2, SO2NR, NRSO2, NRSO2NR, CO2, OC(O), NRCO2, or OC(O)NR;
n is zero or one;
R1 is hydrogen or an optionally substituted group selected from C1-10 aliphatic, C5-10 aryl, C6-12 aralkyl, C3-10 heterocyclyl, or C4-12 heterocyclylalkyl;
each R2 is independently selected from R, halo, CN, OR, N(R)2, SR, C(═
O)R, CO2R, CONR2, NRC(═
O)R, NRCO2(C1-6 aliphatic), OC(═
O)R, SO2R, S(═
O)R, SO2NR2, or NRSO2(C1-6 aliphatic);
each R3 is independently selected from R, halo, CN, OR, N(R)2, SR, C(═
O)R, CO2R, CONR2, NRC(═
O)R, NRCO2(C1-6 aliphatic), OC(═
O)R, SO2R, S(═
O)R, SO2NR2, or NRSO2(C1-6 aliphatic); and
each R is independently selected from hydrogen, a C1-8 aliphatic group, or two R on the same nitrogen are taken together with the nitrogen to form a 4-8 membered heterocyclic ring having 1-3 heteroatoms selected from nitrogen, oxygen or sulfur.
3 Assignments
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Accused Products
Abstract
Described herein are benzisoxazole compounds of formula I:
or a pharmaceutically acceptable derivative or prodrug thereof, wherein A-B is N—O or O—N; Ar is an optionally substituted C5-10 aryl group; R1 is hydrogen or an optionally substituted group selected from C1-10 aliphatic, C5-10 aryl, C6-12 aralkyl, C3-10 heterocyclyl, or C4-12 heterocyclylalkyl; and T, n, R2 and R3 are as described in the specification. These compounds are inhibitors of protein kinases, particularly inhibitors of GSK-3 and JAK mammalian protein kinases. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of utilizing those compounds and compositions in the treatment of various protein kinase mediated disorders.
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Citations
13 Claims
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1. A compound of formula I:
-
or a pharmaceutically acceptable salt thereof, wherein; A-B is N—
O or O—
N;
Ar is an optionally substituted C5-10 aryl group;
T is a C1-4 alkylidene chain wherein one or two methylene units of T are optionally and independently replaced by O, NR, S, C(O), C(O)NR, NRC(O)NR, SO2, SO2NR, NRSO2, NRSO2NR, CO2, OC(O), NRCO2, or OC(O)NR;
n is zero or one;
R1 is hydrogen or an optionally substituted group selected from C1-10 aliphatic, C5-10 aryl, C6-12 aralkyl, C3-10 heterocyclyl, or C4-12 heterocyclylalkyl;
each R2 is independently selected from R, halo, CN, OR, N(R)2, SR, C(═
O)R, CO2R, CONR2, NRC(═
O)R, NRCO2(C1-6 aliphatic), OC(═
O)R, SO2R, S(═
O)R, SO2NR2, or NRSO2(C1-6 aliphatic);
each R3 is independently selected from R, halo, CN, OR, N(R)2, SR, C(═
O)R, CO2R, CONR2, NRC(═
O)R, NRCO2(C1-6 aliphatic), OC(═
O)R, SO2R, S(═
O)R, SO2NR2, or NRSO2(C1-6 aliphatic); and
each R is independently selected from hydrogen, a C1-8 aliphatic group, or two R on the same nitrogen are taken together with the nitrogen to form a 4-8 membered heterocyclic ring having 1-3 heteroatoms selected from nitrogen, oxygen or sulfur. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
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10. A composition comprising a compound according to claim 1 , and a pharmaceutically acceptable carrier, adjuvant or vehicle.
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11. A method of inhibiting GSK-3 or JAK kinase activity in a biological sample, comprising the step of contacting said biological sample with:
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a) a composition according to claim 10;
orb) a compound according to claim 1.
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12. A method of treating an allergic or type I hypersensitivity reaction, asthma, transplant rejection, graft versus host disease, rheumatoid arthritis, amyotrophic lateral sclerosis, multiple sclerosis, Familial amyotrophic lateral sclerosis (FALS), leukemia, or lymphoma in a patient, wherein said method comprises administering to said patient a composition according to claim 10.
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13. A method of treating diabetes or schizophrenia in a patient, wherein said method comprises administering to said patient a composition according to claim 10.
Specification