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What is needed are additional reagents, including additional agents for blocking the JAK-2/STAT-5 signaling pathway, for preventing or inhibiting T-cell mediated immune responses, and for treating or ameliorating T-cell mediated immune responses. The present invention satisfies this need and provides related advantages as well.
The present invention provides a group of compounds that are inhibitors of the cytokine receptor-associated Janus kinase (JAK). The compounds of the invention are useful as JAK kinase inhibitors for use in therapeutic and other applications, especially where inhibition of the JAK-2/STAT-5 signaling pathway is indicated. Examples of therapeutic applications include use of the compounds to modulate cytokine function and modulate the immune response.
In one aspect, the invention provides compounds having the formula:
or a stereoisomer, tautomer, pharmaceutically acceptable salt, or prodrug thereof, wherein:
X is CH or N;
Y is a covalent bond, O, S, SO, SO2, or NH;
R3 is H, OH, or C1-C6 alkyl;
R4 is H, OH, NH2, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C2-C6 alkyl substituted with 0-3 R12, C2-C6 alkenyl substituted with 0-3 R12, C2-C6 alkynyl substituted with 0-3 R12, C1-C6 alkyl substituted with 0-3 R12, C2-C6 alkenyl substituted with 0-3 R12, C2-C6 alkynyl substituted with 0-3 R12, C3-C7 cycloalkyl, heterocycle, aryl, or heteroaryl;
R5 is H, OH, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-
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