Lymphoid-specific tyrosine phosphatase (LYP) inhibitors
AssigneePurdue Research Foundation
InventorsZhong-Yin Zhang, Jianping Lin
Life of this patent
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Abstract
The present disclosure relates to novel lymphoid-specific tyrosine phosphatase (LYP, encoded by the PTPN22 gene) inhibitors, and to methods of making and using the novel LYP inhibitors. Thus, the compounds according to the disclosure may be used for treating diseases or disorders associated with PTPN22 genetic polymorphism, including type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosis, Graves' disease, Addison's disease, vitiligo, juvenile arthritis, Hashimoto thyroiditis, and other rarer diseases. Furthermore, these LYP inhibitors may be served for a novel class of cancer immunotherapy. The compounds can be injected or orally administered.
Claims10
A compound of formula I:
- or a stereoisomer, tautomer, pharmaceutically acceptable salt thereof, wherein:
- R1 and R2 independently represents a group selected from hydrogen, optionally substituted (C1-C4) alkyl, optionally substituted (C4-C8) cycloalkyl, optionally substituted (C2-C4) alkylcarbonyl, optionally substituted (C4-C8) cycloalkylcarbonyl, optionally substituted aryl, optionally substituted arylcarbonyl, optionally substituted heterocyclyl, wherein the heterocyclyl ring is 5-7 membered ring containing 1 to 4 heteroatoms selected from O, S, and N, optionally substituted heterocyclycarbonyl, optionally substituted (C1-C4) alkyl-SO2-, optionally substituted aryl-SO2-;
- wherein the said groups are substituted by hydrogen, halogen, hydroxy, amino, nitro, CF3, cyano, (C1-C4) alkyl, (C1-C4) alkoxy, or (C1-C4) alkyl-amino;
- R3 represents a group selected from H, optionally substituted (C1-C4) alkyl, optionally substituted (C1-C4) alkenyl, optionally substituted (C1-C4) alkynyl, optionally substituted (C4-C8) cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocyclyl, wherein the heteroaryl and heterocyclyl are 5-7 membered rings with 0-3 sites of unsaturation containing 1 to 4 heteroatoms selected from O, S, and N and, wherein the said groups are substituted by hydrogen, halogen, hydroxy, amino, nitro, CF3, cyano, C1-C4 alkyl, C1-C4 alkoxy, or C1-C4 alkyl-amino;
- R4 and R6 independently represents a group selected from hydrogen, optionally substituted (C1-C4) alkyl, optionally substituted (C4-C8) cycloalkyl, optionally substituted aryl or optionally substituted heteroaryl, wherein the heteroaryl is 5-7 membered ring containing 1 to 4 heteroatoms selected from O, S, and N and, wherein the said groups are substituted by hydrogen, halogen, hydroxy, amino, nitro, CF3, cyano, C1-C4 alkyl, C1-C4 alkoxy, or C1-C4 alkyl-amino;
- (R5)n represents a group selected from —H, —F, —Cl, —Br, —I, —CFH2, —CF2H, —CF3, —CN, —OH, —NO2, —NH2, —SO2CH3, SO2NH2, —SO2NHCH3, —CO2-(C1-C4) alkyl, NH(C1-C4) (alkyl) or N(C1-C4)(alkyl)2, (C1-C4) alkyl, (C1-C4) alkenyl, (C1-C4) alkoxy, (C4-C8) cycloalkyl;
- wherein n is 1 or 2;
- X is O or H, wherein —C═X— is —CH2—when X is H;
- and
- Y is C—R5 or N, wherein R5 is as defined above.
Dependencies are inferred from the claim text.