| 摘要 |
The present invention relates to compounds which modulate (e.g., inhibit) the activity of beta-hydroxylase (e.g., Asparatyl (asparaginyl) β-hydroxylase (ASPH)), including novel 2-aryl-5-amino-3(2H)-furanone and 2-heteroaryl-5-amino-3(2H)-furanone compounds, pharmaceutical compositions thereof, methods for their synthesis, and methods of using these compounds to modulate the activity of ASPH in an a cell-free sample, a cell-based assay, and in a subject. Other aspects of the invention relate to use of the compounds disclosed herein to ameliorate or treat cell proliferation disorders. |
| 主权项 |
1. An asparatyl (asparaginyl) beta-hydroxylase (ASPH) inhibitory compound for use in a method of reducing proliferation, migration, invasion, or metastasis of a tumor cell in the treatment of cell proliferative disorder, comprising contacting said tumor cell with the ASPH inhibitory compound, wherein the ASPH inhibitory compound is of Formula Ia or Ib: or a salt, ester, metabolite, prodrug, or solvate thereof, wherein Ar1 is substituted or unsubstituted C6-C20 aryl or 5 to 20-membered heteroaryl; X is C(O), C(S), or S(O)2; W1 is a single bond, O, CR50R51, or NR52 when X is CO and W1 is a single bond, CR50R51, or NR52 when X is SO2; and each of R50, R51, R52, and R53 independently is selected from the group consisting of hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted C7-C26 arylalkyl, substituted or unsubstituted 5 to 20-membered heteroaryl, and substituted or unsubstituted 6-26 membered heteroarylalkyl. |
