| 摘要 |
The invention provides potent inhibitors of small molecule inhibitors of Krüppel-like factor 5 (KLF5) expression. Compounds of the invention are small molecule inhibitors of KLF5 expression which can be effective delay or prevent colon cancer onset, halt growth of existing tumors, and/or decrease reoccurrence. The compounds can be effective vs. many tumor types whose progression is in part mediated by KLF5, including colorectal cancers. Lowering KLF5 levels with an inhibitor of this invention may also impact other disease states, including diabetes, obesity, lipid homeostasis, cardiovascular disease, and arthritis. |
| 主权项 |
1. A KLF5 expression-inhibitory compound of formula (I) wherein
each R is independently H or (C1-C6)alkyl;R1 is aryl, arylalkenyl, heteroaryl, or heteroarylalkenyl, wherein any aryl or heteroaryl of R1 is optionally mono- or independently multi-substituted with J;X═CHR, O, or NR2;Y═CHR or absent;R2 is H, (C1-C6)alkyl, hydroxy(C1-C6)alkyl, (C1-C6)alkylNR2, aryl, benzyl, p-hydroxybenzyl, (C1-C6)alkyl-C(═O)NR2, (C1-C6)alkyl-C(═O)OR, or heteroaryl;R3═H, (C1-C6)alkyl; (C3-C10)cycloalkyl, (C1-C6)alkylNR2, (C1-C6)alkyl(C3-C10)cycloalkyl, or (C1-C6)alkyl-(3- to 10-membered heterocyclyl);R4 is a 5-7 membered heterocyclyl comprising at least one C(═O)NR group or SO2 group, optionally further comprising an additional NR groupJ is halo, CF3, OCF3, CH3, CH2CH3, SO2R, SO2NR2, or C(═O)NR2;or a pharmaceutically acceptable salt thereof. |
