| 摘要 |
Provided are compositions and methods useful for modulation of signaling through the Toll-like receptors TLR7 and/or TLR8. The compositions and methods have use in treating or preventing disease, including cancer, autoimmune disease, infectious disease, inflammatory disorder, graft rejection, and graft-verses-host disease. |
| 主权项 |
1. A compound having the formula I:or a tautomer, enantiomer or salt thereof, wherein:Y is substituted aryl or substituted heteroaryl, wherein said substituted aryl or substituted heteroaryl is substituted with one or more groups independently selected from CN, OH, —C(═O)R9, halogen, and —CH═CHC(═O)R9;
R9 is selected from alkyl, OR15, and NR10R11; R15 is selected from H, alkyl, and —CH2O(alkyl), R10 and R11 are each independently alkyl, wherein said alkyl is optionally substituted with —OH or R10 and R11 together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein said heterocyclic ring is optionally substituted with one or more —OH; R2 is selected from OR14 and NR6R7; R6 and R7 are each independently selected from H, alkyl, cycloalkyl, heterocycle or benzyl, wherein said alkyl, cycloalkyl, or benzyl is optionally substituted with one or more groups independently selected from —F, —OR8, —NR12SO2R13, —C(═O)NR12R13 or R6 and R7 together with the nitrogen atom to which they are attached form a heterocyclic ring, further wherein said heterocyclic ring is optionally substituted with one or more —OH; R8 is selected from hydrogen and alkyl, and R12, R13 and R14 are each independently selected from H and alkyl, wherein said alkyl is optionally substituted with —OH; provided that a) when Y is aryl substituted withorthen R2 is not —OCH2CH3,
or b) when Y is aryl substituted with —C(═O)R9 wherein R9 is NR10R11 and R10 and R11 together with the nitrogen atom to which they are attached form an unsubstituted pyrrolidine ring, then R2 is not —OCH2CH3 or —N(propyl)2. |
