| 摘要 |
This invention provides a family of compounds that inhibit Class II fructose 1,6-bisphosphate aldolase (FBA), which is implicated in the pathogenic activity of a broad range of bacterial and parasitic agents. The compounds were identified by empirical testing, and provide a basis for further derivatization and optimization of 8-hydroxyquinoline-2-carboxylic acid and related compounds. Crystal structure shows that the compounds don't bind directly to the catalytic site of the enzyme, and so are not defined simply as substrate analogs. Instead, they create a pocket by induced fit, resulting a powerful and specific inhibitory effect on FBA activity. |
| 主权项 |
1. A compound according to Formula (I) wherein
R7=H, alkyl, alkenyl, alkynyl, F, Cl, Br, CF3, or OHR6=FR5=H, alkyl, alkenyl, alkynyl, F, Cl, Br, CF3, or OHAH4=H, alkyl, alkenyl, alkynyl, aryl, F, Cl, Br, CF3, or OHAH3=H, alkyl, alkenyl, alkynyl, aryl, F, Cl, Br, CF3, or OHZ2=CO2H, CO2R, CONH2, CONHR, aryl, or heteroaryl, wherein the compound is one of the following compounds:
6-fluoro-8-hydroxyquinoline-2-carboxylic acid,5,6,7-trifluoro-8-hydroxyquinoline-2-carboxylic acid,6-fluoro-2-(1H-imidazol-5-yl)quinolin-8-ol,2-(benzo[d]oxazol-2-yl)-6-fluoroquinolin-8-ol,2-(benzo[d]thiazol-2-yl)-6-fluoroquinolin-8-ol, and2-(1H-benzo[d]limidazol-2-yl)-6-fluoroquinolin-8-ol. |
