| 摘要 |
Iron overload is associated with pathological conditions such as oxidative stress, transfusional iron overload, thalassemia, primary hemochromatosis, secondary hemochromatosis, diabetes, liver disease, heart disease, cancer, radiation injury, neurological or neurodegenerative disorder, Friedreich's ataxia (FRDA), macular degeneration, closed head injury, irritable bowel disease, and reperfusion injury. The present invention provides methods and pharmaceutical compositions using desferrithiocin analogs of Formulae (A) and (J) for treating and/or preventing these pathological conditions, metal (e.g., iron, aluminum, a lanthanide, or an actinide (e.g., uranium)) overload conditions, and infectious diseases (e.g., malaria). |
| 主权项 |
1. A compound of Formula (A):or a pharmaceutically acceptable salt thereof, wherein:
R1 is hydrogen, alkyl, acyl, or an oxygen protecting group; R2 is hydrogen, alkyl, acyl, an oxygen protecting group, —[(CH2)n—O]x—[(CH2)n—O]y—R″, or —[(CH2)n—O]x—[(CH2)n—O]y—(CH2)n—NR10—C(═O)O—R″; each occurrence of R3 is independently alkyl, arylalkyl, or —OR8; R4, R5, and R6 are each independently hydrogen or alkyl; R7 is —OR9 or —SR9; R8 is hydrogen, alkyl, acyl, or an oxygen protecting group; R9 is hydrogen, alkyl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; R10 is hydrogen, alkyl, acyl, or a nitrogen protecting group; R′ is hydrogen or an oxygen protecting group; R″ is hydrogen, alkyl, acyl, or an oxygen protecting group; each occurrence of n is independently an integer from 1 to 8, inclusive; k is an integer from 0 to 2, inclusive; x is an integer from 1 to 8, inclusive; and y is an integer from 0 to 8, inclusive. |
