Orally effective ion chelators related to deferoxamine

C - Chemistry – Metallurgy – 07 – C

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167/255, 167/269

C07C 233/00 (2006.01) A61K 31/16 (2006.01) A61K 31/295 (2006.01)

Patent

CA 1247120

ABSTRACT OF THE DISCLOSURE Compounds are described of the general formula: Image wherein: R1 is acyl of the formula -C(=O)-R5; R2, R3, R4, R6, R7 and R8 are each selected from the group consisting of hydrogen and acyl of the formula: -C(=O)-R5 wherein R5 is selected from the group consisting of alkyls, substituted alkyls, alkenyls, substituted alkenyls, cycloalkyls, substituted cycloalkyls, arylalkylenes, substituted arylalkylenes, alkylenecycloalkyls, alkylene substituted cycloalkyls, alkynyls, substituted alkynyls, aryls and substituted aryls, wherein R2, R3 and R4 are selected such that at least one of R2, R3 and R4 is an acyl. When R2, R3 and R4 include one or more acyls that are not identical to the acyl of R1, these compounds of formula I are novel compounds. The invention also includes processes to produce the compounds of formula I. Compounds of formula I complex and/or chelate tissue tri-valent ions, especially iron and aluminum (Fe+++, Al+++), when administered to a human being, and are therefore useful in therapy in the treatment of diseases in which tissue ion levels in the body have increased or toxic levels. These iron- related diseases include, for example, thalassemia major, sideroachrestic anemic, Blackfan-Diamond anemia, aplastic anemia, sickle cell anemia, hemolytic anemias and hemosiderosis brought about by multiple blood transfusions including treatment for the anemia accompanying conditions requiring kidney dialysis. Aluminum-related diseases or conditions include Alzheimer's disease, senile dementia and dialysis encephalopathy.

472842

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