Analogs of thalidomide as potential angiogenesis inhibitors

C - Chemistry – Metallurgy – 07 – D

Patent

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C07D 403/04 (2006.01) A61K 31/402 (2006.01) A61K 31/4035 (2006.01) A61K 31/454 (2006.01) A61K 31/513 (2006.01) A61P 43/00 (2006.01) C07D 209/48 (2006.01) C07D 401/04 (2006.01)

Patent

CA 2439410

The present invention relates to composition that inhibits angiogenesis-mediated diseases in a subject when administered in an effective amount. The composition comprises one or more compounds having the following formula or pharmaceutically acceptable salts thereof: (see above formula) In the formula, R4 through R7 are fluoride or are another halogen, R4 through R7 may comprise the same or different halogens or R5 and R6 are hydrogen and R4 and R7 are methyl groups. Alternatively, there may be substitutions on the isoindole ring, e.g., R4 through R7 may comprise different groups on the isoindole ring to obtain 4-chloro; 4-nitro; 5,6-dichloro; 4-methyl; 5-methyl; 5,6- dimethyl; and 4,5,6,7-tetrachloro. Further, the isoindole ring may be replaced with succinimides or maleimides. Additionally, other halogens may be substituents at the phenyl ring.

On a isolé et identifié un certain nombre de métabolites de thalidomide possédant des propriétés anti-angiogéniques supérieures. On a également développé des analogues de thalidomide qui miment les effets des métabolites de thalidomide actifs isolés et identifiés, ainsi que des variations de ces analogues de thalidomide. Lesdits composés d'analogues de thalidomide possèdent une capacité améliorée d'inhibition d'angiogénèse indésirable sans présenter les effets indésirables de l'administration de thalidomide.

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