Analogs of indole-3-carbinol metabolites as chemotherapeutic...

C - Chemistry – Metallurgy – 07 – D

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C07D 487/04 (2006.01) A61K 31/404 (2006.01) A61P 35/00 (2006.01) C07D 209/08 (2006.01) C07D 209/42 (2006.01)

Patent

CA 2496203

Novel compounds useful as chemotherapeutic and chemopreventive agents are provided. The compounds are analogs of indole-3-carbinol metabolites wherein the structures and substituents of the compounds are selected to enhance the compounds~ overall efficacy, particularly with respect to therapeutic activity, oral bioavailability, long-term safety, patient tolerability, and therapeutic window. The compounds are useful not only in treatment of cancer but also in prevention of cancer. One preferred class of the novel compounds have the structure of formula (I), wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and R12 are defined herein. Pharmaceutical compositions are provided as well, as are methods of synthesis and use.

L'invention concerne de nouveaux composés utilisés comme agents chimiothérapeutiques et chimiopréventifs. Ces composés sont des analogues de métabolites d'indole-3-carbinol dans lesquels les structures et les substituants des composés sont sélectionnés afin de renforcer l'efficacité générale des composés, notamment en ce qui concerne l'activité thérapeutique, la biodisponibilité orale, la sécurité à long terme, la tolérance du patient et la fenêtre thérapeutique. Ces composés conviennent non seulement au traitement mais également à la prévention du cancer. Une classe préférée des nouveaux composés présente la structure représentée par la formule (I), dans laquelle R?1¿, R?2¿, R?3¿, R?4¿, R?5¿, R?6¿, R?7¿, R?8¿, R?9¿, R?10¿, R?11¿ et R?12¿ sont définis dans le descriptif. L'invention concerne également des compositions pharmaceutiques ainsi que des méthodes de synthèse et d'utilisation des composés selon l'invention.

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