Porphyrin compounds as telomerase inhibitors

A - Human Necessities – 61 – K

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A61K 31/44 (2006.01) C07D 487/22 (2006.01) C07D 519/00 (2006.01)

Patent

CA 2283057

The present invention has identified compounds with extended aromatic chromophores that bind the G-quadruplex formed by the folding of single- stranded human telomeric DNA. These compounds have been shown to be effective telomerase inhibitors and are contemplated to be useful in developing cancer treatments. A model of cationic porphyrin interaction with quadruplex DNA by intercalation has been established and in combination with structure activity relations has provided novel porphyrin compounds that exhibit discrimination between binding duplex and quadruplex DNA and show improved activity against telomerase.

La présente invention concerne des composés dotés de chromophores aromatiques allongés, qui se lient au quadruplex G formé par le repliement d'ADN télomérique humain simple brin. Ces composés constituent des inhibiteurs efficaces de télomérase, et sont utiles dans des traitements de cancer en développement. Un modèle d'interaction de porphyrine cationique avec de l'ADN quadruplex par insertion a été établi, et, en combinaison avec des rapports structure-activité, a permis d'obtenir de nouveaux composés de porphyrine présentant une capacité de distinction entre une liaison avec des ADN duplex et des AND quadruplex, ainsi qu'une activité améliorée contre la télomérase.

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