Compounds capable of cleaving double-stranded dna and method...

C - Chemistry – Metallurgy – 07 – D

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C07D 487/04 (2006.01) A61K 31/407 (2006.01) A61K 31/4178 (2006.01) A61P 35/00 (2006.01) A61P 43/00 (2006.01)

Patent

CA 2328903

Novel chemical species capable of simultaneously alkylating double-stranded DNA and cleaving the same; methods for alkylating and cleaving DNA by using these species; and anticancer agents with the use of these compounds. Compounds represented by the following general formula (I) which are capable of simultaneously alkylating double- stranded DNA and cleaving the same; a method for alkylating DNA and a method for cleaving double stranded DNA by using these compounds; and medicinal compositions with the use of these compounds: B-L-A (I) wherein B represents a chemical structure capable of recognizing the base sequence of DNA, for example, optionally substituted pyrrole-imidazole polyamide; A represents a chemical structure capable of binding to one base of DNA, for example, the alkylation moiety of duocarmycin A; and L represents a linker capable of binding the chemical structures A and B, for example, vinyl.

La présente invention concerne, d'une part de nouvelles espèces chimiques capables, simultanément, d'alkyler la double hélice d'ADN et de la cliver, d'autre part des procédés d'alkylation et de clivage de l'ADN au moyen de ces espèces, et aussi des agents anticancéreux ayant recours à ces composés. L'invention concerne également, d'une part des composés représentés par la formule générale (I) et qui sont capables, simultanément, d'alkyler la double hélice d'ADN et de la cliver, d'autre part des procédés d'alkylation et de clivage de la double hélice d'ADN au moyen de ces composés, et enfin des compositions médicinales utilisant ces composés: B-L-A (I). Dans cette formule, B représente une structure chimique capable de reconnaître la séquence de base de l'ADN, par exemple, le pyrrole-imidazole polyamide éventuellement substitué; A représente une structure chimique capable de se lier à une base de l'ADN, par exemple, le fragment d'alkylation de la duocarmycine A; enfin, L représente un lien capable de se lier aux structures chimiques A et B, par exemple, le vinyle.

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