2-amino-o4-substituted pteridines and their use as...

C - Chemistry – Metallurgy – 07 – D

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C07D 475/04 (2006.01) A61K 31/519 (2006.01) A61P 35/00 (2006.01)

Patent

CA 2552826

Disclosed are pteridine derivatives of formula (I): (I), wherein, for example, R1 and R2 are hydrogen, C1-C6 alkyl, carboxyl, formyl, C1-C6 hydroxyalkyl, C1- C6 carboxyalkyl, C1-C6 formyl alkyl, C1-C6 alkoxy, acyloxy, acyloxyalkyl wherein the alkyl is C1-C6, halogen, or hydroxy, or a group of formula II: (II); and R3 is (a) phenyl or (b) a cyclic group having at least one 5 or 6- membered heterocyclic ring, optionally with a carbocyclic or heterocyclic ring fused thereto, wherein each heterocyclic ring has at least one hetero atom chosen from O, N, or S; or (c) a phenyl group or a cyclic group, the cyclic group optionally with a carbocyclic or heterocyclic ring fused thereto, which is substituted with 1 to 5 substituents. Disclosed also are pharmaceutical compositions, a method of enhancing the chemotherapeutic effectiveness of cancer treatment agents, a method of deactivating the O6-alkylguanine-DNA alkyltransferase enzyme, and a method of inhibiting the reaction of O6- alkylguanine-DNA alkyltransferase enzyme with an alkylated DNA.

Des dérivés de ptéridine de formule (I), dans laquelle, R¿1? et R¿2? désignent, par exemple, hydrogène, alkyle C¿1?-C¿6?, carboxyle, formyle, hydroxyalkyle C¿1?-C¿6?, carboxylalkyle C¿1?-C¿6?, formylalkyle C¿1?-C¿6?, alcoxy C¿1?-C¿6?, acyloxy, acyloxyalkyle, l'alkyle désignant C¿1?-C¿6?, halogène ou hydroxy, ou un groupe de formule II, et R¿3? désigne (a) phényle ou (b) un groupe cyclique ayant au moins un cycle hétérocyclique à 5 ou 6 membres, éventuellement avec un cycle carbocyclique ou hétérocyclique fusionné, chaque cycle hétérocyclique présentant au moins un hétéroatome sélectionné dans O, N, ou S; ou (c) un groupe phényle ou un groupe cyclique, le groupe cyclique contenant éventuellement un cycle carbocyclique ou hétérocyclique fusionné substitué avec 1 à 5 substituants. Des compositions pharmaceutiques, un procédé d'amélioration de l'efficacité chimiothérapeutique des agents de traitement du cancer, un procédé de désactivation de O?6¿-alkylguanine-ADN alkyltransférase et un procédé d'inhibition de la réaction de l'enzyme O?6¿-alkylguanine-ADN alkyltransférase avec un ADN alkylé.

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