O6-alkylguanine-dna alkyltransferase inactivators

Details O6-alkylguanine-dna alkyltransferase inactivators O6-alkylguanine-dna alkyltransferase inactivators

C - Chemistry, Metallurgy

07

D

C07D 473/18 (2006.01) A61K 31/522 (2006.01) A61P 35/00 (2006.01) C07H 15/26 (2006.01)

Patent

CA 2679103

Disclosed are inactivators of O6-alkylguanine-DNA alkyltransferase (AGT) having the formula:(I) wherein R, R1 and R3 are as described herein. The inactivators are highly water soluble. Also disclosed are pharmaceutical compositions comprising an inactivator and a pharmaceutically acceptable carrier, and a method of use of the inactivator in enhancing the chemotherapeutic treatment of tumor cells in a mammal, e.g., a human, with an antineoplastic alkylating agent that causes cytotoxic lesions at the O6-position of guanine.

L'invention concerne des inactivateurs de O6-alkylguanine-ADN alkyltransférase (AGT) de formule : (I) dans laquelle R, R1 et R3 sont tels que décrits dans le présent document. Les inactivateurs sont hautement solubles dans l'eau. L'invention concerne également des compositions pharmaceutiques comprenant un inactivateur et un véhicule pharmaceutiquement acceptable, ainsi qu'un procédé d'utilisation de l'inactivateur pour optimiser le traitement chimiothérapeutique de cellules tumorales chez un mammifère, p. ex. un homme, avec un agent alkylant antinéoplastique qui cause des lésions cytotoxiques au niveau de la position O6 de la guanine.

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