O6-benzylated guanine, guanosine and 2'- deoxyguanosine...

C - Chemistry – Metallurgy – 07 – H

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C07H 19/16 (2006.01) A61K 31/52 (2006.01) A61K 31/70 (2006.01) C07D 473/18 (2006.01)

Patent

CA 2078129

O6-Benzylated guanine guanosine and 2'-deoxyguanosine compounds of formula (1), wherein Z is hydrogen, (.alpha.) or (.beta.), and R is a benzyl group or a substituted benzyl group. cause a depletion of O6-alkylguanine-DNA alkyltransferase (AGT) activity in mammalian cells. These compounds may be administered to a host so as to reduce AGT levels in tumor cells of the host in order to increase host responsiveness to anti-neoplastic alkylating agents. including chloroethylating agents, such as chloroethylnitrosoureas, for chemotherapeutic treatment of a number of neoplasms.

Composés de O6-guanine benzylée, guanosine et de 2'-désoxyguanosine correspondant à la formule (I), où Z représente hydrogène, (alpha) ou (beta), et R représente un groupe benzyle ou un groupe benzyle substitué, provoquant un appauvrissement de l'activité de l'O6-alkylguanine-ADN alkyltransférase (AGT) dans les cellules des mammifères. Ces composés peuvent être administrés à un hôte pour réduire les taux d'AGT dans les cellules tumorales de l'hôte afin d'augmenter la sensibilité de l'hôte aux agents d'alkylation antinéoplastiques, comprenant des agents de chloroéthylène, tels que des chloroéthylnitrosourées, pour traiter par chimiothérapie un certain nombre de néoplasmes.

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