O.sup.6 -substituted guanine compounds and methods for depleting

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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544276, 514587, 514615, 514400, A61K 3132, C07D47318

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active

053589521

ABSTRACT:
O.sup.6 -substituted guanine compounds of the formula ##STR1## wherein R is a benzyl group or a substituted benzyl group, cause a depletion of O.sup.6 -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.

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Moschel et al., "Substituent-Induced effects on the stability of benzylated guanosines . . . ," J. Org. Chem., 1984, 49, pp. 363-372.
Robins et al., "Purine Nucleosides . . . ," J. Org. Chem., vol. 34, No. 7, Jul. 1969, pp. 2160-2163.
Frihart et al., J. Am. Chem. Soc., 95, pp. 7174-7175 (1973).

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