O.sup.6 -benzylated guanine, guanosine and 2'-deoxyguanosine compounds possessing O.sup.6 -alkylguanine-DNA alkyltransferase depleting activity
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United States of America Patent
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Oct 4, 1994
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app pub date -
Nov 21, 1990
filing date -
Mar 13, 1990
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Abstract
O.sup.6 -Benzylated guanine guanosine and 2'-deoxyguanosine compounds of the formula ##STR1## wherein Z is hydrogen, ##STR2## and 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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