Loading patent…
AssigneeThe United States of America as represented by the Department of Health and Human Services
InventorsRobert C. Moschel, M. Eileen Dolan, Anthony E. Pegg
Estimating the term…
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.
A pharmaceutical composition which comprises compounds of the formula, ##STR7## wherein Z is ##STR8## and R is a benzyl group or a substituted benzyl group substituted at the ortho, meta or para position with a substituent selected from the group consisting of halogen, nitro, phenyl, alkyl of 1-4 carbon atoms, alkoxy of 1-4 carbon atoms, alkenyl of up to 4 carbon atoms, alkynyl of up to 4 carbon atoms, amino, monoalkylamino, dialkylamino, trifluoromethyl, hydroxy, hydroxymethyl, and SO.sub.n R.sub.1 wherein n is 0, 1, 2 or 3 and R.sub.1 is hydrogen, alkyl of 1-4 carbon atoms, or phenyl;
The composition of claim , further comprising an anti-neoplastic alkylating agent.
Dependencies are inferred from the claim text.