Substituted benzyloxypyrimidines and their inactivation of O.sup.6 -alkylguanine-DNA alkyltransferase

US5753668A · kind A · utility

Assignees

• The United States of America, as represented by the Department of Health and Human Services · US
• The Penn State Research Foundation · US
• Arch Development Corporation · US

Inventors

• Robert C. Moschel · Frederick, US
• Anthony E. Pegg · Hershey, US
• M. Eileen Dolan · Oak Park, US
• Mi-Young Chae · Frederick, US

Key dates

• Filing date: Jun 11, 1996
• Grant date: May 19, 1998
• Expiry date: Jun 11, 2016

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D487/04
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The present invention provides certain novel nitro or nitroso substituted benzyloxy pyrimidines useful as AGT inactivators. An example of such a pyrimidine is a compound of the formula ##STR1## wherein R.sub.1, is NO.sub.2 or NO, and R.sub.2 is hydrogen, halo, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 hydroxyalkyl, thiol, C.sub.1 -C.sub.4 alkythio, trifluoromethoxy, oxymethanesulfonyl, oxytrifluoromethanesulfonyl, or C.sub.1 -C.sub.4 oxyacyl. The present invention further provides pharmaceutical compositions comprising these compounds, and a method of enhancing the chemotherapeutic treatment of tumor cells in a mammal with an antineoplastic alkylating agent which causes cytotoxic lesions at the O.sup.6 -position of guanine.