Substituted 06-benzylguanines and 6(4)-benzyloxypyrimidines

US5525606A · kind A · utility

Assignees

• The United States of America, as represented by the Department of Health and Human Services · US
• Arch Development Corporation · US
• The Penn State Research Foundation · 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: Aug 1, 1994
• Grant date: Jun 11, 1996
• Expiry date: Aug 1, 2014

Classification

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

Abstract

The present invention provides 8-substituted O.sup.6 -benzylguanines of the formula ##STR1## wherein R.sub.1, R.sub.2, and R.sub.3 are as defined in the specification, and 4(6)-substituted 2-amino-5-nitro-6(4)-benzyloxypyrimidine, and 4(6)-substituted 2-amino-5-nitroso-6(4)-benzyloxypyrimidine derivatives which have been found to be effective AGT inactivators, as well as pharmaceutical compositions comprising such derivatives along with a pharmaceutically acceptable carrier. The present invention further provides 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, by administering to a mammal an effective amount of one of the aforesaid derivatives, 2,4-diamino-6-benzyloxy-s-triazine, 5-substituted 2,4-diamino-6-benzyloxypyrimidines, or 8-aza-O.sup.6 -benzylguanine, and administering to the mammal an effective amount of an antineoplastic alkylating agent which causes cytotoxic lesions at the O.sup.6 -position of guanine.