Substituted O6-benzylguanines

US6333331A · 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 15, 1999
• Grant date: Dec 25, 2001
• Expiry date: Jun 15, 2019

Classification

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

Abstract

The present invention provides AGT inactivating compounds such as substituted O.sup.6 -benzylguanines of the formula ##STR1## 7- or 9-substituted 8-aza-O.sup.6 -benzylguanines, 7,8-disubstituted O.sup.6 -benzylguanines, 7,9-disubstituted O.sup.6 -benzylguanines, 4(6)-substituted 2-amino-5-nitro-6(4)-benzyloxypyrimidines, and 4(6)-substituted 2-amino-5-nitroso-6(4)-benzyloxypyrimidines, as well as pharmaceutical compositions comprising such compounds 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 compounds, 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.