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1. (WO1994029312) O6-SUBSTITUTED GUANINE DERIVATIVES, A PROCESS FOR THEIR PREPARATION AND THEIR USE IN TREATING TUMOUR CELLS

Pub. No.:    WO/1994/029312    International Application No.:    PCT/IE1994/000031
Publication Date: Dec 22, 1994 International Filing Date: Jun 8, 1994
IPC: C07D 473/18
C07H 19/16
Applicants: CANCER RESEARCH CAMPAIGN TECHNOLOGY LIMITED
McMURRY, Thomas, Brian, Hamilton
McELHINNEY, Robert, Stanley
McCORMICK, Joan, Elizabeth
ELDER, Rhoderick, Hugh
KELLY, Jane
MARGISON, Geoffrey, Paul
RAFFERTY, Joseph, Anthony
WATSON, Amanda, Jean
WILLINGTON, Mark, Andrew
Inventors: McMURRY, Thomas, Brian, Hamilton
McELHINNEY, Robert, Stanley
McCORMICK, Joan, Elizabeth
ELDER, Rhoderick, Hugh
KELLY, Jane
MARGISON, Geoffrey, Paul
RAFFERTY, Joseph, Anthony
WATSON, Amanda, Jean
WILLINGTON, Mark, Andrew
Title: O6-SUBSTITUTED GUANINE DERIVATIVES, A PROCESS FOR THEIR PREPARATION AND THEIR USE IN TREATING TUMOUR CELLS
Abstract:
O^_6-hetarylalkyl- or naphthylalkylguanine derivatives of formula (I) wherein Y is H, ribosyl, deoxyribosyl, or R'XCHR'', wherein X is O or S, R'' and R''' are alkyl, or substituted derivatives thereof; R' is H, or alkyl or hydroxyalkyl; R is (i) a cyclic group having at least one 5- or 6-membered heterocyclic ring, optionally with a carbocyclic or heterocyclic ring fused thereto, the or each heterocyclic ring having at least one hereto atom chosen from O, N or S, or a substituted derivative thereof; or (ii) naphthyl or a substituted derivative thereof; and pharmaceutically acceptable salts thereof, exhibit the ability to deplete O^_6-alkylguanine-DNA alkyltransferase (ATase) activity. A process for preparation of the compounds is described. The compounds have utility in combination with alkylating agents in the chemotherapeutic treatment of tumour cells.