PYRIMIDINE DERIVATIVES AND GUANINE DERIVATIVES, AND THEIR USE IN TREATING TUMOUR CELLS

The invention provides compounds exhibiting the ability to deplete O6- alkylguanine-DNA alkyltransferase (ATase) activity in tumour cells. The compounds include certain pyrimidine derivatives of formula (II), wherein R is (i) a cyclic group having at least one 5- or 6-membered heterocyclic ring, opt...

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Hauptverfasser: ELDER, RHODERICK HUGH, CAROLA, CHRISTOPHE, MCMURRY, THOMAS BRIAN HAMILTON, MIDDLETON, MARK ROSS, MCCORMICK, JOAN ELIZABETH, MCELHINNEY, ROBERT STANLEY, WILLINGTON, MARK ANDREW, WATSON, AMANDA JEAN, MARGISON, GEOFFREY PAUL, DONNELLY, DOROTHY JOSEPHINE, KELLY, JANE, MURRAY, PAUL, RAFFERTY, JOSEPH ANTHONY
Format: Patent
Sprache:eng ; fre
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Zusammenfassung:The invention provides compounds exhibiting the ability to deplete O6- alkylguanine-DNA alkyltransferase (ATase) activity in tumour cells. The compounds include certain pyrimidine derivatives of formula (II), wherein 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 hetero atom chosen from O, N, or S, or a substituted derivative thereof; or (ii) phenyl or a substituted derivative thereof, R2 is selected from H, C1-C5 alkyl, halogen or NH2, R4 and R5 which are the same or differe nt are selected from H, NH-Y' or NO n wherein Y' is H, ribosyl, deoxyribosyl, arabinosyl, (a) wherein X is O or S, R" is alkyl and R"' is H or alkyl, or substituted derivatives thereof, n = 1 or 2 or R4 and R5 together with the pyrimidine ring form a 5-or 6-membered ring structure containing one or more hetero atoms, and pharmaceutically acceptable salts thereof. They include certain guanine derivatives of formula (XIII), wherein R6 is as defined at (i) for R above and Y' is as defined above.