| abstract |
The invention provides compounds exhibiting the ability to deplete <u>O</u><6>-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, R<2> is selected from H, C<1>-C<5> alkyl, halogen or NH<2>, R<4> and R<5> which are the same or different are selected from H, NH-Y' or NOn 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 R<4> and R<5> 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 R<6> is as defined at (i) for R above and Y' is as defined above. |