Pyrimidopyrimidine compounds

Abstract

A range of dipyridamole analogues useful for inhibiting transport of nucleosides or purines across cell membranes, thereby to potentiate the activity of various cytotoxic antitumor drugs, is disclosed. These analogues comprise compounds having general structural formula (I) or pharmaceutically acceptable salts thereof; wherein R,is chloro and R,is diethanolamino, or R,and R,are identical and are selected from allyl, halo, diethanolamino, solketalo and a group having the formula: —O—R,or —NHR,, R,being selected from alkyl, hydroxyalkyl, alkoxyalkyl, dialkoxyalkyl and 2-oxo-alkyl wherein the or each alkyl and/or alkoxy moiety has less than six carbon atoms, and R,and R,are identical and are selected from piperidino, N-tetrahydroisoquinolyl, and a benzylamino group having structural formula (II) wherein R,is H, or an optionally substituted alkyl or benzyl group, and R,and R,represent H or optional substituents in the aromatic nucleus selected from halo, alkyl, alkoxy, hydroxy, trifluoromethyl, azido, cyano, nitro, carboxyl, carboxylic ester, amino or a substituted amino NR,R,where R,and R,each represent hydrogen or alkyl, subject to the provisos that (a) if R,and R,are both chloro or diethanolamino, R,and R,are not both benzylamino, i.e. R,and R,do not correspond to structure II with R,, R,and R,each being hydrogen, and (b) if R,and R,are both piperidino, R,and R,are not both chloro, diethanolamino, solketalo or (2,3-dimethoxy)propoxy