PYRIMIDO[5,4-d]PYRIMIDINE DERIVATIVES AS ENT INHIBITORS FOR THE TREATMENT OF CANCERS, AND COMBINATION THEREOF WITH ADENOSINE RECEPTOR ANTAGONISTS

A compound of formula I:

• or a pharmaceutically acceptable salt or solvate thereof, wherein
• R1a and R1b are each independently selected from:
• (i) hydrogen, (ii) alkyl optionally substituted with one or more of hydroxy, halo, oxo, amino, —NHS(O)2NR52, and alkylsulfonyl, (iii) arylalkyl wherein the aryl part of the arylalkyl is substituted by one or more alkyl, haloalkyl, halogen, alkoxy or —CO2H group, (iv) heteroarylalkyl, (v) heterocyclylalkyl wherein the heterocyclyl part of the heterocyclylalkyl is optionally substituted by one or more alkyl group, (vi) aminocarbonylalkyl, (vii) alkylcarbonylaminoalkyl, (viii) alkyloxyalkyl, (ix) alkylcarbonyloxyalkyl and (x) heterocyclylalkyloxyalkyl;
• with the condition that R1a and R1b are not both hydrogen;
• or R1a and R1b are linked together and form with the nitrogen atom to which they are attached a heterocycle selected from piperidine and piperazine, wherein the heterocycle is optionally substituted with one or more substituent selected from alkyl, alkylcarbonyl, alkyloxycarbonyl, alkylsulfonyl, halo, hydroxy, optionally substituted heteroaryl, and oxo;
• or the heterocycle is fused with a group selected from aryl and heteroaryl, wherein the aryl or heteroaryl group is optionally substituted with alkyl or alkoxy;
• R2 represents —NR2aR2b or —OR2c;
• wherein
• R2a and R2b are each independently chosen from:
• (i) hydrogen, (ii) alkyl, (iii) alkyloxyalkyl, (iv) alkylsulfonylaminoalkyl, (v) arylalkyl wherein the aryl part of the arylalkyl is optionally substituted by one or more of alkoxy, alkylsulfonyl, aminosulfonyl, aminocarbonyl, cyano, halo, haloalkyloxy, optionally substituted heteroaryl, sulfoxide and sulfonylamine groups, (vi) aryloxyalkyl, (vii) cyanoalkyl, (viii) cycloalkyl, (ix) heteroarylalkyl wherein the heteroaryl part of the heteroarylalkyl is optionally substituted by one or more of alkyl, halo, haloalkyl and NH2 groups, (x) heterocyclylalkyl and (xi) hydroxyalkyl;
• or R2a and R2b are linked together and form with the nitrogen atom to which they are attached a heterocycle, wherein the heterocycle is optionally substituted with one or more substituent selected from alkoxy, alkyl, alkylcarbonyl, alkylcarbonylamine, alkyloxyalkyl, alkyloxyalkyloxy, alkyloxycarbonyl, alkylsulfonyl, aminocarbonyl, cycloalkyl, cyano, halo, haloalkyl, heteroaryl (optionally substituted by one or more of alkyl, cyano and NH2 groups), hydroxy, hydroxyalkyl and oxo;
• or two substituents present on a same carbon atom of the heterocycle are linked together and form a spiro heterocycle;
• or the heterocycle is fused with a group selected from aryl and heteroaryl, wherein the aryl or heteroaryl group is optionally substituted with alkyl or alkoxy;
• and
• R2c represents is selected from (i) arylalkyl wherein the aryl part of the arylalkyl is optionally substituted by one or more of alkoxy, cyano and halo groups, and (ii) heteroarylalkyl wherein the heteroaryl part of the heteroarylalkyl is optionally substituted by one or more of alkyl and cyano groups;
• R3a and R3b are each independently alkyl or alkylcarbonyl;
• or R3a is hydrogen and R3b is C1-C3 alkyl;
• R4a and R4b are linked together and form with the nitrogen atom to which they are attached a heterocycle, wherein the heterocycle optionally comprises one further heteroatom selected from N, S and O;
• and wherein the heterocycle is optionally substituted with one or more substituent selected from alkoxy, alkyl, haloalkyl, alkyloxycarbonyl, cycloalkyl, halo, heteroaryl optionally substituted by one or more alkyl group, hydroxyl, and oxo;
• or the heterocycle is fused with a group selected from aryl and heteroaryl, wherein the aryl or heteroaryl group is optionally substituted with alkyl, amine, cyano, or alkoxy;
• with the condition that when R4a and R4b form a piperidine or a morpholine, then the piperidine or morpholine is substituted by at least one of the listed substituents;
• and
• each R5 is independently selected from hydrogen and optionally substituted C1-C6 alkyl.