LDHA activity inhibitors

A compound of formula (I), a stereoisomer, tautomer, pharmaceutically acceptable salt or prodrug thereof:

• wherein:
• A1 is —O—, —CH2—, or —S—;
• A2 is NR, wherein R is either H or C1-3 alkyl;
• A3 is N or CR5;
• A4 is N or CR6;
• A5 is N or CR7;
• A6 is N or CR8;
• R1, R2 and R3 are independently selected from H and halogen;
• R4 is selected from:
• H;
• halogen;
• a 4- to 6-membered heterocyclic ring optionally substituted by one or more substituents selected from the group consisting of halogen, hydroxy, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 hydroxyalkyl, —CO2H, —C(O)—O—C1-6 alkyl, —C(O)—C1-6 alkyl, amino, cyano, and nitro groups;
• and
• OR9 in which R9 is a 4- to 6-membered heterocyclic ring optionally substituted by one or more substituents selected from the group consisting of halogen, hydroxy, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 hydroxyalkyl, —CO2H, —C(O)—O—C1-6 alkyl, —C(O)—C1-6 alkyl, amino, cyano, and nitro groups;
• and
• OR10 in which R10 is a C3-8 cycloalkyl group;
• R5 is selected from:
• H;
• hydroxy;
• C1-6 alkyl;
• and
• C1-6 alkoxy;
• R6 is selected from:
• H;
• halogen;
• C1-6 alkyl optionally substituted by one or more substituents selected from the group consisting of halogen, hydroxy, C1-6 alkoxy, C1-6 haloalkyl, C1-6 hydroxyalkyl, amino, cyano, and nitro groups;
• C1-6 alkoxy optionally substituted by one or more substituents selected from the group consisting of halogen, hydroxy, C1-6 alkoxy, C1-6 haloalkyl, C1-6 hydroxyalkyl, amino, cyano, nitro, and C3-8 cycloalkyl groups;
• a 4- to 6-membered heterocyclic ring optionally substituted by one or more substituents selected from the group consisting of halogen, hydroxy, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 hydroxyalkyl, —CO2H,
• C(O)—O—C1-6 alkyl, —C(O)—C1-6 alkyl, amino, cyano, and nitro groups;
• and
• OR11 in which R11 is a 4- to 6-membered heterocyclic ring optionally substituted by one or more substituents selected from the group consisting of halogen, hydroxy, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 hydroxyalkyl, —CO2H, —C(O)—O—C1-6 alkyl, —C(O)—C1-6 alkyl, amino, cyano, and nitro groups;
• and
• OR12 in which R12 is a C3-8 cycloalkyl group;
• R7 and R8 are independently selected from:
• H;
• hydroxy;
• C1-6 alkyl;
• and
• C1-6 alkoxy;
• with the provisos that:
• A3 and A4 are not both N at the same time;
• A5 and A6 are not both N at the same time;
• and
• at least one of R1, R2 and R3 is halogen.