Inhibitors of MLH1 and/or PMS2 for cancer treatment

A compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, having the structural Formula (I), shown below:

• wherein
• R1 and R3 are both hydroxy;
• R2 is hydrogen or fluoro;
• R4 is selected from the group consisting of hydrogen, halogen, (1-6C)alkyl, (3-6C)cycloalkyl and (3-6C)cycloalkyl (1-2C)alkyl, wherein the said (1-6C)alkyl is optionally substituted by one or more R5a and the said (3-6C)cycloalkyl and (3-6C)cycloalkyl (1-2C)alkyl groups are optionally substituted with one or more R5b, where each R5a is independently selected from halogen or (1-4C)alkoxy and each R5b is independently selected from the group consisting of halogen, (1-4C)alkyl and (1-4C)alkoxy;
• R6 is (1-6C)alkyl, (3-8C)cycloalkyl, (3-8C)cycloalkyl (1-2C)alkyl or a 4- to 7-membered heterocyclyl ring comprising one heteroatom selected from N, O or S, or a group having a structure according to formula (A) shown below:
• wherein
• R7 is hydrogen or (1-3C)alkyl;
• n is 1 or 2;
• R8 is aryl or heteroaryl, wherein the said aryl or heteroaryl is optionally substituted with one or more R9;
• where each R9 is independently selected from the group consisting of hydroxy, cyano, halogen, (1-3C)alkyl, (1-3C)alkoxy, (2-3C) alkenyl and (2-3C) alkynyl;
• R10 is —NR11R12, wherein R11 and R12 are linked, such that, together with the nitrogen atom to which they are attached, they form a 5-7 membered monocyclic heterocyclic ring that is fused to either a 5-6 membered monocyclic heteroaromatic ring or a benzene ring, thereby forming a 8-11 membered bicyclic heteroaryl ring;
• wherein any one or more of the rings present in R10 is independently optionally substituted with one or more R13,
• each R13 is independently selected from the group consisting of halogen, cyano, oxo, epoxy and a group
• -L1-X1-Q1
• wherein:
• L1 is absent or (1-3C)alkylene;
• X1 is absent or is selected from the group consisting of —O—, —C(O)—, —C(O)—O—, —O—C(O)—, —S(O)0-2—, —C(O)—N(R14)—, —N(R14)—C(O)—, —NR14—, —N(R14)—C(O)—NR14—, —SO2N(R14)—, and —N(R14)SO2—, wherein R14 is, at each occurrence, independently selected from the group consisting of hydrogen, hydroxy, cyano, (1-4C)alkyl, (2-4C) alkenyl and (2-4C) alkynyl, wherein any (1-4C)alkyl, (2-4C) alkenyl or (2-4C) alkynyl in R14 is independently optionally substituted with one or more groups selected from the group consisting of halogen and hydroxy;
• Q1 is selected from the group consisting of hydrogen, (1-6C)alkyl, (2-6C) alkenyl, (2-6C) alkynyl, (3-8C)cycloalkyl, (3-8C)cycloalkyl (1-3C)alkyl, aryl, aryl (1-3C)alkyl, heterocyclyl, heterocyclyl (1-3C)alkyl, heteroaryl and heteroaryl (1-3C)alkyl, wherein any (1-6C)alkyl, (2-6C) alkenyl, (2-6C) alkynyl, (3-8C)cycloalkyl, (3-8C)cycloalkyl (1-3C)alkyl, aryl, aryl (1-3C)alkyl, heterocyclyl, heterocyclyl (1-3C)alkyl, heteroaryl or heteroaryl (1-3C)alkyl in Q1 is optionally substituted with one or more groups R15;
• and
• each R15 is independently selected from the group consisting of hydroxy, cyano, oxo, halogen, (1-3C)alkyl, (1-3C)alkoxy, —NR15aR15b, —C(O)—R15a, —C(O)—OR15a, —O—C(O)—R15a, —C(O)—NR15aR15b, —N(R15b)C(O)—R15a, —S(O)0-2R15a, —S(O)2NR15aR15b, and —N(R15b)—S(O)2R15a, wherein R15a and R15b are each independently hydrogen or (1-3C)alkyl, and wherein any (1-3C)alkyl moiety present in a R15a or R15b group is optionally further substituted by one or more substituents independently selected from hydroxy, cyano, halogen, —OR15c, —NR15CR15d and —C(O)—R15c, wherein R15c and R15d are both independently selected from hydrogen and (1-2C)alkyl.