(3-((Quinazolin-4-yl) amino)-1h-pyrazol-1-yl)acetamide derivatives and related compounds as aurora kinase inhibitors for the treatment of proliferative diseases such as cancer

A compound of formula (I)

• or a salt, ester or prodrug thereof;
• where:
• X is O or NR6;
• R6 is hydrogen or C1-4alkyl;
• R1 is hydrogen, halo, or —X1R11;
• X1 is a direct bond, —O—, —NH— or —N(C1-6alkyl)-;
• R11 is hydrogen, heterocyclyl or a group selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl,
• C3-6cycloalkyl and C3-6cycloalkenyl which group is optionally substituted by heterocyclyl, halo, hydroxy, C1-4alkoxy or —NR9R10;
• R2 is hydrogen, halo, nitro, cyano or —X2R12;
• X2 is a direct bond, —O—, —NH— or —N(C1-6alkyl)-;
• R12 is hydrogen, heterocyclyl or a group selected from aryl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl,
• C3-6cycloalkyl and C3-6cycloalkenyl which group is optionally substituted by aryl, heterocyclyl, halo, hydroxy or —NR15R16;
• R3 is hydrogen, halo or —X3R13;
• X3 is a direct bond, —CH2═CH2—, —O—, —NH— or —N(C1-6alkyl)-;
• R13 is hydrogen, heterocyclyl or a group selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl,
• C3-6cycloalkyl and C3-6cycloalkenyl which group is optionally substituted by —NR7R8, heterocyclyl, halo, hydroxy or C1-4alkoxy;
• R7 and R8 are independently selected from hydrogen, heterocyclyl, C1-6alkyl, hydroxyC1-6alkyl, C1-3alkoxyC1-6alkyl, C3-6cycloalkyl, C3-6cycloalkylC1-3alkyl, hydroxyC3-6cycloalkyl, hydroxyC1-4alkylC3-6cycloalkyl, hydroxyC3-6cycloalkylC1-3alkyl, C1-3alkoxyC3-6cycloalkyl, C1-3alkoxyC3-6cycloalkylC1-3alkyl, haloC1-6alkyl, haloC3-6cycloalkyl, haloC3-6cycloalkylC1-3alkyl, C2-6alkenyl, C2-6alkynyl, cyanoC1-4alkyl, aminoC1-6alkyl, C1-3alkylaminoC1-6alkyl and bis(C1-3alkyl)aminoC1-6alkyl;
• or R7 and R8 together with the nitrogen to which they are attached form a heterocyclic ring which ring comprises 4 to 7 ring atoms of which one is nitrogen and of which another is optionally selected from N, NH, O, S, SO and SO2, and which ring is optionally substituted on carbon or nitrogen by 1 or 2 groups independently selected from C1-4alkyl, hydroxy, C1-4alkoxy, hydroxyC1-4alkyl, hydroxyC1-4alkoxyC1-4alkyl and C1-4alkoxyC1-4alkoxy, and where a ring —CH2— is optionally replaced with —C(O)—;
• R4 is selected from hydrogen, halo or —X4R14;
• X4 is a direct bond, —O—, —NH— or —N(C1-6alkyl)-;
• R14 is selected from hydrogen, C1-6alkyl, C2-6alkenyl and C2-6alkynyl;
• R5 is aryl or heteroaryl optionally substituted by 1, 2 or 3 substituents independently selected from halo, hydroxy, cyano, nitro, amino, C1-4alkylamino, bis(C1-4alkyl)amino, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C(O)NHR17, NHC(O)R18 and S(O)pR19 where p is 0, 1 or 2;
• R9, R10, R15 and R16 are independently selected from hydrogen, C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkylC1-3alkyl, hydroxyC1-6alkyl, haloC1-6alkyl, aminoC1-6alkyl, C1-6alkylaminoC1-6alkyl and bis(C1-6alkyl)aminoC1-6alkyl;
• R17, R18 and R19 are independently selected from hydrogen, C1-4alkyl, C3-6cycloalkyl, C2-4alkenyl and C2-4alkynyl.