Autotaxin inhibitors

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

• wherein:
• R1 and R2 are independently selected from H, (1-8C)alkyl, (4-7C)cycloalkyl, 4-7 membered heterocyclyl, 5-6 membered heteroaryl, —S(O)yRa or C(O)Ra, wherein Ra is selected from H, (1-4C)alkyl or (1-4C)alkoxy, y is 0, 1 or 2, and wherein any (1-8C)alkyl, (4-7C)cycloalkyl, 4-7 membered heterocyclyl or 5-6 membered heteroaryl is optionally substituted by one or more substituents selected from oxo, (1-4C)alkyl, halo, cyano, nitro, hydroxyl, amino, (1-4C)haloalkyl, (1-4C)alkoxy, (1-4C)haloalkoxy, carboxyl, carbamoyl, sulphamoyl, NRbRc, ORb, C(O)Rb, C(O)ORb, OC(O)Rb, C(O)N(Rb)Rc, N(Rb)C(O)Rc, S(O)yRb (where y is 0, 1 or 2), SO2N(Rb)Rc, N(Rb)SO2Rc or (CH2)zNRbRc (where z is 1, 2 or 3), (4-6C)heterocycyl, 6 membered aryl or 5 or 6 membered heteroaryl, wherein Rb and Rc are each independently selected from H or (1-4C)alkyl;
• or
• R1 and R2 are linked such that, together with the nitrogen atom to which they are attached, they form a 4 to 10 membered mono or bicyclic heterocyclic ring which is optionally substituted by one or more substituents selected from oxo, (1-4C)alkyl, halo, cyano, nitro, hydroxyl, amino, (1-4C)haloalkyl, (1-4C)alkoxy, (1-4C)haloalkoxy, carboxyl, carbamoyl, sulphamoyl, NRdRe, ORd, C(O)Rd, C(O)ORd, OC(O)Rd, C(O)N(Re)Rd, N(Re)C(O)Rd, S(O)yRd (where y is 0, 1 or 2), SO2N(Re)Rd, N(Re)SO2Rd or (CH2)zNRdRe (where z is 1, 2 or 3), (4-6C)heterocycyl, 6 membered aryl or 5 or 6 membered heteroaryl, wherein Rd and Re are each independently selected from H or (1-4C)alkyl;
• L is a (1-3C)alkylene optionally substituted by fluoro, (1-2C)alkyl or oxo;
• R4a, R4b, R4c and R4d are each independently selected from H, halo, (1-2C)alkyl, cyano, nitro, hydroxyl, amino, (1-2C)haloalkyl, (1-2C)alkoxy, or (1-2C)haloalkoxy;
• A is C(═X) or CRfRg;
• wherein X is O, NH or S;
• and
• Rf and Rg are independently selected from H or (1-2C)alkyl;
• Q is selected from —NH—S(O)y—, —S(O), —NH—, —C(O)NRh—, —NRhC(O)—, —NRh—S(O)(NH)—, —S(O)(NH)—NRh—, —C(O)O—, —OC(O)—, —CH2CH2—, —CH2NRh— or —NRhCH2—, wherein y is 0, 1 or 2 and Rh is selected from H or (1-2C)alkyl;
• HET is a 5 or 6 membered nitrogen containing heteroaryl optionally substituted with one or more substituents selected from H, (1-4C)alkyl, halo, cyano, nitro, hydroxyl, amino, (1-4C)haloalkyl, (1-4C)alkoxy, (1-4C)haloalkoxy, carboxyl, carbamoyl, amido or sulphamoyl;
• W is either a group of the formula:
• -Q1-Ri—
• wherein:
• Q1 is attached to HET and is —C(O)— or —CH2—;
• and
• Ri is attached to R3 and is selected from —CHRj—, —NRj—, or —O—, wherein
• Rj is selected from H or (1-2C)alkyl;
• or W is a group of the formula:
• —Rk-Q2-
• wherein:
• Q2 is attached to R3 and is selected from —C(O)— or —CH2—;
• and
• Rk is attached to HET and is selected from CHR|, NR|, O or S(O)y,
• wherein y is 0, 1 or 2 and R| is H or (1-4C)alkyl;
• R3 is selected from (1-6C)alkyl, phenyl, (4-8C)carbocyclyl, heteroaryl or heterocyclyl, each of which is optionally substituted with one or more substituents selected from (1-4C)alkyl, halo, (1-4C)haloalkyl, (1-4C)alkoxy, (1-4C)haloalkoxy, (3-6C)cycloalkyl, (3-6C)cycloalkyl(1-2C)alkyl, (2-4C)alkenyl or (2-4C)alkynyl.