Autotaxin inhibitors

A compound, of formula (Ia)

• or a pharmaceutically acceptable salt thereof,
• wherein
• A is selected from the group consisting of
• R1 is selected from the group consisting of H and C1-4 alkyl;
• R1a is C1-4 alkyl;
• R2 is halogen, —CF3, —CF2H, —OCF3, —OCF2H, —OCH3, —CH3 or CN;
• Y is selected from the group consisting of —CH═CH—, —CH2—CH2—, —O—CH2—, —CH2—O—, —C(CH3)═CH— and —C═C(CH3)—;
• A′ is CR6;
• R6 is selected from H, OH and C1-4 alkoxy;
• Z is selected from the group consisting of —(CR7aR7b)m—;
• R7a and R7b is independently selected from H, OH, C1-4 alkyl and C1-4 alkoxy;
• R8 is selected from H and C1-4 alkyl;
• m, is selected from the group consisting of 0 and 1;
• E is selected from the group consisting of
• (i) oxadiazolyl;
• (ii) pyrazolyl;
• (iii) oxazolyl;
• (iv) isoxazolyl;
• (v) pyridinyl;
• (vi) thiazolyl;
• (vii) triazolyl;
• (viii) pyrimidinyl;
• (ix) tetrazolyl;
• (x) pyrazinyl;
• and
• (xi) furanyl;
• wherein each ring is unsubstituted or substituted with 1 to 3 substituents independently selected from the group consisting of X;
• X is independently selected from the group consisting of C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, hydroxyC1-4alkyl, C1-4alkoxyC1-4alkyl, —(CRXaRXb)q—C3-6 cycloalkyl, halogen, CN, —(CRXaRXb)q-5 or 6 membered heterocyclyl, —(CRXaRXb)q-5 or 6 membered heteroaryl, —(CRXaRXb)q-phenyl, oxo, OH, —(CRXaRXb)q—C(═O)RXc, —(CRXaRXb)q—C(═O)ORXc, —(CRXaRXb)q—NRXdRXe and —(CRXaRXb)q—C(═O)NRXdRXe;
• wherein the C3-6cycloalkyl, heteroaryl, phenyl and heterocyclyl are unsubstituted or substituted by 1 to 3 substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, —(CRXaRXb)q—C3-6cycloalkyl, hydroxyC1-4alkyl, C1-4haloalkyl, C1-4alkoxyC1-4alkyl, halogen and OH;
• RXa and RXb are independently selected from the group consisting of H, OH, C1-4 alkyl and C1-4 alkoxy;
• RXc, RXd and RXe are independently selected from the group consisting of H, C1-4alkyl, —(CRXaRXb)q1—C3-6cycloalkyl, hydroxyC1-4alkyl, C1-4haloalkyl, C1-4alkoxyC1-4alkyl, OH and —(CRXaRXb)q1-5 or 6 membered heterocyclyl;
• wherein the C3-6cycloalkyl and heterocyclyl are unsubstituted or substituted by 1 to 3 substituents independently selected from the group consisting of C1-4 alkyl, C1-4 alkoxy, —(CRXaRXb)q1—C3-6cycloalkyl, C1-4 haloalkyl, hydroxyC1-4alkyl, C1-4alkoxyC1-4alkyl, halogen and OH;
• or
• RXd and RXe together with the nitrogen atom to which they are attached form a 5 to 6 membered heterocyclyl which heterocyclyl is unsubstituted or substituted by 1 to 3 substituents selected from the group consisting of C1-4alkyl, C1-4alkoxy, —(CRXaRXb)q1—C3-6cycloalkyl, hydroxyC1-4alkyl, C1-4haloalkyl, C1-4alkoxyC1-4alkyl, halogen and OH;
• q and q1 are selected from the group consisting of 0, 1 and 2.