Isoxazole-5-carboxamide derivatives

An isoxazole-3-carboxamide derivative having the general Formula I

• wherein
• R1 is phenyl or pyridyl, optionally substituted by 1-3 substituents selected from halogen, (C1-4alkyl and (C1-4)alkyloxy, the alkyl and alkyloxy group being optionally substituted with halogen;
• X is O or NR7;
• R2 is H or (C1-8)alkyl, optionally substituted by OH, (C3-8)cycloalkyl, (C1-3)alkyloxy, (C1-3)alkylSO, (C1-3)alkylSO2, CN, NR8R9, COOR10 or 1 or more halogens;
• or
• R2 is (C3-10)cycloalkyl, (C3-8)cycloalkenyl or (C3-8)cycloalkyl(C1-3)alkyl, each cycloalkyl group optionally substituted by (C1-3)alkyl, hydroxy(C1-3)alkyl, oxo, OH, ═NOH, COOR10 or CN;
• or
• R2 is phenyl or pyridyl, each of which may be fused to a 5- or 6-membered saturated heterocyclic ring containing 1 or 2 heteroatoms selected from NR11, O and S, and each of which may be substituted by NR8R9, halogen, OH, ═NOH, oxo, SH, (C1-3)-alkyl, (C1-3)alkyloxy or hydroxy(C1-3)alkyl, each alkyl group optionally substituted by one or more halogens;
• or
• R2 together with R7 and the N to which they are bonded form a saturated 4-8 membered ring, optionally containing a further heteroatom selected from O and S, the ring being optionally substituted by oxo, OH, COOR10 or CONH2;
• or
• R2 is (CH2)n-Het;
• Het is a saturated 4-8-membered heterocyclic ring containing 1 or 2 heteroatoms selected from NR11, O, S and SO2, optionally substituted by OH or oxo;
• n is 0, 1 or 2;
• R3 is (C1-6)alkyl, (C2-5)alkenyl, or (C2-5)alkynyl, each of which optionally substituted by halogen, OH or phenyl;
• or
• R3 is (C3-10)cycloalkyl, (C3-8)cycloalkenyl or (C3-8)cycloalkyl(C1-3)alkyl, each cycloalkyl group may be fused to a benzo group, and each cycloalkyl group may be substituted by oxo, ═NOH, OH, COOR12, CN, (C1-3)alkyl or hydroxy(C1-3)alkyl;
• or
• R3 is a saturated 4-8-membered heterocyclic ring containing 1 or 2 heteroatoms selected from N, O, S and SO2, optionally substituted by hydroxyl or oxo;
• or
• R3 is phenyl or pyridyl, each of which may be fused to a 5- or 6-membered saturated heterocyclic ring containing 1 or 2 heteroatoms selected from NR5, O and S, and each of which may be substituted by amino, halogen, hydroxy, hydroxyimino, oxo, mercapto, (C1-3-alkyl, (C1-3)-alkyloxy or hydroxy(C1-3)alkyl, each alkyl group optionally substituted by one or more halogens;
• or
• R3 is a bicyclic heteroaromatic ring system containing 1-3 heteroatoms selected from N, O and S, which may be substituted by hydroxy, amino, (C1-3)alkyl or hydroxy-(C1-3)alkyl;
• R4 is H or (C1-4)alkyl;
• or
• R4 together with R3 and the N to which they are bonded form a saturated 4-8 membered ring, optionally containing a further heteroatom selected from O, S and SO2, the ring being optionally substituted by oxo, hydroxyimino, hydroxy, carboxy, carboxamido, (C1-3)alkyl, or hydroxy(C1-3)alkyl or (C1-4)-alkyloxy;
• R5, where present, is H or (C1-4)alkyl;
• R6, where present, is H or (C1-4)alkyl;
• R7 is H, (C1-8)alkyl, (C3-10)cycloalkyl, COR13 or SO2R13;
• R8 and R9 are independently H or (C1-4)alkyl;
• or
• R8 and R9 together with the N to which they are bonded form a 4-7-membered saturated heterocyclic ring;
• R10 is H or (C1-4)alkyl;
• R11 is H or (C1-4)alkyl;
• R12 is H or (C1-4)alkyl;
• R13 is (C1-6)alkyl;
• or a pharmaceutically acceptable salt thereof.