| 主权项 |
1. A compound of formula I,wherein
R1 and R2 independently represent C1-4 alkyl or C3-6 cycloalkyl, or R1 and R2 together combine to form C2-6 alkylene; R3 represents C1-2 alkyl; X1 and X2 are both N, or X1 is C and X2 is either O or S; Ar is phenyl or a 5- or 6-membered heteroaryl group containing one or more heteroatoms selected from the group consisting of N, O and S, which phenyl and heteroaryl groups are optionally substituted by one or more substituents selected from the group consisting of halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, hydroxy, amino and cyano; L is a direct bond or C1-2 alkylene; E represents:
(a) H, halo, hydroxy, NR6aR6b, cyano, C(O)OR6c, C(O)NR6dR6e, SH, S(O)nR8, S(O)2NR6fR6g,(b) C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, which latter four groups are optionally substituted by one or more substituents selected from the group consisting of halo and NR7aR7b,(c) C3-8 cycloalkyl, Het1 or Ar1, which latter three groups are optionally substituted by one or more substituents selected from the group consisting of halo, hydroxy and C1-3 alkyl; R6a to R6g independently represent H or C1-4 alkyl, or any one or more of the pairs R6a and R6b, R6d and R6e, and R6f and R6g, when taken together with the N-atom to which each pair is attached, form a saturated 4- to 7-membered heterocyclic group, which heterocyclic group contains one N atom (the atom to which the pairs of substituents are attached) and, optionally, one or more further heteroatoms selected from the group consisting of O, S and N, and which heterocyclic group is optionally substituted by one or more C1-2 alkyl groups; R7a and R7b, independently on each occurrence, represent H or C1-4 alkyl, or, together with the N-atom to which they are attached, form a 5- to 7-membered heterocyclic group that is fully saturated, partially unsaturated or fully aromatic and which heterocyclic group contains one N atom (the atom to which R7a and R7b are attached) and, optionally, one or more further heteroatoms selected from the group consisting of O, S and N, and which heterocyclic group is optionally substituted by one or more substituents selected from the group consisting of halo, hydroxy, oxo, C1-4 alkyl and C1-4 alkoxy; R8 represents C1-4 haloalkyl, C1-4 alkyl, C3-8 cycloalkyl or Ar2, which latter three groups are optionally substituted by one or more substituents selected from the group consisting of halo, hydroxy and C1-3 alkyl; Ar1 and Ar2 independently represent C6-14 carbocyclic aryl groups, which groups may be monocyclic, bicyclic or tricyclic and which groups contain at least one ring which is fully aromatic, n is 0, 1 or 2; R4 and R5 are each independently C1-3 alkyl, C1-3 haloalkyl, cyano or halo, or R4 and R5 together combine to form C3-5 alkylene or C3-5 alkenylene, which latter two groups are optionally substituted by one or more substituents selected from the group consisting of C1-3 alkyl, C1-3 haloalkyl, cyano and halo, or R4 and R5, together with the C-atoms to which they are attached, form a fused phenyl or Het2 ring, which latter two rings are optionally substituted by one or more substituents selected from the group consisting of C1-3 alkyl, C1-3 haloalkyl, cyano and halo; Het1 and Het2 independently represent 5- to 7-membered heterocyclic groups that are fully saturated, partially unsaturated or fully aromatic, which heterocyclic groups contain one or more heteroatoms selected from the group consisting of N, O and S; one of A and A1 represents N and the other represents CH, or both of A and A1 represent CH; G represents
phenyl optionally substituted by one or more Y1 orHet3 optionally substituted by one or more Y2; G1 represents H; or G and G1 together combine to form C3-6 alkylene optionally substituted by one or more substituents selected from the group consisting of halo, hydroxy and C1-3 alkyl, which latter group is optionally substituted by one or more halo atoms or by hydroxy; each Y1 is independently selected from the group consisting of
halo, hydroxy, cyano, SF5, —OC(O)NH2,P(O)R9aR9b,J1-N(R9c)R9d,J2S(O)2R9e,J3-[CH2(CH2)0-1CH2—O]2-8—R9f,—C≡C—R9g,—N═S(O)R9hR9i,Heta,C1-6 alkyl, C3-6 cycloalkyl, C1-6 alkoxy, C3-6 cycloalkoxy, —S(O)0-1—C1-6 alkyl and —S(O)0-1—C3-6 cycloalkyl which latter six groups are optionally substituted by one or more substituents selected from the group consisting of halo, hydroxy, C1-3 alkyl, C1-3 alkoxy and C3-6 cycloalkyl; each Y2 independently represents oxo or Y1; J1 represents
a direct bond,—C(O)——[C(O)]p—C1-8 alkylene,—C(O)NR10a—CH2-[C1-7 alkylene]-,-Q1-CH2-[C1-5 alkylene]-,the alkylene parts of which latter four groups are optionally substituted by one or more substituents selected from the group consisting of halo, C1-3 alkyl and hydroxy; J2 represents
a direct bond,—O—,—NH—C1-6 alkylene or-Q2-CH2-[C1-5 alkylene]-,the alkylene parts of which latter two groups are optionally substituted by one or more substituents selected from the group consisting of halo, C1-3 alkyl and hydroxy; J3 represents —O— or S(O)0-2; Q1 and Q2 independently represent O or S(O)0-2; p represents 0 or 1; R9a and R9b independently represent C1-3 alkyl or C1-3 alkoxy, or R9a and R9b together combine to form C4-6 alkylene; R9c and R9d independently represent H or C1-8 alkyl, which latter group is optionally substituted by R10b and/or one or more substituents selected from the group consisting of halo and hydroxy; or R9c and R9d, together with the N-atom to which they are attached, form a 4- to 7-membered heterocyclic group that is fully saturated, partially unsaturated or fully aromatic and which heterocyclic group contains one N atom (the atom to which R9c and R9d are attached) and, optionally, one or more further heteroatoms selected from the group consisting of O, S and N, and which heterocyclic group is optionally substituted by one or more substituents selected from the group consisting of halo, hydroxy, oxo, C1-4 alkyl and C1-4 alkoxy; R9e represents C1-6 alkyl, C3-6 cycloalkyl or phenyl, which latter three groups are optionally substituted by one or more substituents selected from the group consisting of halo, hydroxy, C1-3 alkyl, C1-3 alkoxy and C3-6 cycloalkyl; R9f, R9g, R9h and R9i independently represent C1-4 alkyl optionally substituted by one or more halo atoms, or R9f and R9g independently represent H; R10a represents H or C1-3 alkyl optionally substituted by one or more halo atoms; R10b represents C1-4 alkoxy, S—C1-4 alkyl, phenyl or Het4, which latter two groups are optionally substituted by one or more substituents selected from the group consisting of halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, hydroxy, amino and cyano; Het3 represents a 5- to 10-membered heteroaromatic group, which group is monocyclic or bicyclic and contains at least one carbocyclic or heterocyclic ring that is fully aromatic, and which group contains one or more heteroatoms selected from the group consisting of N, O and S; Het4 represents a 4- to 10-membered heterocyclic group that is fully saturated, partially unsaturated or fully aromatic, which heterocyclic group contains one or more heteroatoms selected from the group consisting of N, O and S; and Heta represents a 5- or 6-membered heterocyclic group that is fully saturated, partially unsaturated or fully aromatic, which group contains one or more heteroatoms selected from the group consisting of N, O and S, and which group is optionally substituted by one or more substituents selected from the group consisting of halo, hydroxy, C1-3 alkyl, C1-3 alkoxy and C3-6 cycloalkyl,or a pharmaceutically acceptable salt, solvate or isotopic derivative thereof. |
