| 主权项 |
1. A compound of formula I, wherein
R1 represents C2-6 alkyl, Si(R1a)(R1b)(R1c) C3-7 cycloalkyl, 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 alkyl, cycloalkyl, phenyl and heteroaryl groups are optionally substituted by one or more substituents selected from the group consisting of halo, C1-4 alkyl, C2-3 alkynyl, C3-4 cycloalkyl, C1-4 haloalkyl, C1-4 alkoxy, hydroxy, amino and cyano;R1a and R1b independently represent C1-4 alkyl or C3-6 cycloalkyl, or R1a and R1b together combine to form C2-6 alkylene;R1c 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;R2 represents C1-4 alkyl;R3 represents C1-4 alkyl, C3-6 cycloalkyl, C1-4 alkoxy or hydroxy;or R2 and R3 together combine to form C3-6 alkylene;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 Het1 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 represents a 5- to 7-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;one of A and A1 represents N and the other represents CH,or both A and A1 represent CH;E represents N(G1), O or S;G represents
phenyl optionally substituted by one or more Y1,Het2 optionally substituted by one or more Y2,R6a orC(O)R6b;G1 represents H or C1-3 alkyl;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)R6eR6d,E1-N(R6e)R6f,E2-S(O)2R6g,E3-[CH2(CH2)0-1CH2—O]2-8—R6h,—N═S(O)R6jR6k,Heta, andC1-6 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;E1 represents
a direct bond,—C(O)——[C(O)]p—C1-8 alkylene,—C(O)NR7a—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;E2 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;E3 represents —O— or S(O)0-2;Q1 and Q2 independently represent O or S(O)0-2;p represents 0 or 1;R6a represents C1-8 alkyl, wherein one or two non-adjacent C-atoms of the alkyl group, that are not linked directly to E, are optionally replaced by heteroatoms independently selected from the group consisting of O and N and/or wherein the alkyl group is substituted by one or more R8 substituents;R6b represents C1-8 alkyl, wherein one C-atom of the alkyl group is, or two non-adjacent C-atoms of the alkyl group are, optionally replaced by heteroatoms independently selected from the group consisting of O and N and/or wherein the alkyl group is substituted by one or more R8 substituents;R6c and R6d independently represent C1-3 alkyl or C1-3 alkoxy, or R6c and R6d together combine to form C4-6 alkylene;R6e and R6f independently represent H or C1-8 alkyl, which latter group is optionally substituted by R7b and/or one or more substituents selected from the group consisting of halo and hydroxy orR6e and R6f, 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 R6e and R6f 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;R6g 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;R6h, R6i, R6j and R6k independently represent C1-4 alkyl optionally substituted by one or more halo atoms, or R6h and R6i independently represent H;R7a represents H or C1-3 alkyl optionally substituted by one or more halo atoms;R7b 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;R8 represents, independently on each occurrence, halo, hydroxy, C1-4 alkoxy, oxo, C3-8 cycloalkyl, Het3 or phenyl, which latter three 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;Het2 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;Het3 and Het4 independently represent 4- to 10-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; andHeta 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. |
