Diaryl macrocyclic compound and pharmaceutical composition, and use thereof

A compound of formula (1) or a pharmaceutically acceptable salt or isotope label thereof,

• wherein,
• X is selected from —O—, —S— or —CRaRb—;
• Ra and Rb are each independently selected from the following substituted or unsubstituted groups:
• hydrogen, halogen, a C1˜8 alkyl, a C1˜8 alkoxy, a C1˜8 haloalkyl, a C3˜8 cycloalkyl, a C3˜8 heterocyclyl, a C6˜20 aryl, a C5˜20 heteroaryl, hydroxyl, mercapto, carboxy, ester group, acyl, amino, amide, sulfonyl, cyano, or CRaRb together forms a 3-10 membered cycloalkyl group or a 3-10 membered heterocyclic group containing at least one heteroatom;
• L1 is selected from —O—, —S—, —S(═O)—, —S(═O)2—, —NR6— or a single bond;
• L2 is selected from —O—, —S—, —S(═O)—, —S(═O)2— or —NR6—;
• R1, R2, and R5 are each independently selected from the following substituted or unsubstituted groups:
• hydrogen, halogen, a C1˜8 alkyl, a C1˜8 alkoxy, a C1˜8 haloalkyl, a C3˜8 cycloalkyl, a C3˜8 heterocyclic group, a C6-20 aryl group, a C5-20 heteroaryl group, hydroxyl, mercapto, carboxyl, ester group, acyl, amino, amide, sulfonyl or cyano;
• the substituents R3 and R4 on each C atom are each independently selected from the following substituted or unsubstituted groups:
• hydrogen, halogen, a C1˜8 alkyl, a C1˜8 alkoxy, a C1˜8 haloalkyl, a C3˜8 cycloalkyl, a C3˜8 heterocyclyl, a C6˜20 aryl, a C5˜20 heteroaryl, hydroxy, mercapto, carboxy, ester group, acyl, amino, amido, sulfonyl, cyano, or the substituents R3 and R4 together with X group form a 3-10 membered cycloalkyl group, a 3-10 membered heterocyclic group containing at least one heteroatom, or a 5-10 membered heteroaryl group containing at least one heteroatom;
• or R3 and R4 are each independently a single bond connecting the C atom and the adjacent macrocyclic ring atom;
• R3′ and R4′ are each independently selected from the following substituted or unsubstituted groups consisting of hydrogen, halogen, a C1˜8 alkyl, a C1˜8 alkoxy, a C1˜8 haloalkyl, a C3˜8 cycloalkyl, a C3˜8 heterocyclic group, a C6-20 aryl group, a C5-20 heteroaryl group, hydroxyl group, mercapto group, carboxyl group, ester group, acyl group, amino group, amide group, sulfonyl group, and cyano group;
• R6 is selected from the following substituted or unsubstituted groups:
• hydrogen, halogen, a C1˜8 alkyl, a C1˜8 alkoxy, a C1˜8 haloalkyl, a C3˜8 cycloalkyl, a C3˜8 heterocyclyl, a C6˜20 aryl, a C5˜20 heteroaryl, hydroxyl, mercapto, carboxy, ester, acyl, amino, amido, sulfonyl or cyano;
• Z represents C or heteroatom as a ring atom;
• n represents an integer from 1 to 10;
• the substituents of the above-mentioned groups may be selected from halogen, a C1˜8 alkyl, a C1˜8 haloalkyl, a C1˜8 alkoxy, a C3˜8 cycloalkyl, a C3˜8 heterocyclyl, a C6˜20 aryl, a C5˜20 heteroaryl, hydroxyl, mercapto, carboxy, ester group, acyl, amino, amido, sulfonyl or cyano.