A fused heterocyclic compound represented by formula I, formula II or formula III, pharmaceutically acceptable salt, hydrate, solvate, polymorph or pro-drug thereof,
- Wherein,
- A1 is N or CH;
- A2 is N or CH;
- A3 is N or C;
- A4 is N or C;
- A5 is O, S, N, CR1a or NR5a;
- A6 is O, S, N, CR1b or NR5b;
- When A5 is O or S, A6 is N;
- When A6 is O or S, A5 is N;
- R1a and R1b are each independently a hydrogen, a deuterium, a halogen, an alkyl, an alkoxy, an alkenyl, an alkynyl, a cycloalkyl, a heterocycloalkyl or CN;
- R2 is —(CR8R9)mNR5R6, —(CR8R9)mNR7C(═Y)R5, —(CR8R9)mNR7S(O)2R5, —(CR8R9)mOR5, —(CR8R9)mS(O)2R5, —(CR8R9)mS(O)2NR5R6, —C(OR5)R6R8, —C(═Y)R5, —C(═Y)OR5, —C(═Y)NR5R6, —C(═Y)NR7OR5, —C(═O)NR7S(O)2R5, —C(═O)NR7(CR8R9)mNR5R6, —NR7C(═Y)R6, —NR7C(═Y)OR6, —NR7C(═Y)NR5R6, —NR7S(O)2R5, —NR7S(O)2NR5R6, —SR5, —S(O)2R5, —S(O)2NR5R6, —SC(═Y)R5, —SC(═Y)OR5, —O(CR8R9)mCR5R6, —O(CR8R9)mNR5R6, a C1-12 alkyl, a C2-8 alkenyl, a C2-8 alkynyl, a C3-12 carbocyclic group, a C2-20 heterocyclic group, a C6-20 aryl or a C1-20 heteroaryl;
- (R3)k represents that the hydrogens attached to the morpholine ring are substituted by 0-k occurrences of R3, at each occurrence the R3 is the same or different from each other, and is independently a hydrogen, a deuterium, a halogen, a C1-6 alkyl, or any two of the R3 are linked by a single bond, a C1-6 alkylene or a C1-6 alkylene substituted by one or two heteroatoms to form a ring structure, the heteroatom is O, N, or S;
- A is N or CR4a;
- D is N or CR4d;
- E is N or CR4e;
- G is N or CR4g;
- J is N or CR4j;
- A, D, E, G and J are not N at the same time;
- R4a, R4d, R4e, R4g and R4j are each independently a hydrogen, a halogen, —CN, an alkyl, an alkoxy, an alkenyl, an alkynyl, a cycloalkyl, a heterocycloalkyl, —NR5R6, —OR5, —SR5, —C(O)R5, —NR5C(O)R6, —N(C(O)R6)2, —NR5C(O)NR5R6, —NR7S(O)2R5, —C(═O)OR5 or —C(═O)NR5R6, or R4j and R4g, together with the atoms to which they are attached form a saturated, unsaturated or partially unsaturated 5-membered or 6-membered heterocycle, the 5-membered or 6-membered heterocycle is fused to the 6-membered ring containing A, D, E, G and J;
- Ring Q and ring Q′ are benzene, a 5- to 9-membered alicyclic ring, a 5- to 9-membered heteroalicyclic ring, or a 5- to 6-membered heterocyclic ring;
- ring Q is not a thiophene or a furan;
- (R1)k1 represents that the hydrogens attached to the ring Q or ring Q′ are substituted by 0-k1 occurrences of R1, at each occurrence the R1 is the same or different from each other, and is each independently a halogen, —CN, an alkyl, an alkoxy, an alkenyl, an alkynyl, a cycloalkyl, a heterocycloalkyl, —NR5R6, —OR5, —SR5, —C(O)R5, —NR5C(O)R6, —N(C(O)R6)2, —NR5C(O)NR5′R6, —NR7S(O)2R5, —C(═O)OR5 or —C(═O)NR5R6;
- R5, R5′, R5a, R5b, R6, R7 and R7′ are each independently a hydrogen, a C1-12 alkyl, —(CH2)2-3NH2, a C2-8 alkenyl, a C2-8 alkynyl, a C3-12 carbocyclic group, a C2-20 heterocyclic group, a C6-20 aryl or a C1-20 heteroaryl, or R5, R6 together with the nitrogen or carbon atoms to which they are directly attached form a heterocyclic ring or a cycloalkyl, or R7, R7′ together with the nitrogen atom to which R7 is directly attached form a heterocyclic ring;
- the heterocyclic ring or the cycloalkyl is preferably optionally substituted by the substituent selected from the group consisting of:
- oxo, —(CH2)mOR7, —NR7R7′, —CF3, a halogen, —SO2R7, —C(═O)R7, —NR7C(═Y)R7, —NR7S(O)2R7, —C(═Y)NR7R7, a C1-12 alkyl, a C2-8 alkenyl, a C2-8 alkynyl, a C3-12 carbocyclic group, a C2-20 heterocyclic group, a C6-20 aryl or a C1-20 heteroaryl;
- (CR8R9)m represents that 0 to m (CR8R9) are linked with each other, R5 and R9 are the substituents attached to the formed carbon chain, wherein each R5 and R9 are the same or different from each other, and are each independently a hydrogen, a deuterium, a halogen, —CN, a hydroxyl, an alkoxy, a C1-12 alkyl, a C2-12 alkenyl, a C2-12 alkynyl, a C3-12 cycloalkyl, a C6-12 aryl, a 3- to 12-membered heterocycloalkyl or a 5- to 12-membered heteroaryl;
- or R8, R9 together with the atoms to which they are attached form a saturated or partially unsaturated C3-12 carbon ring or C2-20 heterocyclic ring;
- wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, carbocyclic ring, heterocyclic ring, heterocycloalkyl, aryl, or heterocyclic group can be optionally substituted by the substituent selected from the group consisting of:
- a halogen, a hydroxyl, —CN, —CF3, —NO2, oxo, R5, —C(═Y)R5, —C(═Y)OR5, —C(═Y)NR5R6, —(CR8R9)mNR5R6, —(CR8R9)mOR5, —NR5R6, —NR7C(═Y)R5, —NR7C(═Y)OR6, —NR7C(═Y)NR5R6, —(CR8R9)mNR7SO2R5, ═NR7, OR5, —OC(═Y)R5, —OC(═Y)OR5, —OC(═Y)NR5R6, —OS(O)2(OR5), —OP(═Y)(OR5)(OR6), —OP(OR5)(OR6), —SR5, —S(O)R5, —S(O)2R5, —S(O)2NR5R6, —S(O)(OR5), —S(O)2(OR5), —SC(═Y)R5, —SC(═Y)OR5, —SC(═Y)NR5R6, a C1-12 alkyl, a C2-8 alkenyl, a C2-8 alkynyl, a C3-12 carbocyclic group, a C2-20 heterocyclic group, a C6-20 aryl or a C1-20 heteroaryl;
- Y is O, S or NR7;
- m, k or k1 is independently 0, 1, 2, 3, 4, 5 or 6.