Pyridine derivative and use thereof

A compound of formula I″″, or a tautomer, meso isomer, racemate, enantiomer, diastereomer or mixture thereof, or a pharmaceutically acceptable hydrate, solvate or salt thereof:

• wherein,
• T is selected from S(O)2, C═O, CH2 or NHS(O)2;
• X is selected from NR1, S or S(O)2;
• A1 is selected from CH, CH2, C═O or N, A2 is selected from C, CH or N, A3 is selected from CR8, CR9R10 or N, A4 is selected from CR29, CR9R10 or N;
• Z1 is a bond or O;
• E1 is NR11, CH or CH2;
• B is
• the ring where B1, B2 are located is a 5- to 10-membered nitrogen-containing heterocycloalkyl or a 5- to 10-membered nitrogen-containing heterocycloalkenyl, wherein the cycloalkyl or cycloalkenyl is a monocyclic ring, spirocyclic ring or bridged cyclic ring, B1 is selected from CR12 or N, B2 is selected from CR13 or N, and at least one of B1 and B2 is N;
• or, B is
• the ring where B1 is located is a 4- to 8-membered nitrogen-containing monoheterocycloalkyl, B1 is selected from CR12 or N, B2 is selected from CR13R13′ or NR14;
• or, B is
• the ring where B1, B2 are located is a 5- to 10-membered nitrogen-containing heterocycloalkyl and is a monocyclic ring, spirocyclic ring or bridged cyclic ring, B1 is selected from CR12 or N, B2 is selected from CR13″ or N, and at least one of B1 and B2 is N;
• the ring where B3 is located is a 4- to 10-membered nitrogen-containing heterocycloalkyl and is a monocyclic ring, spirocyclic ring or bridged cyclic ring, B3 is selected from CR12′ or N;
• B1 is connected to L;
• L is selected from a bond or NR15;
• Y is selected from C═O or S(O)2;
• R5, R6 are independently selected from hydrogen, halogen, cyano, alkyl, aliphatic heterocyclyl, aryl, heteroaryl, —ORa, —NRbRc, —C(O)R16, —S(O)R16, —S(O)2R16, —P(O)R16R17, —C(O)NRbRc or —C(O)ORa, wherein the alkyl, aliphatic heterocyclyl, aryl, heteroaryl are optionally substituted by one or more R18;
• each occurrence of R18 is independently selected from halogen, cyano, alkyl, cycloalkyl, aliphatic heterocyclyl, —ORa, —NRbRc, —C(O)R16, —C(O)NRbRc or —C(O)ORa;
• R1, R11, R14, R15 are independently selected from hydrogen, alkyl, cycloalkyl, aliphatic heterocyclyl or —C(O)R19, wherein the alkyl, cycloalkyl, aliphatic heterocyclyl are optionally substituted by one or more substituents selected from the group consisting of:
• halogen, cyano, hydroxy, amino, alkyl, cycloalkyl and aliphatic heterocyclyl;
• n1, n5 are independently selected from 0, 1, 2, 3 or 4;
• each occurrence of R12, R12′, R13, R13′, R13″, R7, R7′ is independently selected from hydrogen, halogen, cyano, alkyl, cycloalkyl, aliphatic heterocyclyl, aryl, heteroaryl, —ORn, —NRoRp, —C(O)R20, —C(O)NRoRp or —C(O)ORn, wherein alkyl, cycloalkyl, aliphatic heterocyclyl, aryl, heteroaryl are optionally substituted by one or more R21;
• each occurrence of R21 is independently selected from halogen, cyano, alkyl, cycloalkyl, aliphatic heterocyclyl, —ORn, —NRoRp, —C(O)R20, —C(O)NRoRp or —C(O)ORn;
• or Z1 is a bond, R5, R6 together with the atoms to which R5, R6 are attached form a 4- to 9-membered cycloalkenyl, or R5, R14 together with the fragment to which R5, R14 are attached form a 4- to 9-membered aliphatic heterocyclyl, or R6, R13 together with the fragment to which R6, R13 are attached form a 4- to 9-membered cycloalkenyl, or R5, R13 together with the fragment to which R6, R13 are attached form a 4- to 9-membered alicyclyl, or R6, R4 together with the fragment to which R6, R14 are attached form a 4- to 9-membered aliphatic heterocyclyl, or R5, R6 together with the atoms to which R5, R6 are attached form a 6- to 10-membered aryl or 5- to 10-membered heteroaryl, wherein the cycloalkenyl, alicyclic heterocyclyl, alicyclyl, aryl and heteroaryl are optionally substituted by one or more substituents selected from the group consisting of:
• halogen, cyano, hydroxy, amino, alkyl, cycloalkyl and alicyclic heterocyclyl;
• R2 is selected from hydrogen, halogen, cyano, alkyl, cycloalkyl, alicyclic heterocyclyl, aryl, heteroaryl, —ORd, —NReRf, —C(O)R22, —C(O)ReRf or —C(O)ORd, wherein the alkyl, cycloalkyl, alicyclic heterocyclyl, aryl, heteroaryl are optionally substituted by one or more R23;
• each occurrence of R23 is independently selected from halogen, cyano, alkyl, cycloalkyl, aliphatic heterocyclyl, —ORd, —NReRf, —C(O)R22, —C(O)NReRf or —C(O)ORd;
• R3 is selected from hydrogen, halogen, cyano, alkyl, cycloalkyl, aliphatic heterocyclyl, aryl, heteroaryl, —OR9, —SRg, —NRhRi, —C(O)R24, —C(O)RhRi or —C(O)ORg, when the ‘’ in ring E is absent, R3 can also be a carbonyl group that together formed by the connected carbon atom, wherein alkyl, cycloalkyl, aliphatic heterocyclyl, aryl, heteroaryl are optionally substituted by one or more R25;
• each occurrence of R25 is independently selected from halogen, cyano, alkyl, cycloalkyl, aliphatic heterocyclyl, —ORg, —NRhRi, —C(O)R24, —C(O)NRhRi or —C(O)ORg;
• R4 is selected from alkyl, cycloalkyl, aliphatic heterocyclyl, aryl or heteroaryl, wherein the alkyl, cycloalkyl, aliphatic heterocyclyl, aryl, heteroaryl are optionally substituted by one or more R26;
• each occurrence of R26 is independently selected from halogen, cyano, alkyl, cycloalkyl, aliphatic heterocyclyl, aryl, heteroaryl, —ORj, —NRkRm, —C(O)R27, —C(O)NRkRm or —C(O)ORj, wherein the alkyl, cycloalkyl, aliphatic heterocyclyl, aryl, heteroaryl are optionally substituted by one or more R28;
• each occurrence of R28 is independently selected from halogen, cyano, alkyl, cycloalkyl, aliphatic heterocyclyl, —ORj, —NRkRm, —C(O)R27, —C(O)NRkRm or —C(O)ORj;
• each occurrence of R8, R9, R10, R29 is independently selected from hydrogen, halogen, cyano, alkyl, cycloalkyl, aliphatic heterocyclyl, aryl, heteroaryl, —ORq, —NRrRs, —C(O)R30, —C(O)NRrRs or —C(O)ORq;
• wherein the alkyl, cycloalkyl, aliphatic heterocyclyl, aryl, heteroaryl are optionally substituted by one or more R31;
• When the ‘’ in ring E is a bond, R11 is absent;
• each occurrence of R31 is independently selected from halogen, cyano, alkyl, cycloalkyl, aliphatic heterocyclyl, —ORq, —NRrRs, —C(O)R30, —C(O)NRrRs or —C(O)ORq;
• each occurrence of Ra, Rb, Rc, Rd, Re, Rf, Rg, Rh, Ri, Rj, Rk, Rm, Rn, Ro, Rp, Rq, Rr, Rs is independently selected from H, alkyl, cycloalkyl, aliphatic heterocyclyl or —C(O)R32, wherein the alkyl, cycloalkyl, alicyclic heterocyclyl are optionally substituted by one or more substituents selected from the group consisting of:
• halogen, cyano, hydroxy, amino, alkyl, cycloalkyl and alkyl substituted or unsubstituted aliphatic heterocyclyl;
• each occurrence of R16, R17, R19, R20, R22, R24, R27, R30, R32 is independently selected from H, alkyl, cycloalkyl or alicyclic heterocyclyl, wherein the alkyl, cycloalkyl, alicyclic heterocyclyl are optionally substituted by one or more substituents selected from the group consisting of:
• halogen, cyano, hydroxy, amino, alkyl, cycloalkyl and aliphatic heterocyclyl.