Nitrogen-containing heterocyclic autotaxin inhibitor, and composition containing same and use thereof

A nitrogen-containing heterocyclic compound as shown in formula (I), or a stereoisomer, a solvate, a deuterated form, a pharmaceutically acceptable salt or a cocrystal thereof,

• wherein M1 is
• L1 is a bond, —(CR1R2)a—(NR7)b—W—(CR3R4)c—(NR8)d—(CR5R6)e— or —C(O)—(CR3R4)c—C═CR7—;
• W is —C(═X)— or a 3-6 membered heterocyclene containing 1-3 heteroatoms selected from N, O or S;
• X is O, S or NRx, wherein Rx is H or cyano;
• each of R1 to R6 is independently selected from H, halogen, C1-4 alkyl or C3-6 cycloalkyl;
• R7 and R8 are each independently selected from H, C1-4 alkyl or C3-6 cycloalkyl;
• alternatively, R1 and R2 on the same carbon atom, R3 and R4 on the same carbon atom, or R5 and R6 on the same carbon atom together with the carbon atom to which they are attached form a 3-6-membered carbocyclic ring, wherein the carbocyclic ring is optionally substituted with 1-4 substituents selected from halogen or C1-4 alkyl;
• a, c and e are independently selected from an integer of 0-5, and b and d are independently 0 or 1;
• A is C3-6 cycloalkylene,
• C2-4 alkynylene, —RaC(O)NRa′—, —RaNRa′C(O)—, —RaNRa′—, —RaC(O)—, —Ra(CRa′Ra″)n— or a bond;
• Ra is
• Ra′ and Ra″ are independently H or C1-4 alkyl;
• n is an integer of 1-2;
• X1 and X2 are independently N or CRA1, and are not both CRA1 at the same time, and X3 is S, O or NRA1;
• X4, X5 and X6 are independently N, NRA1, S, O or CRA1, and are not all CRA1 at the same time;
• each RA1 is independently H, cyano, —RA, halogen, —C1-4 alkyl RA, —NHC(O)RA, —C(O)RA, —C1-4 alkyl-O—C1-4 alkyl, —NHRA, —C(O)NHRA or —ORA;
• RA is C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyloxy, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy or a 3-6 membered heterocyclyl containing 1-3 heteroatoms selected from N, O or S, wherein the alkyl, cycloalkyl, cycloalkyloxy, alkoxy, haloalkyl, haloalkoxy and heterocyclyl are optionally further substituted with 1-6 groups selected from C3-6 cycloalkyl, C1-4 alkyl, halogen, —S(O)2C1-4 alkyl, —OC1-4 alkyl or cyano;
• B is
• Y1 is O, S or NRB3;
• Cy has a structure:
• wherein, represents a single bond or a double bond, Z1 is C or N, ring E is a 5-membered heterocycle containing 1-3 heteroatoms selected from N, O or S, and ring D is a 6-membered ring containing 0-3 heteroatoms selected from N, O or S;
• the 5-membered heterocycle and the 6-membered ring are independently and optionally substituted with 1-3 RB2;
• RB1 and RB2 are each independently selected from H, oxo, OH, halogen, cyano, C1-4 alkyl, halo C1-4 alkyl, C1-4 alkyloxy or C3-6 cycloalkyl;
• RB3 is selected from H, C1-4 alkyl or C3-6 cycloalkyl;
• alternatively, group RA1 on A and group RB1 on B together with the atoms to which they are attached form a 6-10-membered heterocycle containing 1-3 heteroatoms selected from N, S, and O;
• f is an integer of 0-3;
• L2 is —O—, —NR9—, —C(O)NR9—, —NR9C(O)NR9—, —(CR10R11)g—, —NR9—(CR10R11)g— or a bond, wherein g is an integer of 1-3;
• R9 is H or C1-4 alkyl;
• R10 and R11 are each independently H, halogen, C1-4 alkyl or C3-6 cycloalkyl;
• alternatively, R10 and R11 on the same carbon atom together with the carbon atom to which they are attached form a 3-6 membered carbocyclic ring;
• M2 is
• Z2 and Z3 are each independently CRM or N, and Z4 is O, S or NRM1;
• each RM is independently H, C1-4 alkyl, C1-4 alkoxyalkyl, cyano, C3-6 cycloalkyl, C3-6 cycloalkyloxy, —SRm′, —S(O)2Rm′, —C(O)NRmRm′, —NRmC(O)Rm′, C2-6 alkenyl, C2-6 alkynyl, —NRM1, 3-6 membered heterocyclyl containing 1-3 heteroatoms selected from N, O or S or halogen, wherein the alkyl, alkenyl, alkynyl and cycloalkyl are each optionally substituted with 1-3 groups selected from halogen, cyano, C1-4 alkoxy, halo C1-4 alkyl or halo C1-4 alkoxy, and the heterocyclyl is optionally substituted with 1-3 groups selected from halogen, oxo or C1-4 alkyl;
• alternatively, two RM on adjacent ring carbon atoms in M2 together with the carbon atom to which they are attached form a 3-6 membered carbocyclic ring or a 3-6 membered heterocyclyl containing 0-3 heteroatoms selected from N, O or S;
• Rm is H, C1-4 alkyl or halo C1-4 alkyl;
• Rm′ is C1-4 alkyl or halo C1-4 alkyl;
• RM1 is H, C1-4 alkyl, C3-6 cycloalkyl, C1-4 haloalkyl or C1-4 alkoxyalkyl;
• RM2 is halo C1-4 alkoxy;
• each R12 is independently H, halogen, C1-4 alkyl, C3-6 cycloalkyl or halo C1-4 alkyl;
• h is an integer of 0-3;
• i is 0, 1 or 2;
• provided that:
• when M1 is
• L1 is —C(O)—CH2—, A is
• B is
• L2 is —NH—, and M2 is
• RB1 and RB2 are not both H at the same time;
• when M1 is
• L1 is —C(O)—CH2—, A is
• B is
• and L2 is —NH—CH2—, M2 is not
• when M1 is
• L1 is —C(O)—CH2—, A is
• B is
• L2 is —NH—, and M2 is
• at least one substituent RA1 in A is selected from cyano, halogen, C3-4 cycloalkyloxy, cyclopropylmethyloxy, C1-4 haloalkoxy, cyclopropylmethyl, —C1-4 alkyl-O—C1-4 alkyl, —NHC(O) RA, —C(O)NHRA, —C(O)—C3-6 cycloalkyl,
• and when M1 is
• L1 is —C(O)—CH2—, A is
• B is
• L2 is —NH—, and M2 is
• RA1 is not methyl, ethyl or cyclopropyl.