Indolone derivative having irak4 inhibitory activity, and preparation method therefor and use thereof

A compound of formula (I):

• or a stereoisomer, tautomer, diastereomer, racemate, cis/trans isomer, isotopically labeled compound (preferably deuterated compound), N-oxide, metabolite, ester, prodrug, crystal form, hydrate, solvate, or pharmaceutically acceptable salt thereof,
• wherein:
• ring {circle around (A)} is selected from:
• C3-10 cyclohydrocarbyl, 5- to 10-membered heterocyclyl, C6-10 aryl, and 5- to 10-membered heteroaryl;
• X1, X2, X3, and X4 are each independently N or CH;
• and at least one of X1, X2, X3, and X4 is not N;
• Y is O or S;
• Z is N or CR4;
• the characters “a” and “b” respectively indicate bonds between a ring carbon atom connected to Z and two adjacent ring carbon atoms;
• wherein:
• when Z is CR4, the moiety
• is represented by the following structure of formula (i) or (ii):
• when Z is N, the moiety
• is represented by the following structure of formula (iii) or (iv):
• L1 is selected from:
• a direct bond, O, S, C(O), S(O), S(O)2, and NR7;
• R1 is -L2-R1a;
• L2 is —NR1b—*, —S(O)2NR1b—*, —C(O)—NR1b—*, —CR1cR1d—NR1b—*, —NR1b—C(O)—*, or —NR1b—S(O)2—*, wherein the bond indicated by * is connected to R1a;
• R1a is selected from:
• C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, —C1-6 alkylene-O—C1-6 alkyl, —OC1-6 alkylene-OC1-6 alkyl, —C1-6 alkylene-OH, —C1-6 alkylene-SH, —C1-6 alkylene-CN, —C1-6 alkylene-NR1eR1f, and cyclic group Cy1, wherein the cyclic group Cy1 is selected from C3-10 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, and 5- to 10-membered heteroaryl, wherein the C3-10 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, and 5- to 10-membered heteroaryl are each optionally substituted with one or more substituents independently selected from the following groups:
• halogen, OH, SH, —NR1eR1f CN, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, —O—C1-6 alkyl, —O—C1-6 haloalkyl, —S—C1-6 alkyl, —C1-6 alkylene-O—C1-6 alkyl, —OC1-6 alkylene-OC1-6 alkyl, —C1-6 alkylene-OH, —C1-6 alkylene-SH, —C1-6 alkylene-CN, and —C1-6 alkylene-NR1eR1f;
• R1c and R1d and each R2 are independently selected from:
• H, halogen, OH, SH, —NR2aR2b, CN, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, —O—C1-6 alkyl, —O—C1-6 haloalkyl, —S—C1-6 alkyl, —C1-6 alkylene-O—C1-6 alkyl, —OC1-6 alkylene-OC1-6 alkyl, —C1-6 alkylene-OH, —C1-6 alkylene-SH, —C1-6 alkylene-CN, and —C1-6 alkylene-NR2aR2b;
• m is 0, 1, 2, or 3;
• R3 and R7 are each independently selected from:
• H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, —C1-6 alkylene-O—C1-6 alkyl, —C1-6 alkylene-OH, —C1-6 alkylene-SH, —C1-6 alkylene-CN, and —C1-6 alkylene-NR3aR3b;
• R4 is selected from:
• H, D, halogen, OH, SH, —NR4aR4b, CN, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, —C1-6 alkylene-O—C1-6 alkyl, —C1-6 alkylene-OH, —C1-6 alkylene-SH, —C1-6 alkylene-CN, and —C1-6 alkylene-NR4aR4b;
• R5 is selected from:
• halogen, OH, SH, —NR5aR5b, CN, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, —O—C1-6 alkyl, —O—C1-6 haloalkyl, —S—C1-6 alkyl, —C1-6 alkylene-O—C1-6 alkyl, —OC1-6 alkylene-OC1-6 alkyl, —C1-6 alkylene-OH, —C1-6 alkylene-SH, —C1-6 alkylene-CN, —C1-6 alkylene-NR5aR5b, cyclic group Cy2, and —C1-6 alkylene-Cy2, wherein the group Cy2 is selected from C3-10 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, and 5- to 10-membered heteroaryl, wherein the C3-10 cyclohydrocarbyl, 3- to 10-membered heterocyclyl, C6-10 aryl, and 5- to 10-membered heteroaryl are each optionally substituted with one or more substituents independently selected from the following groups:
• halogen, OH, SH, —NR5aR5b, CN, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, —O—C1-6 alkyl, —O—C1-6 haloalkyl, —S—C1-6 alkyl, —C1-6 alkylene-O—C1-6 alkyl, —OC1-6 alkylene-OC1-6 alkyl, —C1-6 alkylene-OH, —C1-6 alkylene-SH, —C1-6 alkylene-CN, and —C1-6 alkylene-NR5aR5b;
• R6 is selected from:
• halogen, OH, SH, —NR6aR6b, CN, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, —O—C1-6 alkyl, —O—C1-6 haloalkyl, —S—C1-6 alkyl, —C1-6 alkylene-O—C1-6 alkyl, —OC1-6 alkylene-OC1-6 alkyl, —C1-6 alkylene-OH, —C1-6 alkylene-SH, —C1-6 alkylene-CN, and —C1-6 alkylene-NR6aR6b;
• n is 0, 1, 2, 3, or 4;
• and
• R1b, R1e, R1f, R2a, R2b, R3a, R3b, R4a, R4b, R5a, R5b, R6a, and R6b are, at each occurrence, independently selected from H and C1-6 alkyl.