Receptor inhibitor, pharmaceutical composition comprising same, and use thereof

A compound or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein the compound has a structure of formula (I″):

• wherein:
• the ring C atom at the position marked with the symbol “*” is connected to the ring C atom at the position marked with the symbol “#” through a U group;
• the U group is C1-3 alkylene;
• X3 is CR10 or N;
• R is
• wherein
• R1a is selected from the group consisting of C1-8 alkyl, C2-8 alkenyl and C2-8 alkynyl, wherein any one of the CH2 moieties in the C1-8 alkyl, C2-8 alkenyl and C2-8 alkynyl is optionally replaced with O or S;
• a saturated or partially unsaturated C3-10 cyclic hydrocarbyl group;
• a saturated or partially unsaturated 3- to 10-membered heterocyclic group;
• C6-10 aryl;
• 5- to 14-membered heteroaryl;
• —C1-6 alkylene-saturated or partially unsaturated C3-10 cyclic hydrocarbyl group;
• —C1-6 alkylene-saturated or partially unsaturated 3- to 10-membered heterocyclic group;
• —C1-6 alkylene-C6-10 aryl;
• and —C1-6 alkylene-(5- to 14-membered heteroaryl);
• R1b is selected from the group consisting of H and R1a;
• X1 is CR10 or N;
• X4 is selected from the group consisting of C(═O);
• and —OC(═O)—, —SC(═O)—, and —NR10—C(═O)—, wherein O, S, NR10 are connected to X1;
• R′ is
• wherein
• R2a is selected from the group consisting of C1-8 alkyl, C2-8 alkenyl and C2-8 alkynyl, wherein any one of the CH2 moieties in the C1-8 alkyl, C2-8 alkenyl and C2-8 alkynyl is optionally replaced with O or S;
• a saturated or partially unsaturated C3-10 cyclic hydrocarbyl group;
• a saturated or partially unsaturated 3- to 10-membered heterocyclic group;
• C6-10 aryl;
• 5- to 14-membered heteroaryl;
• —C1-6 alkylene-saturated or partially unsaturated C3-10 cyclic hydrocarbyl group;
• —C1-6 alkylene-saturated or partially unsaturated 3- to 10-membered heterocyclic group;
• —C1-6 alkylene-C6-10 aryl;
• and —C1-6 alkylene-(5- to 14-membered heteroaryl);
• R2b is selected from the group consisting of H and R2a;
• X2 is CR10 or N;
• X5 is selected from the group consisting of C(═O);
• and —OC(═O)—, and —SC(═O)—, wherein the O, and S are connected to X2;
• provided that one or two of Conditions (i) and (ii) as defined below apply:
• (i) R1a and R1b are each independently C3-10 cyclic hydrocarbyl group, 3- to 10-membered heterocyclic group, C6-10 aryl, or 5- to 14-membered heteroaryl, and an available ring atom on R1a is connected to an available ring atom on R1b through Y group, such that R1a and R1b together with X1 to which they are attached form an optionally substituted saturated or partially unsaturated fused ring system containing 3 or more rings;
• and
• (ii) R2a and R2b are each independently C3-10 cyclic hydrocarbyl group, 3- to 10-membered heterocyclic group, C6-10 aryl, or 5- to 14-membered heteroaryl, and an available ring atom on R2a is connected to an available ring atom on R2b through Z group, such that R2a and R2b together with X2 to which they are attached form an optionally substituted saturated or partially unsaturated fused ring system containing 3 or more rings;
• wherein
• Y is selected from the group consisting of a single bond;
• NR10;
• C1-3 alkylene, in which 1 or 2 CH2 moieties are optionally replaced with a group independently selected from the group consisting of O, S, and NR10;
• and C2-3 alkenylene, in which any one of the CH moieties forming a C═C double bond is optionally replaced with N;
• Z is selected from the group consisting of a single bond;
• NR10;
• C1-3 alkylene, in which 1 or 2 CH2 moieties are optionally replaced with a group independently selected from the group consisting of O, S, and NR10;
• and C2-3 alkenylene, in which any one of the CH moieties forming a C═C double bond is optionally replaced with N;
• R3 is selected from the group consisting of —C(═O)OH and —C(═O)OC1-6 alkyl;
• R4 and R10 are each independently selected from the group consisting of H, halogen, cyano, nitro, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cyclic hydrocarbyl group, 3- to 10-membered heterocyclic group, C6-10 aryl, 5- to 14-membered heteroaryl, C6-12 aralkyl, —OR11, —SR11, —P(O)(OR11)(OR12), —OC(═O)R11, —C(═O)R11, —C(═O)OR11, —C(═O)NR11R12, —C(═O)NR11S(═O)yNR11R12, —C(═O)NR11S(═O)yR12, —S(═O)yR11, —S(═O)yOR11, —S(═O)yNR11R12, —S(═O)yNR11S(═O), OR12, —S(═O)yNR11C(═O)R12, —S(═O)yNR11C(═O)OR12, —NR11R12, -NR11-C(═O)R12, —NR11—C(═O)OR12, —NR11—S(═O)y—R12, —NR11—C(═O)—NR11R12, —C1-6 alkylene-R11, —C1-6 alkylene-OR11, —C1-6 alkylene-OC(═O)R11, —C1-6 alkylene-C(═O)OR11, —C1-6 alkylene-S(═O)xR11, —C1-6 alkylene-S(═O)yOR11, —C1-6 alkylene-OC(═O)NR11R12, —C1-6 alkylene-C(═O)NR11R12, —C1-6 alkylene-C(═O)NR11—S(═O)yR12, —C1-6 alkylene-NR11—C(═O)NR11R12, —C1-6 alkylene-OS(═O)yR11, —C1-6 alkylene-OS(═O)yNR11R12, —C1-6 alkylene-S(═O)yNR11R12, —C1-6 alkylene-NR11—S(═O)yNR11R12, —C1-6 alkylene-NR11R12 and —O—C1-6 alkylene-NR11R12;
• R11 and R12, at each occurrence, are each independently selected from the group consisting of H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkyl-O—, C1-6 alkyl-S—, C3-10 cyclic hydrocarbyl group, 3- to 10-membered heterocyclic group, C6-10 aryl, 5- to 14-membered heteroaryl and C6-12 aralkyl;
• h and k are each independently 1;
• the above alkyl, alkylene, alkenyl, alkenylene, alkynyl, cyclic hydrocarbyl group, heterocyclic group, aryl, heteroaryl and aralkyl, at each occurrence, are each optionally substituted by 1, 2, 3 or more R13, wherein the R13, at each occurrence, is independently selected from the group consisting of halogen, cyano, nitro, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cyclic hydrocarbyl group, 3- to 10-membered heterocyclic group, C6-10 aryl, 5- to 14-membered heteroaryl, C6-12 aralkyl, —OR11, —SR11, —P(O)R11R12, —OC(═O)R11, —C(═O)R11, —C(═O)OR11, —C(═O)NR11R12, —C(═O)NR11S(═O)yNR11R12, —C(═O)NR11S(═O)yR12, —S(═O)yR11, —S(═O)yOR11, —S(═O)yNR11R12, —S(═O)yNR11S(═O)yOR12, —S(═O)yNR11C(═O)R12, S(═O)yNR11C(═O)OR12, —NR11R12, —NR11—C(═O)R12, —NR11—C(═O)OR12, —NR11—S(═O)y—R12, —NR11C(═O)—NR11R12, —C1-6 alkylene-R11, —C1-6 alkylene-OR11, —C1-6 alkylene-OC(═O)R11, —C1-6 alkylene-C(═O)OR11, —C1-6 alkylene-S(═O)xR11, —C1-6 alkylene-S(═O)yOR11, —C1-6 alkylene-OC(═O)NR11R12, —C1-6 alkylene-C(═O)NR11R12, —C1-6 alkylene-C(═O)NR11—S(═O)yR12, —C1-6 alkylene-NR11C(═O)NR11R12, —C1-6 alkylene-OS(═O)yR11, —C1-6 alkylene-OS(═O)yNR11R12, —C1-6 alkylene-S(═O)yNR11R12, —C1-6 alkylene-NR11—S(═O)yNR11R12, —C1-6 alkylene-NR11R12, and —O—C1-6 alkylene-NR11R12, and wherein the alkyl, alkylene, cyclic hydrocarbyl group, heterocyclic group, aryl, heteroaryl and aralkyl recited for the substituent R13 are optionally further substituted by 1, 2, 3 or more substituents independently selected from the group consisting of halogen, OH, oxo, amino, cyano, nitro, C1-6 alkyl, halogenated C1-6 alkyl, hydroxy C1-6 alkyl, C3-6 cyclic hydrocarbyl group, 3- to 10-membered heterocyclic group, C6-10 aryl, 5- to 14-membered heteroaryl and C6-12 aralkyl;
• and wherein the heterocyclic group, aryl or heteroaryl when being a substituent is connected to the rest of the molecule through a ring C atom, or where possible, through a ring N atom;
• x, at each occurrence, is independently 0, 1 or 2;
• and
• y and z, at each occurrence, are each independently 1 or 2.