Tricyclic derivative inhibitors, their preparation and application

Abstract

The present invention relates to a tricyclic derivative inhibitor, its preparation method and application, in particular to a compound represented by general formula (I), its preparation method and pharmaceutical composition containing said compound, and its use in the treatment of cancer and autoimmune diseases, wherein each substituent in general formula (I) is defined as in the specification.

Description

[Technical Field]

[0001] The present invention belongs to the field of biomedicine, and specifically relates to a tricyclic derivative inhibitor and its preparation method and application. [Background technology]

[0002] Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a protease and stent protein, an intracellular signaling molecule that plays an important role in immunity and inflammation. It is involved in NF-kB signaling downstream of B cell and T cell receptors (BCR, TCR). MALT1 forms a CBM complex with CARM1 and BCL10, and mutations in these genes can cause constitutive activation of the NF-kB signaling pathway.

[0003] The growth of ABC-DLBCL is strongly dependent on the sustained activation of the NF-kB signaling pathway. It accounts for 16% of the incidence of lymphomas in China and 40% of DLBCL in China. MALT lymphoma is caused by translocation of the MALT1 and BCL10 genes and accounts for 9% of the incidence of lymphomas in China. MALT inhibitors are also expected to be used in patients with BTK inhibitor-resistant CLL.

[0004] Currently, only Johnson & Johnson's compound JNJ-67856633 has entered clinical trial I. The NCT03900598 study in April 2019 was phase I clinical trial, and the NCT04657224 study in December 2020 was phase Ib clinical trial, both of which were in combination with a BTK inhibitor.

[0005] Currently published MALT1 inhibitor patent applications include: Johnson & Johnson's patented compounds (WO2018119036, WO2019243964, WO2019243965, WO2020208222), Novartis's MLT-985 (WO2015181747, WO2017081641), Lupin's LND-700110 (WO2018020474), and Medvir's cmpd A et al. (WO2018226150), Takeda's patented compounds (WO2020111087), Cornell University's patented compounds (WO2014074815, WO2018165385, WO2018085247), and Toray's patented compounds (WO2017057695, WO2018021520, WO2018159650).

[0006] MALT1 inhibitors are expected to be used as drugs in the pharmaceutical industry. First, it is expected to become a targeted therapy for ABC-DLBCL. The current standard treatment is R-Chop, which has a poor prognosis. Second, it is expected to be a follow-on treatment for CLL and MCL patients who have become resistant to BTK.

[0007] The main problem with current inhibitors is that in vitro activity often declines from enzymatic activity to cellular activity, and improvements in the drug formability of the compounds are needed (e.g., relatively short half-life). Summary of the Invention

[0008] An object of the present invention is to provide a compound represented by general formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the structure of the compound represented by general formula (I) is as follows: [ka] where: Ring A is selected from a cycloalkyl group, a heterocyclyl group, an aryl group, or a heteroaryl group, wherein said cycloalkyl group, heterocyclyl group, aryl group, or heteroaryl group may optionally be further substituted; Ring B is selected from a cycloalkyl group, a heterocyclyl group, an aryl group, or a heteroaryl group, wherein said cycloalkyl group, heterocyclyl group, aryl group, or heteroaryl group may optionally be further substituted; R 1 are independently hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, alkyl group, alkenyl group, alkynyl group, deuterated alkyl group, halogenated alkyl group, alkoxy group, halogenated alkoxy group, hydroxyalkyl group, cycloalkyl group, cycloalkoxy group, heterocyclyl group, aryl group, heteroaryl group, -CR cc =CR dd (CH2) n R aa , -CR cc =CR dd (CH2) n NR aa R bb , -CR cc =CR dd (CH2) n NR ee C(O)R aa , -CR cc =CR dd (CH2) n NR ee C(O)NR aa R bb , -O(CH2) n R cc , -OC(R aa R bb ) n (CH2) m R cc , -NR ee (CH2) n R cc , -(CH2) n -, -(CH2) n R cc , -(CH2) n OR cc , -(CH2) n SR cc , -(CH2) n C(O)R cc , -(CH2) n C(=NR ee )R cc , -(CH2)n C(O)OR cc , -(CH2) n S(O) m R cc , -(CH2) n NR aa R bb , -(CH2) n C(O)NR aa R bb , -(CH2) n NR ee C(O)R cc , -(CH2) n N=S(O)R cc R ee or -(CH2) n NR ee S(O) m R cc wherein the alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl groups may optionally be further substituted; Preferably, R 1 are independently hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, alkyl group, alkenyl group, alkynyl group, deuterated alkyl group, halogenated alkyl group, alkoxy group, halogenated alkoxy group, hydroxyalkyl group, cycloalkyl group, cycloalkoxy group, heterocyclyl group, aryl group, heteroaryl group, -CR cc =CR dd (CH2) n R aa , -CR cc =CR dd (CH2) n NR aa R bb , -CR cc =CR dd (CH2) n NR ee C(O)R aa , -CR cc =CR dd (CH2) n NR ee C(O)NR aa Rbb , -O(CH2) n R cc , -OC(R aa R bb ) n (CH2) m R cc , -NR ee (CH2) n R cc , -(CH2) n -, -(CH2) n R cc , -(CH2) n OR cc , -(CH2) n SR cc , -(CH2) n C(O)R cc , -(CH2) n C(=NR ee )R cc , -(CH2) n C(O)OR cc , -(CH2) n S(O) m R cc , -(CH2) n NR aa R bb , -(CH2) n C(O)NR aa R bb , -(CH2) n NR ee C(O)R cc or -(CH2) n NR ee S(O) m R cc wherein the alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl groups may optionally be further substituted; R 2is selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cycloalkyl, cycloalkoxy, heterocyclyl, aryl or heteroaryl groups, wherein said alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl groups may optionally be further substituted; R 3 is selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cycloalkyl, cycloalkoxy, heterocyclyl, aryl or heteroaryl groups, wherein said alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl groups may optionally be further substituted; R 4 are independently hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, alkyl group, alkenyl group, alkynyl group, oxo group, thio group, deuterated alkyl group, halogenated alkyl group, alkoxy group, halogenated alkoxy group, hydroxyalkyl group, cyano-substituted alkyl group, cycloalkyl group, heterocyclyl group, aryl group, heteroaryl group, -CR 33 =CR 44 (CH2) p R 11 , -CR 33 =CR 44 (CH2) p NR 11 R 22 , -CR 33 =CR 44 (CH2) p NR 55C(O)R 11 , -CR 33 =CR 44 (CH2) p NR 55 C(O)NR 11 R 22 , -O(CH2) p R 33 , -OC(R 11 R 22 ) q (CH2) p R 33 , -NR 55 (CH2) p R 33 , -(CH2) p -, -(CH2) p R 33 , -(CH2) p OR 33 , -(CH2) p SR 33 , -(CH2) p C(O)R 33 , -(CH2) p C(=NR 55 )R 33 , -(CH2) p C(O)OR 33 , -(CH2) p S(O) q R 33 , -(CH2) p NR 11 R 22 , -(CH2) p C(O)NR 11 R 22 , -(CH2) p NR 55 C(O)R 33 or -(CH2) p NR 55 S(O) q R 33 wherein the alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl groups may optionally be further substituted; Or any two adjacent or non-adjacent R4 may be linked to form a cycloalkyl, heterocyclyl, aryl or heteroaryl group, wherein said cycloalkyl, heterocyclyl, aryl or heteroaryl group may be optionally further substituted; R aa and R bb are each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups, and the amino, alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups may optionally be further substituted; Or R aa and R bb together with the adjacent atom(s) form a cycloalkyl group, a heterocyclyl group, an aryl group, or a heteroaryl group, which cycloalkyl group, heterocyclyl group, aryl group, and heteroaryl group may optionally be further substituted; R cc ~R ee are each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups, and the amino, alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups may optionally be further substituted; R 11and R 22 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups, and the amino, alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups may optionally be further substituted; Or R 11 and R 22 together with the adjacent atom(s) form a cycloalkyl group, a heterocyclyl group, an aryl group, or a heteroaryl group, which cycloalkyl group, heterocyclyl group, aryl group, and heteroaryl group may optionally be further substituted; R 33 ~R 55 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups, and the amino, alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups may optionally be further substituted; m is 0, 1, 2 or 3; n is 0, 1, 2 or 3; p is 0, 1, 2 or 3; q is 0, 1, 2 or 3; x is 0, 1, 2, 3 or 4, and y is an integer of 0 to 6.

[0009] In one preferred embodiment of the present invention, the compound, its stereoisomer or a pharmaceutically acceptable salt thereof further comprises the general formula (II): [ka] As shown in the figure.

[0010] In one preferred embodiment of the present invention, ring A is [ka] is selected from wherein M1 is selected from -N- or -C-; M2 is selected from -C(O)-, -C(S)-, -C(NH)-, -NH-, -N-, -CH2-, -CH-, -O-, or -S-; M3 is selected from -N-, -NH-, -CH-, -CH2-, -C(O)-, -C(S)-, or -C(NH)-; M4 is selected from -CH-, -CH2-, or -N-; M6 is selected from -N-, -CH-, or -CH-; M5 or M7 is -O-, -N-, -CH-, -CH=CH-, -CH2-, or absent; and M8 is selected from -N-, -NH-, -O-, -S-, or -CH-; Preferably, M1 is selected from -N- or -C-, M2 is selected from -C(O)-, -C(S)-, -C(NH)-, -NH-, -N-, -CH2-, -CH-, -O- or -S-, M3 is selected from -N-, -NH-, -CH-, -C(O)-, -C(S)- or -C(NH)-, M4 is selected from -CH-, -CH2- or -N-, M6 is selected from -N- or -CH-, M5 or M7 is -CH-, -CH2- or absent, and M8 is selected from -NH-, -O-, -S- or -CH-, Optionally, ring A further comprises 1 to 3 R 4 and any two R 4 together with the adjacent atoms, C 3-8 a cycloalkyl group, a 3- to 8-membered heterocyclyl group containing 1 to 2 atoms selected from oxygen, sulfur, or nitrogen, C 6-10forming an aryl group or a 3- to 8-membered heteroaryl group containing 1 to 2 atoms selected from oxygen, sulfur, or nitrogen; Preferably, ring A further comprises 1 to 3 R 4 and any two R 4 together with the adjacent atoms, C 3-8 a cycloalkyl group, a 3- to 8-membered heterocyclyl group containing 1 to 2 atoms selected from oxygen and nitrogen, C 6-10 An aryl group or a 3- to 8-membered heteroaryl group containing 1 to 2 atoms selected from oxygen and nitrogen, Preferably, Ring A is [ka] is selected from M1 is selected from -N- or -C-; M2 is selected from -C(O)-, -C(S)-, -C(NH)-, -NH-, -N-, -CH2-, -CH-, -O- or -S-; M3 is selected from -N-, -NH-, -CH-, -CH2-, -C(O)-, -C(S)- or -C(NH)-; M4 is selected from -CH-, -CH2- or -N-; M5 is -O-, -N-, -CH-, -CH2- or absent; Preferably, M1 is selected from -N- or -C-, M2 is selected from -C(O)-, -C(S)-, -C(NH)-, -NH-, -N-, -CH2-, -CH-, -O- or -S-, M3 is selected from -N-, -NH-, -CH-, -C(O)-, -C(S)- or -C(NH)-, M4 is selected from -CH-, -CH2- or -N-, and M5 is -CH-, -CH2- or absent, Or, ring A is [ka] is selected from M1 is selected from -N- or -C-, M2 is selected from -C(O)-, -C(S)-, -C(NH)-, -NH-, -N- or -CH-, M3 is selected from -CH- or -N-, M4 is selected from -NH- or -CH-, M6 is selected from -NH- or -CH-, and M8 is selected from -S- or -CH-; Optionally, ring A further comprises 1 to 2 R 4 and any two R 4 together with the adjacent atoms, C 3-6 forming a cycloalkyl group or a 3- to 6-membered heterocyclyl group containing 1 to 2 atoms selected from oxygen and nitrogen; More preferably, Ring A is [ka] is selected from M1 is selected from -N- or -C-; M2 is selected from -C(O)-, -C(S)-, -C(NH)-, -NH-, -N-, -CH2-, -CH-, -O- or -S-; M3 is selected from -N-, -NH-, -CH-, -C(O)-, -C(S)- or -C(NH)-; Optionally, ring A further comprises 1 to 2 R 4 and any two R 4 together with the adjacent atoms, C 3-6 It forms a cycloalkyl group or a 3- to 6-membered heterocyclyl group containing 1 to 2 atoms selected from oxygen and nitrogen.

[0011] In one preferred embodiment of the present invention, ring A is selected from the following groups: [ka] is selected from.

[0012] In one preferred embodiment of the present invention, R 2 represents hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl group, C 2-6Alkenyl group, C 2-6 Alkynyl group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 an aryl group or a 5- to 12-membered heteroaryl group, 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 The aryl and 5- to 12-membered heteroaryl groups are optionally substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, oxo group, thio group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 substituted with one or more substituents selected from aryl groups and 5- to 12-membered heteroaryl groups; Preferably, hydrogen, deuterium, halogen, C 1-3 Alkyl group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3Alkoxy group, C 1-3 hydroxyalkyl group, a 3- to 12-membered heterocyclyl group, or a 5- to 12-membered heteroaryl group, wherein said C 1-3 Alkyl group, C 1-3 Alkoxy group, C 1-3 The hydroxyalkyl group, the 3- to 12-membered heterocyclyl group, or the 5- to 12-membered heteroaryl group may optionally further comprise deuterium, halogen, amino group, nitro group, hydroxy group, cyano group, oxo group, C 1-3 Alkyl group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Hydroxyalkyl group, C 1-3 Halogenated alkoxy groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-8 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 substituted with one or more substituents selected from aryl groups and 5- to 12-membered heteroaryl groups; More preferred are hydrogen, deuterium, fluorine, chlorine, bromine, a methyl group, an ethyl group, a trifluoromethyl group, and a cyclopropyl group.

[0013] In one preferred embodiment of the present invention, R 3 represents hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 an aryl group or a 5- to 12-membered heteroaryl group, 1-6 Alkyl group, C 2-6Alkenyl group, C 2-6 Alkynyl group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 The aryl and 5- to 12-membered heteroaryl groups may optionally be substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, oxo group, thio group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 substituted with one or more substituents selected from aryl groups and 5- to 12-membered heteroaryl groups; Preferably, hydrogen, deuterium, halogen, C 1-3 Alkyl group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 hydroxyalkyl group, a 3- to 12-membered heterocyclyl group, or a 5- to 12-membered heteroaryl group, wherein said C 1-3 Alkyl group, C 1-3 Alkoxy group, C 1-3 The hydroxyalkyl group, the 3- to 12-membered heterocyclyl group, or the 5- to 12-membered heteroaryl group may optionally further comprise deuterium, halogen, amino group, nitro group, hydroxy group, cyano group, oxo group, C 1-3 Alkyl group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3Alkoxy group, C 1-3 Hydroxyalkyl group, C 1-3 Halogenated alkoxy groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-8 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 substituted with one or more substituents selected from aryl groups and 5- to 12-membered heteroaryl groups; More preferred are hydrogen, deuterium, fluorine, chlorine, bromine, a methyl group, an ethyl group, and a trifluoromethyl group.

[0014] In one preferred embodiment of the present invention, the compound, its stereoisomer or its pharmaceutically acceptable salt is further represented by general formula (IA): [ka] where: Ring B is C 3-12 Cycloalkyl groups, 3- to 14-membered heterocyclyl groups, C 6-14 an aryl group or a 5- to 14-membered heteroaryl group; Preferably, ring B is C 6-12 an aryl group or a 5- to 14-membered heteroaryl group containing 1 to 3 nitrogen atoms, oxygen atoms and / or sulfur atoms; More preferably, ring B is selected from a phenyl group, a 5- to 7-membered nitrogen-containing heteroaryl group, a benzo 5- to 7-membered nitrogen-containing heteroaryl group, a 5- to 7-membered nitrogen-containing heteroarylphenyl group, a 5- to 7-membered heteroaryl-fused 5- to 7-membered heteroaryl group, or a tricyclic heteroaryl group; Even more preferably, ring B is selected from a phenyl group, a pyridyl group or a pyridazinyl group; Ring C is C 3-6 selected from a cycloalkyl group, a 3- to 8-membered heterocyclyl group, or a 5- to 8-membered heteroaryl group; Preferably, C 5-6 a cycloalkyl group or a 5- to 6-membered heterocyclyl group, More preferably, it is a cyclopentyl group, a cyclohexyl group, a 5-membered heterocyclyl group containing 1 to 3 nitrogen atoms, oxygen atoms and / or sulfur atoms, or a 6-membered heterocyclyl group containing 1 to 3 nitrogen atoms, oxygen atoms and / or sulfur atoms. Ring F is C 3-6 Cycloalkyl groups, 3- to 8-membered heterocyclyl groups, C 6-12 selected from an aryl group or a 5- to 12-membered heteroaryl group; Preferably, C 5-6 Cycloalkyl groups, 5-6 membered heterocyclyl groups, C 6-8 an aryl group or a 5- to 8-membered heteroaryl group, Ring Q is C 3-6 Cycloalkyl groups, 3- to 8-membered heterocyclyl groups, C 6-12 selected from an aryl group or a 5- to 12-membered heteroaryl group; Preferably, C 5-6 Cycloalkyl groups, 5-6 membered heterocyclyl groups, C 6-8 an aryl group or a 5- to 8-membered heteroaryl group, R 1 are independently hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 Aryl group, 5- to 12-membered heteroaryl group, -CR cc =CR dd (CH2) n R aa , -CR cc =CR dd (CH2) n NR aa R bb , -CR cc =CR dd(CH2) n NR ee C(O)R aa , -CR cc =CR dd (CH2) n NR ee C(O)NR aa R bb , -O(CH2) n R cc , -OC(R aa R bb ) n (CH2) m R cc , -NR ee (CH2) n R cc , -(CH2) n -, -(CH2) n R cc , -(CH2) n OR cc , -(CH2) n SR cc , -(CH2) n C(O)R cc , -(CH2) n C(=NR ee )R cc , -(CH2) n C(O)OR cc , -(CH2) n S(O) m R cc , -(CH2) n NR aa R bb , -(CH2) n C(O)NR aa R bb , -(CH2) n NR ee C(O)R cc , -(CH2) n N=S(O)R cc R ee or -(CH2) n NR ee S(O) m R cc wherein the amino group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Deuterated alkyl groups, C1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 The aryl and 5- to 12-membered heteroaryl groups are optionally substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, oxo group, thio group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 substituted with one or more substituents selected from aryl groups and 5- to 12-membered heteroaryl groups; R 2 represents hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl group, C 3-8 Cycloalkyl groups, 3- to 14-membered heterocyclyl groups, C 6-14 an aryl group or a 5- to 14-membered heteroaryl group; R 3 represents hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl group, C 3-8 Cycloalkyl groups, 3- to 14-membered heterocyclyl groups, C 6-14 an aryl group or a 5- to 14-membered heteroaryl group; R 5 represents hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, oxo group, thio group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-8 Cycloalkyl groups, 3- to 14-membered heterocyclyl groups, C 6-14 Aryl group, 5- to 14-membered heteroaryl group, -(CH2) n2 C(O)R a , -(CH2) n2 C(O)OR a , -(CH2) n2 OR a , -(CH2) n2 R a or -(CH2) n2 S(O) m2 R a wherein the amino group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-8 Cycloalkyl groups, 3- to 14-membered heterocyclyl groups, C6-14 The aryl and 5- to 14-membered heteroaryl groups are optionally substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, oxo group, thio group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-8 Cycloalkyl groups, 3- to 14-membered heterocyclyl groups, C 6-14 substituted with one or more substituents selected from aryl groups and 5- to 14-membered heteroaryl groups; Preferably R 5 represents hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, oxo group, thio group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 Aryl group, 5- to 12-membered heteroaryl group, -(CH2) n2 C(O)R a , -(CH2) n2 C(O)OR a , -(CH2) n2 OR a , -(CH2) n2 R a or -(CH2) n2 S(O) m2 R a wherein the amino group, C 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4Alkynyl group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 The aryl and 5- to 12-membered heteroaryl groups are optionally substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, oxo group, thio group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 substituted with one or more substituents selected from aryl groups and 5- to 12-membered heteroaryl groups; R a is hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 an aryl group or a 5- to 12-membered heteroaryl group, 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 1-3Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 The aryl and 5- to 12-membered heteroaryl groups are optionally substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, oxo group, thio group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 substituted with one or more substituents selected from aryl groups and 5- to 12-membered heteroaryl groups; R aa and R bb are independently hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 aryl group or 5- to 12-membered heteroaryl group, optionally containing deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl group, C 3-12Cycloalkyl groups, -O(CH2) n1 R c1 , -OC(R a1 R b1 ) m1 (CH2) n1 R c1 , -NR a1 (CH2) n1 R c1 , -(CH2) n1 -, -(CH2) n1 R c1 , -(CH2) n1 OR c1 , -(CH2) n1 SR c1 , -(CH2) n1 C(O)R c1 , -(CH2) n1 C(O)OR c1 , -(CH2) n1 S(O) m1 R c1 , -(CH2) n1 NR a1 R b1 , -(CH2) n1 C(O)NR a1 R b1 , -(CH2) n1 NR a1 C(O)R c1 and -(CH2) n1 NR a1 S(O) m1 R c1 and substituted with one or more substituents of Or R aa and R bb together with the adjacent atoms, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 an aryl group or a 5- to 12-membered heteroaryl group, 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 and an aryl group to form a 5- to 12-membered heteroaryl group, optionally containing deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Deuterated alkyl groups, C1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 Aryl group, 5-12 membered heteroaryl group, -O(CH2) n1 R c1 , -OC(R a1 R b1 ) n1 (CH2) m1 R c1 , -NR a1 (CH2) n1 R c1 , -(CH2) n1 -, -(CH2) n1 R c1 , -(CH2) n1 OR c1 , -(CH2) n1 SR c1 , -(CH2) n1 C(O)R c1 , -(CH2) n1 C(O)OR c1 , -(CH2) n1 S(O) m R c1 , -(CH2) n1 NR a1 R b1 , -(CH2) n1 C(O)NR a1 R b1 , -(CH2) n1 NR a1 C(O)R c1 and -(CH2) n1 NR a1 S(O) m1 R c1 and is substituted with one or more substituents selected from the group consisting of R cc represents hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Deuterated alkyl groups, C1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 aryl group or 5- to 12-membered heteroaryl group, optionally containing deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, -O(CH2) n1 R c1 , -OC(R a1 R b1 ) n1 (CH2) m R c1 , -NR a1 (CH2) n1 R c1 , -(CH2) n1 -, -(CH2) n1 R c1 , -(CH2) n1 OR c1 , -(CH2) n1 SR c1 , -(CH2) n1 C(O)R c1 , -(CH2) n1 C(O)OR c1 , -(CH2) n1 S(O) m R c1 , -(CH2) n1 NR a1 R b1 , -(CH2) n1 C(O)NR a1 R b1 , -(CH2) n1 NR a1 C(O)R c1 and -(CH2) n1 NR a1 S(O) m1 R c1 and substituted with one or more substituents of R a1 , R b1 and R c1are independently hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 aryl group or 5- to 12-membered heteroaryl group, optionally containing deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl groups and C 3-12 substituted with one or more substituents of a cycloalkyl group; m is 0, 1, 2 or 3; m1 is 0, 1, 2 or 3; m2 is selected from 1 or 2; n is 0, 1, 2 or 3; n1 is 0, 1, 2 or 3; n2 is selected from 0, 1, 2 or 3; x is selected from 0, 1, 2, 3 or 4, and z is selected from 0, 1, 2 or 3.

[0015] In one preferred embodiment of the present invention, the compound, its stereoisomer or its pharmaceutically acceptable salt is further represented by general formula (III): [ka] where: M a , M b , M c or M d are each independently selected from —N—, —NH—, or —CH—; Ring C is a phenyl group, C 3-6selected from a cycloalkyl group, a 5- to 7-membered heterocyclyl group, or a 5- to 7-membered heteroaryl group; Preferably, it is a 5-membered heterocyclyl group containing 1 to 3 nitrogen atoms and / or 1 to 2 oxygen atoms, a 6-membered heterocyclyl group containing 1 to 3 nitrogen atoms and / or 1 to 2 oxygen atoms, a 5-membered heteroaryl group containing 1 to 3 nitrogen atoms, or a 6-membered heteroaryl group containing 1 to 3 nitrogen atoms, R 2 represents hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-3 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 selected from an aryl group or a 5- to 12-membered heteroaryl group; R 5 represents hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-3 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, oxo group, thio group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 an aryl group or a 5- to 12-membered heteroaryl group, 1-3 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 The aryl and 5- to 12-membered heteroaryl groups are optionally substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-3 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, oxo group, thio group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 substituted with one or more substituents selected from aryl groups and 5- to 12-membered heteroaryl groups; R 5 is preferably selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxy, cyano, nitro, methyl, ethyl, propyl, isopropyl, oxo, methoxy, ethoxy, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, cyclopropyl or cyclobutyl, z is selected from 0, 1, 2 or 3.

[0016] In one preferred embodiment of the present invention, ring B is C 3-12 Cycloalkyl groups, 3- to 14-membered heterocyclyl groups, C 6-14 an aryl group or a 5- to 14-membered heteroaryl group; Preferably, ring B is C 6-12 an aryl group, or a 5- to 14-membered heteroaryl group containing 1 to 3 nitrogen atoms, 1 oxygen atom, and / or 1 sulfur atom; More preferably, ring B is selected from a phenyl group, a 5- to 7-membered nitrogen-containing heteroaryl group, a benzo 5- to 7-membered nitrogen-containing heteroaryl group, a 5- to 7-membered nitrogen-containing heteroarylphenyl group, a 5- to 7-membered heteroaryl-fused 5- to 7-membered heteroaryl group, or a tricyclic heteroaryl group; Even more preferably, ring B is selected from a phenyl group, a pyridyl group or a pyridazinyl group.

[0017] In one preferred embodiment of the present invention, the compound, its stereoisomer, or its pharmaceutically acceptable salt is further represented by general formula (IV) or (V): [ka] Ring D is selected from a phenyl group, a 5-membered heteroaryl group, or a 6-membered heteroaryl group; Preferably, it is a phenyl group, a 5-membered heteroaryl group containing 1 to 3 nitrogen atoms, or a 6-membered heteroaryl group containing 1 to 3 nitrogen atoms, More preferably, it is a phenyl group, a pyridyl group, a pyrimidinyl group, or a pyridazinyl group. Ring E is a phenyl group, C 3-6 selected from a cycloalkyl group, a 5- to 7-membered heterocyclyl group, or a 5- to 7-membered heteroaryl group; Preferably, a phenyl group, C 5-6 a cycloalkyl group, a 5-membered heterocyclyl group containing 1 to 3 nitrogen atoms and / or 1 to 2 oxygen atoms, a 6-membered heterocyclyl group containing 1 to 3 nitrogen atoms and / or 1 to 2 oxygen atoms, a 5-membered heteroaryl group containing 1 to 3 nitrogen atoms, or a 6-membered heteroaryl group containing 1 to 3 nitrogen atoms; More preferred are a phenyl group, a cyclopentyl group, a cyclohexyl group, a pyrrolyl group, a pyrazolyl group, an imidazolyl group, a triazolyl group, a pyridyl group, a pyrimidinyl group, a pyridazinyl group, and a pyrazinyl group.

[0018] In one preferred embodiment of the present invention, the compound, its stereoisomer, or its pharmaceutically acceptable salt is further represented by general formula (IV-A) or (VA): [ka] where: M a , M c , M e , M f or M g are each independently selected from —N— or —CH—.

[0019] In one preferred embodiment of the present invention, the compound, its stereoisomer, or its pharmaceutically acceptable salt is further represented by general formula (IV-B): [ka] where: M a is selected from -N- or -CH-; M c is selected from -N- or -CH-; R6 is selected from a 3- to 7-membered heterocyclyl group or a 5- to 7-membered heteroaryl group, and the 3- to 7-membered heterocyclyl group and the 5- to 7-membered heteroaryl group may optionally further contain deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, oxo group, thio group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 substituted with one or more substituents selected from aryl groups and 5- to 12-membered heteroaryl groups; Preferably, R6 is selected from a 4-membered heterocyclyl group, a 5-membered heterocyclyl group, a 6-membered heterocyclyl group, or a 5-membered heteroaryl group, and the 4-membered heterocyclyl group, the 5-membered heterocyclyl group, the 6-membered heterocyclyl group, and the 5-membered heteroaryl group may optionally further comprise deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, oxo group, thio group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 8-membered heterocyclyl groups, C 6-10 substituted with one or more substituents selected from aryl groups and 5- to 8-membered heteroaryl groups; More preferably, R6 is [ka] and optionally further substituted with one or more substituents selected from the group consisting of deuterium, fluorine, chlorine, bromine, amino, hydroxy, cyano, nitro, methyl, ethyl, oxo, thio, difluoromethyl, trifluoromethyl, methoxy, ethoxy, and trifluoromethoxy.

[0020] In one preferred embodiment of the present invention, the compound, its stereoisomer, or its pharmaceutically acceptable salt is further represented by general formula (IV-C): [ka] where: M a is selected from -N- or -CH-; M c is selected from -N- or -CH-; R6 is selected from a 3- to 7-membered heterocyclyl group or a 5- to 7-membered heteroaryl group, and the 3- to 7-membered heterocyclyl group and the 5- to 7-membered heteroaryl group may optionally further contain deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, oxo group, thio group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 substituted with one or more substituents selected from aryl groups and 5- to 12-membered heteroaryl groups; Preferably, R6 is selected from a 4-membered heterocyclyl group, a 5-membered heterocyclyl group, a 6-membered heterocyclyl group, or a 5-membered heteroaryl group, and the 4-membered heterocyclyl group, the 5-membered heterocyclyl group, the 6-membered heterocyclyl group, and the 5-membered heteroaryl group may optionally further comprise deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, oxo group, thio group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 8-membered heterocyclyl groups, C 6-10 substituted with one or more substituents selected from aryl groups and 5- to 8-membered heteroaryl groups; More preferably, R6 is [ka] and optionally further substituted with one or more substituents selected from deuterium, fluorine, chlorine, bromine, amino, hydroxy, cyano, nitro, methyl, ethyl, oxo, thio, difluoromethyl, trifluoromethyl, methoxy, ethoxy, and trifluoromethoxy.

[0021] In one preferred embodiment of the present invention, [ka] teeth, [ka] is selected from Said M a , M b , M c , M d , R 5 wherein rings C and z are as defined in any one of the above embodiments; is preferably [ka] is selected from R 7 represents hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 Aryl group, 5- to 12-membered heteroaryl group, -(CH2) n2 C(O)R a , -(CH2) n2 C(O)OR a , -(CH2) n2OR a , -(CH2) n2 R a or -(CH2) n2 S(O) m2 R a wherein the amino group, C 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 The aryl and 5- to 12-membered heteroaryl groups are optionally substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, oxo group, thio group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 substituted with one or more substituents selected from aryl groups and 5- to 12-membered heteroaryl groups; R a is hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 an aryl group or a 5- to 12-membered heteroaryl group, 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 The aryl and 5- to 12-membered heteroaryl groups are optionally substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, oxo group, thio group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 substituted with one or more substituents selected from aryl groups and 5- to 12-membered heteroaryl groups; n2 is selected from 0, 1, 2 or 3; m2 is selected from 1 or 2; Said M a and M c is as defined in any one of the above embodiments.

[0022] In one preferred embodiment of the present invention, [ka] teeth, [ka] [ka] is selected from.

[0023] In one preferred embodiment of the present invention, ring C is [ka] is selected from Preferably, ring C is [ka] is selected from.

[0024] In one preferred embodiment of the present invention, the compound, its stereoisomer or its pharmaceutically acceptable salt is further represented by general formula (VI): [ka] R 7 represents hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 Aryl group, 5- to 12-membered heteroaryl group, -(CH2) n2 C(O)R a , -(CH2) n2 C(O)OR a , -(CH2) n2 OR a , -(CH2) n2 R aor -(CH2) n2 S(O) m2 R a wherein the amino group, C 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 The aryl and 5- to 12-membered heteroaryl groups are optionally substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, oxo group, thio group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 substituted with one or more substituents selected from aryl groups and 5- to 12-membered heteroaryl groups; R 7 is preferably selected from hydrogen, deuterium, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, cyclopropyl, cyclobutyl, benzyl or p-methoxybenzyl; R a is hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 1-3Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 an aryl group or a 5- to 12-membered heteroaryl group, 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 The aryl and 5- to 12-membered heteroaryl groups are optionally substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, oxo group, thio group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 substituted with one or more substituents selected from aryl groups and 5- to 12-membered heteroaryl groups; n2 is selected from 0, 1, 2 or 3; m2 is selected from 1 or 2.

[0025] In one preferred embodiment of the present invention, the compound, its stereoisomer or its pharmaceutically acceptable salt may further be represented by the general formula (VI-A), (VI-B), (VI-C), (VI-D), (VI-E), (VI-F) or (VI-G): [ka] As shown in the figure.

[0026] In one preferred embodiment of the present invention, R 1 are independently hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 Aryl group, 5- to 12-membered heteroaryl group, -CR cc =CR dd (CH2) n R aa , -CR cc =CR dd (CH2) n NR aa R bb , -CR cc =CR dd (CH2) n NR ee C(O)R aa , -CR cc =CR dd (CH2) n NR ee C(O)NR aa R bb , -O(CH2) n R cc , -OC(R aa R bb ) n (CH2) mR cc , -NR ee (CH2) n R cc , -(CH2) n -, -(CH2) n R cc , -(CH2) n OR cc , -(CH2) n SR cc , -(CH2) n C(O)R cc , -(CH2) n C(=NR ee )R cc , -(CH2) n C(O)OR cc , -(CH2) n S(O) m R cc , -(CH2) n NR aa R bb , -(CH2) n C(O)NR aa R bb , -(CH2) n NR ee C(O)R cc , -(CH2) n N=S(O)R cc R ee or -(CH2) n NR ee S(O) m R cc wherein the amino group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 The aryl and 5- to 12-membered heteroaryl groups are optionally substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 Alkyl group, C2-6 Alkenyl group, C 2-6 Alkynyl group, oxo group, thio group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 substituted with one or more substituents selected from aryl groups and 5- to 12-membered heteroaryl groups; R 1 are independently preferably hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 Aryl group, 5- to 12-membered heteroaryl group, -CR cc =CR dd (CH2) n R aa , -CR cc =CR dd (CH2) n NR aa R bb , -CR cc =CR dd (CH2) n NR ee C(O)R aa , -CR cc =CR dd (CH2) n NR ee C(O)NR aa R bb , -O(CH2) n R cc, -OC(R aa R bb ) n (CH2) m R cc , -NR ee (CH2) n R cc , -(CH2) n -, -(CH2) n R cc , -(CH2) n OR cc , -(CH2) n SR cc , -(CH2) n C(O)R cc , -(CH2) n C(=NR ee )R cc , -(CH2) n C(O)OR cc , -(CH2) n S(O) m R cc , -(CH2) n NR aa R bb , -(CH2) n C(O)NR aa R bb , -(CH2) n NR ee C(O)R cc or -(CH2) n NR ee S(O) m R cc wherein the amino group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 The aryl and 5- to 12-membered heteroaryl groups are optionally substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, oxo group, thio group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 substituted with one or more substituents selected from aryl groups and 5- to 12-membered heteroaryl groups; R 1 is more preferably hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-3 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 Aryl group, 5-12 membered heteroaryl group, -O(CH2) n R cc , -OC(R aa R bb ) n (CH2) m R cc , -(CH2) n -, -(CH2) n R cc or -(CH2) n OR cc wherein the amino group, C 1-3 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 The aryl and 5- to 12-membered heteroaryl groups are optionally substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-3 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, oxo group, thio group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 substituted with one or more substituents selected from aryl groups and 5- to 12-membered heteroaryl groups; R aa and R bb are independently hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 aryl group or 5- to 12-membered heteroaryl group, optionally containing deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, -O(CH2) n1 R c1 , -OC(R a1 Rb1 ) m1 (CH2) n1 R c1 , -NR a1 (CH2) n1 R c1 , -(CH2) n1 -, -(CH2) n1 R c1 , -(CH2) n1 OR c1 , -(CH2) n1 SR c1 , -(CH2) n1 C(O)R c1 , -(CH2) n1 C(O)OR c1 , -(CH2) n1 S(O) m1 R c1 , -(CH2) n1 NR a1 R b1 , -(CH2) n1 C(O)NR a1 R b1 , -(CH2) n1 NR a1 C(O)R c1 and -(CH2) n1 NR a1 S(O) m1 R c1 and substituted with one or more substituents of Or R aa and R bb together with the adjacent atoms, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 An aryl group or a 5- to 12-membered heteroaryl group is formed, and 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 The aryl and 5- to 12-membered heteroaryl groups are optionally substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 Aryl group, 5-12 membered heteroaryl group, -O(CH2) n1 R c1 , -OC(R a1 R b1 ) n1 (CH2) m R c1 , -NR a1 (CH2) n1 R c1 , -(CH2) n1 -, -(CH2) n1 R c1 , -(CH2) n1 OR c1 , -(CH2) n1 SR c1 , -(CH2) n1 C(O)R c1 , -(CH2) n1 C(O)OR c1 , -(CH2) n1 S(O) m R c1 , -(CH2) n1 NR a1 R b1 , -(CH2) n1 C(O)NR a1 R b1 , -(CH2) n1 NR a1 C(O)R c1 and -(CH2) n1 NR a1 S(O) m1 R c1 and is substituted with one or more substituents selected from the group consisting of R cc represents hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 aryl group or 5- to 12-membered heteroaryl group, optionally containing deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, -O(CH2) n1 R c1 , -OC(R a1 R b1 ) n1 (CH2) m R c1 , -NR a1 (CH2) n1 R c1 , -(CH2) n1 -, -(CH2) n1 R c1 , -(CH2) n1 OR c1 , -(CH2) n1 SR c1 , -(CH2) n1 C(O)R c1 , -(CH2) n1 C(O)OR c1 , -(CH2) n1 S(O) m R c1 , -(CH2) n1 NR a1 R b1 , -(CH2) n1 C(O)NR a1 R b1 , -(CH2) n1 NR a1 C(O)R c1 and -(CH2) n1 NR a1 S(O) m1 R c1 and substituted with one or more substituents of R a1 ~R c1 are independently hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C2-6 Alkynyl group, C 1-6 Deuterated alkyl groups, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, cyano-substituted C 1-6 Alkyl group, C 3-12 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 aryl group or 5- to 12-membered heteroaryl group, optionally containing deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 Alkyl groups and C 3-12 substituted with one or more substituents of a cycloalkyl group; m1 is 0, 1, 2 or 3, and n1 is 0, 1, 2 or 3.

[0027] In a further preferred embodiment of the present invention, R 1 is selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxy, cyano, nitro, methyl, ethyl, propyl, isopropyl, oxo, methoxy, ethoxy, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, cyclopropyl, cyclobutyl, oxetanyl, azetidinyl, triazolyl, oxazolyl, isoxazolyl, pyrazolyl, pyrrolyl or thiazolyl, wherein the cyclopropyl, cyclobutyl, oxetanyl, azetidinyl, triazolyl, oxazolyl, isoxazolyl, pyrazolyl, pyrrolyl and thiazolyl groups are optionally selected from deuterium, fluorine, chlorine, bromine, amino, hydroxy, cyano, nitro, C 1-3 Alkyl group, oxo group, thio group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl and cyano-substituted C 1-3The alkyl group is substituted with one or more substituents.

[0028] The present invention further provides a compound represented by general formula (XA), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: [ka] where: M a , M b , M c , M d , R 5 , rings C and z are as defined in any one of the above embodiments.

[0029] The present invention further provides a compound represented by general formula (XB), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: [ka] where: R 8 are hydrogen, deuterium, and C 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 an aryl group or a 5- to 12-membered heteroaryl group, 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 The aryl and 5- to 12-membered heteroaryl groups are optionally substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, oxo group, thio group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 substituted with one or more substituents selected from aryl groups and 5- to 12-membered heteroaryl groups; Preferably, R 8 are hydrogen, deuterium, and C 1-3 alkyl groups, M a , M b , M c , M d , R 2 , R 5 , rings C and z are as defined in any one of the above embodiments.

[0030] The present invention further provides a compound represented by general formula (XC), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: [ka] where: M a , M c , R 5 , R 7 and z are as defined in any one of the above embodiments.

[0031] The present invention further provides a compound represented by general formula (XD), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: [ka] where: R 8 are hydrogen, deuterium, and C 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 an aryl group or a 5- to 12-membered heteroaryl group, 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12 The aryl and 5- to 12-membered heteroaryl groups are optionally substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-3 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, oxo group, thio group, C 1-3 Deuterated alkyl groups, C 1-3 Halogenated alkyl groups, C 1-3 Alkoxy group, C 1-3 Halogenated alkoxy groups, C 1-3 Hydroxyalkyl, cyano-substituted C 1-3 Alkyl group, C 3-6 Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C 6-12substituted with one or more substituents selected from aryl groups and 5- to 12-membered heteroaryl groups; Preferably, R 8 are hydrogen, deuterium, and C 1-3 alkyl groups, M a , M c and R 7 is as defined in any one of the above embodiments.

[0032] The present invention further relates to a method for preparing a compound according to general formula (XB), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, [ka] A compound of general formula (XE) [ka] to obtain a compound of general formula (XB), M a , M b , M c , M d , R 2 , R 5 , R 8 , rings C and z are as defined in any one of the above embodiments.

[0033] The present invention further relates to a method for preparing a compound according to general formula (III), a stereoisomer thereof or a pharmaceutically acceptable salt thereof, [ka] A compound of general formula (XF) is subjected to amide condensation in the presence of a condensing agent to obtain a compound of general formula (III), the condensing agent is selected from phosphorus oxychloride, thionyl chloride, oxalyl chloride, diisopropyl azodicarboxylate, diethyl azodicarboxylate, carbodiimide hydrochloride, N,N'-diisopropylcarbodiimide, dicyclohexylcarbodiimide, HATU, HBTU, HOBT, TCFH, PyBop, or PyClock; M a , M b , M c , M d , R 2 , R 5 , R 1 , Ring B, Ring C, x and z are as defined in any one of the above embodiments.

[0034] The present invention further relates to a method for preparing a compound according to general formula (XD), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, [ka] A compound of general formula (XG) [ka] to obtain a compound of general formula (XD), M a , M c , R 2 , R 5 , R 8 and R 7 is as defined in any one of the above embodiments.

[0035] The present invention further relates to a method for preparing a compound according to general formula (VI), a stereoisomer thereof or a pharmaceutically acceptable salt thereof, [ka] A compound of general formula (XH) is subjected to amide condensation in the presence of a condensing agent to obtain a compound of general formula (VI), the condensing agent is selected from phosphorus oxychloride, thionyl chloride, oxalyl chloride, diisopropyl azodicarboxylate, diethyl azodicarboxylate, carbodiimide hydrochloride, N,N'-diisopropylcarbodiimide, dicyclohexylcarbodiimide, HATU, HBTU, HOBT, TCFH, PyBop, or PyClock; M a , M c , R 2 , R 7 , R 1 , ring B and x are as defined in any one of the above embodiments.

[0036] The present invention further relates to pharmaceutical compositions, which comprise a therapeutically effective amount of a compound of general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers, diluents or excipients.

[0037] The present invention further relates to the application of the compound of general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition in the manufacture of a MALT1 inhibitor drug.

[0038] The present invention further relates to the application of the compound represented by general formula (I), its stereoisomer or pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof in the manufacture of a medicament for treating cancer or autoimmune diseases.

[0039] The present invention further includes a method of treating cancer or an autoimmune disease.

[0040] The cancer or autoimmune disease of the present invention is selected from B-cell lymphoma, non-Hodgkin's lymphoma, mantle cell lymphoma, follicular lymphoma, mucosa-associated lymphoid tissue lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, psoriatic arthritis, psoriasis, ulcerative colitis, Crohn's disease, systemic lupus erythematosus, asthma and chronic obstructive pulmonary disease.

[0041] The method of treatment according to the present invention comprises administering to a subject a therapeutically effective amount of a compound of the present invention. In one embodiment, the present invention provides a method of treatment, including cancer or an autoimmune disease in a mammal, comprising administering to said mammal a therapeutically effective amount of a compound of the present invention, or a pharmaceutically acceptable salt, ester, prodrug, solvate, hydrate, or derivative thereof. Detailed Description of the Invention

[0042] Unless stated to the contrary, terms used in the specification and claims have the following meanings.

[0043] The term "alkyl group" refers to a saturated aliphatic hydrocarbon group, which is a straight or branched chain group containing 1 to 20 carbon atoms, preferably an alkyl group containing 1 to 8 carbon atoms, more preferably an alkyl group containing 1 to 6 carbon atoms, and most preferably an alkyl group containing 1 to 3 carbon atoms. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, and 5-methylhexyl groups. , 2,3-dimethylpentyl, 2,4-dimethylpentyl, 2,2-dimethylpentyl, 3,3-dimethylpentyl, 2-ethylpentyl, 3-ethylpentyl, n-octyl, 2,3-dimethylhexyl, 2,4-dimethylhexyl, 2,5-dimethylhexyl, 2,2-dimethylhexyl, 3,3-dimethylhexyl, 4,4-dimethylhexyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 2-methyl-2-ethylpentyl, 2-methyl-3-ethylpentyl, n-nonyl, 2-methyl-2-ethylhexyl, 2-methyl-3-ethylhexyl, 2,2-diethylpentyl, n-decyl, 3,3-diethylhexyl, 2,2-diethylhexyl, and various branched chain isomers thereof.More preferred are lower alkyl groups containing 1 to 6 carbon atoms, and non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, and 2,3-dimethylbutyl. The alkyl group may be substituted or unsubstituted. When substituted, the substituent may be substituted at any available linkage site, and the substituent is preferably one or more groups independently selected from alkyl groups, alkenyl groups, alkynyl groups, alkoxy groups, alkylthio groups, alkylamino groups, halogens, mercapto groups, hydroxy groups, nitro groups, cyano groups, cycloalkyl groups, heterocycloalkyl groups, aryl groups, heteroaryl groups, cycloalkoxy groups, heterocycloalkoxy groups, cycloalkylthio groups, heterocycloalkylthio groups, oxo groups, carboxyl groups, and carboxylate groups, and in the present invention, is preferably a methyl group, an ethyl group, an isopropyl group, a tert-butyl group, a halogenated alkyl group, a deuterated alkyl group, an alkyl group substituted with an alkoxy group, and an alkyl group substituted with a hydroxy group.

[0044] The term "alkylene group" refers to an alkyl group in which one hydrogen atom is further substituted, e.g., a "methylene group" refers to -CH-, an "ethylene group" refers to -(CH)-, a "propylene group" refers to -(CH)-, a "butylene group" refers to -(CH)-, etc. The term "alkenyl group" refers to an alkyl group as defined above consisting of at least two carbon atoms and at least one carbon-carbon double bond, e.g., vinyl, 1-propenyl, 2-propenyl, 1-, 2-, or 3-butenyl, etc. The alkenyl group may be substituted or unsubstituted, and when substituted, the substituents are preferably one or more groups independently selected from alkyl groups, alkenyl groups, alkynyl groups, alkoxy groups, alkylthio groups, alkylamino groups, halogens, mercapto groups, hydroxy groups, nitro groups, cyano groups, cycloalkyl groups, heterocycloalkyl groups, aryl groups, heteroaryl groups, cycloalkoxy groups, heterocycloalkoxy groups, cycloalkylthio groups, and heterocycloalkylthio groups.

[0045] The term "cycloalkyl group" refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon substituent, where the ring of the cycloalkyl group contains 3 to 20 carbon atoms, preferably 3 to 12 carbon atoms, and more preferably 3 to 6 carbon atoms. Non-limiting examples of monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl, etc. Polycyclic cycloalkyl groups include spirocyclic, fused-ring, and bridged-ring cycloalkyl groups, preferably cyclopropyl, cyclobutyl, cyclohexyl, cyclopentyl, and cycloheptyl.

[0046] The term "spirocycloalkyl group" refers to a 5- to 20-membered polycyclic group in which monocyclic rings share one carbon atom (called a spiro atom), which may contain one or more double bonds, but in which none of the rings has a completely conjugated π-electron system. It is preferably 6- to 14-membered, more preferably 7- to 10-membered. Depending on the number of shared spiro atoms between the rings, spirocycloalkyl groups are classified as monospirocycloalkyl groups, bisspirocycloalkyl groups, or polyspirocycloalkyl groups, with monospirocycloalkyl groups and bisspirocycloalkyl groups being preferred. More preferred are 3-membered / 6-membered, 3-membered / 5-membered, 4-membered / 4-membered, 4-membered / 5-membered, 4-membered / 6-membered, 5-membered / 5-membered, or 5-membered / 6-membered monospirocycloalkyl groups. Non-limiting examples of spirocycloalkyl groups include: [ka] Including, Also included are spirocycloalkyl groups in which the monospirocycloalkyl group and the heterocycloalkyl group share a spiro atom, non-limiting examples of which are: [ka] Includes:

[0047] The term "fused cycloalkyl group" refers to a 5- to 20-membered all-carbon polycyclic group in which each ring in the system shares an adjacent pair of carbon atoms with another ring in the system, where one or more rings may contain one or more double bonds, but no ring has a completely conjugated π-electron system. Preferably, it has 6 to 14 members, more preferably 7 to 10 members. Depending on the number of rings, it may be divided into bicyclic, tricyclic, tetracyclic, or polycyclic fused cycloalkyl groups, preferably bicyclic or tricyclic, more preferably 5-membered / 5-membered or 5-membered / 6-membered bicyclic cycloalkyl groups. Non-limiting examples of fused cycloalkyl groups are: [ka] Includes:

[0048] A "bridged cycloalkyl group" refers to a 5- to 20-membered all-carbon polycyclic group in which any two rings share two carbon atoms that are not directly linked, and it may contain one or more double bonds, but no ring has a completely conjugated π-electron system. It is preferably 6- to 14-membered, more preferably 7- to 10-membered. Depending on the number of rings, bridged cycloalkyl groups may be classified as bicyclic, tricyclic, tetracyclic, or polycyclic, and are preferably bicyclic, tricyclic, or tetracyclic, and more preferably bicyclic or tricyclic. Non-limiting examples of bridged cycloalkyl groups include the following: [ka]

[0049] The ring of the cycloalkyl group can be fused onto the ring of an aryl group, a heteroaryl group, or a heterocycloalkyl group, where the ring connected to the base skeleton is a cycloalkyl group, non-limiting examples of which include an indanyl group, a tetrahydronaphthyl group, a benzocycloheptyl group, etc. The cycloalkyl group can be optionally substituted or unsubstituted, and when substituted, the substituents are preferably one or more groups independently selected from alkyl groups, alkenyl groups, alkynyl groups, alkoxy groups, alkylthio groups, alkylamino groups, halogens, mercapto groups, hydroxy groups, nitro groups, cyano groups, cycloalkyl groups, heterocycloalkyl groups, aryl groups, heteroaryl groups, cycloalkoxy groups, heterocycloalkoxy groups, cycloalkylthio groups, heterocycloalkylthio groups, oxo groups, carboxyl groups, and carboxylate groups.

[0050] The term "heterocyclyl group" refers to a saturated or partially unsaturated mono- or polycyclic hydrocarbon substituent containing 3 to 20 ring atoms, wherein one or more of the ring atoms is nitrogen, oxygen, or S(O). m(where m is an integer of 0 to 2), but does not include the ring moieties -OO-, -OS-, or -SS-, and the other ring atoms are carbon. Preferably, it contains 3 to 12 ring atoms, of which 1 to 4 are heteroatoms, more preferably 3 to 8 ring atoms, and even more preferably, it contains 3 to 8-membered heterocyclyl groups containing 1 to 3 nitrogen atoms, optionally substituted with 1 to 2 oxygen atoms, sulfur atoms, or oxo groups, and includes nitrogen-containing monocyclic heterocyclyl groups, nitrogen-containing spiroheterocyclyl groups, and nitrogen-containing fused heterocyclyl groups, and even more preferably it contains 3 to 7 ring atoms, of which 1 to 4 are heteroatoms, and in one embodiment, the heterocyclyl group contains 3, 4, 5, 6, 7, or 8 ring atoms.

[0051] Non-limiting examples of monocyclic heterocyclyl groups include pyrrolidinyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, dihydroimidazolyl, dihydrofuryl, dihydropyrazolyl, dihydropyrrolyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, azepanyl, 1,4-diazacycloheptyl, and pyranyl groups, and preferably pyrrolidinyl, morpholinyl, piperidinyl, azepanyl, 1,4-diazacycloheptyl, and piperazinyl groups. Polycyclic heterocyclyl groups include spirocyclic, fused-ring, and bridged-ring heterocyclyl groups, where such spirocyclic, fused-ring, and bridged-ring heterocyclyl groups are optionally linked to other groups via a single bond or further tandemly linked to other cycloalkyl, heterocyclyl, aryl, and heteroaryl groups via any two or more atoms on the ring.

[0052] The term "spiroheterocyclyl group" refers to a 5- to 20-membered polycyclic heterocyclyl group in which the monocyclic rings share one atom (called a spiroatom), where one or more of the ring atoms is nitrogen, oxygen, or S(O). m(where m is an integer of 0 to 2), and the other ring atoms are carbon. It may contain one or more double bonds, but none of the rings has a completely conjugated π-electron system. It is preferably 6 to 14-membered, more preferably 7 to 10-membered. Depending on the number of shared spiro atoms between the rings, spiroheterocyclyl groups are divided into monospiroheterocyclyl groups, bisspiroheterocyclyl groups, and polyspiroheterocyclyl groups, and preferred are monospiroheterocyclyl groups and bisspiroheterocyclyl groups. More preferred are 3-membered / 5-membered, 3-membered / 6-membered, 4-membered / 4-membered, 4-membered / 5-membered, 4-membered / 6-membered, 5-membered / 5-membered, or 5-membered / 6-membered monospiroheterocyclyl groups. Non-limiting examples of spiroheterocyclyl groups are: [ka] Includes:

[0053] The term "fused heterocyclyl group" refers to a 5- to 20-membered polycyclic heterocyclyl group in which each ring in the system shares an adjacent pair of carbon atoms with another ring in the system, one or more rings may contain one or more double bonds, but no ring has a completely conjugated pi-electron system, and wherein one or more ring atoms is nitrogen, oxygen, or S(O) m (where m is an integer of 0 to 2), and the other ring atoms are carbon. Preferably, it is 6 to 14-membered, more preferably 7 to 10-membered. Depending on the number of rings constituting it, it may be classified as a bicyclic, tricyclic, tetracyclic or polycyclic fused heterocyclyl group, preferably a bicyclic or tricyclic, more preferably a 5-membered / 5-membered or 5-membered / 6-membered bicyclic fused heterocyclyl group. Non-limiting examples of fused heterocyclyl groups are: [ka] Includes:

[0054] The term "bridged heterocyclyl group" refers to a 5- to 14-membered polycyclic heterocyclyl group in which any two rings share two atoms that are not directly linked, which may contain one or more double bonds, but no ring has a completely conjugated pi-electron system, and in which one or more ring atoms is not nitrogen, oxygen, or S(O). m (where m is an integer of 0 to 2), and the other ring atoms are carbon. Preferably, it is 6 to 14-membered, more preferably 7 to 10-membered. Depending on the number of rings, it may be classified as a bicyclic, tricyclic, tetracyclic or polycyclic bridged heterocyclyl group, preferably a bicyclic, tricyclic or tetracyclic group, more preferably a bicyclic or tricyclic group. Non-limiting examples of bridged heterocyclyl groups are: [ka] Includes:

[0055] The ring of the heterocyclyl group may be fused onto the ring of an aryl group, a heteroaryl group, or a cycloalkyl group, where the ring connected to the base skeleton is a heterocyclyl group, non-limiting examples of which include: [ka] Includes:

[0056] Heterocyclyl groups may be optionally substituted or unsubstituted, and if substituted, the substituents are preferably one or more groups independently selected from alkyl groups, alkenyl groups, alkynyl groups, alkoxy groups, alkylthio groups, alkylamino groups, halogens, mercapto groups, hydroxy groups, nitro groups, cyano groups, cycloalkyl groups, heterocycloalkyl groups, aryl groups, heteroaryl groups, cycloalkoxy groups, heterocycloalkoxy groups, cycloalkylthio groups, heterocycloalkylthio groups, oxo groups, carboxyl groups, or carboxylate groups.

[0057] The term "aryl group" refers to a 6- to 14-membered all-carbon monocyclic or fused polycyclic (i.e., rings sharing adjacent pairs of carbon atoms) group having a conjugated π-electron system, preferably 6- to 12-membered, such as phenyl and naphthyl groups. Phenyle is more preferred. The ring of the aryl group may be fused to a heteroaryl group, heterocyclyl group, or cycloalkyl group, including 5- to 10-membered benzoheteroaryl groups, 3- to 8-membered benzocycloalkyl groups, and 3- to 8-membered benzoheteroalkyl groups, preferably 5- to 6-membered benzoheteroaryl groups, 3- to 6-membered benzocycloalkyl groups, and 3- to 6-membered benzoheteroalkyl groups, where the heterocyclyl group is a heterocyclyl group containing 1 to 3 nitrogen, oxygen, or sulfur atoms, or further containing a 3-membered nitrogen-containing fused ring containing a benzene ring.

[0058] Here, the ring connected to the basic skeleton is an aryl group ring, and non-limiting examples thereof include: [ka] Includes:

[0059] The aryl group may be substituted or unsubstituted, and if substituted, the substituents are preferably one or more groups independently selected from alkyl groups, alkenyl groups, alkynyl groups, alkoxy groups, alkylthio groups, alkylamino groups, halogens, mercapto groups, hydroxy groups, nitro groups, cyano groups, cycloalkyl groups, heterocycloalkyl groups, aryl groups, heteroaryl groups, cycloalkoxy groups, heterocycloalkoxy groups, cycloalkylthio groups, heterocycloalkylthio groups, carboxyl groups, or carboxylate groups.

[0060] The term "heteroaryl group" refers to a heteroaromatic system containing 1 to 4 heteroatoms and 5 to 14 ring atoms, where the heteroatoms are oxygen, sulfur, and nitrogen. The heteroaryl group is preferably 5 to 12-membered, more preferably 5 to 8-membered, even more preferably 5 to 7-membered, and even more preferably 5 or 6-membered, such as an imidazolyl group, furyl group, thienyl group, thiazolyl group, pyrazolyl group, oxazolyl group, pyrrolyl group, triazolyl group, tetrazolyl group, pyridyl group, pyrimidinyl group, thiadiazole group, or pyridinyl group, preferably a triazolyl group, thienyl group, imidazolyl group, pyrazolyl group, oxazolyl group, pyrimidinyl group, or thiazolyl group, more preferably a pyrazolyl group, pyrrolyl group, imidazolyl group, triazolyl group, oxazolyl group, or pyridyl group. The ring of the heteroaryl group can be fused onto the ring of an aryl group, a heterocyclyl group, or a cycloalkyl group, where the ring connected to the base skeleton is the ring of the heteroaryl group, non-limiting examples of which include: [ka] Includes:

[0061] Heteroaryl groups may be optionally substituted or unsubstituted, and if substituted, the substituents are preferably one or more groups independently selected from alkyl groups, alkenyl groups, alkynyl groups, alkoxy groups, alkylthio groups, alkylamino groups, halogens, mercapto groups, hydroxy groups, nitro groups, cyano groups, cycloalkyl groups, heterocycloalkyl groups, aryl groups, heteroaryl groups, cycloalkoxy groups, heterocycloalkoxy groups, cycloalkylthio groups, heterocycloalkylthio groups, carboxyl groups, or carboxylate groups.

[0062] The term "alkoxy" refers to -O-(alkyl) and -O-(unsubstituted cycloalkyl), where alkyl is as defined above. Non-limiting examples of alkoxy groups include methoxy, ethoxy, propoxy, butoxy, cyclopropoxy, cyclobutoxy, cyclopentyloxy, and cyclohexyloxy. An alkoxy group may be optionally substituted or unsubstituted; if substituted, the substituents are preferably one or more groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, carboxyl, or carboxylate.

[0063] "Halogenated alkyl group" refers to an alkyl group that is substituted with one or more halogens, where alkyl group is as defined above.

[0064] A "halogenated alkoxy group" refers to an alkoxy group substituted with one or more halogens, where alkoxy groups are as defined above.

[0065] "Hydroxyalkyl group" refers to an alkyl group substituted with a hydroxy group, where alkyl group is as defined above.

[0066] An "alkenyl group" is an alkenyl group, further referred to as an alkylene group, where the alkenyl group may be further substituted with other related groups, such as alkyl groups, alkenyl groups, alkynyl groups, alkoxy groups, alkylthio groups, alkylamino groups, halogens, mercapto groups, hydroxy groups, nitro groups, cyano groups, cycloalkyl groups, heterocycloalkyl groups, aryl groups, heteroaryl groups, cycloalkoxy groups, heterocycloalkoxy groups, cycloalkylthio groups, heterocycloalkylthio groups, carboxyl groups, or carboxylate groups.

[0067] An "alkynyl group" is (CH≡C-), wherein the alkynyl group may be further substituted with other related groups, such as alkyl groups, alkenyl groups, alkynyl groups, alkoxy groups, alkylthio groups, alkylamino groups, halogens, mercapto groups, hydroxy groups, nitro groups, cyano groups, cycloalkyl groups, heterocycloalkyl groups, aryl groups, heteroaryl groups, cycloalkoxy groups, heterocycloalkoxy groups, cycloalkylthio groups, heterocycloalkylthio groups, carboxyl groups, or carboxylate groups.

[0068] The term "alkenylcarbonyl group" refers to -C(O)-(alkenyl group), where the definition of alkenyl group is as defined above. Non-limiting examples of alkenylcarbonyl groups include vinylcarbonyl, propenylcarbonyl, and butenylcarbonyl groups. An alkenylcarbonyl group may be optionally substituted or unsubstituted; if substituted, the substituents are preferably one or more groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, carboxyl, or carboxylate groups.

[0069] "Hydroxy" refers to an -OH group.

[0070] "Halogen" refers to fluorine, chlorine, bromine or iodine.

[0071] An "amino group" refers to -NH2.

[0072] A "cyano group" refers to -CN.

[0073] A "nitro group" refers to -NO2.

[0074] A "carbonyl group" refers to -C(O)-.

[0075] A "carboxyl group" refers to -C(O)OH.

[0076] "THF" refers to tetrahydrofuran.

[0077] "EtOAc" refers to ethyl acetate.

[0078] "MeOH" refers to methanol.

[0079] "DMF" refers to N,N-dimethylformamide.

[0080] "DIPEA" refers to diisopropylethylamine.

[0081] "TFA" refers to trifluoroacetic acid.

[0082] "MeCN" refers to acetonitrile.

[0083] "DMA" refers to N,N-dimethylacetamide.

[0084] "Et2O" refers to ether.

[0085] "DCE" refers to 1,2 dichloroethane.

[0086] "DIPEA" refers to N,N-diisopropylethylamine.

[0087] "NBS" refers to N-bromosuccinimide.

[0088] "NIS" refers to N-iodosuccinimide.

[0089] "Cbz-Cl" refers to benzyl chloroformate.

[0090] "Pd2(dba)3" refers to tri(dibenzylideneacetone)dipalladium.

[0091] "Dppf" refers to 1,1'-bisdiphenylphosphinoferrocene.

[0092] "HATU" refers to O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate.

[0093] "KHMDS" refers to potassium hexamethyldisilazane.

[0094] "LiHMDS" refers to lithium bistrimethylsilylamide.

[0095] "MeLi" refers to methyllithium.

[0096] "n-BuLi" refers to n-butyllithium.

[0097] "NaBH(OAc)3" refers to sodium triacetoxyborohydride.

[0098] "NaOH" refers to sodium hydride.

[0099] "Boc" refers to a t-butoxycarbonyl group.

[0100] Various terms such as "X is selected from A, B, or C," "X is selected from A, B, and C," "X is A, B, or C," and "X is A, B, and C" all mean the same thing, i.e., X can be one or more of A, B, and C.

[0101] Any hydrogen atom described in the present invention may be substituted with its isotope, deuterium, and any hydrogen atom in the compounds of the examples of the present invention may also be substituted with a deuterium atom.

[0102] "Optionally" or "optionally" means that the subsequently described event or circumstance may, but need not, occur, and the description includes cases where the event or circumstance has occurred or not occurred. For example, "a heterocyclyl group optionally substituted with an alkyl group" means that the alkyl group may, but need not, be present, and the description includes cases where the heterocyclyl group is substituted with an alkyl group and cases where the heterocyclyl group is not substituted with an alkyl group.

[0103] "Substituted" refers to the fact that one or more hydrogen atoms in a group, preferably up to 5, more preferably 1 to 3 hydrogen atoms, are independently replaced with the corresponding number of substituents. Needless to say, substituents are present only at their possible chemical positions, and those skilled in the art can determine (experimentally or theoretically) possible or impossible substitutions without much effort. For example, an amino group or a hydroxy group having free hydrogen may be unstable if it is bound to a carbon atom having an unsaturated (e.g., olefinic) bond.

[0104] A "pharmaceutical composition" is meant to contain a mixture of one or more compounds described herein, or physiologically / pharmaceutically acceptable salts or prodrugs thereof, with other chemical components, as well as other components, such as physiologically / pharmaceutically acceptable carriers and excipients. The purpose of a pharmaceutical composition is to facilitate administration to an organism and promote absorption of the active ingredients, thereby exerting their biological activity.

[0105] "Pharmaceutically acceptable salt" refers to a salt of a compound of the present invention, which is safe and effective when used in a mammalian body and possesses the desired biological activity. DETAILED DESCRIPTION OF THE INVENTION

[0106] The present invention will be further described below in conjunction with examples, but these examples are not intended to limit the scope of the present invention. Example

[0107] The structures of the compounds of the present invention were confirmed by nuclear magnetic resonance (NMR) and / or mass spectrometry (MS). The NMR displacements (δ) were 10 -6 The NMR data were measured using a Bruker AVANCE-400 nuclear magnetometer in deuterated dimethyl sulfoxide (DMSO-d), deuterated chloroform (CDCl), and deuterated methanol (CD3OD). The internal standard was tetramethylsilane (TMS).

[0108] For MS measurements, a FINNIGAN LCQAd(ESI) mass spectrometer (manufacturer: Thermo, model number: Finnigan LCQ advantage MAX) was used.

[0109] For the HPLC measurements, an Agilent 1200DAD high pressure liquid chromatograph (Sunfire C18 150×4.6 mm chromatography column) and a Waters 2695-2996 high pressure liquid chromatograph (Gimini C18 150×4.6 mm chromatography column) were used.

[0110] Kinase mean inhibition rate and IC 50 The values ​​were measured using a NovoStar plate reader (BMG, Germany).

[0111] Yantai Yellow Sea HSGF254 or Qingdao GF254 silica gel plates were used for thin-layer chromatography (TLC). The silica gel plates used were 0.15mm to 0.2mm in diameter, and 0.4mm to 0.5mm in diameter for product separation and purification by thin-layer chromatography.

[0112] For column chromatography, Yantai Yellow Sea silica gel 200-300 mesh silica gel was generally used as the carrier.

[0113] Known starting materials of the present invention can be synthesized by methods known in the art or can be purchased from ABCR GmbH & Co. KG, Acros Organics, Aldrich Chemical Company, Accela ChemBio Inc., Darui Chemicals, etc.

[0114] Unless otherwise specified in the examples, all reactions can be carried out under an argon gas atmosphere or a nitrogen gas atmosphere.

[0115] The argon or nitrogen gas atmosphere means that a balloon of argon or nitrogen gas with a volume of about 1 L is connected to the reaction flask.

[0116] The hydrogen gas atmosphere is defined as a balloon of hydrogen gas with a volume of approximately 1 L connected to the reaction flask.

[0117] For the pressurized hydrogenation reaction, a Parr 3916EKX hydrogenation apparatus and a Seiran QL-500 hydrogen gas generator or an HC2-SS hydrogenation apparatus were used.

[0118] The hydrogenation reaction was usually repeated three times by evacuating and filling with hydrogen gas.

[0119] For the microwave reaction, a CEM Discover-S 908860 microwave reactor was used.

[0120] Unless otherwise stated in the examples, the solutions are aqueous solutions.

[0121] Unless otherwise specified in the examples, the reaction temperature is room temperature, 20°C to 30°C.

[0122] In the examples, thin layer chromatography (TLC) was used to monitor the reaction process. The developer systems used in the reactions were as follows: A: dichloromethane and methanol system; B: n-hexane and ethyl acetate system; C: petroleum ether and ethyl acetate system; and D: acetone. The volume ratio of the solvents was adjusted depending on the polarity of the compounds.

[0123] The eluent system for column chromatography and the developer system for thin-layer chromatography used to purify the compounds include the following: A: n-hexane and ethyl acetate; B: n-hexane and tetrahydrofuran; the volume ratio of the solvents is adjusted according to the polarity of the compounds, and can also be adjusted by adding a small amount of alkaline or acidic reagents such as triethylamine and acetic acid.

[0124] Intermediate 1 1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid [ka] Step 1 6-Bromobenzo[cd]indol-2(1H)-one Benzo[cd]indol-2(1H)-one (20 g, 118.2 mmol) was dissolved in 150 mL of glacial acetic acid, and liquid bromine (37.8 g, 236.5 mmol) was added dropwise to the reaction mixture in an ice bath. The mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure to give the title product, 6-bromobenzo[cd]indol-2(1H)-one (18.7 g), in a 63.8% yield. MS m / z(ESI):248[M+1].

[0125] Step 2 6-Bromo-1-(4-methoxybenzyl)benzo[cd]indol-2(1H)-one 6-Bromobenzo[cd]indol-2(1H)-one (10 g, 40.3 mmol) was dissolved in 200 mL of dimethylformamide, and 4-methoxybenzyl bromobenzoate (12.2 g, 61.5 mmol) and potassium carbonate (11.3 g, 82 mmol) were added. The mixture was stirred at room temperature for 16 hours. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure, and the residue was purified using silica gel column chromatography with eluent system A to give the title product, 6-bromo-1-(4-methoxybenzyl)benzo[cd]indol-2(1H)-one (10.7 g), in a 72.1% yield. MS m / z(ESI):368[M+1].

[0126] Step 3 6-Hydrazino-1-(4-methoxybenzyl)benzo[cd]indol-2(1H)-one Palladium (π-cinnamyl) chloride dimer (229.4 mg, 0.44 mmol) and N-[2-di(1-adamantane)phosphinephenyl]morpholine (415.5 mg, 0.89 mmol) were dissolved in 5 mL of dioxane and stirred at room temperature for 15 minutes. 6-Bromo-1-(4-methoxybenzyl)benzo[cd]indol-2(1H)-one (3.3 g, 8.96 mmol) and sodium tert-butanol (1.72 g, 17.90 mmol) were dissolved in 50 mL of dioxane and added to the reaction solution. The mixture was stirred at room temperature for 5 minutes. Hydrazine hydrate (897.3 mg, 17.92 mmol) was added to the reaction solution and stirred at 50 °C for 2 hours. The reaction mixture was filtered, the filter cake was washed with 20 mL of ethyl acetate, and the filtrate was concentrated under reduced pressure to obtain the title product 6-hydrazino-1-(4-methoxybenzyl)benzo[cd]indol-2(1H)-one (2.66 g), yield: 93.0%. MS m / z(ESI):319[M+1].

[0127] Step 4 1-(1-(4-Methoxybenzyl)-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxylate ethyl ester 6-Hydrazino-1-[(4-methoxybenzyl)benzo[cd]indol-2(1H)-one (2.66 g, 8.33 mmol), potassium carbonate (2.3 g, 16.7 mmol), and ethyl ethoxy-2-methylenetrifluoroacetoacetate (4 g, 16.7 mmol) were dissolved in 50 mL of ethanol and stirred at 80 °C for 3 hours. The reaction mixture was concentrated under reduced pressure, and the residue obtained was purified using silica gel column chromatography with eluent system A to obtain the title product, ethyl 1-(1-(4-methoxybenzyl)-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (880 mg), yield: 21.3%. MS m / z(ESI):496[M+1].

[0128] Step 5 1-(1-(4-Methoxybenzyl)-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid Ethyl 1-(1-(4-methoxybenzyl)-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (880 mg, 1.78 mmol) and sodium hydride (350 mg, 8.9 mmol) were dissolved in 2 mL of tetrahydrofuran and 1 mL of water, and the mixture was stirred at 60°C for 16 hours to react. The reaction mixture was adjusted to a pH of less than 7 by adding 2M hydrochloric acid, extracted with ethyl acetate (50 mL x 3), the organic phases were combined, washed successively with water (50 mL x 1) and saturated sodium chloride solution (50 mL x 1), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the title product 1-(1-(4-methoxybenzyl)-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (770 mg), yield: 93%. MS m / z(ESI):468[M+1]

[0129] Step 6 1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 1-(1-(4-Methoxybenzyl)-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (770 mg, 1.65 mmol) was dissolved in 20 mL of trifluoroacetic acid and stirred at 90 ° C for 16 hours. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure, and the residue obtained was purified using silica gel column chromatography with eluent system A to obtain the title intermediate 1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (450 mg), yield: 78.5%. MS m / z(ESI):348[M+1] 1 H NMR(400MHz,DMSO-d6)δ 11.09(s,1H),8.33(s,1H),8.12(d,1H),7.86(dd,1H),7.69(d,1H),7.61(d,1H),7.08(d,1H).

[0130] Example 1 1-(2-carbonyl-1,2-dihydropyrrolo[2,3,4-ij]isoquinolin-5-yl)-5-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 8-Bromo-4-chloroisoquinolin-1(2H)-one 8-Bromoisoquinolin-1(2H)-one 1a (5.00 g, 22.32 mmol) was dissolved in 50 mL of N,N-dimethylformamide. N-chlorobutanediimide (3.15 g, 23.59 mmol) was added to the reaction mixture in an ice bath and stirred at room temperature for 12 hours. Extraction with ethyl acetate (50 mL × 3) was performed. The combined organic phases were washed sequentially with water (50 mL × 1) and saturated sodium chloride solution (50 mL × 1), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system A to give 8-bromo-4-chloroisoquinolin-1(2H)-one 1b (4.70 g) in 81.5% yield. MS m / z(ESI):258[M+1]

[0131] Step 2 8-Bromo-1,4-dichloroisoquinoline 8-Bromo-4-chloroisoquinolin-1(2H)-one 1b (4.70 g, 18.18 mmol) was dissolved in 50 mL of phosphorus oxychloride and stirred at 100° C. for 16 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system A to give the title product 8-bromo-1,4-dichloroisoquinoline 1c (4.50 g), yield: 89.3%. MS m / z (ESI): 276 [M+1]

[0132] Step 3 8-Bromo-4-chloro-1-iodoisoquinoline 8-Bromo-1,4-dichloroisoquinoline 1c (4.50 g, 16.25 mmol) and sodium iodide (4.90 g, 32.69 mmol) were dissolved in 50 mL of acetonitrile, and the reaction mixture was added and stirred at room temperature for 5 minutes. Trimethylchlorosilane (3.30 mg, 30.37 mmol) was added to the reaction mixture, and the mixture was stirred at 80 °C for 12 hours. The reaction mixture was concentrated under reduced pressure, and the residue obtained was purified using silica gel column chromatography with eluent system A to give the title product 8-bromo-4-chloro-1-iodoisoquinoline 1d (3.50 g), yield: 58.6%. MS m / z(ESI):368[M+1]

[0133] Step 4 8-Bromo-4-chloro-1-cyanoisoquinoline 8-Bromo-4-chloro-1-iodoisoquinoline 1d (3.50 g, 9.50 mmol), zinc cyanide (700 mg, 5.96 mmol), and tetrakis(triphenylphosphine)palladium (550 mg, 0.48 mmol) were dissolved in 50 mL of dimethylformamide and stirred at 80 °C for 13 h. The mixture was extracted with ethyl acetate (50 mL × 3), and the combined organic phases were washed sequentially with water (50 mL × 1) and saturated sodium chloride solution (50 mL × 1), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system A to give the title product, 8-bromo-4-chloro-1-cyanoisoquinoline 1e (2.00 g), in a 79.1% yield. MS m / z(ESI):267[M+1]

[0134] Step 5 4-chloro-8-(4-methoxybenzyl)amino-1-cyanoisoquinoline 8-Bromo-4-chloro-1-cyanoisoquinoline 1e (2.00 g, 7.48 mmol) and 4-methoxybenzylamine (1.10 g, 8.02 mmol) were dissolved in 10 mL of dioxane, and cesium carbonate (4.9 g, 15.04 mmol) and bis(diallyliumacetone)palladium (430 mg, 0.76 mmol) were added. The mixture was stirred at 90 °C for 16 h. Extraction with ethyl acetate (50 mL × 3) was performed. The combined organic phases were washed with water (50 mL × 1) and saturated sodium chloride solution (50 mL × 1), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system A to give the title product, 4-chloro-8-(4-methoxybenzyl)amino-1-cyanoisoquinoline 1f (2.10 g), in an 86.2% yield. MS m / z (ESI): 324 [M+1]

[0135] Step 6 5-chloro-1-(4-methoxybenzyl)pyrrolo[2,3,4-ij]isoquinolin-2(1H)-one 4-Chloro-8-((4-methoxybenzyl)amino)isoquinoline-1-carbonitrile 1f (2.10 g, 6.48 mmol) was dissolved in 20 mL of concentrated sulfuric acid and reacted with stirring at 100° C. for 16 hours. The reaction mixture was added to ice water and filtered to obtain the title product, 5-chloro-1-(4-methoxybenzyl)pyrrolo[2,3,4-ij]isoquinolin-2(1H)-one 1g (450 mg), yield: 21.3%. MS m / z (ESI): 325 [M+1]

[0136] Step 7 5-Hydrazino-1-(4-methoxybenzyl)pyrrolo[2,3,4-ij]isoquinolin-2(1H)-one Palladium (π-cinnamyl) chloride dimer (35 mg, 0.068 mmol) and N-[2-di(1-adamantane)phosphinephenyl]morpholine (64 mg, 0.14 mmol) were dissolved in 5 mL of dioxane and stirred at room temperature for 15 minutes. 5-Chloro-1-(4-methoxybenzyl)pyrrolo[2,3,4-ij]isoquinolin-2(1H)-one 1 g (450 mg, 1.38 mmol) and sodium tert-butanol (265 mg, 2.76 mmol) were dissolved in 50 mL of dioxane and added to the reaction mixture. The mixture was stirred at room temperature for 5 minutes. Hydrazine hydrate (897 mg, 17.92 mmol) was added to the reaction mixture and stirred at 50 °C for 2 hours. After filtering the reaction mixture, the filter cake was washed with ethyl acetate (20 mL), and the filtrate was concentrated under reduced pressure to obtain the title product, 5-hydrazino-1-(4-methoxybenzyl)pyrrolo[2,3,4-ij]isoquinolin-2(1H)-one 1h (500 mg), as a crude product. MS m / z(ESI):320[M+1]

[0137] Step 8 1-(1-(4-Methoxybenzyl)-2-carbonyl-1,2-dihydropyrrolo[2,3,4-ij]isoquinolin-5-yl)-2-trifluoromethyl-1H-pyrrole-3-carboxylate ethyl ester 5-Hydrazino-1-(4-methoxybenzyl)pyrrolo[2,3,4-ij]isoquinolin-2(1H)-one 1h (500 mg, 1.56 mmol) and ethyl ethoxy-2-methylenetrifluoroacetoacetate (750 mg, 3.12 mmol) were dissolved in 10 mL of ethanol and stirred at 80 °C for 3 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified using silica gel column chromatography with eluent system A to give the title product, ethyl 1-(1-(4-methoxybenzyl)-2-carbonyl-1,2-dihydropyrrolo[2,3,4-ij]isoquinolin-5-yl)-2-trifluoromethyl-1H-pyrrole-3-carboxylate 1i (200 mg), yield: 25.9%. MS m / z(ESI):496[M+1]

[0138] Step 9 1-(1-(4-Methoxybenzyl)-2-carbonyl-1,2-dihydropyrrolo[2,3,4-ij]isoquinolin-5-yl)-2-trifluoromethyl-1H-pyrrole-3-carboxylic acid Ethyl 1-(1-(4-methoxybenzyl)-2-carbonyl-1,2-dihydropyrrolo[2,3,4-ij]isoquinolin-5-yl)-2-trifluoromethyl-1H-pyrrole-3-carboxylate 1i (200 mg, 0.40 mmol) and sodium hydride (350 mg, 8.75 mmol) were dissolved in 4 mL of tetrahydrofuran and 2 mL of water, and the mixture was stirred at 30°C for 16 hours. The reaction mixture was adjusted to a pH of less than 7 by adding 2M hydrochloric acid, extracted with ethyl acetate (50 mL × 3), the organic phases were combined, washed successively with water (50 mL × 1) and saturated sodium chloride solution (50 mL × 1), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the title product 1-(1-(4-methoxybenzyl)-2-carbonyl-1,2-dihydropyrrolo[2,3,4-ij]isoquinolin-5-yl)-2-trifluoromethyl-1H-pyrrole-3-carboxylic acid 1j (100 mg), yield: 53.0%. MS m / z(ESI):468[M+1]

[0139] Step 10 1-(2-oxo-1,2-dihydropyrrolo[2,3,4-ij]isoquinolin-5-yl)-2-trifluoromethyl-1H-pyrrole-3-carboxylic acid 1-(1-(4-Methoxybenzyl)-2-carbonyl-1,2-dihydropyrrolo[2,3,4-ij]isoquinolin-5-yl)-2-trifluoromethyl-1H-pyrrole-3-carboxylic acid 1j (100 mg, 0.21 mmol) was dissolved in 10 mL of trifluoroacetic acid and stirred at 90 °C for 16 hours. The reaction mixture was concentrated under reduced pressure, and the residue obtained was purified using silica gel column chromatography with eluent system C to give the title compound 1-(2-oxo-1,2-dihydropyrrolo[2,3,4-ij]isoquinolin-5-yl)-2-trifluoromethyl-1H-pyrrole-3-carboxylic acid 1k (75 mg), yield: 65.7%. MS m / z(ESI):348[M+1]

[0140] Step 11 1-(2-carbonyl-1,2-dihydropyrrolo[2,3,4-ij]isoquinolin-5-yl)-2-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrrole-3-carboxamide 1-(2-Oxo-1,2-dihydropyrrolo[2,3,4-ij]isoquinolin-5-yl)-2-trifluoromethyl-1H-pyrrole-3-carboxylic acid 1k (70 mg, 0.20 mmol), 2-trifluoromethyl-4-aminopyridine (31 mg, 0.19 mmol), pyridine (76 mg, 0.96 mmol), and phosphorus oxychloride (73 mg, 0.48 mmol) were dissolved in 5 mL of dichloromethane and stirred at room temperature for 2 hours. Dichloromethane (50 mL) was added to the reaction mixture, which was then washed with water (50 mL × 1), saturated sodium chloride solution (50 mL × 1), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue obtained was purified using silica gel column chromatography with eluent system A to obtain the title product 1-(1-(4-methoxybenzyl)-2-carbonyl-1,2-dihydropyrrolo[2,3,4-ij]isoquinolin-5-yl)-2-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrrole-3-carboxamide 1 (80 mg), yield: 81.24%. MS m / z(ESI):492[M+1].

[0141] Example 2 1-(2-oxo-1,2-dihydropyrrolo[2,3,4-ij]isoquinolin-6-yl)-5-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 1-cyano-8-bromoisoquinoline Oxido-8-bromoisoquinoline 2a (22.50 g, 0.10 mol, prepared according to the method described in Patent WO2004002992) was dissolved in 500 mL of 1,4-dioxane, and 1,8-diazabicyclo[5.4.0]-7-undecene (33.0 mL, 0.22 mol) and cyanotrimethylsilane (22.5 mL, 0.18 mol) were added. The mixture was stirred at 120 °C for 18 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography using eluent system E (PE / THF = 1:1) to give the title product 1-cyano-8-bromoisoquinoline 2b (9.90 g) in a 42.3% yield. MS m / z (ESI): 233, 235 [M+1]

[0142] Step 2 8-Bromoisoquinoline-1-carboxylic acid 1-Cyano-8-bromoisoquinoline 2b (9.90 g, 42.48 mmol) was dispersed in 50 mL of water, and sodium hydride (10 g, 0.25 mol) was added. The mixture was stirred at 85 °C for 6 h. The reaction mixture was quenched with 15 mL of concentrated hydrochloric acid and extracted with ethyl acetate (100 mL × 2). The combined organic phases were washed with saturated sodium bicarbonate solution (100 mL × 2), saturated sodium chloride solution (100 mL × 2), and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to give the crude title product, 8-bromoisoquinoline-1-carboxylic acid 2c (10.50 g). This product was directly used in the next step without further purification. MS m / z(ESI):252,254[M+1] Using the synthesis method described in US Patent No. 2016 / 0240789A1, the title product pyrrolo[2,3,4-ij]isoquinolin-2(1H)-one 2d (4.00 g) was obtained from crude 8-bromoisoquinoline-1-carboxylic acid 2c (10.50 g, 41.66 mmol), with a yield of 56.4%. MS m / z (ESI): 171 [M+1] Referring to the synthesis method in Step 1 of Example 1, 6-bromopyrrolo[2,3,4-ij]isoquinolin-2(1H)-one 2e (5.40 g) was obtained from pyrrolo[2,3,4-ij]isoquinolin-2(1H)-one 2d (4.00 g, 23.51 mmol), with a yield of 92.3%. MS m / z (ESI): 249, 251 [M+1]

[0143] Step 5 6-Bromo-1-(4-methoxybenzyl)pyrrolo[2,3,4-ij]isoquinolin-2(1H)-one 6-Bromopyrrolo[2,3,4-ij]isoquinolin-2(1H)-one 2e (5.40 g, 21.68 mmol) was dissolved in 200 mL of dimethylformamide, and 4-methoxybenzyl bromo (12.90 g, 64.16 mmol) and potassium carbonate (8.96 g, 64.83 mmol) were added. The mixture was stirred at 80 °C for 16 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified using silica gel column chromatography with eluent system A to give the title product 6-bromo-1-(4-methoxybenzyl)pyrrolo[2,3,4-ij]isoquinolin-2(1H)-one 2f (6.49 g), yield: 81.0%. MS m / z(ESI):369,371[M+1]

[0144] Step 6 to Step 10 1-(2-oxo-1,2-dihydropyrrolo[2,3,4-ij]isoquinolin-6-yl)-5-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide Referring to the synthesis method of Steps 7 to 11 of Example 1, the title product 1-(2-oxo-1,2-dihydropyrrolo[2,3,4-ij]isoquinolin-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 2f (1.00 g, 2.71 mmol) was obtained as 1-(2-oxo-1,2-dihydropyrrolo[2,3,4-ij]isoquinolin-6-yl)-5-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide 2 (32 mg), yield: 2.4%. MS m / z (ESI): 493.1 [M+1] 1 H NMR(400MHz,DMSO-d6)δ 11.22(broads,1H),10.98(broads,1H),8.86(d,1H),8.79(d,1H),8.28(s,1H),8.11(d,1H),8.05(d,1H),7.97(d,1H),7.84(d,1H),6.52(s,1H).

[0145] Example 3 1-(2-carbonyl-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 8-Bromo-4-chloro-N-(4-methoxybenzyl)isoquinolin-1-amine 8-Bromo-1,4-dichloroisoquinoline 3a (5.00 g, 18.05 mmol) was dissolved in 50 mL of acetonitrile, and 4-methoxybenzylamine (4.90 g, 35.72 mol) was added to the reaction mixture. The mixture was stirred at 80 °C for 12 hours. After extraction with ethyl acetate (50 mL × 3), the organic phases were combined and washed with water (50 mL × 1) and saturated sodium chloride solution (50 mL × 1), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system A to give 8-bromo-4-chloro-N-(4-methoxybenzyl)isoquinolin-1-amine 3b (4.7 g) in a 68.9% yield. MS m / z(ESI):377[M+1] Referring to the synthesis methods of Steps 4, 6 to 11 of Example 1 in order, 1-(2-carbonyl-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide 3 (10 mg) was obtained from 8-bromo-4-chloro-N-(4-methoxybenzyl)isoquinolin-1-amine 3b (4.70 g, 12.44 mmol) in a yield of 0.2%. MS m / z(ESI):492[M+1]. 1 H NMR(400MHz,MeOD)δ 8.63(d,J=5.6Hz,1H),8.37(s,1H),8.30(s,1H),8.23(d,J=2.0Hz,1H),8.16(d,J=7.0H z,1H),8.05(dd,J=8.2,7.0Hz,1H),7.97(dd,J=5.6,2.1Hz,1H),7.71(d,J=8.2Hz,1H).

[0146] Example 4 1-(2,2-Dimethyl-1-carbonyl-1,2-dihydroacenaphthylene-5-yl)-5-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 5-Bromo-2,2-dimethylacenaphthylene-1(2H)-one 5-Bromo-acenaphthylen-1(2H)-one 4a (200 mg, 0.81 mmol, synthesized using the known method [Patent US6667303B1]) was dissolved in 4 mL of tetrahydrofuran and 1 mL of dimethylformamide, and sodium hydride (97.12 mg, 60% purity, 2.43 mmol) was added in small amounts several times in an ice bath. Iodomethane (230 mg, 1.62 mmol) was weighed and added, and the mixture was stirred at 60 °C for 4 hours. The reaction mixture was quenched with 50 mL of water under ice bath, extracted with ethyl acetate (50 mL × 2), the organic phases were combined, washed with saturated sodium chloride solution (50 mL × 1), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue obtained was purified by silica gel column chromatography using eluent system A to obtain the title product 5-bromo-2,2-dimethylacenaphthylene-1(2H)-one 4b (210 mg), yield: 94.3%. MS m / z (ESI): 276 [M+1] By following the synthesis method of Example 1, steps 7 to 9 and 11 in order, 1-(2,2-dimethyl-1-carbonyl-1,2-dihydroacenaphthylen-5-yl)-5-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide 4 (8.3 mg) was obtained with a yield of 2.1%. MS m / z(ESI):518[M+1] 1 H NMR(400MHz,DMSO-d6)δ 11.37(s,1H),8.72(d,1H),8.61(s,1H),8.28(d,1H),8.11(d,1H),8.02(dd,1H),7.97(dd,2H),7.84(d,1H),7.69(d,1H),1.48(s,6H).

[0147] Example 5 N-(6-(2H-1,2,3-triazol-2-yl)-5-chloropyridin-3-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Step 11 of Example 1, intermediate 1 (18 mg, 0.052 mmol) and 6-(2H-1,2,3-triazol-2-yl)-3-amino-5-chloropyridine 5a (10 mg, 0.052 mmol, obtained by synthesizing using the known method "Patent US20180170909A1") were used to obtain the title product N-(6-(2H-1,2,3-triazol-2-yl)-5-chloropyridin-3-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide 5 (16 mg), with a yield of 58.6%. MS m / z(ESI):525,527[M+1] 1 H NMR(400MHz,DMSO-d6)δ 11.3(broads,1H),11.0(s,1H),9.11(d,1H),8.93(d,1H),8.59(s,1H),8.2 2(s,2H),8.10(d,1H),7.84(dd,1H),7.77(d,1H),7.62(d,1H),7.13(d,1H).

[0148] Example 6 1-(2H-Naphthalenebenzo[1,8-bc]furan-5-yl)-5-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 5-Bromo-8-hydroxymethyl-naphthalene-1-phenol 5-Bromo-2H-naphthalene[1,8-bc]benzofuran-2-one 6a (2.48 g, 10 mmol) was dissolved in 30 mL of tetrahydrofuran. At 0 °C, lithium aluminum hydride (760 mg, 20 mmol) was added. The mixture was allowed to react at room temperature for 2 hours. 0.76 mL of water, 0.76 mL of 15% sodium hydride solution, and 2.28 mL of water were added, in that order. After filtration, the filtrate was dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product, which was purified by silica gel column chromatography using eluent system A to give the title product, 5-bromo-8-hydroxymethyl-naphthalene-1-phenol 6b (2.05 g), in an 81.3% yield.

[0149] Step 2 5-Bromo-2H-naphthalene[1,8-bc]benzofuran 5-Bromo-8-hydroxymethyl-naphthalene-1-phenol 6b (1.50 g, 5.93 mmol) was dissolved in 30 mL of tetrahydrofuran. Triphenylphosphine (1.57 g, 6 mmol) and diisopropyl azodicarboxylate (1.21 g, 6 mmol) were added at 0 °C, and the mixture was allowed to react at room temperature for 2 hours. The reaction mixture was concentrated to give the crude product, which was purified by silica gel column chromatography using eluent system A to give the title product, 5-bromo-2H-naphthalene[1,8-bc]benzofuran 6c (1.05 g), in a 70.0% yield. Referring to the synthesis method of Steps 7, 9 to 11 in Example 1, 5-bromo-2H-naphthalene[1,8-bc]benzofuran 6c (200 mg, 0.85 mmol) was reacted to give 1-(2H-naphthalene[1,8-bc]benzofuran-5-yl)-5-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide 6 (50 mg), yield: 12.3%. MS m / z(ESI):479[M+1] 1H NMR(400MHz,DMSO-d6)δ 8.71(s,1H),8.26(s,1H),8.31(s,1H),8.10-8.01(m,2H),7.58-7.51(m,1 H),7.18(s,1H),6.98(t,1H),6.34-6.27(m,1H),4.98(d,1H),3.12(s,2H).

[0150] Example 7 1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-5-yl)-5-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis methods of Step 5 of Example 2 and Steps 7 to 11 of Example 1 in order, 5-bromo-benzo[cd]indol-2(1H)-one 7a (400 mg, 1.61 mmol, prepared according to the known method of US Patent No. US2016 / 0240789A1) gave 1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-5-yl)-5-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide 7 (23 mg), with a yield of 2.9%. MS m / z (ESI): 492 [M+1] 1 H NMR(400MHz,DMSO-d6)δ 11.28(s,1H),11.08(s,1H),8.72(d,1H),8.60(s,1H),8.25(d,1H),8.19(d,1H),8.03-7.97(m,2H),7.60(dd,1H),7.10(d,1H),7.01(d,1H).

[0151] Example 8 1-(2-oxo-1,2-dihydropyrrolo[2,3,4-de]isoquinolin-6-yl)-5-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis methods of Step 5 in Example 2 and Steps 7 to 11 in Example 1 in order, 1-(2-oxo-1,2-dihydropyrrolo[2,3,4-ij]isoquinolin-6-yl)-5-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide 8 (18 mg) was obtained from 6-bromopyrrolo[2,3,4-de]isoquinolin-2(1H)-one 8a (1.0 g, 4.01 mmol) in a yield of 0.9%. MS m / z (ESI): 493.1 [M+1] 1 H NMR(400MHz,DMSO-d6)δ 11.30(broads,1H),10.91(broads,1H),8.82(d,1H),8.76(t,1H),8.37(s,1H),8.16(s,1H),8.05(d,1H),7.91(d,1H),7.70(d,1H),6.66(s,1H).

[0152] Example 9 1-(1,3-Dicarbonyl-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)-2-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-3-carboxamide [ka] Step 1 6-Bromo-1H-benzo[de]isoquinoline-1,3(2H)-dione 6-Bromo-1H,3H-benzo[de]isochromene-1,3-dione 9a (5.00 g, 18.04 mmol) was dissolved in 50 mL of aqueous ammonia and stirred at 100 °C for 12 h. After extraction with ethyl acetate (50 mL × 3), the organic phases were combined, washed sequentially with water (50 mL × 1) and saturated sodium chloride solution (50 mL × 1), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give 6-bromo-1H-benzo[de]isoquinoline-1,3(2H)-dione 9b (4.50 g), yield: 90.6%. MS m / z (ESI): 276 [M+1] Referring to the synthesis methods of Step 5 of Example 2 and Steps 7 to 11 of Example 1 in order, 1-(1,3-dicarbonyl-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)-2-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-3-carboxamide 9 (18 mg) was obtained from 6-bromo-1H-benzo[de]isoquinoline-1,3(2H)-dione 9b (4.50 g, 16.30 mmol), with a yield of 0.2%. MS m / z(ESI):519[M+1]. 1 H NMR(400MHz,DMSO)δ 11.32(s,1H),8.72(d,J=5.5Hz,1H),8.57(s,1H),8.46(s,1H),8.35-8.19(m,2H),8.06-7.93(m ,1H),7.86(d,J=7.6Hz,1H),7.77(t,J=7.9Hz,1H),7.69(d,J=7.7Hz,1H),7.29(d,J=8.5Hz,1H).

[0153] Example 10 1-(1-carbonyl-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)-2-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-3-carboxamide [ka] Step 1 Ethyl 1-(2-(4-methoxybenzyl)-1-carbonyl-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)-2-trifluoromethyl-1H-pyrrole-3-carboxylate Ethyl 1-(2-(4-methoxybenzyl)-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)-2-(trifluoromethyl)-1H-pyrrole-3-carboxylate 9e (500 mg, 0.96 mmol) was dissolved in tetrahydrofuran solution (20 mL), and borane was added to the tetrahydrofuran solution (1 M, 1.5 mL) with stirring at 0°C and 20°C, and the mixture was allowed to react for 2 hours. Extract with ethyl acetate (50 mL × 3), combine the organic phases, wash sequentially with water (50 mL × 1) and saturated sodium chloride solution (50 mL × 1), dry over anhydrous sodium sulfate, filter, and concentrate the filtrate under reduced pressure to obtain ethyl 1-(2-(4-methoxybenzyl)-1-carbonyl-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)-2-trifluoromethyl-1H-pyrrole-3-carboxylate 10a (300 mg), yield: 61.6%. MS m / z (ESI): 509 [M+1] Referring to the synthesis method of Steps 9 to 11 of Example 1, 1-(2-(4-methoxybenzyl)-1-carbonyl-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)-2-trifluoromethyl-1H-pyrrole-3-carboxylate ethyl 10a (300 mg, 0.59 mmol) was used to obtain 1-(1-carbonyl-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)-2-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-3-carboxamide 10 (4 mg), yield: 1.3%. MS m / z(ESI):505[M+1]. 1 H NMR(400MHz,DMSO)δ 11.32(s,1H),8.72(d,J=5.5Hz,1H),8.57(s,1H),8.46(s,1H),8.30-8.16(m,1H),8.05-7.95(m,1H) ,7.86(d,J=7.6Hz,1H),7.77(t,J=7.9Hz,1H),7.69(d,J=7.7Hz,1H),7.32-6.98(m,2H),5.06(s,2H).

[0154] Example 11 1-(2-carbonyl-2,3-dihydro-1H-benzo[de]quinolin-6-yl)-2-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-3-carboxamide [ka] Step 1 6-Bromo-1H-benzo[de]quinolin-2(3H)-one 5-Bromoacenaphthylen-1(2H)-one 4a (5.00 g, 20.23 mmol, synthesized according to the method described in US Patent No. 6,667,303 B1) was dissolved in 20 mL of polyphosphoric acid solution, and sodium azide (1.90 g, 29.23 mmol) was added with stirring at 55°C. The mixture was then reacted at 55°C for 2 hours. After extraction with ethyl acetate (50 mL x 3), the combined organic phases were washed with water (50 mL x 1) and saturated sodium chloride solution (50 mL x 1), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give 6-bromo-1H-benzo[de]quinolin-2(3H)-one 11a (3 g), yield: 56.7%. MS m / z(ESI):262[M+1] Referring to the synthesis methods of Step 5 in Example 2 and Steps 7 to 11 in Example 1 in order, 1-(2-carbonyl-2,3-dihydro-1H-benzo[de]quinolin-6-yl)-2-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-3-carboxamide 11 (20 mg) was obtained from 6-bromo-1H-benzo[de]quinolin-2(3H)-one 11a (1.05 g, 4.01 mmol), with a yield of 1.0%. MS m / z(ESI):505[M+1].

[0155] Example 12 1-(3-carbonyl-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)-2-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-3-carboxamide [ka] Referring to Step 1 of Example 10 and Steps 9 to 11 of Example 1 in sequence, 1-(2-(4-methoxybenzyl)-1,3-dicarbonyl-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)-2-(trifluoromethyl)-1H-pyrrole-3-carboxylate ethyl 9e (500 mg, 0.96 mmol) was used to obtain 1-(3-carbonyl-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)-2-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-3-carboxamide 12 (4 mg), with a yield of 0.8%. MS m / z (ESI): 505 [M+1] 1 H NMR(400MHz,MeOD)δ 8.64(d,J=5.6Hz,1H),8.45-8.31(m,2H),8.25(d,J=2.0Hz,1H),7.99(dd,J=5.6,2.0 Hz,1H),7.80(d,J=7.6Hz,1H),7.71-7.58(m,2H),7.18(d,J=7.8Hz,1H),5.12(s,2H).

[0156] Example 13 N-(3,7-dichloropyrazolo[1,5-a]pyridin-5-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide [ka] Step 1 5-Bromo-7-chloropyrazolo[1,5-a]pyridine 5-Bromo-pyrazolo[1,5-a]pyridine 13a (1.0 g, 5.08 mmol) was dissolved in 15 mL of anhydrous tetrahydrofuran, and a 2 M solution of diisopropylaminolithium in tetrahydrofuran (3 mL, 6 mmol) was added dropwise at -78 °C. The mixture was stirred at -78 °C for 1 hour. A 1 M solution of hexachloroethane in anhydrous tetrahydrofuran (6 mL, 6 mmol) was then added dropwise at -78 °C. The mixture was stirred at -78 °C for 1 hour. 200 mL of saturated ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined, washed with saturated sodium chloride solution (30 mL × 2), and dried over anhydrous sodium sulfate. Filtration, concentration of the filtrate under reduced pressure, and purification of the resulting residue using silica gel column chromatography with eluent system B gave the title product 5-bromo-7-chloropyrazolo[1,5-a]pyridine 13b (750 mg), yield: 63.5%. MS m / z (ESI): 231 [M+1]

[0157] Step 2 tert-Butyl N-(7-chloropyrazolo[1,5-a]pyridin-5-yl)-carbamate 5-Bromo-7-chloropyrazolo[1,5-a]pyridine 13b (750 mg, 3.24 mmol) was dissolved in 10 mL of 1,4-dioxane, and tris(dibenzylideneacetone)dipalladium (149 mg, 0.16 mmol), 4,5-bisdiphenylphosphine-9,9-dimethyloxanthene (184 mg, 0.32 mmol), cesium carbonate (3.16 g, 9.70 mmol), and tert-butyl carbamate (756 mg, 6.45 mmol) were added. The mixture was stirred at 100 °C for 1 h. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system B to give the title product (7-chloropyrazolo[1,5-a]pyridin-5-yl)-tert-butyl carbamate 13c (750 mg) in 86.5% yield. MS m / z(ESI):268[M+1]

[0158] Step 3 tert-Butyl N-(3,7-dichloropyrazolo[1,5-a]pyridin-5-yl)-carbamate Referring to the synthesis method of Step 1 of Example 1, (7-chloropyrazolo[1,5-a]pyridin-5-yl)-tert-butyl carbamate 13c (750 mg, 2.79 mmol) was used to obtain (3,7-dichloropyrazolo[1,5-a]pyridin-5-yl)-tert-butyl carbamate 13d (400 mg), with a yield of 47.5%. MS m / z (ESI): 302, 304 [M+1]

[0159] Step 4 5-Amino-3,7-dichloropyrazolo[1,5-a]pyridine Tert-butyl (3,7-dichloropyrazolo[1,5-a]pyridin-5-yl)-carbamate 13d (400 mg, 1.32 mmol) was dissolved in 5 mL of 4 M hydrogen chloride in 1,4-dioxane and stirred for 3 hours at 60° C. The reaction mixture was concentrated under reduced pressure to give the crude title product 5-amino-3,7-dichloropyrazolo[1,5-a]pyridine 13e (366 mg), which was directly used in the next step without further purification. MS m / z(ESI):202,204[M+1]. Referring to the synthesis method of Step 11 of Example 1, N-(3,7-dichloropyrazolo[1,5-a]pyridin-5-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide 13 (16 mg) was obtained from intermediate 1 (31 mg, 0.089 mmol) and crude 5-amino-3,7-dichloropyrazolo[1,5-a]pyridine 13e (18 mg, 0.089 mmol), with a yield of 33.8%. MS m / z(ESI):531,533[M+1]. 1H NMR(400MHz,DMSO-d6)δ 11.12(broads,1H),11.03(broads,1H),8.52(s,1H),8.31(s,1H),8.23(d,1H) ,8.15(d,1H),7.91(t,1H),7.72(d,1H),7.60(d,1H),7.49(d,1H),7.12(d,1H).

[0160] Example 14 N-(7-methyl-3-chloropyrazolo[1,5-a]pyridin-5-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide [ka] Step 1 5-Bromo-7-methoxypyrazolo[1,5-a]pyridine 5-Bromo-7-chloropyrazolo[1,5-a]pyridine 13b (320 mg, 1.38 mmol) was dissolved in 10 mL of methanol, and sodium methanol (375 mg, 6.95 mmol) was added. The mixture was refluxed and stirred for 5 hours. The reaction mixture was concentrated under reduced pressure, and the residue obtained was purified using silica gel column chromatography with eluent system B to obtain the title product 5-bromo-7-methoxypyrazolo[1,5-a]pyridine 14a (292 mg), yield: 93.2%. MS m / z(ESI):227[M+1] Referring to the synthesis methods of Step 1 in Example 1, Steps 2 and 4 in Example 13, and Step 11 in Example 1 in order, N-(3,7-dichloropyrazolo[1,5-a]pyridin-5-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide 14 (30 mg) was obtained from 5-bromo-7-methoxypyrazolo[1,5-a]pyridine 14a (292 mg, 1.29 mmol), with a yield of 4.4%. MS m / z(ESI):527,529[M+1]. 1H NMR(400MHz,DMSO-d6)δ 11.13(broads,1H),11.06(broads,1H),8.52(s,1H),8.31(s,1H),8.23(d,1H),8.15( d,1H),7.91(t,1H),7.72(d,1H),7.60(d,1H),7.49(s,1H),7.12(s,1H),4.35(s,3H).

[0161] Example 15 1-(2H-Naphthalene[1,8-bc]benzofuran-5-yl)-5-trifluoromethyl-N-(2-trifluoromethyl-pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Step 11 of Example 1, 5-chloroquinolin-3-amine 15a (20 mg, 0.11 mmol) was reacted to obtain 1-(2H-naphthalene[1,8-bc]benzofuran-5-yl)-5-trifluoromethyl-N-(2-trifluoromethyl-pyridin-4-yl)-1H-pyrazole-4-carboxamide 15 (23 mg), yield: 41.0%. MS m / z (ESI): 508 [M+1] + . 1 H NMR(400MHz,DMSO-d6)δ 11.21(s,1H),11.12(s,1H),9.23(d,1H),9.16(s,1H),8.58(s,1H),8.16(d,1H),8.03 (d,1H),7.95-7.89(m,1H),7.83(d,1H),7.75-7.67(m,2H),7.62(d,1H),7.13(d,1H).

[0162] Example 16 N-(5-chloro-7-(trifluoromethyl)pyrrolo[1,2-b]pyridazin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide [ka] Step 1 Pyrrolo[1,2-b]pyridazine-3-carboxylic acid 16a (2.00 g, 14.0 mmol, synthesized according to the method described in US Pat. No. 6,667,303 B1) was dissolved in 10 mL of concentrated sulfuric acid and stirred at 60° C. for 12 hours. 50 mL of water was added to the reaction mixture in an ice bath to quench the sodium hydride, and the mixture was filtered to give the title product, pyrrolo[1,2-b]pyridazine-3-carboxylic acid 16b (1.20 g), in a 53.0% yield. MS m / z(ESI):163[M+1]

[0163] Step 2 tert-Butyl pyrrolo[1,2-b]pyridazine-3-carbamate Pyrrolo[1,2-b]pyridazine-3-carboxylic acid 16b (1.20 g, 7.40 mmol) was dissolved in 10 mL of tert-butanol, and triethylamine (2.20 g, 21.74 mmol) and diphenylphosphoryl azide (2.20 g, 7.99 mmol) were added. The mixture was stirred at 100 °C for 2 h. Extraction with ethyl acetate (50 mL × 3) was performed. The combined organic phases were washed with water (50 mL × 1) and saturated sodium chloride solution (50 mL × 1), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system A to give the title product, tert-butyl pyrrolo[1,2-b]pyridazin-3-ylcarbamate 16c (800 mg), in a 46.3% yield. MS m / z(ESI):234[M+1]

[0164] Step 3 7-Iodopyrrolo[1,2-b]pyridazine-3-carbamic acid tert-butyl ester tert-Butyl pyrrolo[1,2-b]pyridazine-3-carbamate 16c (800 mg, 3.43 mmol) was dissolved in 10 mL of tetrahydrofuran, and N-iododibutylimide (1.67 g, 7.42 mmol) was added. The mixture was stirred at 100 °C for 2 h. Extraction with ethyl acetate (50 mL × 3) was performed. The combined organic phases were washed with water (50 mL × 1) and saturated sodium chloride solution (50 mL × 1), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified using silica gel column chromatography with eluent system A to give the title product tert-butyl 7-iodopyrrolo[1,2-b]pyridazine-3-carbamate 16d (800 mg) in a 65.0% yield. MS m / z(ESI):360[M+1]

[0165] Step 4 7-Trifluoromethylpyrrolo[1,2-b]pyridazine-3-carbamic acid tert-butyl ester A three-neck flask was charged with tert-butyl 7-iodopyrrolo[1,2-b]pyridazine-3-carbamate 16d (800 mg, 2.23 mmol), cuprous iodide (850 mg, 4.46 mmol), methyl fluorosulfonyldifluoroacetate (865 mg, 4.50 mmol), and 10 mL of N,N-dimethylformamide. The mixture was heated at 80 °C for 12 h under nitrogen gas protection. The residue obtained was purified by silica gel column chromatography using eluent system A to give tert-butyl 5-trifluoromethylpyrazole[1,2-b]pyridazine-3-carbamate 16e (100 mg) in a 14.9% yield. MS m / z(ESI): 302 [M+1]. Referring to the synthesis methods of Steps 2 and 4 of Example 13 and Step 11 of Example 1 in order, N-(5-chloro-7-(trifluoromethyl)pyrrolo[1,2-b]pyridazin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide 16 (5 mg) was obtained from tert-butyl 5-trifluoromethylpyrazole[1,2-b]pyridazine-3-carbamate 16e (100 mg, 0.33 mmol), with a yield of 2.7%. MS m / z(ESI):565[M+1].

[0166] Example 17 N-(7-chloro-5-(trifluoromethyl)pyrrolo[1,2-b]pyridazin-3-yl)-1-(2-carbonyl-1,2,2a1,5a-tetrahydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis methods of Step 1 of Example 1, Steps 3 to 4 of Example 16, Step 4 of Example 13, and Step 11 of Example 1, N-(7-chloro-5-(trifluoromethyl)pyrrolo[1,2-b]pyridazin-3-yl)-1-(2-carbonyl-1,2,2a)-2-methyl-2-pyridazin-3-yl)-2-methyl-2-pyridazin-3-yl-1 ... 1 ,5a-tetrahydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 17 (11 mg) was obtained, yield: 6.0%. MS m / z(ESI):565[M+1].

[0167] Example 18 N-(6-(2H-1,2,3-triazol-2-yl)-5-trifluoromethylpyridin-3-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Step 11 of Example 1, intermediate 1 (18 mg, 0.052 mmol) and 6-(2H-1,2,3-triazol-2-yl)-3-amino-5-trifluoromethylpyridine 18a (12 mg, 0.052 mmol, obtained by synthesizing using the known method "Patent US20180170909A1") were used to obtain the title product N-(6-(2H-1,2,3-triazol-2-yl)-5-trifluoromethylpyridin-3-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide 18 (16 mg), with a yield of 55.1%. MS m / z (ESI): 559 [M+1] 1 H NMR(400MHz,DMSO-d6)δ 11.4(broads,1H),11.1(s,1H),9.18(d,1H),8.90(d,1H),8.57(s,1H),8.2 1(s,2H),8.15(d,1H),7.91(dd,1H),7.74(d,1H),7.61(d,1H),7.12(d,1H).

[0168] Example 19 1-(2-carbonyl-1,2,2a1,5a-tetrahydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(1-(trifluoromethyl)isoquinolin-7-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 7-Bromo-1-(trifluoromethyl)isoquinoline Referring to step 4 of Example 16, steps 2 and 4 of Example 13, and step 11 of Example 1 in order, 7-Bromo-1-iodoisoquinoline 19a (1.00 g, 2.99 mmol) gave the title product 1-(2-carbonyl-1,2,2a1,5a-tetrahydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(1-(trifluoromethyl)isoquinolin-7-yl)-1H-pyrazole-4-carboxamide 19 (0.11 g), yield: 6.8%. MS m / z (ESI): 544.4 [M + 1] 1 H NMR(400MHz,DMSO-d6):δ 11.33(s,1H),10.82(s,1H),8.32(s,1H),8.45(d,1H),8.21(d,1H),8.12(d,1H),7.92(d,1H) ,7.87(d,1H),7.71(d,1H),7.52(d,2H),7.25(d,1H),7.13(s,1H),6.83(m,1H),6.23(m,1H).

[0169] Example 20 N-(5-chloro-1-trifluoromethylisoquinolin-7-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide [ka] Step 1 7-Bromo-1-chloroisoquinolin-5-amine 7-Bromo-1-chloro-5-nitroisoquinoline 20a (3.50 g, 12.2 mmol) was dissolved in 30 mL of ethanol and 10 mL of water. Iron powder (6.83 g, 122 mmol) and ammonium chloride (6.81 g, 127.31 mmol) were added and the mixture was reacted at 60 °C for 2 h. The reaction mixture was cooled to room temperature and filtered. The filtrate was extracted with dichloromethane (50 mL × 3). The combined organic phases were washed with saturated sodium chloride solution (50 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated to give crude 7-bromo-1-chloroisoquinolin-5-amine 20b (2.51 g) in 80.1% yield. MS m / z(ESI):257[M+1]

[0170] Step 2 7-Bromo-1,5-dichloroisoquinoline 7-Bromo-1-chloroisoquinolin-5-amine 20b (2.51 g, 9.81 mmol) was dissolved in 30 mL of concentrated hydrochloric acid. Sodium nitrite (1.35 g, 19.62 mmol) was added at 0 °C. The mixture was allowed to react for 1 hour at 0 °C. Cuprous chloride (1.94 g, 19.62 mmol) was added. The mixture was allowed to react for 2 hours at room temperature. After filtration, the filtrate was adjusted to pH 7 with 10 M sodium hydride solution. Extraction was performed with dichloromethane (50 mL × 3). The combined organic phases were washed with saturated sodium chloride solution (50 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product. The residue was purified by silica gel column chromatography using eluent system A to give the title product, 7-bromo-1,5-dichloroisoquinoline 20c (1.1 g), in a yield of 40.7%. MS m / z (ESI): 276 [M+1] Referring to the synthesis methods of Step 3 in Example 1, Step 4 in Example 16, Steps 3 to 4 in Example 14, and Step 11 in Example 1 in order, 7-bromo-1,5-dichloroisoquinoline 20c (500 mg, 1.81 mmol) was reacted to give N-(5-chloro-1-trifluoromethylisoquinolin-7-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide 20 (45 mg), yield: 4.3%. MS m / z (ESI): 576 [M+1] 1 H NMR(400MHz,DMSO-d6)δ 11.41(s,1H),11.15(s,1H),9.27(d,1H),9.19(s,1H),8.60(s,1H),8.16(d,1H) ,7.95-7.89(m,1H),7.82(dd,1H),7.74(d,1H),7.64-7.53(m,2H),7.13(d,1H).

[0171] Example 21 1-(2-carbonyl-1,2,2a1,5a-tetrahydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(5-(trifluoromethyl)-4a,8a-dihydro-1,6-naphthyridin-3-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis methods of Step 3 of Example 1, Step 4 of Example 16, Steps 3 to 4 of Example 14, and Step 11 of Example 1 in order, 3-bromo-5-chloro-1,6-naphthyridine 21a (1.00 g, 4.11 mmol) was reacted with 1-(2-carbonyl-1,2,2a1,5a-tetrahydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(5-(trifluoromethyl)-4a,8a-dihydro-1,6-naphthyridin-3-yl)-1H-pyrazole-4-carboxamide 21 (101 mg), yield: 4.5%. MS m / z(ESI):547[M+1].

[0172] Example 22 1-(2-carbonyl-1,2,2a1,5a-tetrahydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(4-(trifluoromethyl)quinazolin-6-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 6-Bromo-4-(trifluoromethyl)quinazolin-2(1H)-one 4-Bromo-2-trifluoroacetylaniline 22a (1 g, 3.73 mmol, synthesized using a known method [US Patent 20140107096]) and potassium cyanide (605 mg, 7.46 mmol) were dissolved in a mixture of 1 mL of acetic acid and 10 mL of water in an ice bath and stirred at room temperature for 16 hours. The reaction mixture was poured into 100 mL of water, filtered, and the filter cake was dried. The filter cake was dissolved in toluene and heated to reflux for 4 hours. The water in the reaction mixture was removed using a water separator. After spin-drying the reaction mixture, the residue was purified using silica gel column chromatography with eluent system A to obtain the title product, 6-bromo-4-(trifluoromethyl)quinazolin-2(1H)-one 22b (566 mg), in a 51.7% yield. MS m / z (ESI): 293 [M+1]

[0173] Step 2 6-Bromo-2-chloro-4-trifluoromethylquinazoline 6-Bromo-4-(trifluoromethyl)quinazolin-2(1H)-one 22b (566 mg, 1.93 mmol) was dissolved in 10 mL of phosphorus oxychloride and reacted at 105° C. for 16 hours. The reaction mixture was concentrated under reduced pressure in an anhydrous environment, and the residue was purified by silica gel column chromatography using eluent system A to give the title product 6-bromo-2-chloro-4-(trifluoromethyl)quinazoline 22c (573 mg) in a yield of 95.3%. MS m / z(ESI):311[M+1] Referring to the synthesis method of Step 3 of Example 14, 2-chloro-4-trifluoromethyl-6-tert-butylcarbamate 22d (321 mg) was obtained from 6-bromo-2-chloro-4-(trifluoromethyl)quinazoline 22c (573 mg, 1.84 mmol), with a yield of 50.2%. MS m / z(ESI):348[M+1].

[0174] Step 4 4-Trifluoromethylquinazoline-6-carbamic acid tert-butyl ester 2-Chloro-4-trifluoromethyl-6-tert-butyl carbamate 22d (321 mg, 0.92 mmol) was dissolved in 10 mL of tetrahydrofuran, and palladium carbon (approximately 1 g, 10% purity) was added under nitrogen gas protection. The mixture was reacted at room temperature for 1 hour. The reaction mixture was filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure. The residue was purified using silica gel column chromatography with eluent system A to give the title product 4-trifluoromethyl-6-tert-butyl carbamate 22e (220 mg) in a 76.1% yield. MS m / z(ESI):314[M+1]. Referring to the synthesis methods of Step 4 of Example 13 and Step 11 of Example 1 in order, 1-(2-carbonyl-1,2,2a1,5a-tetrahydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(4-(trifluoromethyl)quinazolin-6-yl)-1H-pyrazole-4-carboxamide 22 (8.3 mg) was obtained from tert-butyl 4-trifluoromethylquinazoline-6-carbamate 22e (220 mg, 0.70 mmol), with a yield of 2.2%. MS m / z(ESI):545[M+1].

[0175] Example 23 N-(3-chloro-1-(trifluoromethyl)isoquinolin-7-yl)-1-(2-carbonyl-1,2,2a1,5a-tetrahydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Step 1 Methyl 7-bromo-1-(trifluoromethyl)isoquinoline-3-carboxylate Methyl (Z)-3-(4-bromophenyl)-2-isocyanoacrylate 23a (1 g, 3.77 mmol, synthesized according to a previously published method [Wang, Hao; et al., Chemical Communications (Cambridge, United Kingdom) (2014), 50(88), 13485-13488]), S-(trifluoromethyl)dibenzothiophenium tetrafluoroborate (1.92 g, 5.66 mmol), (4,4'-di-tert-butyl-2,2'-bipyridine)bis[(2-pyridine)phenyl]iridium(III) hexafluorophosphate (36 mg, 0.04 mmol), and disodium hydrogen phosphate (0.8 g, 5.66 mmol) were dissolved in 10 mL of ethanol and reacted for 3 hours under irradiation of a 13 W white LED lamp at room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography using eluent system B to give the title product 7-bromo-3-(trifluoromethyl)isoquinolin-1(2H)-one 23b (463 mg), yield: 36.9%. MS m / z (ESI): 334 [M+1] Referring to the synthesis method of Step 2 of Example 16, methyl 7-bromo-1-(trifluoromethyl)isoquinoline-3-carboxylate 23b (463 mg, 1.39 mmol) gave 7-bromo-1-(trifluoromethyl)isoquinolin-3-amine 23c (238 mg), yield: 59.1%. MS m / z(ESI):291[M+1].

[0176] Step 3 7-Bromo-3-chloro-1-(trifluoromethyl)isoquinoline 7-Bromo-1-(trifluoromethyl)isoquinolin-3-amine 23c (238 mg, 0.82 mmol) was dissolved in 3 mL of 2 M hydrochloric acid in an ice bath, and sodium nitrite (67 mg, 0.98 mmol) was dissolved in 2 mL of water and added to the reaction solution. The mixture was stirred at room temperature for 1 hour. Cuprous chloride (162 mg, 1.64 mmol) was dissolved in 2 mL of water and added to the reaction solution. The mixture was heated at 65 °C for 1 hour and stirred. The reaction solution was concentrated under reduced pressure, and the residue obtained was purified using silica gel column chromatography with eluent system B to give the title product 7-bromo-3-chloro-1-(trifluoromethyl)isoquinoline 23d (114 mg) in a 36.9% yield. MS m / z (ESI): 310 [M+1] Referring to the synthesis methods of Steps 2 and 4 of Example 13 and Step 11 of Example 1 in order, N-(3-chloro-1-(trifluoromethyl)isoquinolin-7-yl)-1-(2-carbonyl-1,2,2a1,5a-tetrahydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 23 (12 mg) was obtained from 7-bromo-3-chloro-1-(trifluoromethyl)isoquinoline 23d (114 mg, 0.37 mmol) in a yield of 5.6%. MS m / z(ESI):578[M+1].

[0177] Example 24 N-(4-Methoxy-1-trifluoromethylisoquinolin-7-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide [ka] Step 1 7-Bromo-4-methoxyisoquinoline-N-oxide 7-Bromo-4-methoxyisoquinoline 24a (1 g, 4.20 mmol) was dissolved in 30 mL of dichloromethane. Chloroperoxybenzoic acid (860 mg, 5 mmol) was added and the mixture was allowed to react at room temperature for 2 hours. The reaction mixture was washed with saturated sodium carbonate solution (50 mL x 2) and sodium chloride solution (50 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product. The residue was purified by silica gel column chromatography using eluent system A to give the title product, 7-bromo-4-methoxyisoquinoline-N-oxide 24b (900 mg), in 84.3% yield. MS m / z (ESI): 254 [M+1]

[0178] Step 2 7-Bromo-1-chloro-4-methoxyisoquinoline 7-Bromo-4-methoxyisoquinoline-N-oxide 24b (900 mg, 3.60 mmol) was dissolved in 10 mL of phosphorus oxychloride and reacted at 100° C. for 2 hours. The reaction mixture was concentrated to dryness, and the residue was poured into 50 mL of ice water. The pH was adjusted to 7 with 10 N sodium hydride solution, and the crude product was obtained by filtration. The residue was purified by silica gel column chromatography using eluent system A to give the title product 7-bromo-1-chloro-4-methoxyisoquinoline 24c (650 mg) in a yield of 67.3%. MS m / z (ESI): 272 [M+1] Referring to the synthesis methods of Step 3 in Example 1, Step 4 in Example 16, Steps 3 to 4 in Example 14, and Step 11 in Example 1 in order, 7-bromo-1-chloro-4-methoxyisoquinoline 24c (500 mg, 1.83 mmol) was reacted to obtain N-(5-chloro-1-trifluoromethylisoquinolin-7-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide 24 (55 mg), yield: 5.3%. MS m / z (ESI): 572 [M+1] 1H NMR(400MHz,DMSO-d6)δ 11.11(s,1H),10.87(s,1H),9.27(d,1H),9.19(s,1H),8.60(s,1H),8.46(d,1H),8.01 -7.85(m,1H),7.82(s,1H),7.69(d,1H),7.52-7.33(m,2H),7.03(d,1H),4.13(s,3H).

[0179] Example 25 N-(5,8-di(trifluoromethyl)-1,6-naphthyridin-3-yl)-1-(2-carbonyl-1,2,2a 1 ,5a-tetrahydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide [ka] Step 1 (4-amino-2,5-di(trifluoromethyl)pyridin-3-yl)methanol Ethyl 4-amino-2,5-bis(trifluoromethyl)nicotinate 25a (1.00 g, 3.31 mmol) was dissolved in 10 mL of tetrahydrofuran, purged with nitrogen gas three times, and cooled to 0 °C in an ice-water bath. A solution of lithium tetrahydroaluminum in tetrahydrofuran (6.62 mL, 6.62 mmol) was added dropwise to the reaction mixture, and the mixture was stirred at 0 °C for 1 h. The reaction was quenched by adding 0.5 mL of 20% aqueous sodium hydride. The reaction mixture was filtered, the filtrate was spin-dried, and the filter cake was washed with water (20 mL × 2). The filter cake and filtrate were concentrated under reduced pressure. The residue obtained was purified using silica gel column chromatography with eluent system A to give the title product (4-amino-2,5-di(trifluoromethyl)pyridin-3-yl)methanol 25b (0.45 g) in a 52.3% yield. MS m / z (ESI): 261.1 [M+1]

[0180] Step 2 4-Amino-2,5-di(trifluoromethyl)nicotinaldehyde (4-Amino-2,5-di(trifluoromethyl)pyridin-3-yl)methanol 25b (0.45 g, 1.73 mmol) was dissolved in 10 mL of dichloromethane, and manganese dioxide (1.50 g, 17.30 mmol) was added. The mixture was stirred for 2 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give the title product, 4-amino-2,5-di(trifluoromethyl)nicotinaldehyde 25c (0.33 g), in a 73.9% yield. MS m / z (ESI): 259.2 [M+1]

[0181] Step 3 3-Nitro-5,8-di(trifluoromethyl)-1,6-naphthyridine A 10 M sodium hydride solution (3.0 mL, 30 mmol) was added to the reaction flask, which was then cooled to 0°C in an ice-water bath. Nitromethane (0.5 mL, 9.25 mmol) was added dropwise, and the mixture was stirred at 0°C for 15 minutes and then further reacted at room temperature for 20 minutes. The reaction mixture was then placed in a room temperature water bath, and nitromethane (0.5 mL, 9.25 mmol) was slowly added dropwise to the mixture. The mixture was stirred at room temperature for 25 minutes and then poured into 50 mL of ice water. 3 mL of concentrated hydrochloric acid and 50 mL of ethyl ether were added, and the mixture was stirred until the ice melted. The mixture was separated, dried over anhydrous sodium sulfate, and filtered. The filtered mixture was mixed with 25 mL of ice water and 5 mL of 5 M hydrochloric acid. 4-Amino-2,5-di(trifluoromethyl)nicotinaldehyde 25c (0.32 g, 1.24 mmol) was dissolved in a mixture of 35 mL of ethanol, 30 mL of water, and 1 mL of 5 M hydrochloric acid and added dropwise to the reaction mixture. After completion, the reaction mixture was heated to 50 °C and stirred for 16 hours. The reaction mixture was concentrated under reduced pressure to 20 mL, extracted with ethyl acetate (30 mL × 3), the combined organic phases were washed with saturated sodium chloride solution (20 mL × 1), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue obtained was purified by silica gel column chromatography using eluent system A to give the title product, 3-nitro-5,8-di(trifluoromethyl)-1,6-naphthyridine 25d (0.18 g) in a 46.7% yield. MS m / z (ESI): 312.4 [M+1]

[0182] Step 4 5,8-Di(trifluoromethyl)-1,6-naphthyridin-3-amine 3-Nitro-5,8-di(trifluoromethyl)-1,6-naphthyridine 25d (0.18 g, 0.58 mmol), iron powder (0.16 g, 2.89 mmol), and ammonium chloride (0.15 g, 2.89 mmol) were dissolved in a mixture of 3 mL of ethanol, 3 mL of tetrahydrofuran, and 2 mL of water, and the mixture was stirred at 80° C. for 2 hours. The reaction mixture was filtered and concentrated to give the title product, 5,8-di(trifluoromethyl)-1,6-naphthyridine-3-amine 25e (110 mg), in a 67.5% yield. MS m / z (ESI): 282.1 [M+1]

[0083] Referring to the synthesis method in Step 11 of Example 1, N-(5,8-di(trifluoromethyl)-1,6-naphthyridin-3-yl)-1-(2-carbonyl-1,2,2a)-2H-pyrazol-3-yl was synthesized from 5,8-di(trifluoromethyl)-1,6-naphthyridin-3-amine 25e (60 mg, 0.21 mmol). 1 ,5a-tetrahydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide 25 (36 mg) was obtained, yield: 28.0%. MS m / z (ESI): 613.1 [M+1] 1 H NMR(400MHz,DMSO-d6):δ 11.28(s,1H),11.12(s,1H),9.47(d,1H),8.82(s,1H),8.53(s,1H),8.47(d,1H) ,8.25(d,1H),8.15(d,1H),7.98(d,1H),7.92(d,1H),7.72(d,1H),7.60(d,2H).

[0183] Example 26 N-(4-trifluoromethoxy-1-trifluoromethylisoquinolin-7-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide [ka] Step 1 7-Bromo-4-trifluoromethoxyisoquinoline 7-Bromo-4-hydroxyisoquinoline 26a (2 g, 8.91 mmol) was dissolved in 20 mL of N,N-dimethylformamide. Potassium fluoride (1.09 g, 18.82 mmol), cuprous iodide (3.97 g, 20.89 mmol), and 1-trifluoromethyl-1,2-phenyliodonyl-3(1H)-one (11.3 g, 35.60 mmol) were added and the mixture was reacted at 90 °C for 16 h. The reaction mixture was cooled to room temperature and poured into 200 mL of water. Filtration, the filtrate was extracted with ethyl acetate (50 mL × 3), the organic phases were combined, washed with saturated sodium chloride solution (50 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. The residue obtained was purified using silica gel column chromatography with eluent system A to obtain the title product 7-bromo-4-trifluoromethoxyisoquinoline 26b (1.20 g), yield: 46.2%. MS m / z (ESI): 292 [M+1] Referring to the synthesis methods of Steps 1 to 2 of Example 24, Step 3 of Example 1, Step 4 of Example 16, Steps 3 to 4 of Example 14, and Step 11 of Example 1 in order, N-(4-trifluoromethoxy-1-trifluoromethylisoquinolin-7-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide 26 (45 mg) was obtained from 7-bromo-4-trifluoromethoxyisoquinoline 26b (1.20 g, 4.11 mmol), with a yield of 1.8%. MS m / z(ESI):626[M+1] 1 H NMR(400MHz,DMSO-d6)δ 11.31(s,1H),11.17(s,1H),9.47(d,1H),9.39(s,1H),8.80(s,1H),8.66(d,1H) ),8.21-7.95(m,1H),7.92(s,1H),7.75(d,1H),7.52-7.33(m,2H),7.03(d,1H).

[0184] Example 27 1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 6-Bromo-1-(4-methoxybenzyl)benzo[cd]indol-2(1H)-one 6-Bromobenzo[cd]indol-2(1H)-one (1 g, 4.10 mmol) was dissolved in 20 mL of acetonitrile, and 4-methoxybenzyl bromobenzoate (1.22 g, 6.15 mmol) and potassium carbonate (1.13 g, 8.2 mmol) were added. The mixture was stirred at room temperature for 16 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system A to give the title product 6-bromo-1-(4-methoxybenzyl)benzo[cd]indol-2(1H)-one 27b (1.07 g), yield: 71.0%. MS m / z(ESI):368[M+1]. By following the synthesis method of Steps 7 to 11 of Example 1, 1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 27 (20 mg) was obtained. MS m / z (ESI): 492 [M+1] 1H NMR(400MHz,DMSO-d6)δ 11.27(s,1H),11.12(s,1H),8.72(d,1H),8.54(s,1H),8.25(d,1H),8.15( d,1H),7.99(dd,1H),7.91(dd,1H),7.72(d,1H),7.60(d,1H),7.12(d,1H).

[0185] Example 28 N-(2-(difluoromethyl)pyridin-4-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Steps 5 and 6 of Example 27, N-(2-(difluoromethyl)pyridin-4-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 28 (5 mg) was obtained from 1-(1-(4-methoxybenzyl)-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid 28a (50 mg, 0.107 mmol), with a yield of 9.9%. MS m / z(ESI):474[M+1].

[0186] Example 29 1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(6-(trifluoromethyl)pyridazin-4-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 6-(trifluoromethyl)pyridazine-4-carbamic acid tert-butyl ester Methyl 6-(trifluoromethyl)pyridazine-4-carboxylic acid 29a (200 mg, 1.04 mmol, obtained using the method disclosed in US20200347052) was dissolved in 10 mL of tert-butanol. Diphenylphosphoryl azide (573 mg, 2.08 mmol) and triethylamine (210 mg, 2.08 mmol) were added and the mixture was reacted at 100 °C for 2 hours. The reaction mixture was cooled to room temperature, and the solvent was spin-dried. 20 mL of ethyl acetate was added and extracted (20 mL × 3). The combined organic phases were washed with saturated sodium chloride solution (10 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product. The residue was purified using silica gel column chromatography with eluent system A to give the title tert-butyl 6-(trifluoromethyl)pyridazine-4-carbamate 29b (40 mg) in a 14.6% yield. MS m / z(ESI):264[M+1]

[0187] Step 2 6-(trifluoromethyl)pyridazin-4-amine tert-Butyl 6-(trifluoromethyl)pyridazine-4-carbamate 29b (40 mg, 0.15 mmol) was dissolved in 2 mL of ethanol and 1 mL of (4 M) hydrochloric acid and reacted at 20° C. for 2 h. The mixture was concentrated to give the title product 6-(trifluoromethyl)pyridazin-4-amine 29c (20 mg), yield: 80.7%. MS m / z(ESI):164[M+1]

[0188] Step 3 1-(1-(4-Methoxybenzyl)-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(6-(trifluoromethyl)pyridazin-4-yl)-1H-pyrazole-4-carboxamide 6-(Trifluoromethyl)pyridazin-4-amine 29c (20 mg, 0.123 mmol) and 1-(1-(4-methoxybenzyl)-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid (60 mg, 0.13 mmol) were dissolved in 10 mL of dichloromethane. Phosphorus oxychloride (60 mg, 0.391 mmol) and pyridine (30 mg, 0.379 mmol) were added, and the mixture was allowed to react at 20 °C for 2 hours. The reaction mixture was cooled to room temperature, and the solvent was removed by spin drying. Add 20 mL and extract with ethyl acetate (20 mL × 3), combine the organic phases, wash with saturated sodium chloride solution (10 mL × 2), dry over anhydrous sodium sulfate, filter, and concentrate to obtain the crude product. Purify the obtained residue using silica gel column chromatography with eluent system A to obtain the title 1-(1-(4-methoxybenzyl)-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(6-(trifluoromethyl)pyridazin-4-yl)-1H-pyrazole-4-carboxamide 29d (4 mg), yield: 5.3%. MS m / z(ESI): 613 [M+1].

[0189] Step 4 1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(6-(trifluoromethyl)pyridazin-4-yl)-1H-pyrazole-4-carboxamide 1-(1-(4-Methoxybenzyl)-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(6-(trifluoromethyl)pyridazin-4-yl)-1H-pyrazole-4-carboxamide 29d (4 mg, 0.0065 mmol) was dissolved in 3 mL of trifluoroacetic acid and reacted at 100° C. for 12 hours. The reaction solution was cooled to room temperature, and the solvent was spin-dried. Add 20 mL and extract with ethyl acetate (20 mL × 3). Combine the organic phases, wash with saturated sodium chloride solution (10 mL × 2), dry over anhydrous sodium sulfate, filter, and concentrate to obtain the crude product. Purify the residue obtained using silica gel column chromatography with eluent system A to obtain the title 1-(1-(4-methoxybenzyl)-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(6-(trifluoromethyl)pyridazin-4-yl)-1H-pyrazole-4-carboxamide 29 (2 mg), yield: 62.2%. MS m / z(ESI):493[M+1] 1H NMR(400MHz,DMSO-d6)δ 11.27(s,1H),11.12(s,1H),8.72(s,1H),8.54(s,1H),8.15(d,1H),7.99(dd,1H),7.91(dd,1H),7.72(d,1H),7.60(d,1H),7.12(d,1H).

[0190] Example 30 N-(6-((dimethyl(carbonyl)-6-thiazinyl)amino)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Step 1 Dimethyl((5-nitro-3-(trifluoromethyl)pyridin-2-yl)imino)-6-sulfanone 2-Chloro-5-nitro-3-(trifluoromethyl)pyridine 30a (150 mg, 0.66 mmol), dimethylsulfinyl imide (67 mg, 0.73 mmol), tris(dibenzylideneacetone)dipalladium (60 mg, 0.06 mmol), 4,5-bisdiphenylphosphine-9,9-dimethyloxanthene (38 mg, 0.06 mmol), and cesium carbonate (323 mg, 0.99 mmol) were dissolved in 5 mL of tetrahydrofuran and heated at 60 °C for 16 h under nitrogen gas protection. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography using eluent system A to give the title product, dimethyl((5-nitro-3-(trifluoromethyl)pyridin-2-yl)imino)-6-sulfanone 30b (100 mg), in a 53.3% yield. MS m / z(ESI):284[M+1]

[0191] Step 2 Dimethyl((5-amino-3-(trifluoromethyl)pyridin-2-yl)imino)-6-sulfanone Dimethyl((5-nitro-3-(trifluoromethyl)pyridin-2-yl)imino)-6-thiane 30b (100 mg, 0.35 mmol) was dissolved in 5 mL of tetrahydrofuran, and 5% palladium carbon (375 mg) was added under nitrogen gas protection. The mixture was stirred at room temperature under hydrogen gas for 1 hour. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give the title product, dimethyl((5-amino-3-(trifluoromethyl)pyridin-2-yl)imino)-6-sulfanone 30c (79 mg), in 88.9% yield. MS m / z (ESI): 254 [M+1] Referring to the synthesis method in Step 11 of Example 1, N-(6-((dimethyl(carbonyl)-6-thiazinyl)amino)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 30 (27 mg) was obtained from dimethyl((5-amino-3-(trifluoromethyl)pyridin-2-yl)imino)-6-sulfanone 30c (38 mg, 0.15 mmol) in a yield of 31.1%. MS m / z (ESI): 583.1 [M+1] 1H NMR(400MHz,DMSO)δ 11.11(s,1H),10.71(s,1H),8.64(d,J=2.6Hz,1H),8.46(s,1H),8.32(d,J=2.6Hz,1H),8.15(d,J=7.0Hz,1H), 7.90(dd,J=8.3,7.0Hz,1H),7.70(d,J=7.5Hz,1H),7.59(d,J=8.3Hz,1H),7.11(d,J=7.5Hz,1H),3.44(s,6H).

[0192] Example 31 N-(6-(1H-pyrazol-1-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis methods of Example 30, Step 1 to Step 2, and Example 1, Step 11, in order, 2-chloro-5-nitro-3-(trifluoromethyl)pyridine 31a (150 mg, 0.66 mmol) was reacted to give N-(6-(1H-pyrazol-1-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 31 (27 mg), yield: 7.3%. MS m / z(ESI):558[M+1]. 1H NMR(400MHz,DMSO)δ 11.64(d,J=5.8Hz,1H),11.26(s,1H),8.72(d,J=5.5Hz,1H),8.53(s,1H),8.45(dt,J=8.0,1.1Hz,1H),8.24(d,J=2.0 Hz,1H),7.96(ddd,J=9.0,6.5,1.6Hz,2H),7.68(t,J=7.9Hz,1H),7.30(dd,J=7.3,5.8Hz,1H),5.65(d,J=7.3Hz,1H).

[0193] Example 32 N-(6-(5-cyano-1H-pyrazol-1-yl)-(5-trifluoromethylpyridin-3-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide [ka] Step 1 1-(5-nitro-3-trifluoromethylpyridin-2-yl)-5-cyano-1H-pyrazole 2-Chloro-5-nitro-3-trifluoromethylpyridine 32a (2.26 g, 10 mmol) was dissolved in 25 mL of acetonitrile, and 5-cyano-1H-pyrazole 32b (0.8 mL, 11 mmol) and potassium carbonate (1.79 g, 13 mmol) were added. The mixture was stirred at 40° C. for 12 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography using eluent system A (PE / EA=2:1) ​​to give the title product 1-(5-nitro-3-trifluoromethylpyridin-2-yl)-5-cyano-1H-pyrazole 32c (1.15 g) in a 40.6% yield. MS m / z(ESI):284[M+1]

[0194] Step 2 1-(5-amino-3-trifluoromethylpyridin-2-yl)-5-cyano-1H-pyrazole 1-(5-nitro-3-trifluoromethylpyridin-2-yl)-5-cyano-1H-pyrazole 32c (1.15 g, 4.06 mmol) was dispersed in a mixed solvent of 18 mL of ethanol and 3 mL of water, and iron powder (1.36 g, 24.36 mmol) and ammonium chloride (1.30 g, 24.36 mmol) were added and the mixture was stirred at 80 ° C. for 1 hour. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The resulting residue was thoroughly dissolved in 30 mL of ethyl acetate, filtered, and the filtrate was concentrated under reduced pressure to give the title product, 1-(5-amino-3-trifluoromethylpyridin-2-yl)-5-cyano-1H-pyrazole 32d (0.88 g). This product was directly used in the next step without further purification. MS m / z (ESI): 254 [M+1]

[0195] Step 3 N-(6-(5-cyano-1H-pyrazol-1-yl)-(5-trifluoromethylpyridin-3-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide Referring to the synthesis method of Step 11 of Example 1, crude 1-(5-amino-3-trifluoromethylpyridin-2-yl)-5-cyano-1H-pyrazole 32d (40 mg, 0.16 mmol) and intermediate 1 (56 mg, 0.16 mmol) were used to obtain the title product N-(6-(5-cyano-1H-pyrazol-1-yl)-(5-trifluoromethylpyridin-3-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide (10 mg), yield: 10.7%. MS m / z(ESI):583[M+1] 1 H NMR(400MHz,DMSO-d6)δ 11.44(br.s,1H),11.14(s,1H),9.16(d,1H),8.88(d,1H),8.61(d,1H),8.57(s,1 H),8.16(d,1H),7.92(t,1H),7.74(d,1H),7.61(t,1H),7.32(t,1H),7.13(t,1H).

[0196] Example 33 1-(2-oxo-1,2-1,2-dihydrobenzo[cd]indol-6-yl)-N-(6-(thiazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Step 1 2-(5-nitro-3-(trifluoromethyl)pyridin-2-yl)thiazole 2-Bromo-5-nitro-3-(trifluoromethyl)pyridine 33a (1 g, 3.70 mmol) and 2-(tri-n-butylmethyltinalkyl)thiazole 33b (1.87 g, 4.99 mmol) were dissolved in 10 mL of toluene, and tetrakis(triphenylphosphine)palladium (577 mg, 0.50 mmol) was added. The mixture was stirred at 100 °C for 2 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system A to give the title product, 2-(5-nitro-3-(trifluoromethyl)pyridin-2-yl)thiazole 33c (510 mg), in a 49.8% yield. MS m / z(ESI):276[M+1]. Referring to the synthesis methods of Step 4 of Example 25 and Step 11 of Example 1, 1-(2-oxo-1,2-1,2-dihydrobenzo[cd]indol-6-yl)-N-(6-(thiazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 33 (31 mg) was obtained from 2-(5-nitro-3-(trifluoromethyl)pyridin-2-yl)thiazole 33c (510 mg, 1.85 mmol), with a yield of 2.9%. MS m / z (ESI): 575 [M+1] 1H NMR(400MHz,DMSO-d6)δ 11.31(s,1H),11.13(s,1H),9.21(d,J=2.1Hz,1H),8.80(d,J=2.1Hz,1H),8.55(s,1H),8.15(d,J=6.9Hz,1H),8.07(d,J= 3.2Hz,1H),7.98(d,J=3.2Hz,1H),7.94-7.86(m,1H),7.73(d,J=7.5Hz,1H),7.61(d,J=8.3Hz,1H),7.12(d,J=7.5Hz,1H).

[0197] Example 34 N-(6-(oxazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Step 1 2-(5-nitro-3-(trifluoromethyl)pyridin-2-yl)oxazole 2-Bromo-5-nitro-3-(trifluoromethyl)pyridine 34a (302 mg, 1.12 mmol) was dissolved in 10 mL of toluene, tributyl(oxazol-2-yl)stannane (0.20 g, 0.56 mmol, 0.1 mL) and tetrakistriphenylphosphine palladium (64 mg, 0.056 mmol) were added, and the mixture was purged with nitrogen three times. The reaction was heated to 110 °C for 15 h. The reaction was cooled to room temperature and concentrated. The residue was added to 10 mL of water and extracted with ethyl acetate (30 mL × 3). The organic phases were combined, washed with saturated aqueous sodium chloride (30 mL × 1), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified using silica gel column chromatography with eluent system C to give the title product 2-(5-nitro-3-(trifluoromethyl)pyridin-2-yl)oxazole 34b (20 mg), yield: 13.8%. MS m / z (ESI): 260 [M+1]

[0198] Step 2 6-(oxazol-2-yl)-5-(trifluoromethyl)pyridin-3-amine 2-(5-Nitro-3-(trifluoromethyl)pyridin-2-yl)oxazole 34b (0.20 g, 0.77 mmol) was dissolved in ethanol (5 mL) and water (2 mL). Iron powder (215 mg, 3.85 mmol) and ammonium chloride (199 mg, 3.85 mmol) were added, and the mixture was purged with nitrogen three times. The reaction mixture was heated to 70 °C for 2 h. The reaction mixture was cooled to room temperature, filtered, and the filter cake was washed with ethanol (10 mL × 3). The filtrate was concentrated. The residue was dissolved in DCM / MeOH (10 / 1, 30 mL), stirred for 1 h, filtered, and concentrated to give the title product 6-(oxazol-2-yl)-5-(trifluoromethyl)pyridin-3-amine 34c (50 mg), yield: 28.3%. MS m / z (ESI): 230 [M+1]

[0199] Step 3 N-(6-(oxazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 1-(2-Carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (20 mg, 0.058 mmol), 6-(oxazol-2-yl)-5-(trifluoromethyl)pyridin-3-amine 34c (16 mg, 0.069 mmol), and DMAP (3 mg, 0.024 mmol) were dissolved in 5 mL of dichloromethane, purged with nitrogen gas three times, cooled to 0 °C, and pyridine (14 mg, 0.17 mmol) and phosphorus oxychloride (26 mg, 0.17 mmol) were added. The reaction was warmed to 25 °C and allowed to react for 2 h. The reaction was quenched with water and concentrated. The residue obtained was purified using silica gel column chromatography with eluent system A to give the title product N-(6-(oxazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 34 (1.8 mg), yield: 5.2%. MS m / z (ESI): 559 [M+1] 1 H NMR(400MHz,DMSO):δ 11.34(s,1H),11.13(s,1H),9.27(d,J=2.3Hz,1H),8.81(d,J=2.3Hz,1H),8.56(s,1H),8.39(s,1H),8.15(d,J=7.0H) z,1H),7.92(dd,J=8.3,7.0Hz,1H),7.73(d,J=7.5Hz,1H),7.61(d,J=8.2Hz,1H),7.53(s,1H),7.12(d,J=7.5Hz,1H).

[0200] Example 35 N-(6-(4,5-dimethyloxazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Step 1 5-Bromo-N-(butyl-3-yn-2-yl)-3-(trifluoromethyl)methylpyridineamide 5-Bromo-3-(trifluoromethyl)pyridine-2-carboxylic acid 35a (0.60 g, 2.22 mmol), HATU (1.68 g, 4.44 mmol), and butyl-3-yn-2-amine (307 mg, 4.44 mmol) were dissolved in 10 mL of acetonitrile, purged with nitrogen gas three times, and triethylamine (675 mg, 6.67 mmol, 0.93 mL) was added. The reaction was stirred at 25 °C for 1 h. Water was added to quench the reaction, followed by extraction with ethyl acetate (50 mL × 3). The combined organic phases were washed with saturated aqueous sodium chloride (30 mL × 1), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue obtained was purified using silica gel column chromatography with eluent system A to give the title product 5-bromo-N-(butyl-3-yn-2-yl)-3-(trifluoromethyl)methylpyridinamide 35b (0.65 g), yield: 91.1%. MS m / z(ESI):322[M+1]

[0201] Step 2 2-(5-Bromo-3-(trifluoromethyl)pyridin-2-yl)-4,5-dimethyloxazole A microwave reactor was charged with 5-bromo-N-(butyl-3-yn-2-yl)-3-(trifluoromethyl)methylpyridinamide 35b (0.65 g, 2.02 mmol), acetonitrile (5 mL), and triethylamine (205 mg, 2.02 mmol). Nitrogen gas was passed through the reactor for 3 minutes, and then gold trichloride (184 mg, 0.61 mmol) was added rapidly and sealed. The reaction was heated at 80 °C in a microwave reactor for 4 hours. The reaction was quenched with water and extracted with ethyl acetate (50 mL × 3). The combined organic phases were washed with saturated aqueous sodium chloride (30 mL × 1), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography using eluent system C to give the title product 2-(5-bromo-3-(trifluoromethyl)pyridin-2-yl)-4,5-dimethyloxazole 35c (0.32 g), yield: 49.2%. MS m / z(ESI):322[M+1]

[0202] Step 3 Butyl (6-(4,5-dimethyloxazol-2-yl-5-(trifluoromethyl)pyridin-3-yl)carbamate 2-(5-Bromo-3-(trifluoromethyl)pyridin-2-yl)-4,5-dimethylamine 35c (0.32 g, 1.00 mmol) and 5-bisdiphenylphosphine-9,9-dimethyloxanthene (58 mg, 0.10 mmol) were dissolved in 10 mL of 1,4-dioxane, purged with nitrogen gas three times, and (diallyliumacetone)palladium (57 mg, 0.10 mmol) was added. The reaction mixture was heated to 100 °C and reacted for 2 h. The mixture was cooled to room temperature and quenched by air circulation. The reaction mixture was filtered, concentrated, and spin-dried. The residue was purified using silica gel column chromatography with eluent system C to give the title product (6-(4,5-dimethyloxazol-2-yl-5-(trifluoromethyl)pyridin-3-yl)butylcarbamate 35d (0.14 g), yield: 39.3%. MS m / z(ESI):358[M+1]

[0203] Step 4 6-(4,5-dimethyloxazol-2-yl)-5-(trifluoromethyl)pyridin-3-amine Butyl (6-(4,5-dimethyloxazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)carbamate 35d (130 mg, 0.36 mmol) was dissolved in 5 mL of 4 M hydrogen chloride in 1,4-dioxane, and the reaction mixture was reacted at 25° C. for 1 h. The reaction mixture was concentrated to give the title product 6-(4,5-dimethyloxazol-2-yl)-5-(trifluoromethyl)pyridin-3-amine 35e (80 mg), yield: 85.1%. MS m / z(ESI):258[M+1]

[0204] Step 5 N-(6-(4,5-dimethyloxazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide Referring to the synthesis method of Step 11 of Example 1, intermediate 1 (35 mg, 0.10 mmol) and 6-(4,5-dimethyloxazol-2-yl)-5-(trifluoromethyl)pyridin-3-amine 35e (52 mg, 0.20 mmol, obtained by synthesizing using the known method "Patent US20180170909A1") were used to obtain the title product N-(6-(4,5-dimethyloxazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 35 (24 mg), yield 40.1%. MS m / z(ESI):587[M+1] 1 H NMR(400MHz,DMSO):δ 11.29(s,1H),11.12(s,1H),9.23(d,J=2.3Hz,1H),8.77(d,J=2.3Hz,1H),8.55(s,1H),8.15(d,J=6.9Hz,1H),7.91( dd,J=8.3,7.0Hz,1H),7.73(d,J=7.6Hz,1H),7.60(d,J=8.2Hz,1H),7.12(d,J=7.5Hz,1H),2.36(s,3H),2.14(s,3H).

[0205] Example 36 N-(6-(1H-1,2,3-triazol-1-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Step 1 5-nitro-2-(1H-1,2,3-triazol-1-yl)-3-(trifluoromethyl)pyridine 2-Bromo-3-trifluoromethyl-5-nitro-pyridine 36a (1.40 g, 5.18 mmol) and potassium carbonate (1.43 g, 10.36 mmol) were dissolved in 10 mL of acetonitrile in a single-neck flask. 1,2,3-Triazazole (537 mg, 7.77 mmol) was added, and the system was purged with nitrogen gas three times. The reaction mixture was heated to 40 °C and stirred for 2 h. The mixture was cooled to room temperature, filtered, and concentrated. The residue was purified by silica gel column chromatography using eluent system C to give the title product 5-nitro-2-(1H-1,2,3-triazol-1-yl)-3-(trifluoromethyl)pyridine 36b (0.50 g), yield: 42.7%. MS m / z(ESI):226[M+1]

[0206] Step 2 6-(1H-1,2,3-triazol-1-yl)-5-(trifluoromethyl)pyridin-3-amine 5-Nitro-2-(1H-1,2,3-triazol-1-yl)-3-(trifluoromethyl)pyridine 36b (0.25 g, 1.11 mmol), reduced iron powder (309 mg, 5.54 mmol), and ammonium chloride (285 mg, 5.54 mmol) were dissolved in 10 mL of ethanol and 5 mL of water. The mixture was purged with nitrogen three times and heated to 70 °C for 1 h. The reaction mixture was cooled to room temperature, filtered, and the filter cake was diluted with ethanol (10 mL × 3). The residue was dissolved in DCM / MeOH (10 / 130 mL), stirred for 1 h, filtered, and concentrated to give the title product 6-(1H-1,2,3-triazol-1-yl)-5-(trifluoromethyl)pyridin-3-amine 36c (150 mg), yield: 69.4%. MS m / z (ESI): 196 [M+1]

[0207] Step 3 N-(6-(1H-1,2,3-triazol-1-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide Referring to the synthesis method of Step 11 of Example 1, intermediate 1 (80 mg, 0.23 mmol) and 6-(1H-1,2,3-triazol-1-yl)-5-(trifluoromethyl)pyridin-3-amine 36c (64 mg, 0.27 mmol, obtained by synthesizing using the known method "Patent US20180170909A1") were used to obtain the title product 6-(1H-1,2,3-triazol-1-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 36 (21 mg), yield: 16.4%. MS m / z (ESI): 559 [M+1] 1 H NMR(400MHz,DMSO):δ 11.40(s,1H),11.12(s,1H),9.20(d,J=2.4Hz,1H),8.90(d,J=2.4Hz,1H),8.68(d,J=1.2Hz,1H),8.57(s,1H),8.15(d,J=6.9H) z,1H),8.02(d,J=1.2Hz,1H),7.92(dd,J=8.3,7.0Hz,1H),7.73(d,J=7.5Hz,1H),7.61(d,J=8.2Hz,1H),7.12(d,J=7.5Hz,1H).

[0208] Example 37 N-(6-(1-methyl-1H-pyrazol-3-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Step 1 2-(1-methyl-1H-pyrazol-3-yl)-5-nitro-3-(trifluoromethyl)pyridine 2-Bromo-5-nitro-3-(trifluoromethyl)pyridine 37a (1 g, 3.70 mmol) and 1-methyl-1H-pyrazole-5-boronic acid pinacol ester 37b (1.04 g, 5 mmol) were dissolved in 10 mL of toluene and 2 mL of water, and tetrakis(triphenylphosphine)palladium (577 mg, 0.50 mmol) and potassium carbonate (1.38 g, 10 mmol) were added. The mixture was stirred at 100 °C for 1 h. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system A to give the title product 2-(1-methyl-1H-pyrazol-3-yl)-5-nitro-3-(trifluoromethyl)pyridine 37c (620 mg) in a 61.1% yield. MS m / z(ESI):273[M+1]. Referring to the synthesis methods of Step 4 of Example 25 and Step 11 of Example 1, N-(6-(1-methyl-1H-pyrazol-3-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 37 (30 mg) was obtained from 2-(1-methyl-1H-pyrazol-3-yl)-5-nitro-3-(trifluoromethyl)pyridine 37c (620 mg, 2.27 mmol), with a yield of 2.3%. MS m / z (ESI): 572 [M+1] 1 H NMR(400MHz,DMSO-d6)δ 11.13(d,J=5.1Hz,2H),9.15(d,J=2.1Hz,1H),8.68(d,J=2.2Hz,1H),8.54(s,1H),8.15(d,J=6.9Hz,1H),7.91(dd,J=8.2,7.1Hz,1 H),7.79(d,J=2.2Hz,1H),7.72(d,J=7.5Hz,1H),7.61(d,J=8.3Hz,1H),7.12(d,J=7.5Hz,1H),6.65(d,J=2.2Hz,1H),3.92(s,3H).

[0209] Example 38 N-(6-N-methyl-1,1-dioxidetetrahydro-2H-thiopyran-4-carboxamide)-5-(trifluoromethylpyridin-3-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide [ka] Step 1 Tetrahydro-2H-thiopyran-4-carboxamide 1,1-dioxide Tetrahydro-2H-thiopyran-4-carboxylic acid 1,1-dioxide 38a (1.59 g, 8.92 mmol) was dissolved in 25 mL of dichloromethane, and 0.1 mL of N,N-dimethylformamide and oxalyl chloride (4.5 mL, 53.53 mmol) were added. The mixture was stirred at room temperature for 0.5 h. The reaction mixture was concentrated under reduced pressure, and 5 mL of aqueous ammonia was added to the residue. The filtered material was washed twice with water (5 mL × 2) and dried to give the title product, tetrahydro-2H-thiopyran-4-carboxamide 1,1-dioxide 38b (900 mg), in a 56.9% yield. MS m / z (ESI): 178 [M+1]

[0210] Step 2 N-(5-nitro-3-trifluoromethylpyridin-2-yl)-tetrahydro-2H-thiopyran-4-carboxamide 1,1-dioxide Sodium hydride (320 mg, 13.33 mmol) was dispersed in 15 mL of N,N-dimethylformamide, and tetrahydro-2H-thiopyran-4-carboxamide 1,1-dioxide 38b (704 mg, 3.97 mmol) was added. oAfter stirring at C for 1 hour, 2-chloro-5-nitro-3-trifluoromethylpyridine (900 mg, 3.97 mmol) was added and the mixture was stirred at room temperature for 12 hours. 5 mL of saturated ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate (10 mL × 3). The organic phases were combined, washed with saturated aqueous sodium chloride (25 mL × 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue obtained was purified using silica gel column chromatography with eluent system A to give the title product N-(5-nitro-3-trifluoromethylpyridin-2-yl)-tetrahydro-2H-thiopyran-4-carboxamide 1,1-dioxide 38c (219 mg), yield: 15.0%. MS m / z(ESI):368[M+1]

[0211] Step 3 N-methyl-N-(5-nitro-3-trifluoromethylpyridin-2-yl)-tetrahydro-2H-thiopyran-4-carboxamide 1,1-dioxide N-(5-nitro-3-trifluoromethylpyridin-2-yl)-tetrahydro-2H-thiopyran-4-carboxamide 1,1-dioxide 38c (219 mg, 0.60 mmol) was dissolved in 5 mL of N,N-dimethylformamide, and potassium carbonate (248 mg, 1.80 mmol) and iodomethane (256 mg, 1.80 mmol) were added. The reaction was stirred at room temperature for 3 hours. The reaction mixture was added with 5 mL of saturated ammonium chloride solution, extracted with ethyl acetate (10 mL × 3), the organic phases were combined, washed with saturated aqueous sodium chloride (25 mL × 2), dried over anhydrous sodium sulfate, filtered, the filtrate was concentrated under reduced pressure, and the residue obtained was purified using silica gel column chromatography with eluent system A to obtain the title product N-methyl-N-(5-nitro-3-trifluoromethylpyridin-2-yl)-tetrahydro-2H-thiopyran-4-carboxamide 1,1-dioxide 38d (66 mg), yield: 29.0%. MS m / z(ESI):382[M+1]

[0212] Step 4 to Step 5 N-(6-N-methyl-1,1-dioxidetetrahydro-2H-thiopyran-4-carboxamide)-5-(trifluoromethylpyridin-3-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide By sequentially following the synthesis methods of Step 2 of Example 32 and Step 11 of Example 1, the title product N-(6-N-methyl-1,1-dioxidetetrahydro-2H-thiopyran-4-carboxamide)-5-(trifluoromethylpyridin-3-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide 38 (20 mg) was obtained from N-methyl-N-(5-nitro-3-trifluoromethylpyridin-2-yl)-tetrahydro-2H-thiopyran-4-carboxamide 1,1-dioxide 38d (66 mg, 0.17 mmol), with a yield of 17.0%. MS m / z(ESI):681[M+1] 1 H NMR(400MHz,DMSO-d6)δ 11.47-11.02(br.s,1H),11.13(s,1H),9.06(s,1H),8.86(d,1H),8.51(s,1H),8.16(d,1H),7.92( t,1H),7.73(d,1H),7.61(d,1H),7.12(t,1H),3.08(s,3H),3.05-2.87(m,3H),2.40-1.73(m,6H).

[0213] Example 39 N-(6-(2H-tetrazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-oxo-1,2-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Step 1 5-nitro-2-(2H-tetraazol-2-yl)-3-(trifluoromethyl)pyridine 2-Chloro-5-nitro-3-(trifluoromethyl)pyridine 39a (1 g, 4.42 mmol) and tetraazole (350 mg, 5 mmol) were dissolved in 20 mL of acetonitrile, triethylamine (1 g, 10 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography using eluent system A to give the title product, 5-nitro-2-(2H-tetraazol-2-yl)-3-(trifluoromethyl)pyridine 39b (420 mg), in a 36.0% yield. MS m / z(ESI):261[M+1]. Referring to the synthesis methods of Step 4 of Example 25 and Step 11 of Example 1, N-(6-(2H-tetrazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-oxo-1,2-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 39 (20 mg) was obtained from 5-nitro-2-(2H-tetrazol-2-yl)-3-(trifluoromethyl)pyridine 39b (420 mg, 1.62 mmol), with a yield of 2.3%. MS m / z (ESI): 560 [M+1]

[0214] Example 40 1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-N-(6-(tetrahydrofuran-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Step 1 6-Bromo-5-(trifluoromethyl)pyridin-3-amine 2-Bromo-5-nitro-3-(trifluoromethyl)pyridine 40a (2 g, 7.38 mmol) was dissolved in 20 mL of ethanol and 5 mL of water. Ammonium chloride (1 g, 18.7 mmol) and reduced iron powder (1 g, 17.9 mmol) were added and the mixture was reacted at 80 °C for 2 hours. The reaction mixture was cooled to room temperature and poured into 50 mL of water. After filtration, the filtrate was extracted with ethyl acetate (50 mL × 3). The combined organic phases were washed with saturated sodium chloride solution (50 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product. The residue was purified by silica gel column chromatography using eluent system A to give the title product, 6-bromo-5-(trifluoromethyl)pyridin-3-amine 40b (1.4 g), in 78.7% yield. MS m / z (ESI): 242 [M+1]

[0215] Step 2 N-[6-bromo-5-(trifluoromethyl)-3-pyridine]-Nt-butoxycarbonyl-carbamic acid tert-butyl ester 6-Bromo-5-(trifluoromethyl)pyridin-3-amine 40b (1.4 g, 5.8 mmol) and di-tert-butyl dicarbonate (3 g, 13.7 mmol) were dissolved in 20 mL of dichloromethane. Triethylamine (2 g, 19.7 mmol) and 4-dimethylaminopyridine (100 mg, 0.82 mmol) were added, and the mixture was allowed to react at 20 °C for 12 hours. The reaction mixture was cooled to room temperature and poured into 200 mL of water. Filtration, the filtrate was extracted with ethyl acetate (50 mL × 3), the organic phases were combined, washed with saturated sodium chloride solution (50 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product, and the residue obtained was purified using silica gel column chromatography with eluent system A to obtain the title product N-[6-bromo-5-(trifluoromethyl)-3-pyridine]-Nt-butoxycarbonyl-carbamic acid tert-butyl ester 40c (2.4 g), yield: 93.6%. MS m / z(ESI):442[M+1]

[0216] Step 3 Nt-Butoxycarbonyl-N-[6-(2,3-dihydrofuran-5-yl)-5-(trifluoromethyl)-3-pyridine]carbamic acid tert-butyl ester N-[6-Bromo-5-(trifluoromethyl)-3-pyridine]-Nt-butoxycarbonyl-carbamic acid tert-butyl ester 40c (2.40 g, 5.40 mmol), potassium carbonate (1.5 g, 10.8 mmol), palladium acetate (122 mg, 0.54 mmol), and 2,3-dihydrofuran (760 mg, 10.8 mmol) were dissolved in 15 mL of N,N-dimethylformamide. Triphenylphosphine (283 mg, 1.08 mmol) was added and the reaction mixture was heated to 110 °C for 2 hours. The reaction mixture was cooled to room temperature, and 20 mL of water was added. Filtration, the filtrate was extracted with ethyl acetate (20 mL × 3), the organic phases were combined, washed with saturated sodium chloride solution (10 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product, and the residue obtained was purified using silica gel column chromatography with eluent system A to obtain the title product Nt-butoxycarbonyl-N-[6-(2,3-dihydrofuran-5-yl)-5-(trifluoromethyl)-3-pyridine]carbamic acid tert-butyl ester 40d (200 mg), yield: 8.5%. MS m / z(ESI):431[M+1].

[0217] Step 4 Nt-Butoxycarbonyl-N-[6-tetrahydrofuran-2-yl-5-(trifluoromethyl)-3-pyridine]carbamic acid tert-butyl ester Nt-Butoxycarbonyl-N-[6-(2,3-dihydrofuran-5-yl)-5-(trifluoromethyl)-3-pyridine]carbamic acid tert-butyl ester 40d (200 mg, 0.47 mmol) was dissolved in 10 mL of tetrahydrofuran. Pd / C (200 mg) was added, and the reaction was carried out under hydrogen gas (15 psi) at 20 °C for 12 hours. The reaction mixture was cooled to room temperature, filtered, and concentrated to give the crude product. The residue was purified by silica gel column chromatography using eluent system A to give the title Nt-butoxycarbonyl-N-[6-tetrahydrofuran-2-yl-5-(trifluoromethyl)-3-pyridine]carbamic acid tert-butyl ester 40e (60 mg), yield: 29.8%. MS m / z(ESI):433[M+1]. Referring to the synthesis methods of Steps 5 and 6 of Example 29, 1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-N-(6-(tetrahydrofuran-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 40 (10 mg) was obtained from Nt-butoxycarbonyl-N-[6-tetrahydrofuran-2-yl-5-(trifluoromethyl)-3-pyridine]carbamic acid tert-butyl ester 40e (60 mg, 0.139 mmol), with a yield of 12.8%. MS m / z(ESI):562[M+1]. 1H NMR(400MHz,CD3OD)δ 9.09(d,J=2.4Hz,1H),8.62(d,J=2.5Hz,1H),8.34(s,1H),8.15(d,J=7.0Hz,1H),7.87(dd,J=8.3,7.0Hz,1H),7.66(dd,J=7.9,6.3Hz,2H),7 .13(d,J=7.5Hz,1H),5.38-5.23(m,1H),4.20(q,J=7.0Hz,1H),3.97(td,J=7.6,5.5Hz,1H),2.32(td,J=7.5,4.0Hz,1H),2.26-1.96(m,3H).

[0218] Example 41 1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-N-(5-trifluoromethyl-6-(4-trifluoromethyl-2H-1,2,3-triazol-2-yl)pyridin-3-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 to Step 3 1-(2-oxido-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-N-(5-trifluoromethyl-6-(4-trifluoromethyl-2H-1,2,3-triazol-2-yl)pyridin-3-yl)-1H-pyrazole-4-carboxamide Referring to the synthesis methods of step 1 to step 2 of Example 32 and step 11 of Example 1 in order, 5-trifluoromethyl-1H-1,2,3-triazole (137 mg, 1 mmol, prepared by using the known method "Patent US2020 / 102311A1") and 2-chloro-5-nitro-3-trifluoromethylpyridine (230 mg, 1 mmol) to obtain the title product 1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-N-(5-trifluoromethyl-6-(4-trifluoromethyl-2H-1,2,3-triazol-2-yl)pyridin-3-yl)-1H-pyrazole-4-carboxamide (11 mg), yield: 1.8%. MS m / z(ESI):627[M+1]

[0219] Example 42 N-(6-(1-oxido-4,5-dihydro-3H-1λ) 6 -isothiazol-1-yl)-5-trifluoromethylpyridin-3-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide [ka] Step 1 3-((5-nitro-3-trifluoromethylpyridin-2-yl)sulfide)-1-propylamine 5-Nitro-3-trifluoromethylpyridine-2-thiol 42a (2.24 g, 10 mmol) was dissolved in 25 mL of acetonitrile, and potassium carbonate (1.52 g, 11.02 mmol) and 3-iodo-1-propylamine 42b (2.41 g, 12.11 mmol, prepared according to a known method [Chemistry-European Journal, 2021, 27(63), 15716-15721]) were added. The mixture was stirred at room temperature for 12 hours. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified using silica gel column chromatography with eluent system A to give the title product 3-((5-nitro-3-trifluoromethylpyridin-2-yl)sulfide)-1-propylamine 42c (1.81 g), yield: 64.3%. MS m / z(ESI):282[M+1]

[0220] Step 2 1-(5-nitro-3-trifluoromethylpyridin-2-yl)-1-oxo-3H-4,5-dihydroisothiazole 3-((5-nitro-3-trifluoromethylpyridin-2-yl)sulfide)-1-propylamine 42c (1.81 g, 6.44 mmol) was dissolved in 25 mL of methanol, and ammonium formate (1.22 g, 19.30 mmol) and iodobenzene acetate (6.21 g, 19.30 mmol) were added. The mixture was stirred at room temperature for 12 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified using silica gel column chromatography with eluent system A to give the title product 1-(5-nitro-3-trifluoromethylpyridin-2-yl)-1-oxo-3H-4,5-dihydroisothiazole 42d (0.45 g), yield: 23.7%. MS m / z(ESI):296[M+1]

[0221] Step 3 to Step 4 Referring to the synthesis methods of Step 2 of Example 32 and Step 11 of Example 1, the title product N-(6-(1-oxide-4,5-dihydro-3H-1λ)-2-methyl-2-pyridin-2-yl)-1-oxo-3H-4,5-dihydroisothiazole 42d (0.15 g, 0.51 mmol) was synthesized. 6 -isothiazol-1-yl)-5-trifluoromethylpyridin-3-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide 42 (31 mg) was obtained, yield: 10.0%. MS m / z (ESI): 595 [M+1]

[0222] Example 43 1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-N-(6-(4-trifluoromethoxymethyl-2H-1,2,3-triazol-2-yl)-5-trifluoromethylpyridin-3-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide [ka] Step 1 4-Trifluoromethoxymethyl-2H-1,2,3-triazole 4-Bromomethyl-2H-1,2,3-triazole 43a (1.62 g, 10 mmol, prepared according to the published method [Tetrahedron, 2005, 61(21), 4983-4987]) was dissolved in 25 mL of acetonitrile, and trifluoromethyl trifluoromethanesulfonate (4.4 g, 20 mmol) and silver trifluoromethanesulfonate (5.14 g, 20 mmol) were added. The mixture was stirred at room temperature for 12 hours. After filtration, the reaction mixture was concentrated under reduced pressure to give the crude title product, 4-trifluoromethoxymethyl-2H-1,2,3-triazole 43b (1.81 g), which was directly used in the next step without further purification. MS m / z(ESI):167[M+1]

[0223] Step 2 to Step 4 By following the synthesis methods of Steps 1 to 2 of Example 32 and Step 11 of Example 1 in order, the title product 1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-N-(6-(4-trifluoromethoxymethyl-2H-1,2,3-triazol-2-yl)-5-trifluoromethylpyridin-3-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide (15 mg) was obtained from crude 4-trifluoromethoxymethyl-2H-1,2,3-triazole 43b (0.49 g, 3 mmol), with a yield of 0.8%. MS m / z(ESI):657[M+1]

[0224] Example 44 N-(5-chloro-6-(1H-pyrazol-1-yl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Example 30, Step 1, 2,3-dichloro-5-nitropyridine 44a (150 mg, 0.79 mmol) was reacted to obtain 3-chloro-5-nitro-2-(1H-pyrazol-1-yl)pyridine 44b (110 mg), yield: 62.0%. MS m / z(ESI):225[M+1].

[0225] Step 2 3-chloro-5-amino-2-(1H-pyrazol-1-yl)pyridine 3-Chloro-5-nitro-2-(1H-pyrazol-1-yl)pyridine 44b (110 mg, 0.49 mmol) was dissolved in 5 mL of ethanol and 5 mL of water, and iron powder (82 mg, 1.47 mmol) and ammonium chloride (261 mg, 4.90 mmol) were added. The mixture was heated at 85 °C for 1 h with stirring. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system B to give the title product 3-chloro-5-amino-2-(1H-pyrazol-1-yl)pyridine 44c (89 mg) in a 93.4% yield. MS m / z (ESI): 195 [M+1] Referring to the synthesis method in Step 11 of Example 1, 3-chloro-5-amino-2-(1H-pyrazol-1-yl)pyridine 44c (89 mg, 0.45 mmol) was reacted to give N-(5-chloro-6-(1H-pyrazol-1-yl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 44 (21 mg), yield: 8.9%. MS m / z(ESI):524[M+1]. 1H NMR(400MHz,DMSO)δ 11.15(d,J=11.2Hz,2H),8.80(d,J=2.2Hz,1H),8.60(d,J=2.3Hz,1H),8.54(s,1H),8.26(d,J=2.5Hz,1H),8.16(d,J=6.9Hz,1H),7.92( dd,J=8.3,7.0Hz,1H),7.82(d,J=1.7Hz,1H),7.73(d,J=7.5Hz,1H),7.61(d,J=8.3Hz,1H),7.13(d,J=7.5Hz,1H),6.57(t,J=2.2Hz,1H).

[0226] Example 45 N-(5-chloro-6-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Step 1 5-Bromo-3-chloromethylpyridine amide 5-Bromo-3-chloropyridine formic acid 45a (5 g, 21.15 mmol), ammonium chloride (2 g, 37.4 mmol), and 2-(7-azobenzotriazazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (8.40 g, 22.08 mmol) were dissolved in 30 mL of N,N-dimethylformamide, followed by the addition of triethylamine (4 g, 39.53 mmol) and the reaction mixture was allowed to react for 2 hours at 20° C. The reaction mixture was cooled to room temperature and poured into 50 mL of water. Filtration, the filtrate was extracted with ethyl acetate (50 mL × 3), the organic phases were combined, washed with saturated sodium chloride solution (50 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product, and the residue obtained was purified using silica gel column chromatography with eluent system A to obtain the title product 5-bromo-3-chloromethylpyridine amide 45b (3 g), yield: 60.2%. MS m / z(ESI):236[M+1]

[0227] Step 2 5-Bromo-3-chloro-2-(1H-1,2,4-triazol-3-yl)pyridine 5-Bromo-3-chloromethylpyridine amide 45b (3 g, 12.74 mmol) was dissolved in 20 mL of N,N-dimethylformamide dimethyl acetal and reacted at 100 °C for 2 h. After spin-drying, hydrazine hydrate (1 g, 20 mmol) and 50 mL of acetic acid were added and reacted at 90 °C for 12 h. The reaction mixture was cooled to room temperature and poured into 100 mL of water. After filtration, the filtrate was extracted with ethyl acetate (50 mL × 3). The combined organic phases were washed with saturated sodium chloride solution (50 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product. The residue was purified by silica gel column chromatography using eluent system A to give the title product, 5-bromo-3-chloro-2-(1H-1,2,4-triazol-3-yl)pyridine 45c (1 g), in a 30.2% yield. MS m / z(ESI):260[M+1].

[0228] Step 3 5-Bromo-3-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridine 5-Bromo-3-chloro-2-(1H-1,2,4-triazol-3-yl)pyridine 45c (1 g, 3.85 mmol) was dissolved in 20 mL of N,N-dimethylformamide, and then cesium carbonate (1.40 g, 4.30 mmol) and iodomethane (540 mg, 3.80 mmol) were added and the mixture was allowed to react for 2 hours at 20° C. The reaction mixture was cooled to room temperature and poured into 30 mL of water. Filtration, the filtrate was extracted with ethyl acetate (50 mL × 3), the organic phases were combined, washed with saturated sodium chloride solution (50 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product, and the residue obtained was purified using silica gel column chromatography with eluent system A to obtain the title product 5-bromo-3-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridine 45d (500 mg), yield: 47.4%. MS m / z(ESI):274[M+1]. Referring to the synthesis methods of Step 2 of Example 13 and Steps 5 and 6 of Example 29, N-(5-chloro-6-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 45 (20 mg) was obtained from 5-bromo-3-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridine 45d (500 mg, 1.83 mmol) in a yield of 2.0%. MS m / z(ESI):539[M+1]. 1H NMR(400MHz,CD3OD)δ 8.96(d,J=2.2Hz,1H),8.65(d,J=2.2Hz,1H),8.35(s,1H),8.16(d,J=7.0Hz,1H),8.09(s,1H) ,7.88(dd,J=8.3,7.0Hz,1H),7.67(dd,J=7.9,5.8Hz,2H),7.13(d,J=7.5Hz,1H),3.94(s,3H).

[0229] Examples 46 and 47 N-(5-chloro-6-(3-methyl-1H-1,2,4-triazol-1-yl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide and N-(5-chloro-6-(5-methyl-1H-1,2,4-triazol-1-yl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Step 1 3-chloro-2-(3-methyl-1H-1,2,4-triazol-1-yl)-5-nitropyridine and 3-chloro-2-(5-methyl-1H-1,2,4-triazol-1-yl)-5-nitropyridine 2,3-Dichloro-5-nitropyridine 46a (3 g, 15.54 mmol), cesium carbonate (5 g, 15.34 mmol), and 3-methyl-1H-1,2,4-triazole (1.3 g, 15.65 mmol) were dissolved in 30 mL of N,N-dimethylformamide and reacted for 12 hours at 20° C. The reaction mixture was cooled to room temperature and poured into 50 mL of water. Filtration, the filtrate was extracted with ethyl acetate (50 mL × 3), the organic phases were combined, washed with saturated sodium chloride solution (50 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. The residue obtained was purified using silica gel column chromatography with eluent system A to obtain the title product 3-chloro-2-(3-methyl-1H-1,2,4-triazol-1-yl)-5-nitropyridine 46b and 3-chloro-2-(5-methyl-1H-1,2,4-triazol-1-yl)-5-nitropyridine 47b (2 g), yield: 53.7%. MS m / z (ESI): 240 [M+1]

[0111] Referring to the synthesis methods of Step 1 in Example 40 and Steps 5 and 6 in Example 29, 3-chloro-2-(3-methyl-1H-1,2,4-triazol-1-yl)-5-nitropyridine 46b and 3-chloro-2-(5-methyl-1H-1,2,4-triazol-1-yl)-5-nitropyridine 47b (2 g, 8.35 mmol) were used to prepare N-(5-chloro-6-(3-methyl-1H-1,2,4-triazol-1-yl)pyridin-3-yl)-1-(2-carbonyl-1,2- N-(5-chloro-6-(5-methyl-1H-1,2,4-triazol-1-yl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 46 (20 mg) was obtained, yield: 0.4%, and N-(5-chloro-6-(5-methyl-1H-1,2,4-triazol-1-yl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 47 (10 mg) was obtained, yield: 0.2%. MS m / z(ESI):539[M+1]. Example 46: 1H NMR (400MHz, DMSO)δ 11.30(s,1H),11.13(s,1H),8.88(d,J=2.3Hz,1H),8.68(d,J=2.3Hz,1H),8.54(s,1H),8.16(d,J=6.9Hz,1H),8.12( s,1H),7.92(dd,J=8.3,7.0Hz,1H),7.73(d,J=7.5Hz,1H),7.61(d,J=8.3Hz,1H),7.13(d,J=7.5Hz,1H),2.37(s,3H). Example 47: 1H NMR (400MHz, DMSO)δ 11.15(s,2H),8.91(s,1H),8.80(d,J=2.3Hz,1H),8.64(d,J=2.2Hz,1H),8.53(s,1H),8.15(d,J=6.9Hz,1H), 7.91(dd,J=8.3,7.0Hz,1H),7.72(d,J=7.5Hz,1H),7.61(d,J=8.2Hz,1H),7.12(d,J=7.5Hz,1H),2.39(s,3H).

[0230] Example 48 N-(6-(acridin-1-yl)-5-chloropyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis methods of Step 1 in Example 30, Step 2 in Example 44, and Step 11 in Example 1 in turn, 2,3-dichloro-5-nitropyridine 48a (150 mg, 0.70 mmol) was reacted to give N-(6-(acridizidin-1-yl)-5-chloropyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 48 (5 mg), yield: 1.4%. MS m / z(ESI):513[M+1]. 1H NMR(400MHz,DMSO)δ 11.11(s,1H),10.59(s,1H),8.43(s,1H),8.35(d,J=2.2Hz,1H),8.14(d,J=6.9Hz,1H),8.06(d,J=2.2Hz,1H),7.90(dd,J=8. 3,7.0Hz,1H),7.69(d,J=7.5Hz,1H),7.58(d,J=8.3Hz,1H),7.11(d,J=7.5Hz,1H),4.13(t,J=7.5Hz,4H),2.32-2.20(m,2H).

[0231] Example 49 N-(5-difluoromethyl-6-(2H-1,2,3-triazol-2-yl)-pyridin-3-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Step 11 of Example 1, 5-difluoromethyl-6-(2H-1,2,3-triazol-2-yl)pyridin-3-amine (21 mg, 0.10 mmol, prepared by the known method "WO2018020474") and intermediate 1 (34 mg, 0.10 mmol) was used to obtain the title product N-(5-difluoromethyl-6-(2H-1,2,3-triazol-2-yl)-pyridin-3-yl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide (21 mg), yield: 38.8%. MS m / z(ESI):541[M+1] 1 H NMR(400MHz,DMSO-d6)δ 11.13(bs,2H),9.07(d,1H),8.78(d,1H),8.56(s,1H),8.25(s,2H),8.16( d,1H),7.92(dd,1H),7.74(d,1H),7.62(d,1H),7.40(t,1H),7.13(t,1H).

[0232] Example 50 N-(4-(2H-1,2,3-triazazol-2-yl)-3-(trifluoromethyl)phenyl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Step 11 of Example 1, intermediate 1 (70 mg, 0.22 mmol) and 4-(2H-1,2,3-triazazol-2-yl)-3-(trifluoromethyl)aniline 50a (100 mg, 0.44 mmol, obtained by synthesizing using the known method "Patent WO2018020474A1") were used to obtain the title product N-(4-(2H-1,2,3-triazazol-2-yl)-3-(trifluoromethyl)phenyl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 50 (35 mg), yield: 28.5%. MS m / z(ESI):558[M+1] 1 H NMR(400MHz,DMSO-d6)δ 11.12(d,J=4.4Hz,2H),8.54(s,1H),8.41(d,J=2.2Hz,1H),8.23(dd,J=8.7,2.2Hz,1H),8.17-8.12(m,3H),7.92( dd,J=8.2,7.1Hz,1H),7.82(d,J=8.8Hz,1H),7.72(d,J=7.5Hz,1H),7.61(d,J=8.3Hz,1H),7.12(d,J=7.5Hz,1H).

[0233] Example 51 N-(4-(1H-pyrazol-1-yl)-3-(trifluoromethyl)phenyl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Step 1 1-(4-nitro-2-(trifluoromethyl)phenyl)-1H-pyrazole 1-Fluoro-4-nitro-2-(trifluoromethyl)benzene 51a (1.00 g, 4.78 mmol), potassium carbonate (661 mg, 4.78 mmol), pyrazole (488 mg, 7.17 mmol), and DMF (3 mL) were added to a large microwave tube, and the reaction was heated to 100 °C in a microwave reactor for 2 h. The reaction mixture was filtered and concentrated. The residue was dissolved in 100 mL of ethyl acetate, washed with water (20 mL × 2), saturated aqueous sodium chloride (30 mL × 1), dried over anhydrous sodium sulfate, filtered, concentrated, and the residue was purified by silica gel column chromatography using eluent system C to give the title product, 1-(4-nitro-2-(trifluoromethyl)phenyl)-1H-pyrazole 51b (1.00 g), in 81.3% yield. MS m / z(ESI):258[M+1] Referring to the synthesis method from Step 2 to Step 3 of Example 36, N-(4-(1H-pyrazol-1-yl)-3-(trifluoromethyl)phenyl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 51 (29 mg) was obtained from 1-(4-nitro-2-(trifluoromethyl)phenyl)-1H-pyrazole 51b (0.30 g, 1.17 mmol), with a yield of 32.5%. MS m / z(ESI):558[M+1] 1 H NMR(400MHz,DMSO):δ 11.12(s,1H),11.07(s,1H),8.53(s,1H),8.35(d,J=2.4Hz,1H),8.19-8.12(m,2H),8.02(d,J=2.4Hz,1H),7.92(dd ,J=8.3,7.0Hz,1H),7.78-7.69(m,2H),7.63(dd,J=13.5,8.5Hz,2H),7.13(d,J=7.5Hz,1H),6.53(t,J=2.2Hz,1H).

[0234] Example 52 1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-N-(4-(pyrrolidine-1-carbonyl)-3-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis methods of Step 1 in Example 45 and Steps 2 to 4 in Example 46, 1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-N-(4-(pyrrolidine-1-carbonyl)-3-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide (20 mg) was obtained from 4-nitro-2-(trifluoromethyl)benzoic acid 52a (2 g, 8.50 mmol) in a yield of 0.4%. MS m / z(ESI):588[M+1]. 1H NMR(400MHz,CD3OD)δ 8.30(s,1H),8.23(d,J=2.1Hz,1H),8.15(d,J=7.0Hz,1H),8.06(dd,J=8.4,2.2Hz,1H),7.87(dd,J=8.3,7.0Hz,1H),7.66(dd,J =9.2,7.9Hz,2H),7.50(d,J=8.3Hz,1H),7.13(d,J=7.5Hz,1H),3.60(t,J=6.9Hz,2H),3.22(t,J=6.7Hz,2H),2.04-1.84(m,5H).

[0235] Example 53 N-(3-chloro-4-(2H-1,2,3-triazazol-2-yl)phenyl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Intermediate 1 (70 mg, 0.22 mmol), 3-chloro-4-(2H-1,2,3-triazazol-2-yl)aniline 53a (85 mg, 0.44 mmol, synthesized by the known method "Patent WO2018020474A1"), pyridine (76 mg, 0.96 mmol), and phosphorus oxychloride (73 mg, 0.48 mmol) were dissolved in 5 mL of dichloromethane and reacted with stirring at room temperature for 2 hours. Dichloromethane (50 mL) was added to the reaction mixture, which was then washed successively with water (50 mL × 1) and saturated sodium chloride solution (50 mL × 1), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue obtained was purified using silica gel column chromatography with eluent system A to give the title product N-(3-chloro-4-(2H-1,2,3-triazazol-2-yl)phenyl)-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 53 (36 mg), yield: 31.2%. MS m / z (ESI): 524 [M+1] 1 H NMR(400MHz,DMSO-d6)δ 11.12(s,1H),11.00(s,1H),8.52(s,1H),8.19-8.13(m,4H),7.95-7.84 (m,2H),7.77-7.69(m,2H),7.61(d,J=8.3Hz,1H),7.12(d,J=7.5Hz,1H).

[0236] Example 54 N-(3-chloro-4-(1H-pyrazol-1-yl)phenyl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Step 1 3-chloro-4-(1H-pyrazol-1-yl)aniline A three-neck flask was charged with 3-chloro-4-iodoaniline 54a (1.00 g, 3.95 mmol), pyrazole (564 mg, 8.29 mmol), cesium carbonate (2.44 g, 7.50 mmol), cuprous iodide (75 mg, 0.39 mmol), and (1R,2R)-(-)-N,N'-dimethyl-1,2-cyclohexanediamine (168 mg, 1.18 mmol). The flask was purged with nitrogen three times. An additional 10 mL of DMF was added, and the mixture was heated to 140 °C for 3 h. The reaction mixture was cooled to room temperature, filtered, and concentrated. The residue was dissolved in 100 mL of ethyl acetate, washed sequentially with water (20 mL × 2) and saturated aqueous sodium chloride (30 mL × 1), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified using silica gel column chromatography with eluent system C to give the title product 3-chloro-4-(1H-pyrazol-1-yl)aniline 54b (650 mg), yield: 85.1%. MS m / z (ESI): 194 [M+1]

[0237] Step 2 N-(3-chloro-4-(1H-pyrazol-1-yl)phenyl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide Referring to the synthesis method of Step 11 of Example 1, intermediate 1 (30 mg, 0.09 mmol) and 6-(4,5-dimethyloxazol-2-yl)-5-(trifluoromethyl)pyridin-3-amine 54b (35 mg, 0.18 mmol, obtained by synthesizing using the known method "Patent US20180170909A1") were used to obtain the title product N-(3-chloro-4-(1H-pyrazol-1-yl)phenyl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 54 (15 mg), yield: 31.9%. MS m / z(ESI):523[M+1] 1H NMR(400MHz,DMSO):δ 11.12(s,1H),11.07(s,1H),8.53(s,1H),8.35(d,J=2.4Hz,1H),8.19-8.12(m,2H),8.02(d,J=2.4Hz,1H),7.92(dd ,J=8.3,7.0Hz,1H),7.78-7.69(m,2H),7.63(dd,J=13.5,8.5Hz,2H),7.13(d,J=7.5Hz,1H),6.53(t,J=2.2Hz,1H).

[0238] Example 55 5-Cyclopropyl-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 Ethyl 5-cyclopropyl-1-(1-(4-methoxybenzyl)-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxylate 6-Hydrazino-1-[(4-methoxybenzyl)benzo[cd]indol-2(1H)-one (5.10 g, 15.99 mmol), potassium carbonate (4.14 g, 30 mmol), and 2-(cyclopropylcarbonyl)-3-(dimethylamino)ethyl acrylate (6.33 g, 30 mmol) were dissolved in 50 mL of ethanol and stirred at 80 °C for 3 h. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography using eluent system A to give the title product, ethyl 5-cyclopropyl-1-(1-(4-methoxybenzyl)-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxylate 55a (1.60 g), yield: 21.4%. MS m / z(ESI):468[M+1]. Step 2 5-Cyclopropyl-1-(1-(4-methoxybenzyl)-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxylic acid Ethyl 5-cyclopropyl-1-(1-(4-methoxybenzyl)-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxylate 55a (1.6 g, 3.42 mmol) and sodium hydride (673 mg, 17.11 mmol) were dissolved in 10 mL of tetrahydrofuran and 5 mL of water and stirred at 60 °C for 16 h. The reaction mixture was adjusted to a pH of less than 7 by adding 2M hydrochloric acid, extracted with ethyl acetate (50 mL × 3), the organic phases were combined, washed successively with water (50 mL × 1) and saturated sodium chloride solution (50 mL × 1), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the title product 5-cyclopropyl-1-(1-(4-methoxybenzyl)-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxylic acid 55b (1.45 g), yield: 96.5%. MS m / z(ESI):440[M+1]

[0239] Step 3 5-Cyclopropyl-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxylic acid 5-Cyclopropyl-1-(1-(4-methoxybenzyl)-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxylic acid 55b (1.45 g, 3.30 mmol) was dissolved in 20 mL of trifluoroacetic acid and stirred at 90 °C for 16 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified using silica gel column chromatography with eluent system A to give the title product 5-cyclopropyl-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxylic acid 55c (794 mg), yield: 75.2%. MS m / z(ESI):320[M+1]

[0240] Step 4 5-Cyclopropyl-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide 5-Cyclopropyl-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxylic acid 55c (64 mg, 0.20 mmol), 2-trifluoromethyl-4-aminopyridine (31 mg, 0.19 mmol), pyridine (76 mg, 0.96 mmol), and phosphorus oxychloride (73 mg, 0.48 mmol) were dissolved in 5 mL of dichloromethane and stirred at room temperature for 2 h. Dichloromethane (50 mL) was added to the reaction mixture, which was then washed successively with water (50 mL × 1) and saturated sodium chloride solution (50 mL × 1), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue obtained was purified using silica gel column chromatography with eluent system A to give the title product 5-cyclopropyl-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide 55 (32 mg), yield: 34.4%. MS m / z(ESI):464[M+1]. 1 H NMR(400MHz,DMSO-d6)δ 11.05(s,1H),10.63(s,1H),8.67(d,J=5.5Hz,1H),8.32(s,1H),8.29(d,J=1.8Hz,1H),8.13(d,J=6.9Hz,1H),8.01(dd,J=5.6,1. 7Hz,1H),7.91-7.84(m,1H),7.70(dd,J=24.2,7.9Hz,2H),7.11(d,J=7.5Hz,1H),2.01(td,J=8.6,4.3Hz,1H),0.75-0.50(m,4H).

[0241] Example 56 N-(6-(2H-1,2,3-triazazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-5-cyclopropyl-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Step 11 of Example 1, the title product N-(6-(2H-1,2,3-triazazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-5-cyclopropyl-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxamide 56 (31 mg) was obtained from 55c (70 mg, 0.22 mmol) and 6-(2H-1,2,3-triazol-2-yl)-3-amino-5-trifluoromethylpyridine 56a (100 mg, 0.44 mmol, synthesized according to the known method "Patent US20180170909A1") in a yield of 26.6%. MS m / z (ESI): 531 [M+1] 1 H NMR(400MHz,DMSO-d6)δ 11.05(s,1H),10.74(s,1H),9.21(d,J=2.4Hz,1H),8.93(d,J=2.4Hz,1H),8.36(s,1H),8.21(s,2H),8.13(d,J=6.9Hz,1H),7. 92-7.86(m,1H),7.72(dd,J=20.8,7.9Hz,2H),7.12(d,J=7.5Hz,1H),2.10-1.98(m,1H),0.77-0.67(m,2H),0.66-0.54(m,2H).

[0242] Example 57 N-(6-(1H-pyrazol-1-yl)-5-(trifluoromethyl)pyridin-3-yl)-5-cyclopropyl-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Step 11 of Example 1, 5-cyclopropyl-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxylic acid 55c (50 mg, 0.16 mmol) was reacted with 3-trifluoromethyl-5-amino-2-(1H-pyrazol-1-yl)pyridine 31c (35 mg, 0.16 mmol) to give N-(6-(1H-pyrazol-1-yl)-5-(trifluoromethyl)pyridin-3-yl)-5-cyclopropyl-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxamide 57 (23 mg), yield: 25.6%. MS m / z(ESI):530[M+1].

[0243] Example 58 N-(6-(1H-pyrazol-1-yl)-5-(difluoromethyl)pyridin-3-yl)-5-cyclopropyl-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Step 11 of Example 1, 5-cyclopropyl-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxylic acid 55c (50 mg, 0.16 mmol) was reacted with 3-difluoromethyl-5-amino-2-(1H-pyrazol-1-yl)pyridine 49a (34 mg, 0.16 mmol) to give N-(6-(1H-pyrazol-1-yl)-5-(difluoromethyl)pyridin-3-yl)-5-cyclopropyl-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxamide 57 (17 mg), yield: 20%. MS m / z(ESI):513[M+1].

[0244] Example 59 N-(5-chloro-6-(2H-1,2,3-triazol-2-yl)pyridin-3-yl)-5-cyclopropyl-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Step 11 of Example 1, 5-cyclopropyl-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxylic acid 55c (50 mg, 0.16 mmol) was reacted with 5-chloro-6-(1H-pyrazol-1-yl)pyridin-3-amine 59a (31 mg, 0.16 mmol) to give N-(5-chloro-6-(1H-pyrazol-1-yl)pyridin-3-yl)-5-cyclopropyl-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxamide 59 (13 mg), yield: 16.3%. MS m / z(ESI):496[M+1].

[0245] Example 60 N-(5-chloro-6-(2H-1,2,3-triazol-2-yl)-pyridin-3-yl)-5-cyclopropyl-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxamide [ka] Using the synthesis method of Step 11 of Example 1, 55c (35 mg, 0.10 mmol) and 6-(2H-1,2,3-triazol-2-yl)-3-amino-5-chloropyridine 60a (20 mg, 0.10 mmol, obtained by synthesizing using the known method "Patent US20180170909A1"), the title product N-(5-chloro-6-(2H-1,2,3-triazol-2-yl)-pyridin-3-yl)-5-cyclopropyl-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxamide 60 (25 mg) was obtained in a yield of 50.3%. MS m / z(ESI):497[M+1] 1 H NMR(400MHz,DMSO-d6)δ 11.04(s,1H),10.61(s,1H),8.88(d,1H),8.70(d,1H),8.33(s,1H),8.18(s,2H),8.13(d,1H),7.88( dd,1H),7.74(d,1H),7.68(d,1H),7.11(d,1H),2.02(ddd,1H),0.77-0.68(m,2H),0.64-0.55(m,2H).

[0246] Example 61 N-(4-(2H-1,2,3-triazol-2-yl)-3-(trifluoromethyl)phenyl)-5-cyclopropyl-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Step 11 of Example 1, 5-cyclopropyl-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxylic acid 55c (50 mg, 0.16 mmol) was reacted with 3-chloro-5-amino-2-(1H-pyrazol-1-yl)pyridine 50c (36 mg, 0.16 mmol) to give N-(4-(2H-1,2,3-triazol-2-yl)-3-(trifluoromethyl)phenyl)-5-cyclopropyl-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxamide 61 (21 mg), yield: 24.8%. MS m / z(ESI):530[M+1]. 1H NMR(400MHz,DMSO)δ 11.04(s,1H),10.50(s,1H),8.44(d,J=2.3Hz,1H),8.32(s,1H),8.25(dd,J=8.8,2.4Hz,1H),8.14(d,J=13.5Hz,3H),7.88(dd,J=8.3,6.9H z,1H),7.76(dd,J=10.3,8.6Hz,2H),7.68(d,J=7.5Hz,1H),7.11(d,J=7.5Hz,1H),2.09-1.97(m,1H),0.76-0.68(m,2H),0.63-0.55(m,2H).

[0247] Example 62 N-(4-(1H-pyrazol-1-yl)-3-trifluoromethylphenyl)-5-cyclopropyl-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxamide [ka] Using the synthesis method of Step 11 of Example 1, 55c (35 mg, 0.10 mmol) and 4-(1H-pyrazol-1-yl)-3-trifluoromethylaniline 62a (23 mg, 0.10 mmol, synthesized according to the known method of Patent WO2006122806), the title product N-(4-(1H-pyrazol-1-yl)-3-trifluoromethylphenyl)-5-cyclopropyl-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxamide 62 (18 mg) was obtained in a yield of 34.1%. MS m / z(ESI):529[M+1]

[0248] Example 63 N-(3-chloro-4-(2H-1,2,3-triazol-2-yl)phenyl)-5-cyclopropyl-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Step 11 of Example 1, the title product N-(3-chloro-4-(2H-1,2,3-triazol-2-yl)phenyl)-5-cyclopropyl-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxamide 63 (19 mg) was obtained from 55c (35 mg, 0.10 mmol) and 3-chloro-4-(2H-1,2,3-triazol-2-yl)aniline 63a (19 mg, 0.10 mmol, synthesized according to the known method of Patent WO2018020474A1), with a yield of 38.3%. MS m / z(ESI):496[M+1] 1H NMR(400MHz,DMSO-d6)δ 11.03(s,1H),10.35(s,1H),8.28(s,1H),8.20(d,1H),8.14(s,2H),8.12(d,1H),7.92-7.84(m,2H) ,7.75(d,1H),7.67(dd,2H),7.11(d,1H),2.06-1.95(m,1H),0.75-0.66(m,2H),0.65-0.54(m,2H).

[0249] Example 64 N-(3-chloro-4-(1H-pyrazol-1-yl)phenyl)-5-cyclopropyl-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Step 11 of Example 1, 5-cyclopropyl-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxylic acid 55c (50 mg, 0.16 mmol) was reacted with 3-chloro-4-(1H-pyrazol-1-yl)aniline 54b (31 mg, 0.16 mmol) to give N-(3-chloro-4-(1H-pyrazol-1-yl)phenyl)-5-cyclopropyl-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxamide 64 (13 mg), yield: 16.4%. MS m / z(ESI):495[M+1]. 1H NMR(400MHz,DMSO)δ 11.04(s,1H),9.66(s,1H),8.63-8.54(m,1H),8.27(s,1H),8.15-8.05(m,2H),7.93-7.83(m,3H),7.83-7.75(m,2H),7.67(d ,J=7.5Hz,1H),7.11(d,J=7.4Hz,1H),6.62-6.54(m,1H),2.04(tt,J=8.5,5.5Hz,1H),0.77-0.66(m,2H),0.64-0.55(m,2H).

[0250] Example 65 5-Difluoromethyl-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Steps 8 to 11 of Example 1, 6-hydrazino-1-[(4-methoxybenzyl]benzo[cd]indol-2(1H)-one (320 mg, 1 mmol) and (Z)-2-ethoxymethylene-4,4-bisfluoro-3-oxobutyric acid ethyl ester 65a (444 mg, 2 mmol, synthesized according to the known method of Patent WO2019039429A1) gave the title product 5-difluoromethyl-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide 65 (19 mg), yield 4.0%. MS m / z(ESI):474[M+1] 1 H NMR(400MHz,DMSO-d6)δ 11.10(s,1H),11.02(s,1H),8.72(d,1H),8.62(s,1H),8.32(d,1H),8.13( d,1H),8.03(d,1H),7.87(dd,1H),7.67(d,1H),7.62(d,2H),7.50(t,1H).

[0251] Example 66 N-(6-(2H-1,2,3-triazol-2-yl)-5-trifluoromethylpyridin-3-yl)-5-difluoromethyl-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Step 11 of Example 1, the title product N-(6-(2H-1,2,3-triazol-2-yl)-5-trifluoromethylpyridin-3-yl)-5-difluoromethyl-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxamide 66 (19 mg) was obtained from 65d (35 mg, 0.10 mmol) and 3-trifluoromethyl-4-(2H-1,2,3-triazol-2-yl)aniline 66a (23 mg, 0.10 mmol), with a yield of 35.1%. MS m / z(ESI):541[M+1] 1 H NMR(400MHz,DMSO-d6)δ 11.10(s,2H),9.22(d,1H),8.94(d,1H),8.64(s,1H),8.22(s,2H),8.14( d,1H),7.88(dd,1H),7.69(d,1H),7.63(d,1H),7.63(t,1H),7.12(d,1H).

[0252] Example 67 N-(6-(2H-1,2,3-triazol-2-yl)-5-chloropyridin-3-yl)-5-difluoromethyl-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Step 11 of Example 1, the title product N-(6-(2H-1,2,3-triazol-2-yl)-5-chloropyridin-3-yl)-5-difluoromethyl-1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-1H-pyrazole-4-carboxamide 67 (17 mg) was obtained from 65d (35 mg, 0.10 mmol) and 3-chloro-4-(2H-1,2,3-triazol-2-yl)aniline 67a (20 mg, 0.10 mmol), with a yield of 38.3%. MS m / z(ESI):507[M+1] 1H NMR(400MHz,DMSO-d6)δ 11.09(s,1H),11.02(s,1H),8.91(d,1H),8.70(d,1H),8.63(s,1H),8.20(s,2H) ,8.13(d,1H),7.87(dd,1H),7.68(d,1H),7.62(d,1H),7.59(t,1H),7.11(d,1H).

[0253] Example 68 N-(6-(2H-1,2,3-triazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis methods in Steps 11 and 12 of Example 3, N-(6-(2H-1,2,3-triazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 68 (20 mg) was obtained from 6-(2H-1,2,3-triazol-2-yl)-5-(trifluoromethyl)pyridin-3-amine 68a (50 mg, 0.22 mmol) in a yield of 16.4%. MS m / z(ESI):560[M+1]. 1H NMR(400MHz,CD3OD)δ 8.30(s,1H),8.23(d,J=2.1Hz,1H),8.15(d,J=7.0Hz,1H),8.06(dd,J=8.4,2.2Hz,1H),7.87(d d,J=8.3,7.0Hz,1H),7.66(dd,J=9.2,7.9Hz,2H),7.50(d,J=8.3Hz,1H),7.13(d,J=7.5Hz,1H).

[0254] Example 69 N-(6-(1H-pyrazol-1-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis methods in Steps 11 and 12 of Example 3, N-(6-(1H-pyrazol-1-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 69 (20 mg) was obtained from 6-(1H-pyrazol-1-yl)-5-(trifluoromethyl)pyridin-3-amine 69a (50 mg, 0.22 mmol) in a yield of 16.4%. MS m / z(ESI):559[M+1]. 1H NMR(400MHz,CD3OD)δ 9.06(s,1H),8.84(s,1H),8.40(s,1H),8.31(s,1H),8.17(s,2H),8.06(t,J=7.5Hz,1H),7.78(s,1H),7.72(d,J=8.2Hz,1H),6.57(s,1H).

[0255] Example 70 N-(5-chloro-6-(2H-1,2,3-triazol-2-yl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis methods in Steps 11 and 12 of Example 3, N-(5-chloro-6-(2H-1,2,3-triazol-2-yl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 70 (20 mg) was obtained from 5-chloro-6-(2H-1,2,3-triazol-2-yl)pyridin-3-amine 70a (50 mg, 0.26 mmol) in a yield of 14.9%. MS m / z(ESI):526[M+1]. 1 H NMR(400MHz,CD3OD)δ 9.06(s,1H),8.84(s,1H),8.40(s,1H),8.31(s,1H),8.17(s,2H),8.06(t,J=7.5Hz,1H),7.78(s,1H),6.57(s,1H).

[0256] Example 71 N-(5-chloro-6-(1H-pyrazol-1-yl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Referring to Steps 1 and 2 of Example 36 and Steps 3 and 4 of Example 73 in order, N-(5-chloro-6-(1H-pyrazol-1-yl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 71 (13 mg) was obtained from 5-nitro-2,3-dichloropyridine 71a (1.00 g, 5.18 mmol), with a yield of 0.5%. MS m / z (ESI): 525 [M+1]

[0257] Example 72 N-(3-(difluoromethyl)-4-(2H-1,2,3-triazol-2-yl)phenyl)-1-(2-carbonyl-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Step 1 2-Bromo-5-nitronicotinaldehyde 2-Bromo-5-nitronicotinic acid 72a (2.00 g, 8.10 mmol) was dissolved in dichloromethane (30 mL), purged with nitrogen gas three times, and cooled to -78 °C. Diisobutylaluminum hydride (12.15 mL, 12.15 mmol, 1 M hexane) was added dropwise to the reaction mixture, and the mixture was allowed to react at -78 °C for 2 h. The reaction was quenched by adding 10 mL of saturated ammonium chloride and extracted with dichloromethane (50 mL × 3). The combined organic phases were washed with saturated aqueous sodium chloride (30 mL × 1), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified using silica gel column chromatography with eluent system C to give the title product, 2-bromo-5-nitronicotinaldehyde 72b (1.50 g), in 80.1% yield. MS m / z (ESI): 232 [M+1]

[0258] Step 2 2-Bromo-3-(difluoromethyl)-5-nitropyridine 2-Bromo-5-nitronicotinaldehyde 72b (1.20 g, 5.19 mmol) was dissolved in dichloromethane (20 mL), purged with nitrogen gas three times, and cooled to -78 °C. Diethylamine sulfur trifluoride (1.67 g, 10.39 mmol, 1.4 mL) was added dropwise to the reaction mixture. After completion, the mixture was allowed to warm to 25 °C and stirred for 2 h. The reaction was quenched with aqueous sodium carbonate and extracted with dichloromethane (50 mL × 3). The combined organic phases were washed with saturated aqueous sodium chloride (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified using silica gel column chromatography using eluent system C to give the title product, 2-bromo-3-(difluoromethyl)-5-nitropyridine 72c (1.10 g), in 83.7% yield. MS m / z (ESI): 254 [M+1]

[0259] Step 3 to Step 6 Referring to the synthesis method of Steps 1 to 4 of Example 73, N-(3-(difluoromethyl)-4-(2H-1,2,3-triazol-2-yl)phenyl)-1-(2-carbonyl-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 72 (11 mg) was obtained from 2-bromo-3-(difluoromethyl)-5-nitropyridine 72c (1.10 g, 4.35 mmol), with a yield of 0.5%. MS m / z(ESI):541[M+1]

[0260] Example 73 N-(4-(2H-1,2,3-triazol-2-yl)-3-(trifluoromethyl)phenyl)-1-(2-carbonyl-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Step 1 2-(4-nitro-2-(trifluoromethyl)phenyl)-2H-1,2,3-triazole A reaction flask was charged with 1-fluoro-4-nitro-2-(trifluoromethyl)benzene 73a (3.00 g, 14.35 mmol), potassium carbonate (5.95 g, 43.04 mmol), 1,2,3-triazazole (1.49 g, 21.52 mmol), and DMF (40 mL). The mixture was purged with nitrogen three times and heated to 100 °C for 2 h. After cooling to room temperature, the mixture was filtered and concentrated. The residue was dissolved in 100 mL of ethyl acetate, washed with water (20 mL × 2), saturated aqueous sodium chloride (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified using silica gel column chromatography with eluent system C to give the title product, 2-(4-nitro-2-(trifluoromethyl)phenyl)-2H-1,2,3-triazole 73b (2.20 g), in a 59.4% yield. MS m / z(ESI):259[M+1]

[0261] Step 2 4-(2H-1,2,3-triazol-2-yl)-3-(trifluoromethyl)aniline Referring to the synthesis method of Step 2 of Example 34, 4-(2H-1,2,3-triazol-2-yl)-3-(trifluoromethyl)aniline 73c (1.50 g) was obtained from 2-(4-nitro-2-(trifluoromethyl)phenyl)-2H-1,2,3-triazole 73b (2.20 g, 8.52 mmol), with a yield of 77.1%. MS m / z(ESI):229[M+1]

[0262] Step 3 N-(4-(2H-1,2,3-triazol-2-yl)-3-(trifluoromethyl)phenyl)-1-(1-(4-methoxybenzyl)-2-carbonyl-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 1-[2-[(4-methoxyphenyl)methyl]-3-carbonyl-2,11-diazatricyclo[6.3.1.04,12]dodecan-1(11),4(12),5,7,9-pentaen-9-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid (80 mg, 0.17 mmol), 4-(2H-1,2,3-triazol-2-yl)-3-(trifluoromethyl)pyrazole-4-carboxylic acid Methyl)aniline 73c (77.94 mg, 0.34 mmol) and DMAP (4.17 mg, 0.034 mmol) were dissolved in dichloromethane (5 mL), purged with nitrogen gas three times, and cooled to -10 °C. Pyridine (68 mg, 0.85 mmol, 69 μL) and phosphorus oxychloride (131 mg, 0.85 mmol, 80 μL) were added, and the reaction was warmed to 25 °C and incubated for 2 h. The reaction was quenched with water and concentrated. The mixture was extracted with ethyl acetate (30 mL × 3), and the combined organic phases were washed with saturated aqueous sodium chloride (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue obtained was purified using silica gel column chromatography with eluent system C to obtain the title product N-(4-(2H-1,2,3-triazol-2-yl)-3-(trifluoromethyl)phenyl)-1-(1-(4-methoxybenzyl)-2-carbonyl-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 73d (56 mg), yield: 48.3%. MS m / z(ESI):679[M+1]

[0263] Step 4 N-(4-(2H-1,2,3-triazol-2-yl)-3-(trifluoromethyl)phenyl)-1-(2-carbonyl-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide N-(4-(2H-1,2,3-triazol-2-yl)-3-(trifluoromethyl)phenyl)-1-(1-(4-methoxybenzyl)-2-carbonyl-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 73d (56 mg, 0.082 mmol) was dissolved in acetonitrile (5 mL) and water (1 mL), and ceric ammonium nitrate (88 mg, 0.17 mmol) was added. The mixture was reacted at 25 °C for 1 h. The reaction was quenched with water and concentrated. After extraction with ethyl acetate (20 mL × 3), the combined organic phases were washed with saturated aqueous sodium chloride (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified using silica gel column chromatography with eluent system A to give the title product N-(4-(2H-1,2,3-triazol-2-yl)-3-(trifluoromethyl)phenyl)-1-(2-carbonyl-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 73 (18 mg), yield: 39.1%. MS m / z (ESI): 559 [M+1] 1 H NMR(400MHz,DMSO-d6)δ 11.74(d,1H),11.15(s,1H),8.58(s,1H),8.41(m,2H),8.20(m,4H),8.09(dd,1H),7.83(d,1H),7.68(d,1H).

[0264] Example 74 N-(4-(1H-pyrazol-1-yl)-3-(trifluoromethyl)phenyl)-1-(2-carbonyl-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Referring to Step 1 and Step 2 of Example 73, 1-[2-[(4-methoxyphenyl)methyl]-3-carbonyl-2,11-diazatricyclo[6.3.1.04,12]dodecan-1(11),4(12),5,7,9-pentaen-9-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid 74a (50 mg, 0.11 mmol) gave the title product N-(4-(1H-pyrazol-1-yl)-3-(trifluoromethyl)phenyl)-1-(2-carbonyl-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 74 (15 mg), yield: 24.5%. MS m / z(ESI):558[M+1] 1 H NMR(400MHz,DMSO):δ 11.09(s,1H),8.57(s,1H),8.42(s,1H),8.34(d,J=2.4Hz,1H),8.20(d,J=6.9Hz,1H),8.13-8.07(m,1 H),8.02(d,J=2.4Hz,1H),7.75(d,J=1.9Hz,1H),7.67(dd,J=14.3,8.4Hz,2H),6.53(t,J=2.1Hz,1H).

[0265] Example 75 N-(3-chloro-4-(2H-1,2,3-triazol-2-yl)phenyl)-1-(2-carbonyl-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis methods in Steps 11 and 12 of Example 3, N-(3-chloro-4-(2H-1,2,3-triazol-2-yl)phenyl)-1-(2-carbonyl-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-formyl 75 (12 mg) was obtained from 3-chloro-4-(2H-1,2,3-triazol-2-yl)aniline 75a (50 mg, 0.26 mmol) in a yield of 8.9%. MS m / z(ESI):525[M+1]. 1H NMR(400MHz,CD3OD)δ 8.33(d,J=12.5Hz,2H),8.23-8.12(m,2H),8.06(dd,J=8.2,7.0Hz,1H),7.99(s ,2H),7.81(dd,J=8.7,2.3Hz,1H),7.72(d,J=8.2Hz,1H),7.62(d,J=8.7Hz,1H).

[0266] Example 76 N-(3-chloro-4-(1H-pyrazol-1-yl)phenyl)-1-(2-carbonyl-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Referring to Step 1 to Step 2 of Example 73, 1-[2-[(4-methoxyphenyl)methyl]-3-carbonyl-2,11-diazatricyclo[6.3.1.04,12]dodecan-1(11),4(12),5,7,9-pentaen-9-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid 76a (50 mg, 0.11 mmol) gave the title product N-(3-chloro-4-(1H-pyrazol-1-yl)phenyl)-1-(2-carbonyl-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 76 (13 mg), yield: 21.2%. MS m / z (ESI): 524 [M+1]

[0267] Example 77 5-Cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis methods of Step 1 of Example 55, Steps 5 and 6 of Intermediate 1, and Step 11 of Example 1, 5-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 77 (51 mg) was obtained from 6-hydrazino-1-(4-methoxybenzyl)pyrrolo[4,3,2-ij]isoquinolin-2(1H)-one 3e (400 mg, 1.25 mmol) in a yield of 8.8%. MS m / z(ESI):465[M+1] 1 H NMR(400MHz,DMSO-d6)δ 11.64(s,1H),10.64(s,1H),8.67(d,J=5.5Hz,1H),8.40(s,1H),8.35(s,1H),8.28(d,J=1.8Hz,1H),8.17(d,J= 7.0Hz,1H),8.08-7.98(m,2H),7.81(d,J=8.2Hz,1H),2.13-2.03(m,1H),0.82-0.71(m,2H),0.62-0.53(m,2H).

[0268] Example 78 N-(6-(2H-1,2,3-triazazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-5-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method in Step 11 of Example 1, 2-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrrole-3-carboxylic acid 77c (70 mg, 0.22 mmol) and 6-(2H-1,2,3-triazol-2-yl)-3-amino-5-trifluoromethylpyridine 78a (100 mg, 0.44 mmol, known method [patent document]) were synthesized. From the product (synthesized using the method described in US20180170909A1), the title product N-(6-(2H-1,2,3-triazazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-5-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrazole-4-carboxamide 78 (41 mg) was obtained in a yield of 35.2%. MS m / z (ESI): 531 [M+1] 1 H NMR(400MHz,DMSO)δ 11.64(s,1H),10.76(s,1H),9.21(d,J=2.3Hz,1H),8.92(d,J=2.3Hz,1H),8.40(d,J=8.4Hz,2H),8.21-8.15 (m,3H),8.08-8.02(m,1H),7.82(d,J=8.2Hz,1H),2.15-2.04(m,1H),0.85-0.72(m,2H),0.66-0.55(m,2H).

[0269] Example 79 N-(6-(1H-pyrazol-1-yl)-5-(trifluoromethyl)pyridin-3-yl)-5-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method in Step 11 of Example 1, 2-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrrole-3-carboxylic acid 77c (70 mg, 0.22 mmol) and 6-(1H-pyrazol-1-yl)-5-(trifluoromethyl)pyridin-3-amino 79a (100 mg, 0.44 mmol, synthesized by a known method From the product (synthesized according to Patent WO2018020474A1), the title product N-(6-(1H-pyrazol-1-yl)-5-(trifluoromethyl)pyridin-3-yl)-5-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrazole-4-carboxamide 79 (35 mg) was obtained in a yield of 30.1%. MS m / z (ESI): 530 [M+1]

[0270] Example 80 N-(5-chloro-6-(2H-1,2,3-triazazol-2-yl)pyridin-3-yl)-5-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method in Step 11 of Example 1, 2-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrrole-3-carboxylic acid 77c (70 mg, 0.22 mmol) and 6-(2H-1,2,3-triazol-2-yl)-3-amino-5-chloropyridine 80a (86 mg, 0.44 mmol, synthesized by a known method The title product, N-(5-chloro-6-(2H-1,2,3-triazazol-2-yl)pyridin-3-yl)-5-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrazole-4-carboxamide 80 (36 mg), was obtained in 32.9% yield from the product (synthesized according to US20180170909A1). MS m / z(ESI):498[M+1]

[0271] Example 81 N-(5-chloro-6-(1H-pyrazol-1-yl)pyridin-3-yl)-5-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Step 11 of Example 1, 2-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrrole-3-carboxylic acid 77c (70 mg, 0.22 mmol) and 5-chloro-6-(1H-pyrazol-1-yl)pyridin-3-amine 81a (85 mg, 0.44 mmol, obtained by synthesizing using a known method as described in US Patent No. 20180170909A1) gave the title product N-(5-chloro-6-(1H-pyrazol-1-yl)pyridin-3-yl)-5-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrazole-4-carboxamide 81 (35 mg), yield 32.1%. MS m / z(ESI):497[M+1]

[0272] Example 82 5-Cyclopropyl-N-(5-(difluoromethyl)-6-(2H-1,2,3-triazazol-2-yl)pyridin-3-yl)-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Step 11 of Example 1, 2-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrrole-3-carboxylic acid 77c (70 mg, 0.22 mmol) and 5-(difluoromethyl)-6-(2H-1,2,3-triazazol-2-yl)pyridin-3-amine 49a (93 mg, 0.44 mmol) were used to obtain the title product 5-cyclopropyl-N-(5-(difluoromethyl)-6-(2H-1,2,3-triazazol-2-yl)pyridin-3-yl)-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrazole-4-carboxamide 82 (31 mg), yield 27.5%. MS m / z(ESI):514[M+1]

[0273] Example 83 N-(4-(2H-1,2,3-triazazol-2-yl)-3-(trifluoromethyl)phenyl)-5-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method in Step 11 of Example 1, 2-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrrole-3-carboxylic acid 77c (70 mg, 0.22 mmol) and 4-(2H-1,2,3-triazazol-2-yl)-3-(trifluoromethyl)aniline 50a (100 mg, 0.44 mmol, prepared by a known method) were synthesized. From this, the title product N-(4-(2H-1,2,3-triazazol-2-yl)-3-(trifluoromethyl)phenyl)-5-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrazole-4-carboxamide 83 (37 mg) was obtained in a yield of 31.7%. MS m / z (ESI): 531 [M+1] 1 H NMR(400MHz,DMSO)δ 11.04(s,1H),10.50(s,1H),8.44(d,J=2.3Hz,1H),8.32(s,1H),8.25(dd,J=8.8,2.4Hz,1H),8.14(d,J=13.5Hz,3H),7.88(dd,J=8.3,6.9H z,1H),7.76(dd,J=10.3,8.6Hz,1H),7.68(d,J=7.5Hz,1H),7.11(d,J=7.5Hz,1H),2.09-1.97(m,1H),0.76-0.68(m,2H),0.63-0.55(m,2H).

[0274] Example 84 N-(4-(1H-pyrazol-1-yl)-3-(trifluoromethyl)phenyl)-5-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Step 11 of Example 1, the title product N-(4-(1H-pyrazol-1-yl)-3-(trifluoromethyl)phenyl)-5-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrazole-4-carboxamide 84 (35 mg) was obtained from 2-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrrole-3-carboxylic acid 77c (70 mg, 0.22 mmol) and 4-(1H-pyrazol-1-yl)-3-(trifluoromethyl)aniline 51c (100 mg, 0.44 mmol), with a yield of 30.1%. MS m / z (ESI): 530 [M+1]

[0275] Example 85 N-(3-chloro-4-(2H-1,2,3-triazazol-2-yl)phenyl)-5-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Step 11 of Example 1, the title product N-(3-chloro-4-(2H-1,2,3-triazazol-2-yl)phenyl)-5-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrazole-4-carboxamide 85 (40 mg) was obtained from 2-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrrole-3-carboxylic acid 77c (70 mg, 0.22 mmol) and 3-chloro-4-(2H-1,2,3-triazazol-2-yl)aniline 53a (85 mg, 0.44 mmol), with a yield of 34.4%. MS m / z(ESI):497[M+1]

[0276] Example 86 N-(3-chloro-4-(1H-pyrazol-1-yl)phenyl)-5-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Step 11 of Example 1, the title product N-(3-chloro-4-(1H-pyrazol-1-yl)phenyl)-5-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrazole-4-carboxamide 86 (45 mg) was obtained from 2-cyclopropyl-1-(2-oxo-1,2-dihydropyrrole[4,3,2-ij]isoquinolin-6-yl)-1H-pyrrole-3-carboxylic acid 77c (70 mg, 0.22 mmol) and 3-chloro-4-(1H-pyrazol-1-yl)aniline 54a (85 mg, 0.44 mmol), with a yield of 41.4%. MS m / z(ESI):496[M+1] 1 H NMR(400MHz,DMSO)δ 11.04(s,1H),9.66(s,1H),8.63-8.54(m,1H),8.27(s,1H),8.15-8.05(m,2H),7.93-7.83(m,2H),7.83-7.75(m,2H),7.67(d ,J=7.5Hz,1H),7.11(d,J=7.4Hz,1H),6.62-6.54(m,1H),2.04(tt,J=8.5,5.5Hz,1H),0.77-0.66(m,2H),0.64-0.55(m,2H).

[0277] Example 87 N-(6-(2H-1,2,3-triazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydropyrrolo[2,3,4-de]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Step 3 to Step 4 of Example 73, N-(6-(2H-1,2,3-triazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(1-(4-methoxybenzyl)-2-carbonyl-1,2-dihydropyrrolo[2,3,4-de]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 8 was obtained. From 7a (45 mg, 0.096 mmol), the title product N-(6-(2H-1,2,3-triazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydropyrrolo[2,3,4-de]isoquinolin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-formyl 87 (15 mg) was obtained, yield: 27.9%. MS m / z (ESI): 560 [M+1] 1 H NMR(400MHz,DMSO):δ 11.47(s,1H),11.27(s,1H),9.18(d,J=2.4Hz,1H),8.90(d,J=2.4Hz,1H),8 .63(s,1H),8.42(d,J=6.9Hz,1H),8.21(d,J=9.9Hz,3H),8.12-8.04(m,2H).

[0278] Example 88 1-(8-Isopropyl-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Step 10 of Example 1, ethyl 1-(1-(4-methoxybenzyl)-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate 27d (2 g, 4.04 mmol) was reacted to obtain ethyl 1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate 88b (1.49 g), with a yield of 98%. MS m / z(ESI):376[M+1].

[0279] Step 2 Ethyl 1-(8-bromo-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate Ethyl 1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate 88b (200 mg, 0.53 mmol) was dissolved in 5 mL of chloroform, and liquid bromine (170 mg, 1.07 mmol) was added dropwise to the reaction mixture in an ice bath. The mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure to give the title product, ethyl 1-(8-bromo-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate 88c (240 mg), in a 99.2% yield. MS m / z(ESI):455[M+1].

[0280] Step 3 1-(8-Isopropyl-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide Ethyl 1-(8-bromo-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate 88c (160 mg, 0.35 mmol), isopropenylboronic acid pinacol ester (89 mg, 0.53 mmol), tetrakistriphenylphosphine palladium (32 mg, 0.03 mmol), potassium phosphate (149.55 mg, 0.70 mmol), and 2-di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl (29 mg, 0.07 mmol) were dissolved in 4 mL of dioxane and 2 mL of water and heated at 100 °C for 2 h under nitrogen gas protection in a microwave oven. The reaction mixture was concentrated under reduced pressure, and the residue obtained was purified by silica gel column chromatography using eluent system A to obtain the title product 1-(8-isopropyl-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 88d (110 mg), yield: 75.2%. MS m / z(ESI):416[M+1].

[0281] Step 4 Ethyl 1-(8-isopropyl-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate 1-(8-isopropyl-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 88d (110 mg, 0.26 mmol) was dissolved in 5 mL of tetrahydrofuran, and 5% palladium carbon (56.3 mg, 0.03 mmol) was added under nitrogen gas protection. The reaction mixture was stirred at room temperature for 1 hour under hydrogen gas. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give the title product, ethyl 1-(8-isopropyl-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid ester 88e (108 mg), yield: 98.2%. MS m / z(ESI):418[M+1]. Referring to the synthesis methods of Steps 9 and 11 of Example 1, 1-(8-isopropyl-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid ester 88e (108 mg, 0.26 mmol) was used to obtain 1-(8-isopropyl-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 30 (12 mg), yield: 8.6%. MS m / z(ESI):534[M+1] 1H NMR(400MHz,DMSO)δ 11.26(s,2H),8.72(d,J=5.5Hz,1H),8.53(s,1H),8.26(d,J=2.0Hz,1H),8.13(d,J=7.0Hz,1H),7.99(dd,J=5.5,2.0H z,1H),7.85(dd,J=8.3,7.0Hz,1H),7.71(s,1H),7.59(d,J=8.2Hz,1H),3.39(p,J=6.8Hz,1H),1.30(d,J=6.8Hz,6H).

[0282] Example 89 1-(8-ethyl-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis methods of Steps 3 and 4 of Example 88 and Steps 9 and 11 of Example 1, 1-(8-ethyl-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate 88c (100 mg, 0.22 mmol) was used to obtain 1-(8-ethyl-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 89 (15 mg), yield: 13.2%. MS m / z (ESI): 520 [M+1] 1H NMR(400MHz,DMSO)δ 11.39(s,1H),11.28(s,1H),9.19(d,J=2.4Hz,1H),8.91(d,J=2.4Hz,1H),8.57(s,1H),8.22(s,1H),8.13(d,J=6.9 Hz,1H),7.86(dd,J=8.2,7.0Hz,1H),7.68(s,1H),7.59(d,J=8.2Hz,1H),2.92-2.81(m,2H),1.26(t,J=7.5Hz,3H).

[0283] Example 90 1-(8-chloro-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 Ethyl 1-(8-chloro-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate Ethyl 1-(2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate 88b (300 mg, 0.80 mmol) was dissolved in 4 mL of carboxylic acid, and sulfuryl chloride (323 mg, 2.4 mmol) was added in an ice bath. The mixture was heated at 60 °C for 3 hours. A small amount of methanol was added to the reaction mixture to quench the excess acid chloride. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography using eluent system A to give the title product, ethyl 1-(8-chloro-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate 90b (320 mg), in a 97.7% yield. MS m / z(ESI):410[M+1]. Referring to the synthesis methods of Steps 9 and 11 of Example 1, ethyl 1-(8-chloro-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate 90b (80 mg, 0.20 mmol) was used to obtain 1-(8-chloro-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 90 (21 mg), yield: 20.0%. MS m / z (ESI): 526 [M+1] 1H NMR(400MHz,DMSO)δ 11.71(s,1H),11.28(s,1H),8.72(d,J=5.5Hz,1H),8.57(s,1H),8.26(d,J=2.0Hz,1H),8. 21(d,J=7.0Hz,1H),8.00(dd,J=5.5,2.0Hz,1H),7.97-7.88(m,2H),7.60(d,J=8.2Hz,1H).

[0284] Example 91 1-(8-methyl-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 Ethyl 1-(8-methyl-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate Ethyl 1-(8-bromo-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate 88c (180 mg, 0.40 mmol) and tetrakis(triphenylphosphine)palladium (92 mg, 0.08 mmol) were dissolved in 1 mL of tetrahydrofuran, and 2 mL of a 1 M solution of dimethylzinc in tetrahydrofuran was added in an ice bath. The reaction mixture was heated at 60 °C for 16 h. A small amount of methanol was added to the reaction mixture to quench the excess dimethylzinc. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography using eluent system A to give the title product, ethyl 1-(8-methyl-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate 91b (100 mg), in a 64.8% yield. MS m / z(ESI):390[M+1]. Referring to the synthesis methods of Steps 9 and 11 of Example 1, ethyl 1-(8-methyl-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate 91b (100 mg, 0.26 mmol) was used to obtain 1-(8-methyl-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 91 (8 mg), yield: 6.1%. MS m / z (ESI): 506 [M+1] 1H NMR(400MHz,DMSO)δ 11.20(s,1H),9.10(d,J=2.4Hz,1H),8.84(d,J=2.4Hz,1H),8.49(s,1H),8.14(s,2H),8.05(d ,J=6.9Hz,1H),7.77(dd,J=8.3,7.0Hz,1H),7.56(s,1H),7.49(d,J=8.3Hz,1H),2.42(s,3H).

[0285] Example 92 1-(8-methyl-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 Ethyl 1-(8-cyano-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate Ethyl 1-(8-bromo-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate 88c (100 mg, 0.22 mmol), zinc cyanide (31 mg, 0.26 mmol), and tetrakistriphenylphosphine palladium (25 mg, 0.02 mmol) were dissolved in 4 mL of dimethylformamide, and the reaction was heated at 60 °C in a microwave oven under nitrogen gas protection for 16 h. The reaction mixture was poured into 50 mL of ethyl acetate and washed with saturated aqueous sodium chloride (50 mL × 2). The organic phase was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue obtained was purified using silica gel column chromatography with eluent system A to obtain the title product ethyl 1-(8-cyano-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate 92b (60 mg), yield: 68.1%. MS m / z(ESI):401[M+1]. Referring to the synthesis methods of Steps 9 and 11 of Example 1, ethyl 1-(8-cyano-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate 92b (60 mg, 0.15 mmol) was used to obtain 1-(8-cyano-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-formyl 92 (6 mg), yield: 8.0%. MS m / z(ESI):517[M+1] 1H NMR(400MHz,DMSO)δ 12.21(s,1H),11.28(s,1H),8.72(d,J=5.5Hz,1H),8.58(s,1H),8.28-8.20(m,2H),8.11(s,1H),8.06-7.97(m,2H),7.59(d,J=8.3Hz,1H).

[0286] Example 93 1-(8-Methoxy-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis methods of Steps 9 and 11 of Example 1, ethyl 1-(8-bromo-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate 88c (210 mg, 0.20 mmol) was used to obtain 1-(8-bromo-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 93c (108 mg), yield: 41.1%. MS m / z (ESI): 570 [M+1]

[0287] Step 3 1-(8-Methoxy-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide Ethyl 1-(8-bromo-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate 93c (100 mg, 0.18 mmol), sodium chloride (96 mg, 1.79 mmol), and cuprous chloride (100 mg, 1.01 mmol) were dissolved in 4 mL of dimethylformamide and 2 mL of methanol, and the reaction was heated under nitrogen gas protection at 100 °C for 16 h in a sealed tube. The reaction mixture was poured into 50 mL of ethyl acetate and washed with saturated aqueous sodium chloride (50 mL × 2). The organic phase was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified using silica gel column chromatography with eluent system B to obtain the title product 1-(8-methoxy-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 93 (6 mg), yield: 6.6%. MS m / z(ESI):522[M+1]. 1 H NMR(400MHz,DMSO)δ 11.06(d,J=76.0Hz,2H),8.71(d,J=5.5Hz,1H),8.54(s,1H),8.41(d,J=8.2Hz,1H),8.25(d, J=2.0Hz,1H),8.20(d,J=7.0Hz,1H),7.98(dt,J=8.3,5.8Hz,2H),7.02(s,1H),4.15(s,3H).

[0288] Example 94 1-(2-Imine-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate ethyl ester Ethyl 1-(1-(4-methoxybenzyl)-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (2 g, 4.04 mmol) was dissolved in 10 mL of trifluoroacetic acid and stirred at 70° C. for 16 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified using silica gel column chromatography with eluent system A to give the title product, ethyl 1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate 94a (1.50 g), yield: 99.0%. MS m / z(ESI):376[M+1]

[0289] Step 2 1-(2-((4-Methoxybenzyl)amine)benzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate ethyl Ethyl 1-(2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate 94a (1.50 g, 4 mmol) and 4-methoxybenzylamine (822 mg, 6 mmol) were dissolved in 1 mL of phosphorus oxychloride and 10 mL of toluene and stirred at 100 °C for 1 h. The reaction mixture was concentrated under reduced pressure, and the residue was purified using silica gel column chromatography with eluent system A to give the title product, ethyl 1-(2-((4-methoxybenzyl)amino)benzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate 94b (900 mg), yield: 45.5%. MS m / z(ESI):495[M+1] Referring to the synthesis method of Steps 9, 11, and 10 of Example 1 in order, 1-(2-imine-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 94 (35 mg) was obtained from ethyl 1-(2-((4-methoxybenzyl)amine)benzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate 94b (300 mg, 0.61 mmol), with a yield of 11.8%. MS m / z(ESI):491[M+1]. 1 H NMR(400MHz,DMSO-d6)δ 11.29(s,1H),8.71(d,J=5.5Hz,1H),8.50(s,1H),8.29-8.21(m,2H),8.17(d,J=6.9Hz,1H),7.99(dd,J=5.5,1.7H z,1H),7.79-7.70(m,1H),7.54(d,J=7.4Hz,1H),7.41(d,J=8.1Hz,1H),7.06(d,J=7.4Hz,1H),3.79-3.51(m,1H).

[0290] Example 95 1-(2-Thio-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 1-(2-thio-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid 1-(2-Carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid 95a (50 mg, 0.14 mmol) and Lawesson's reagent (100 mg, 0.25 mmol) were dissolved in 10 mL of toluene and reacted at 100 °C for 1 h (microwave). The reaction mixture was cooled to room temperature and poured into 10 mL of water. Filtration, the filtrate was extracted with ethyl acetate (20 mL × 3), the organic phases were combined, washed with saturated sodium chloride solution (50 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product, and the residue obtained was purified using silica gel column chromatography with eluent system A to obtain the title product 1-(2-thio-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid 95b (30 mg), yield: 57.3%. MS m / z(ESI):364[M+1] Referring to the synthesis method in Step 11 of Example 1, 1-(2-thio-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid 95b (30 mg, 0.083 mmol) was used to obtain 1-(2-thio-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 95 (8 mg), yield: 19.1%. MS m / z(ESI):508[M+1]. 1H NMR(400MHz,CD3OD)δ 8.63(d,J=5.6Hz,1H),8.35(s,1H),8.24(dd,J=4.6,2.6Hz,2H),7.98(dd,J=5.6,2.1Hz ,1H),7.84(dd,J=8.3,7.2Hz,1H),7.67(dd,J=10.8,7.9Hz,2H),7.23(d,J=7.6Hz,1H).

[0291] Example 96 1-(1-oxo-2H-naphtho[1,8-cd]isothiazol-5-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 N-(8-bromonaphthalen-1-yl)-tert-butylsulfenamide 8-Bromo-1-naphthylamine 96a (5 g, 22.62 mmol) was dissolved in 50 mL of dichloromethane, and pyridine (3.95 g, 50 mmol) and tert-butylsulfenyl chloride (4.20 g, 30 mmol) were added sequentially. The mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography using eluent system A to give the title product N-(8-bromonaphthalen-1-yl)-tert-butylsulfenamide 96b (4 g) in a 54.4% yield. MS m / z(ESI):326[M+1]

[0292] Step 2 1-oxo-2H-naphtho[1,8-cd]isothiazole N-(8-bromonaphthalen-1-yl)-tert-butylsulfenamide 96b (4 g, 12.31 mmol) and azodiisobutyronitrile (2.46 g, 15 mmol) were dissolved in 100 mL of toluene. Tri-n-butylhydrotin (4.41 g, 15 mmol) was added dropwise at 90 °C, and the mixture was stirred at 90 °C for 2 h. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography using eluent system A to give the title product, 1-oxo-2H-naphtho[1,8-cd]isothiazole 96c (1.20 g), in a 51.6% yield. MS m / z (ESI): 190 [M+1] Referring to the synthesis methods of Steps 1 to 6 of Intermediate 1 and Step 11 of Example 1 in order, 1-(1-oxo-2H-naphtho[1,8-cd]isothiazol-5-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 96 (41 mg) was obtained from 1-oxo-2H-naphtho[1,8-cd]isothiazol-5-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 96 (41 mg), yield: 1.3%. MS m / z(ESI):512[M+1].

[0293] Example 97 1-(2-oxo-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis methods of Step 5 of Example 2 and Steps 7 to 11 of Example 1 in order, the title product 1-(2-oxo-1,2-dihydropyrrolo[4,3,2-ij]isoquinolin-6-yl)-5-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide 97 (126 mg) was obtained from 6-bromopyrrole[2,3,4-ij]isoquinolin-2(1H)-one 97a (2.49 g, 10 mmol, prepared according to the known method of Patent WO2022081928A1). Yield: 2.6%. MS m / z(ESI):493[M+1]

[0294] Example 98 1-(2-carbonyl-1,2-dihydropyrrolo[4,3,2-de]isoquinolin-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis methods of Step 1 of Example 8, Step 2 of Example 34, Step 4 of Example 8, Steps 1 to 6 of Intermediate 1, and Step 3 of Example 34 in order, 4-bromo-5-nitroisoquinoline 98a (10.00 g, 39.68 mmol) was reacted to obtain 1-(2-carbonyl-1,2-dihydropyrrolo[4,3,2-de]isoquinolin-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 98 (6 mg), yield: 4.3%. MS m / z(ESI):493[M+1] 1 H NMR(400MHz,DMSO):δ 11.36(s,1H),11.17(s,1H),9.66(s,1H),9.32(s,1H),8.37(d,J=6.4Hz,1H), 8.12(s,1H),7.66(d,J=8.4Hz,1H),7.34-7.12(m,2H),6.78(d,J=9.2Hz,1H).

[0295] Example 99 1-(2-oxo-1,2-dihydropyrrolo[4,3,2-de]quinolin-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 5-Nitroquinoline-4-carboxylic acid 4-Carboxyquinoline 99a (10 g, 57.80 mmol) was dissolved in 30 mL of concentrated sulfuric acid, and 10 mL of concentrated nitric acid was added at 0° C. The mixture was stirred for 1 h at 0° C. The reaction mixture was poured into 200 mL of crushed ice, and the pH was adjusted to 2 with 50% aqueous sodium hydride. The solid was collected by filtration and dried under reduced pressure to give the title product, 5-nitroquinoline-4-carboxylic acid 99b (6 g), in a 47.6% yield. MS m / z(ESI):219[M+1]

[0296] Step 2 5-Aminoquinoline-4-carboxylic acid 5-Nitroquinoline-4-carboxylic acid 99b (6 g, 27.52 mmol) was dissolved in 500 mL of methanol. 5% palladium on carbon (1 g) was added. The air was removed and hydrogen gas was introduced, and this process was repeated three times. The reaction was stirred at 40 °C for 16 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give the title product, 5-aminoquinoline-4-carboxylic acid 99c (3 g), in a 58.0% yield. MS m / z (ESI): 189 [M+1]

[0297] Step 3 2-oxo-1,2-dihydropyrrolo[4,3,2-de]quinoline 5-Aminoquinoline-4-carboxylic acid 99c (3 g, 15.96 mmol) was dissolved in 50 mL of acetic acid. The mixture was stirred at 100 °C for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography using eluent system A to give the title product 2-oxo-1,2-dihydropyrrolo[4,3,2-de]quinoline 99d (600 mg) in a 22.1% yield. MS m / z (ESI): 171 [M+1] Referring to the synthesis methods of Steps 1 to 6 of Intermediate 1 and Step 11 of Example 1 in order, 1-(2-oxo-1,2-dihydropyrrolo[4,3,2-de]quinolin-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 99 (21 mg) was obtained from 2-oxo-1,2-dihydropyrrolo[4,3,2-de]quinoline 99d (600 mg, 3.53 mmol), with a yield of 1.2%. MS m / z(ESI):493[M+1]. 1H NMR(400MHz,DMSO)δ 11.37(s,2H),9.25(d,J=4.4Hz,1H),9.19(d,J=2.1Hz,1H),8.90(d,J=2.3Hz,1H),8.54( s,1H),8.22(s,1H),8.09(d,J=4.4Hz,1H),7.99(d,J=7.5Hz,1H),7.17(d,J=7.5Hz,1H).

[0298] Example 100 1-(2-oxo-1,2-dihydropyrrole[4,3,2-de]quinazolin-6-yl)-5-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis methods of Step 5 of Example 2 and Steps 7 to 11 of Example 1 in order, the title product 1-(2-oxo-1,2-dihydropyrrole[4,3,2-de]quinazolin-6-yl)-5-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide 100 (213 mg) was obtained from 6-bromopyrrole[4,3,2-de]quinazolin-2(1H)-one 100a (2.50 g, 10.00 mmol, prepared according to the known method of Patent WO2022081928A1), with a yield of 4.3%. MS m / z(ESI):494[M+1]

[0299] Example 101 1-(4-oxo-4,5-dihydropyrrole[4,3,2-de]cinnolin-8-yl)-5-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis methods of Step 5 of Example 2 and Steps 7 to 11 of Example 1 in order, the title product 1-(4-oxo-4,5-dihydropyrrole[4,3,2-de]cinnolin-8-yl)-5-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide 101 (263 mg) was obtained from 8-bromopyrrole[4,3,2-de]cinnolin-4(5H)-one 101a (2.50 g, 10 mmol, prepared according to the known method of Patent WO2022081928A1), with a yield of 5.3%. MS m / z(ESI):494[M+1]

[0300] Example 102 1-(1-methyl-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 6-Bromobenzo[cd]indol-2(1H)-one Referring to the synthesis method of Step 1 of Intermediate 1, the title product 6-bromobenzo[cd]indol-2(1H)-one 102b (6.80 g) was obtained from benzo[cd]indol-2(1H)-one 102a (5.00 g, 29.55 mmol), with a yield of 93.2%. MS m / z(ESI):248[M+1]

[0301] Step 2 6-Bromo-1-methylbenz[cd]indol-2(1H)-one 6-Bromobenzo[cd]indol-2(1H)-one 102b (3 g, 12.09 mmol) was dissolved in tetrahydrofuran (30 mL), purged with nitrogen gas three times, and the reaction mixture was cooled to 0°C. Sodium hydride (967 mg, 24.19 mmol, 60% purity) was added to the mixture under a nitrogen atmosphere, and the mixture was stirred at 0°C for 0.5 hours. Iodomethane (2.06 g, 14.51 mmol) was added dropwise to the mixture, and the mixture was reacted at 0°C for 3 hours. The reaction was quenched by adding water (5 mL), extracted with ethyl acetate (100 mL × 3), the organic phases were combined, washed with saturated sodium chloride solution (50 mL), dried over anhydrous sodium sulfate, filtered, the filtrate was concentrated under reduced pressure, and the residue was purified using silica gel column chromatography with eluent system A to give the title product 6-bromo-1-methylbenzo[cd]indol-2(1H)-one 102c (2 g), yield: 63.1%. MS m / z(ESI):263[M+1]

[0302] Step 3 to Step 6 Referring to the synthesis methods of Step 3 to Step 5 of Intermediate 1 and Step 3 of Example 34 in order, 6-bromo-1-methylbenzo[cd]indol-2(1H)-one 102c (2.00 g, 7.63 mmol) was reacted to obtain 1-(1-methyl-2-carbonyl-1,2-dihydrobenzo[cd]indol-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 102 (41 mg), yield: 1.1%. MS m / z (ESI): 506 [M+1] 1 H NMR(400MHz,DMSO):δ 11.30(s,1H),8.72(d,J=5.5Hz,1H),8.54(s,1H),8.25(d,J=1.7Hz,1H),8.19(d,J=7.0Hz,1H),7.99(dd,J=5.4,1.7H z,1H),7.91(dd,J=8.2,7.1Hz,1H),7.81(d,J=7.5Hz,1H),7.61(d,J=8.3Hz,1H),7.31(d,J=7.6Hz,1H),3.44(s,3H).

[0303] Example 103 N-(6-(2H-1,2,3-triazol-2-yl)-5-trifluoromethylpyridin-3-yl)-1-(2-oxo-1,2-dihydropyrrole[4,3,2-de]quinazolin-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide [ka] Referring to step 11 of Example 1, 1-(2-oxo-1,2-dihydropyrrole[4,3,2-de]quinazolin-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 100f (35 mg, 0.10 mmol) gave the title product N-(6-(2H-1,2,3-triazol-2-yl)-5-trifluoromethylpyridin-3-yl)-1-(2-oxo-1,2-dihydropyrrole[4,3,2-de]quinazolin-6-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide 103 (23 mg), yield: 41.0%. MS m / z(ESI):561[M+1]

[0304] Example 104 1-(1,2-Dihydroacenaphthylene-5-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Steps 7 to 9 and Step 11 of Example 1, 1-(1,2-dihydroacenaphthylen-5-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 104 (10 mg) was obtained from 5-bromo-1,2-dihydroacenaphthylene 104a (2 g, 8.6 mmol) in a yield of 0.2%. MS m / z(ESI):477[M+1]. 1H NMR(400MHz,DMSO)δ 11.30(s,1H),8.72(d,J=5.6Hz,1H),8.53(s,1H),8.26(d,J=2.0Hz,1H),8.00(dd,J=5.5,2.0Hz,1H),7.6 6(d,J=7.3Hz,1H),7.58(t,J=7.6Hz,1H),7.47(dd,J=7.2,3.7Hz,2H),7.00(d,J=8.3Hz,1H),3.48(s,4H).

[0305] Example 105 1-(2-carbonyl-1,2,3,4-tetrahydro-5-oxa-1,2a-diazaacenaphthylen-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 7-Bromo-5-nitro-3,4-dihydro-2H-benzo[b][1,4]oxazine 2-Amino-5-bromo-3-nitrophenol 105a (10 g, 42.91 mmol, synthesized using a known method "Charifson, Paul S.; et al. Journal of Medicinal Chemistry, 2008, vol. 51, #17, pp. 5243-5263") and potassium carbonate (18.00 g, 130.43 mmol) were dissolved in DMF (100 mL), and the system was ventilated with nitrogen gas three times. Dibromoethane (9.62 g, 51.72 mmol) was added dropwise to the system, which was then heated to 100°C and reacted for 5 hours. The system was cooled to room temperature, filtered, concentrated, and the residue was dissolved in 200 mL of ethyl acetate, washed successively with water (50 mL × 3), saturated sodium chloride solution (50 mL × 1), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using eluent system C to obtain the title product 7-bromo-5-nitro-3,4-dihydro-2H-benzo[b][1,4]oxazine 105b (5.20 g), yield: 46.8%. MS m / z (ESI): 260 [M+1]

[0306] Step 2 7-Bromo-3,4-dihydro-2H-benzo[b][1,4]oxazin-5-amine Referring to the synthesis method of Step 2 of Example 34, the title product 7-bromo-3,4-dihydro-2H-benzo[b][1,4]oxazin-5-amine 105c (3.81 g) was obtained from 7-bromo-3,4-dihydro-2H-benzo[b][1,4]oxazin-5-amine 105b (5.20 g, 20.07 mmol), with a yield of 82.6%. MS m / z (ESI): 230 [M+1]

[0307] Step 3 6-Bromo-3,4-dihydro-5-oxa-1,2a-diazaacenaphthylene-2(1H)-one 7-Bromo-3,4-dihydro-2H-benzo[b][1,4]oxazin-5-amine 105c (3.81 g, 16.63 mmol) was dissolved in tetrahydrofuran (50 mL), and the mixture was purged with nitrogen gas three times and cooled to 0°C in an ice-water bath. Triethylamine (5.05 g, 49.90 mmol) was added dropwise to the mixture, and triphosgene (2.47 g, 8.32 mmol) was dissolved in tetrahydrofuran (10 mL) and added dropwise to the mixture. After completion of the reaction, the mixture was allowed to react at 0°C for 2 hours. The reaction was quenched by adding aqueous sodium bicarbonate solution, concentrated, extracted with ethyl acetate (80 mL × 3), washed successively with water (50 mL) and saturated sodium chloride solution (50 mL × 1), dried over anhydrous sodium sulfate, filtered, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography using eluent system C to obtain the title product 6-bromo-3,4-dihydro-5-oxa-1,2a-diazaacenaphthylene-2(1H)-one 105d (1.92 g), yield: 45.3%. MS m / z(ESI):256[M+1]

[0308] Step 4 to Step 8 1-(2-carbonyl-1,2,3,4-tetrahydro-5-oxa-1,2a-diazaacenaphthylen-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide Referring to the synthesis methods of Steps 2 to 6 of Intermediate 1 and Step 3 of Example 34 in order, 6-bromo-3,4-dihydro-5-oxa-1,2a-diazaacenaphthylen-2(1H)-one 105d (1.80 g, 7.06 mmol) was reacted to obtain 1-(2-carbonyl-1,2,3,4-tetrahydro-5-oxa-1,2a-diazaacenaphthylen-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 105 (12 mg), yield: 0.3%. MS m / z (ESI): 499 [M+1] 1 H NMR(400MHz,DMSO):δ 11.41(s,1H),10.91(s,1H),8.47(d,J=6.8Hz,1H),8.25(s,1H),7.68-7.43 (m,2H),7.16(d,J=8.8Hz,2H),4.37(t,J=7.2Hz,2H),3.58(t,J=6.8Hz,2H).

[0309] Example 106 1-(2-carbonyl-1,2,5,6-tetrahydro-4H-imidazo[4,5,1-ij]quinolin-7-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 5-Bromo-1,2,3,4-tetrahydroquinolin-8-amine 5-Bromoquinolin-8-amine 106a (2.90 g, 13 mmol) was dissolved in acetic acid (30 mL), purged with nitrogen gas three times, platinum dioxide (295 mg, 1.30 mmol) was added, purged with hydrogen gas three times, and the system was reacted with hydrogen gas at 25 °C for 24 h. The reaction was quenched by purging with air, filtered, and concentrated. The residue was dissolved in 100 mL of ethyl acetate, washed with 1 M sodium hydride solution (20 mL), washed with saturated aqueous sodium chloride solution (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The title product, 5-bromo-1,2,3,4-tetrahydroquinolin-8-amine 106b (2.51 g), was obtained in 85.1% yield. MS m / z(ESI):228[M+1]

[0310] Step 2 7-Bromo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one 5-Bromo-1,2,3,4-tetrahydroquinolin-8-amine 106b (1.8 g, 7.93 mmol) was dissolved in tetrahydrofuran (80 mL), and the system was purged with nitrogen gas three times. The system was cooled to 0°C, and triethylamine (2.41 g, 23.78 mmol, 3.3 mL) and triphosgene (1.65 g, 5.55 mmol) were added to the system, and the system was reacted at 0°C for 1 hour. The reaction was quenched by adding 20 mL of water, concentrated, extracted with ethyl acetate (50 mL × 3), washed with saturated sodium chloride solution (50 mL), dried over anhydrous sodium sulfate, filtered, the filtrate was concentrated, and the residue was purified using silica gel column chromatography with eluent system C to give the title product 7-bromo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one 106c (0.82 g), yield: 39.8%. MS m / z (ESI): 254 [M+1]

[0311] Step 3 to Step 8 Referring to the synthesis methods of Steps 2 to 5 of Intermediate 1 and Steps 11 to 12 of Example 87 in order, 7-bromo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one 106c (1.65 g, 6.52 mmol) was reacted to obtain 1-(2-carbonyl-1,2,5,6-tetrahydro-4H-imidazo[4,5,1-ij]quinolin-7-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 106 (11 mg), yield: 0.3%. MS m / z(ESI):497[M+1] 1 H NMR(400MHz,DMSO):δ 10.56(s,1H),9.76(s,1H),8.42(d,J=8.4Hz,1H),8.21(s,1H),7.62-7.53(m,2H), 7.25-7.06(m,2H),3.88(t,J=8.0Hz,2H),3.46(t,J=6.4Hz,2H),1.85-1.72(m,2H).

[0312] Example 107 1-(5-carbonyl-2,3-dihydro-5H-[1,4]oxazolyl[2,3,4-ij]quinolin-7-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 2-amino-3-hydroxybenzoic acid methyl ester Methyl 3-hydroxy-2-nitrobenzoate 107a (5 g, 25.36 mmol) was dissolved in 20 mL of ethanol and 5 mL of water. Ammonium chloride (2 g, 37.39 mmol) and reduced iron powder (2 g, 35.81 mmol) were added and the mixture was reacted at 80 °C for 2 h. The reaction mixture was cooled to room temperature and poured into 50 mL of water. After filtration, the filtrate was extracted with ethyl acetate (50 mL × 3). The combined organic phases were washed with saturated sodium chloride solution (50 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product. The residue was purified by silica gel column chromatography using eluent system A to give the title product, methyl 2-amino-3-hydroxybenzoate 107b (3 g), in a 70.8% yield. MS m / z(ESI):168[M+1]

[0313] Step 2 3-Carbonyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-5-carboxylic acid methyl ester Methyl 2-amino-3-hydroxybenzoate 107b (3 g, 17.95 mmol) was dissolved in 20 mL of acetonitrile. Triethylamine (2 g, 19.76 mmol) and chloroacetyl chloride (2 g, 17.71 mmol) were added, and the mixture was allowed to react at 20 °C for 12 hours. The reaction mixture was cooled to room temperature and poured into 50 mL of water. After filtration, the filtrate was extracted with ethyl acetate (50 mL × 3). The combined organic phases were washed with saturated sodium chloride solution (50 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product. The residue was purified by silica gel column chromatography using eluent system A to give the title product, methyl 3-carbonyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-5-carboxylate 107c (1.5 g), in a 40.3% yield. MS m / z(ESI):208[M+1]

[0314] Step 3 3,4-Dihydro-2H-benzo[b][1,4]oxazine-5-carboxylic acid methyl ester Methyl 3-carbonyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-5-carboxylate 107c (1.5 g, 7.24 mmol) was dissolved in 20 mL of tetrahydrofuran. Boron trifluoride etherate (2 g, 7.00 mmol, 50%) and sodium borohydride (500 mg, 13.22 mmol) were added at 0 °C, followed by reaction at 0 °C for 2 h. The reaction mixture was cooled to room temperature and poured into 50 mL of water. Filtration, the filtrate was extracted with ethyl acetate (50 mL × 3), the organic phases were combined, washed with saturated sodium chloride solution (50 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product, and the residue obtained was purified using silica gel column chromatography with eluent system A to obtain the title product methyl 3,4-dihydro-2H-benzo[b][1,4]oxazine-5-carboxylate 107d (1 g), yield: 71.5%. MS m / z (ESI): 194 [M+1]

[0315] Step 4 4-Acetyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-5-carboxylic acid methyl ester Methyl 3,4-dihydro-2H-benzo[b][1,4]oxazine-5-carboxylate 107d (1 g, 5.18 mmol) was dissolved in 20 mL of acetonitrile. Acetyl chloride (500 mg, 6.37 mmol) and triethylamine (700 mg, 6.92 mmol) were added and the mixture was allowed to react at 20 °C for 2 hours. The reaction mixture was cooled to room temperature and poured into 50 mL of water. After filtration, the filtrate was extracted with ethyl acetate (50 mL × 3). The combined organic phases were washed with saturated sodium chloride solution (50 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product. The residue was purified by silica gel column chromatography using eluent system A to give the title product, methyl 4-acetyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-5-carboxylate 107e (600 mg), in a 49.3% yield. MS m / z(ESI):236[M+1]

[0316] Step 5 7-Hydroxy-2,3-dihydro-5H-[1,4]oxazolyl[2,3,4-ij]quinolin-5-one Methyl 4-acetyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-5-carboxylate 107d (600 mg, 2.55 mmol) was dissolved in 20 mL of tetrahydrofuran. Bis(trimethylsilyl)aminosodium (2 mL, 2N) was added at 0 °C, and the mixture was allowed to react for 2 hours at 0 °C. The reaction mixture was cooled to room temperature and poured into 50 mL of water. After filtration, the filtrate was extracted with ethyl acetate (50 mL × 3). The combined organic phases were washed with saturated sodium chloride solution (50 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product. The residue was purified by silica gel column chromatography using eluent system A to give the title product, 7-hydroxy-2,3-dihydro-5H-[1,4]oxazolyl[2,3,4-ij]quinolin-5-one 107f (400 mg), in a 77.1% yield. MS m / z (ESI): 204 [M+1]

[0317] Step 6 7-Chloro-2,3-dihydro-5H-[1,4]oxazolyl[2,3,4-ij]quinolin-5-one 7-Hydroxy-2,3-dihydro-5H-[1,4]oxazolyl[2,3,4-ij]quinolin-5-one 107f (400 mg, 1.97 mmol) was dissolved in 20 mL of phosphorus oxychloride. The reaction mixture was heated at 100°C for 2 hours. The mixture was cooled to room temperature and poured into 50 mL of water. After filtration, the filtrate was extracted with ethyl acetate (50 mL x 3). The combined organic phases were washed with saturated sodium chloride solution (50 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product. The residue was purified using silica gel column chromatography with eluent system A to give the title product, 7-chloro-2,3-dihydro-5H-[1,4]oxazolyl[2,3,4-ij]quinolin-5-one 107g (250 mg), in a 57.3% yield. MS m / z (ESI): 222 [M+1]

[0318] Step 7 7-Hydrazino-2,3-dihydro-5H-[1,4]oxazolyl[2,3,4-ij]quinolin-5-one 7-Chloro-2,3-dihydro-5H-[1,4]oxazolyl[2,3,4-ij]quinolin-5-one 107g (250 mg, 1.13 mmol) was dissolved in 20 mL of hydrazine hydrate. The reaction was allowed to proceed at 100°C for 2 hours. The reaction mixture was cooled to room temperature and poured into 50 mL of water. The mixture was filtered and concentrated to give the title product, 7-hydrazino-2,3-dihydro-5H-[1,4]oxazolyl[2,3,4-ij]quinolin-5-one 107h (200 mg), in a yield of 81.6%. MS m / z(ESI):218[M+1] Referring to the synthesis methods of Steps 8, 9, and 11 of Example 1, 1-(5-carbonyl-2,3-dihydro-5H-[1,4]oxazolyl[2,3,4-ij]quinolin-7-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 107 (20 mg) was obtained from 7-hydrazino-2,3-dihydro-5H-[1,4]oxazolyl[2,3,4-ij]quinolin-5-one 107h (200 mg, 0.92 mmol), with a yield of 4.3%. MS m / z(ESI):510[M+1]. 1H NMR(400MHz,DMSO)δ 8.35-8.21(m,1H),8.15(dd,J=8.3,1.2Hz,1H),7.85(t,J=8.0Hz,1H),7.72(t,J=5. 3Hz,1H),7.47-7.34(m,2H),7.02-6.83(m,2H),4.72(d,J=5.3Hz,2H),3.74(s,3H).

[0319] Example 108 1-(3-carbonyl-2,3-dihydronaphtho[1,8-de][1,2]oxazin-7-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 8-Bromo-N-hydroxy-1-naphthylamide 8-Bromo-1-naphthyl acid 108a (5 g, 19.91 mmol) was dissolved in 20 mL of dichloromethane. 2-(7-Azobenzotriazazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (10 g, 26.30 mmol) and triethylamine (4 g, 39.53 mmol) were added and the mixture was allowed to react at 20 °C for 1 hour. Hydroxylamine hydrochloride (1.5 g, 21.58 mmol) was then added and the mixture was allowed to react at 20 °C for 1 hour. The reaction mixture was cooled to room temperature and poured into 50 mL of water. Filtration, the filtrate was extracted with ethyl acetate (50 mL × 3), the organic phases were combined, washed with saturated sodium chloride solution (50 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product, and the residue obtained was purified using silica gel column chromatography with eluent system A to obtain the title product 8-bromo-N-hydroxy-1-naphthylamide 108b (2 g), yield: 37.7%. MS m / z(ESI):266[M+1]

[0320] Step 2 Naphtho[1,8-de][1,2]oxazin-3(2H)-one 8-Bromo-N-hydroxy-1-naphthylamide 108b (2 g, 7.52 mmol) was dissolved in 20 mL of dioxane. Cesium carbonate (4 g, 12.28 mmol), 4,5-bisdiphenylphosphine-9,9-dimethylxanthene (500 mg, 0.86 mmol), and tris(dibenzylideneacetone)dipalladium (500 mg, 0.55 mmol) were added, and the mixture was reacted at 110 °C for 12 h. The reaction mixture was cooled to room temperature and poured into 50 mL of water. The filtrate was extracted with ethyl acetate (50 mL × 3), the organic phases were combined, washed with saturated sodium chloride solution (50 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. The residue obtained was purified using silica gel column chromatography with eluent system A to obtain the title product naphtho[1,8-de][1,2]oxazin-3(2H)-one 108c (900 mg), yield: 64.7%. MS m / z (ESI): 186 [M+1]

[0321] Step 3 2-(4-Methoxybenzyl)naphtho[1,8-de][1,2]oxazin-3(2H)-one Naphtho[1,8-de][1,2]oxazin-3(2H)-one 108c (900 mg, 4.86 mmol) was dissolved in 20 mL of tetrahydrofuran. Cesium carbonate (4 g, 12.28 mmol) and 4-methoxybenzyl (1 g, 6.38 mmol) were added and the mixture was reacted at 100 °C for 12 hours. The reaction mixture was cooled to room temperature and poured into 50 mL of water. After filtration, the filtrate was extracted with ethyl acetate (50 mL × 3). The combined organic phases were washed with saturated sodium chloride solution (50 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product. The residue was purified by silica gel column chromatography using eluent system A to give the title product, 2-(4-methoxybenzyl)naphtho[1,8-de][1,2]oxazin-3(2H)-one 108d (1 g), in a 67.3% yield. MS m / z(ESI):306[M+1] Referring to the synthesis methods of Steps 6 to 9 and Steps 11 to 12 of Example 3, 1-(3-carbonyl-2,3-dihydronaphtho[1,8-de][1,2]oxazin-7-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 108 (10 mg) was obtained from 2-(4-methoxybenzyl)naphtho[1,8-de][1,2]oxazin-3(2H)-one 108d (1 g, 3.28 mmol), with a yield of 0.6%. MS m / z(ESI):508[M+1].

[0322] Example 109 1-(3-carbonyl-2,3-dihydro-1H-benzo[de]cinnolin-7-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Example 108, 1-(3-carbonyl-2,3-dihydro-1H-benzo[de]cinnolin-7-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 109 (10 mg) was obtained from 8-bromo-1-naphthyl acid 109a (5 g, 19.91 mmol), with a yield of 0.1%. MS m / z(ESI):507[M+1].

[0323] Example 110 1-(1H-naphtho[1,8-de][1,2,3]triazin-7-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] The known method of Patent WO2022081927A was used to prepare 7-bromo-1H-naphtho[1,8-de][1,2,3]triazine. Referring to the synthesis method of Steps 5 to 9 of Example 108, 7-bromo-1H-naphtho[1,8-de][1,2,3]triazine 110a (5 g, 20.15 mmol) was used to obtain 1-(1H-naphtho[1,8-de][1,2,3]triazin-7-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 110 (10 mg), with a yield of 0.1%. MS m / z(ESI):492[M+1].

[0324] Example 111 N-(6-(2H-1,2,3-triazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydro-1,2,4-triazacyclopenta[cd]inden-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis method of Step 2 of Intermediate 1 and Steps 7 to 11 of Example 1, 5-iodo-1,2a1,4-triazacyclopenta[cd]inden-2(1H)-one 111a (230 mg, 0.81 mmol, prepared according to the known method of Patent WO2022089406A1) gave N-(6-(2H-1,2,3-triazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydro-1,2,4-triazacyclopenta[cd]inden-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 111 (18 mg), yield: 4.0%. MS m / z(ESI):549[M+1]

[0325] Example 112 N-(6-(2H-1,2,3-triazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydro-1,2a1,3-triazacyclopenta[cd]inden-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Step 1 (3-Bromo-6-chloropyridin-2-yl)methanol Methyl 3-bromo-6-chloropyridine-2-carboxylate 112a (2 g, 7.98 mmol) was dissolved in 20 mL of methanol, and sodium borohydride (1.51 g, 39.92 mmol) was added batchwise in an ice bath. The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was poured into 100 mL of saturated aqueous sodium chloride solution, extracted with dichloromethane (100 mL × 3), and the combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title product (3-bromo-6-chloropyridin-2-yl)methanol 112b (1.60 g), yield: 89.9%. MS m / z(ESI):223[M+1].

[0326] Step 2 2-((3-bromo-6-chloropyridin-2-yl)methyl)isodihydroindole-1,3-dione Methyl 3-bromo-6-chloro-pyridine-2-carboxylate 112b (1 g, 4.50 mmol) and triphenylphosphine (2.36 g, 8.99 mmol) were dissolved in 20 mL of tetrahydrofuran, and phthalimide (727 mg, 4.94 mmol) and diethyl azodicarboxylate (1.72 g, 9.89 mmol) were slowly added in an ice bath. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue obtained was purified by silica gel column chromatography using eluent system B to give the title product 2-((3-bromo-6-chloropyridin-2-yl)methyl)isodihydroindole-1,3-dione 112c (1.31 g), yield: 82.3%. MS m / z(ESI):352[M+1].

[0327] Step 3 (3-Bromo-6-chloropyridin-2-yl)ethylamine 2-((3-Bromo-6-chloropyridin-2-yl)methyl)isodihydroindole-1,3-dione 112c (800 mg, 2.28 mmol) was dissolved in 20 mL of ethanol and hydrazine hydrate (145 mg, 4.55 mmol, 98% purity) was added. The reaction was stirred at room temperature for 1 hour. The reaction solution was poured into 100 mL of water and extracted with ethyl acetate (100 mL × 3). The combined organic phases were dried over anhydrous sodium sulfate and evaporated under reduced pressure to give the title product (3-bromo-6-chloropyridin-2-yl)methylamine 112d (480 mg), yield: 95.2%. MS m / z(ESI):222[M+1].

[0328] Step 4 Methyl 8-bromo-5-chloroimidazo[1,5-a]pyridine-3-carboxylate (3-Bromo-6-chloropyridin-2-yl)ethylamine 112d (400 mg, 1.81 mmol) and oxalylchloromonoethyl (278 mg, 2.03 mmol) were dissolved in 10 mL of tetrahydrofuran, and triethylamine (206 mg, 2.03 mmol) was added. The reaction was stirred at room temperature for 6 hours. After spin-drying, the residue was dissolved in 6 mL of phosphorus oxychloride and heated at 105 °C for 2 hours. The reaction was concentrated under reduced pressure, and the residue was purified using silica gel column chromatography with eluent system A to give the title product, methyl 8-bromo-5-chloroimidazo[1,5-a]pyridine-3-carboxylate 112e (510 mg), in a 93.1% yield. MS m / z(ESI):288[M+1].

[0329] Step 5 Methyl 8-bromo-5-aminoimidazo[1,5-a]pyridine-3-carboxylate Methyl 8-bromo-5-chloroimidazo[1,5-a]pyridine-3-carboxylate 112e (510 mg, 1.77 mmol) was dissolved in 10 mL of 7 M ammonia in methanol, and the reaction was allowed to proceed for 16 hours at 80 °C in a sealed tube. The reaction mixture was concentrated under reduced pressure, and the residue was purified using silica gel column chromatography with eluent system A to give the title product, methyl 8-bromo-5-aminoimidazo[1,5-a]pyridine-3-carboxylate 112f (320 mg), in a 65.1% yield. MS m / z(ESI):270[M+1].

[0330] Step 6 5-Bromo-1,2,3-triazacyclopenta[cd]inden-2(1H)-one Methyl 8-bromo-5-aminoimidazo[1,5-a]pyridine-3-carboxylate 112f (320 mg, 1.19 mmol) was dissolved in 10 mL of acetonitrile, 10 mL of 25% sodium chloride in methanol was added, and the reaction was heated at 70 °C for 16 hours. The pH of the reaction mixture was adjusted to acidic with 2 M hydrochloric acid, and the residue obtained was purified using silica gel column chromatography with eluent system C to give the title product 5-bromo-1,2,3-triazacyclopenta[cd]inden-2(1H)-one 112g (208 mg), yield: 65.6%. MS m / z(ESI):238[M+1]. Referring to the synthesis method of Step 2 of Intermediate 1 and Steps 7 to 11 of Example 1, N-(6-(2H-1,2,3-triazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydro-1,2a1,3-triazacyclopenta[cd]inden-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 112 (9 mg) was obtained from 5-bromo-1,2,3-triazacyclopenta[cd]inden-2(1H)-one 112g (208 mg, 0.88 mmol), with a yield of 1.8%. MS m / z(ESI):549[M+1]

[0331] Example 113 N-(6-(2H-1,2,3-triazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydro-1,4,4a-triazacyclopenta[cd]inden-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis methods of Step 3 to Step 4 of Example 8, Step 1 of Example 13, Step 7 of Example 8, Step 4 to Step 6 of Intermediate 1, and Step 11 of Example 1 in order, 4-bromopyrazolo[1,5-a]pyridine-3-carbonitrile 113a (15 g, 6.78 mmol) was reacted to obtain N-(6-(2H-1,2,3-triazol-2-yl)-5-(trifluoromethyl)pyridin-3-yl)-1-(2-carbonyl-1,2-dihydro-1,4,4a-triazacyclopenta[cd]inden-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide 113 (8 mg), the yield: 0.2%. MS m / z(ESI):549[M+1] 1 H NMR(400MHz,DMSO):δ 11.10(s,1H),10.82(s,1H),8.26-8.12(m,2H),8.54(s,1H),8.02(s,2H),7.85(s,1H),7.46(d,J=5.6Hz,1H),6.92(d,J=7.6Hz,1H).

[0332] Example 114 N-(6-(2H-1,2,3-triazol-2-yl)-5-trifluoromethylpyridin-3-yl)-1-(4-oxo-4,5-dihydropyrrole[4,3,2-de]quinazolin-8-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide [ka] Referring to step 11 of Example 1, 1-(4-oxo-4,5-dihydropyrrole[4,3,2-de]quinazolin-8-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 101f (35 mg, 0.10 mmol) gave the title product N-(6-(2H-1,2,3-triazol-2-yl)-5-trifluoromethylpyridin-3-yl)-1-(4-oxo-4,5-dihydropyrrole[4,3,2-de]quinazolin-8-yl)-5-trifluoromethyl-1H-pyrazole-4-carboxamide 114 (21 mg), yield: 37.4%. MS m / z(ESI):561[M+1]

[0333] Example 115 1-(2-carbonyl-1,2-dihydro-1,2a-diazabenzo[cd]azulen-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Step 1 Cycloheptatrieno[d]imidazol-2-ol 2-(Methylthio)cycloheptatrieno[d]imidazole 115a (10 g, 56.82 mmol, synthesized according to a known method, "Journal of the American Chemical Society, 1954, Vol. 76, pp. 3352-3353") was dissolved in concentrated hydrochloric acid (50 mL), heated to reflux for 2 h, cooled to room temperature, added with ethanol (80 mL), and stirred at room temperature for 1 h. After filtration, the filter cake was dissolved in water (80 mL), and the pH was adjusted to 7-8 with saturated sodium bicarbonate solution. The filter cake was washed with water (10 mL x 2) and dried. The title product, cycloheptatrieno[d]imidazol-2-ol 115b (6.51 g), was obtained in a 79.8% yield. MS m / z(ESI):147[M+1]

[0334] Step 2 Methyl 3-(2-carbonyl-3,3a-dihydrocycloheptatrieno[d]imidazol-1(2H)-yl)propionate Cycloheptatrieno[d]imidazol-2-ol 115b (5 g, 34.21 mmol) was dissolved in DMF (50 mL), potassium carbonate (14.18 g, 102.63 mmol) and methyl bromopropionate (11.43 g, 68.42 mmol) were added, and the mixture was purged with nitrogen gas three times and heated to 80 °C for 2 h. The mixture was cooled to room temperature, filtered, and concentrated. The residue was purified by silica gel column chromatography using eluent system C to give the title product, methyl 3-(2-carbonyl-3,3a-dihydrocycloheptatrieno[d]imidazol-1(2H)-yl)propionate 115c (7.20 g), in an 89.8% yield. MS m / z (ESI): 235 [M+1]

[0335] Step 3 3-(2-carbonyl-3,3a-dihydrocycloheptatrieno[d]imidazol-1(2H)-yl)propionic acid Referring to the synthesis method of Step 5 of Intermediate 1, methyl 3-(2-carbonyl-3,3a-dihydrocycloheptatrieno[d]imidazol-1(2H)-yl)propionate 115c (7.20 g, 30.74 mmol) was reacted to give 3-(2-carbonyl-3,3a-dihydrocycloheptatrieno[d]imidazol-1(2H)-yl)propionic acid 115d (6.30 g), yield: 93.2%. MS m / z (ESI): 221 [M+1]

[0336] Step 4 1,3,4,5a-tetrahydro-1,2a-diazabenzo[cd]azulene-2,5-dione 3-(2-carbonyl-3,3a-dihydrocycloheptatrieno[d]imidazol-1(2H)-yl)propionic acid 115d (6.20 g, 28.15 mmol) was dissolved in dichloromethane (70 mL), and nitrogen gas was purged three times. The system was cooled to 0 ° C., and sulfoxide chloride (6.70 g, 56.31 mmol) was added dropwise to the system. After completion, the temperature was raised to 25 ° C. and the reaction was continued for 2 hours. After concentration, the residue was dissolved in dichloromethane (100 mL), aluminum trichloride (11.26 g, 84.45 mmol) was added, and the system was reacted at 40 ° C. for 1 hour. The mixture was quenched with sodium bicarbonate solution, extracted with dichloromethane (200 mL × 3), washed with saturated sodium chloride solution (100 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by silica gel column chromatography using eluent system C to give the title product 1,3,4,5a-tetrahydro-1,2a-diazabenzo[cd]azulene-2,5-dione 115e (3.60 g), yield: 63.2%. MS m / z(ESI):203[M+1]

[0337] Step 5 3,4,5,5a-Tetrahydro-1,2a-diazabenzo[cd]azulen-2(1H)-one 1,3,4,5a-Tetrahydro-1,2a-diazabenzo[cd]azulene-2,5-dione 115e (3.50 g, 17.31 mmol) was dissolved in trifluoroacetic acid (40 mL), and the system was purged with nitrogen gas three times. The system was cooled to 0°C, and triethylsilane (2.42 g, 20.77 mmol) was added dropwise to the system, and the system was reacted at 0°C for 2 hours. After concentration, the residue was added with water (30 mL), extracted with ethyl acetate (80 mL × 3), washed successively with sodium bicarbonate solution (50 mL × 2) and saturated sodium chloride solution (50 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by silica gel column chromatography using eluent system C to obtain the title product 3,4,5,5a-tetrahydro-1,2a-diazabenzo[cd]azulen-2(1H)-one 115f (2.81 g), yield: 86.3%. MS m / z (ESI): 189 [M+1]

[0338] Step 6 1,2a-Diazabenzo[cd]azulen-2(1H)-one 3,4,5,5a-Tetrahydro-1,2a-diazabenzo[cd]azulen-2(1H)-one 115f (2.50 g, 13.28 mmol) was dissolved in acetonitrile (40 mL), triethylamine (6.72 g, 66.41 mmol) was added, and the mixture was reacted at 70 °C for 12 hours. After concentration, the residue was added with water (20 mL), extracted with ethyl acetate (60 mL × 3), washed with saturated sodium chloride solution (50 mL × 1), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified using silica gel column chromatography with eluent system C to obtain the title product 1,2a-diazabenzo[cd]azulen-2(1H)-one 115f (1.80 g), yield: 73.6%. MS m / z (ESI): 185 [M+1]

[0339] Step 7 to Step 13 1-(2-carbonyl-1,2-dihydro-1,2a-diazabenzo[cd]azulen-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide Referring to the synthesis methods of Steps 1 to 6 of Intermediate 1 and Step 11 of Example 1 in order, 1,2a-diazabenzo[cd]azulen-2(1H)-one 115g (7.80g, 42.35mmol) was reacted to obtain 1-(2-carbonyl-1,2-dihydro-1,2a-diazabenzo[cd]azulen-6-yl)-5-(trifluoromethyl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1H-pyrazole-4-carboxamide 115 (14mg), yield: 0.07%. MS m / z(ESI):507[M+1] 1H NMR(400MHz,DMSO):δ 10.21(s,1H),9.15(d,J=5.6Hz,1H),8.48(d,J=3.6Hz,1H),8.16(s,1H),7.6 5(d,J=7.0Hz,1H),7.51(s,1H),7.36(s,1H),6.92-6.63(m,4H),6.22(s,1H).

[0340] Example 116 1-(1-oxo-1,2-dihydro-2,9a-diazabenzo[cd]azulen-5-yl)-5-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide [ka] Referring to the synthesis methods of Step 5 of Example 2 and Steps 7 to 11 of Example 1 in order, the title product 1-(1-oxo-1,2-dihydro-2,9a-diazabenzo[cd]azulen-5-yl)-5-trifluoromethyl-N-(2-trifluoromethylpyridin-4-yl)-1H-pyrazole-4-carboxamide 116 (240 mg) was obtained from 5-bromo-2,9a-diazabenzo[cd]azulen-1-(2H)-one 116a (2.63 g, 10.00 mmol, prepared according to the known method of Patent WO2022081928A1), with a yield of 4.7%. MS m / z(ESI):507[M+1].

[0341] Biological Test Evaluation The present invention will be further explained below in conjunction with test examples, but these examples are not intended to limit the scope of the present invention.

[0342] Test Example 1: Measurement of MALT1 enzyme activity inhibitory effect of the compound of the present invention 1.1 Experimental Objective: IC for inhibiting MALT1 enzyme activity by compounds at the Km concentration using Ac-LRSR-AMC as a substrate 50 was tested.

[0343] 1.2 Laboratory equipment and reagents: device:

[0344] [Table 1] reagent:

[0345] [Table 2]

[0346] 1.3 Experimental Method: The product of enzymatic cleavage of Ac-LRSR-AMC by MALT1 generates fluorescence and can be detected at 460 nm. The highest compound concentration was 1000 nM, and three-fold dilutions were performed to obtain a total of 11 concentrations (1000 nM to 0.017 nM). The reaction mixture consisted of 10 nM FL MALT1 protein, 200 mM Ac-LRSR-AMC, 50 mM Tris pH 7.5, 0.6 M citrate, 1 mM DTT, 1 mM EDTA, 0.05% BSA, and 1.5% DMSO. The compound and enzyme were preincubated at room temperature for 50 minutes, followed by addition of the substrate and incubation for 4 hours.

[0347] 1.4 Experimental data processing method: 1. Inhibition rate (%): The raw data (460 nm reading) was calculated using the following formula to obtain the inhibition rate: Inhibition rate % = [(mean value of positive control wells - value of sample wells) / (mean value of positive control wells - mean value of negative control wells)] × 100, where the positive control wells are enzyme reaction wells without compound, and the negative control wells are reaction wells without enzyme addition.

[0348] 2. Curve fitting: A fitting equation analysis was performed for compound concentrations and corresponding inhibition rates using log(inhibitor) vs. response - variable slope (four parameters) in GraphPad Prism 6, and the compound IC was calculated by fitting the curve.50 got the value.

[0349] The fitting formula is Y=Bottom+(Top-Bottom) / (1+10^((LogIC 50 -X)*HillSlope)

[0350] 1.5 Experimental Conclusions:

[0351] [Table 3]

[0352] 1.6 Experimental Conclusions The data in the table show that the compounds of the examples of the present invention have good inhibitory activity against MALT1 enzyme activity.

[0353] Test Example 2: Measurement of the inhibitory effect of the compounds of the present invention on the proliferation of TMD8 and OCI-Ly3 cells 2.1 Experimental Objective: The growth inhibitory effect of the compounds on TMD8 and OCI-Ly3 cells is evaluated by cell growth inhibition experiments.

[0354] 2.2 Laboratory equipment and reagents: device:

[0355] [Table 4] reagent:

[0356] [Table 5]

[0357] 2.3 Experimental Method: The growth inhibitory effects of compounds on TMD8 and OCI-Ly3 cells were detected using the CellTiter-Glo method. The highest concentration of compound detection was 1000 nM, and the compounds were diluted 3-fold to a total of nine concentrations (1000 nM to 0.15 nM). After plating the cells at the appropriate density, compounds were added the next day and incubated for 96 hours before detection using the CellTiter-Glo Luminescent Cell Detection Kit.

[0358] 2.4 Experimental data processing method: 1. Inhibition rate (%): Inhibition rate % = [(mean value of positive control wells - value of sample wells) / (mean value of positive control wells - mean value of negative control wells)] x 100, where the positive control wells are wells without compound and the negative control wells are PBS wells.

[0359] 2. Curve fitting: Using log(inhibitor) vs. response - Variable slope (four parameters) in GraphPad Prism 6, fitting equation analysis was performed for compound concentrations and corresponding inhibition rates, and the compound IC was calculated by fitting the curve. 50 got the value. The fitting formula is Y=Bottom+(Top-Bottom) / (1+10^((LogIC 50 -X)*HillSlope)

[0360] 2.5 Experimental conclusions:

[0361] [Table 6]

[0362] 2.6 Experimental Conclusions The data in the table show that the compounds of the examples of the present invention have good growth inhibitory activity against TMD8 and OCI-Ly3 cells.

[0363] Test example 3: Intracellular MALT1 protease activity detection experiment 3.1 Research purpose: Test compounds for their ability to inhibit MALT1 protease activity in a cellular environment by detecting the shearing level of the substrate BCL-10 by MALT1 in TMD8 cells.

[0364] 3.2 Laboratory equipment and reagents: 3.2.1 Equipment:

[0365] [Table 7] 3.2.2 Reagents:

[0366] [Table 8]

[0367] 3.3 Experimental Method: The content of unsheared BCL-10 protein in cells was detected using a sandwich ELISA to assess the inhibitory effect of compounds on intracellular MALT1 protease activity. The highest compound concentration was 10,000 nM, and three-fold dilutions were performed to obtain a total of nine concentrations (10,000 nM to 1.5 nM). Cells were plated at an appropriate density and first treated with the appropriate compound concentration for 30 minutes. Cells were then stimulated with eBioscience cell stimulation cocktail for 2 hours, after which the cell lysis mixture was harvested. The lysis mixture was added to a detection plate pre-embedded with recombinant BCL-10 antibody (Abcam, #Ab33905) and incubated overnight at 4°C. The following day, a BCL-10 detection antibody (Santacruz, #Sc-5273HRP) was added and inc...

Claims

1. A compound represented by general formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, 【Chemistry 1】 where: Ring A is 【Chemistry 2】 is selected from wherein M 1 is selected from —N— or —C—; M 2 is selected from —C(O)—, —C(S)—, —C(NH)—, —NH—, —N—, —CH 2 —, —CH—, —O— or —S—; M 3 is selected from —N—, —NH—, —CH—, —CH 2 —, —C(O)—, —C(S)— or —C(NH)—; M 4 is selected from —CH—, —CH 2 — or —N—; M 6 is selected from —N—, —CH— or —CH—; M 5 or M 7 is —O—, —N—, —CH—, —CH═CH—, —CH 2 — or absent; and M 8 is selected from —N—, —NH—, —O—, —S— or —CH—; Preferably, M 1 is selected from —N— or —C—, M 2 is selected from —C(O)—, —C(S)—, —C(NH)—, —NH—, —N—, —CH 2 —, —CH—, —O— or —S—, M 3 is selected from —N—, —NH—, —CH—, —C(O)—, —C(S)— or —C(NH)—, M 4 is selected from —CH—, —CH 2 — or —N—, M 6 is selected from —N— or —CH—, M 5 or M 7 is —CH—, —CH 2 — or absent, and M 8 is selected from —NH—, —O—, —S— or —CH—, optionally, ring A is further substituted with 1 to 3 R 4 , and any two R 4 s together with adjacent atoms form a C 3-8 cycloalkyl group, a 3-8 membered heterocyclyl group containing 1 to 2 atoms selected from oxygen, sulfur, or nitrogen, a C 6-10 aryl group, or a 3-8 membered heteroaryl group containing 1 to 2 atoms selected from oxygen, sulfur, or nitrogen; Preferably, ring A is further substituted with 1 to 3 R 4 , and any two R 4 s together with adjacent atoms form a C 3-8 cycloalkyl group, a 3- to 8-membered heterocyclyl group containing 1 to 2 atoms selected from oxygen or nitrogen, a C 6-10 aryl group, or a 3- to 8-membered heteroaryl group containing 1 to 2 atoms selected from oxygen or nitrogen; Preferably, Ring A is 【Transformation 3】 is selected from M 1 is selected from —N— or —C—; M 2 is selected from —C(O)—, —C(S)—, —C(NH)—, —NH—, —N—, —CH 2 —, —CH—, —O— or —S—; M 3 is selected from —N—, —NH—, —CH—, —CH 2 —, —C(O)—, —C(S)— or —C(NH)—; M 4 is selected from —CH—, —CH 2 — or —N—; M 5 is —O—, —N—, —CH—, —CH 2 — or absent; Preferably, M 1 is selected from —N— or —C—, M 2 is selected from —C(O)—, —C(S)—, —C(NH)—, —NH—, —N—, —CH 2 —, —CH—, —O— or —S—, M 3 is selected from —N—, —NH—, —CH—, —C(O)—, —C(S)— or —C(NH)—, M 4 is selected from —CH—, —CH 2 — or —N—, and M 5 is —CH—, —CH 2 — or absent; Or, ring A is 【Chemistry 4】 is selected from M 1 is selected from —N— or —C—; M 2 is selected from —C(O)—, —C(S)—, —C(NH)—, —NH—, —N— or —CH—; M 3 is selected from —CH— or —N—; M 4 is selected from —NH— or —CH—; M 6 is selected from —NH— or —CH—; and M 8 is selected from —S— or —CH—; optionally, ring A is further substituted with 1 to 2 R 4 , and any two R 4 s together with adjacent atoms form a C 3-6 cycloalkyl group, or a 3- to 6-membered heterocyclyl group containing 1 to 2 atoms selected from oxygen or nitrogen; More preferably, Ring A is 【Transformation 5】 is selected from M 1 is selected from —N— or —C—; M 2 is selected from —C(O)—, —C(S)—, —C(NH)—, —NH—, —N—, —CH 2 —, —CH—, —O— or —S—; M 3 is selected from —N—, —NH—, —CH—, —C(O)—, —C(S)— or —C(NH)—; optionally, ring A is further substituted with 1 to 2 R 4 , and any two R 4 s together with adjacent atoms form a C 3-6 cycloalkyl group, or a 3- to 6-membered heterocyclyl group containing 1 to 2 atoms selected from oxygen or nitrogen; More preferably, ring A is one of the following groups: 【Transformation 6】 is selected from Ring B is selected from a cycloalkyl group, a heterocyclyl group, an aryl group, or a heteroaryl group, wherein said cycloalkyl group, heterocyclyl group, aryl group, or heteroaryl group may optionally be further substituted; R １ are independently hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, alkyl group, alkenyl group, alkynyl group, deuterated alkyl group, halogenated alkyl group, alkoxy group, halogenated alkoxy group, hydroxyalkyl group, cycloalkyl group, cycloalkoxy group, heterocyclyl group, aryl group, heteroaryl group, -CR ｃｃ =CR ｄｄ (CH ２ ) ｎ R ａａ , -CR ｃｃ =CR ｄｄ (CH ２ ) ｎ NR ａａ R ｂｂ , -CR ｃｃ =CR ｄｄ (CH ２ ) ｎ NR ｅｅ C(O)R ａａ , -CR ｃｃ =CR ｄｄ (CH ２ ) ｎ NR ｅｅ C(O)NR ａａ R ｂｂ , -O(CH ２ ) ｎ R ｃｃ , -OC(R ａａ R ｂｂ ) ｎ (CH ２ ) ｍ R ｃｃ , -NR ｅｅ (CH ２ ) ｎ R ｃｃ , -(CH ２ ) ｎ -, -(CH ２ ) ｎ R ｃｃ , -(CH ２ ) ｎ OR ｃｃ , -(CH ２ ) ｎ SR ｃｃ , -(CH ２ ) ｎ C(O)R ｃｃ , -(CH ２ ) ｎ C (=NR ｅｅ ) R ｃｃ , -(CH ２ ) ｎ C(O)OR ｃｃ , -(CH ２ ) ｎ S (O) ｍ R ｃｃ , -(CH ２ ) ｎ NR ａａ R ｂｂ , -(CH ２ ) ｎ C(O)NR ａａ R ｂｂ , -(CH ２ ) ｎ NR ｅｅ C(O)R ｃｃ , -(CH ２ ) ｎ N=S(O)R ｃｃ R ｅｅ or -(CH ２ ) ｎ NR ｅｅ S (O) ｍ R ｃｃ wherein the alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl groups may optionally be further substituted; Preferably, R １ are independently hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, alkyl group, alkenyl group, alkynyl group, deuterated alkyl group, halogenated alkyl group, alkoxy group, halogenated alkoxy group, hydroxyalkyl group, cycloalkyl group, cycloalkoxy group, heterocyclyl group, aryl group, heteroaryl group, -CR ｃｃ =CR ｄｄ (CH ２ ) ｎ R ａａ , -CR ｃｃ =CR ｄｄ (CH ２ ) ｎ NR ａａ R ｂｂ , -CR ｃｃ =CR ｄｄ (CH ２ ) ｎ NR ｅｅ C(O)R ａａ , -CR ｃｃ =CR ｄｄ (CH ２ ) ｎ NR ｅｅ C(O)NR ａａ R ｂｂ , -O(CH ２ ) ｎ R ｃｃ , -OC(R ａａ R ｂｂ ) ｎ (CH ２ ) ｍ R ｃｃ , -NR ｅｅ (CH ２ ) ｎ R ｃｃ , -(CH ２ ) ｎ -, -(CH ２ ) ｎ R ｃｃ , -(CH ２ ) ｎ OR ｃｃ , -(CH ２ ) ｎ SR ｃｃ , -(CH ２ ) ｎ C(O)R ｃｃ , -(CH ２ ) ｎ C (=NR ｅｅ ) R ｃｃ , -(CH ２ ) ｎ C(O)OR ｃｃ , -(CH ２ ) ｎ S (O) ｍ R ｃｃ , -(CH ２ ) ｎ NR ａａ R ｂｂ , -(CH ２ ) ｎ C(O)NR ａａ R ｂｂ , -(CH ２ ) ｎ NR ｅｅ C(O)R ｃｃ or -(CH ２ ) ｎ NR ｅｅ S (O) ｍ R ｃｃ wherein the alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl groups may optionally be further substituted; R ２ is selected from hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 alkyl group, C 2-6 alkenyl group, C 2-6 alkynyl group, C 1-6 deuterated alkyl group, C 1-6 halogenated alkyl group, C 1-6 alkoxy group, C 1-6 halogenated alkoxy group, C 1-6 hydroxyalkyl group, cyano-substituted C 1-6 alkyl group, C 3-12 cycloalkyl group, 3- to 12-membered heterocyclyl group, C 6-12 aryl group, and 5- to 12-membered heteroaryl group, and the alkyl group, the C 3-12 cycloalkyl group, the 3- to 12-membered heterocyclyl group, the C 6-12 aryl group and the 5- to 12-membered heteroaryl group are optionally substituted by one or more substituents selected from the group consisting of deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 alkyl group, C 2-6 alkenyl group, C 2-6 alkynyl group, oxo group, thio group, C 1-6 deuterated alkyl group, C 1-6 halogenated alkyl group, C 1-6 alkoxy group, C 1-6 halogenated alkoxy group, C 1-6 hydroxyalkyl group, cyano-substituted C 1-6 alkyl group, C 3-12 cycloalkyl group, the 3- to 12-membered heterocyclyl group, the C 6-12 aryl group and the 5- to 12-membered heteroaryl group; Preferably, the alkyl group is selected from hydrogen, deuterium, halogen, a C 1-3 alkyl group, a C 1-3 deuterated alkyl group, a C 1-3 halogenated alkyl group, a C 1-3 alkoxy group, a C 1-3 hydroxyalkyl group, a 3- to 12-membered heterocyclyl group, or a 5- to 12-membered heteroaryl group, wherein the C 1-3 alkyl group, C 1-3 alkoxy group, C 1-3 hydroxyalkyl group, a 3- to 12-membered heterocyclyl group, or a 5- to 12-membered heteroaryl group may optionally further comprise deuterium, halogen, amino group, nitro group, hydroxy group, cyano group, oxo group, a C 1-3 alkyl group, a C 1-3 deuterated alkyl group, a C 1-3 halogenated alkyl group, a C 1-3 alkoxy group, a C 1-3 hydroxyalkyl group, a C 1-3 halogenated alkoxy group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 3-8 substituted by one or more substituents selected from the group consisting of a cycloalkyl group, a 3- to 12-membered heterocyclyl group, a C 6-12 aryl group and a 5- to 12-membered heteroaryl group; More preferably, it is hydrogen, deuterium, fluorine, chlorine, bromine, a methyl group, an ethyl group, a trifluoromethyl group, or a cyclopropyl group. R ３ is selected from hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 alkyl group, C 2-6 alkenyl group, C 2-6 alkynyl group, C 1-6 deuterated alkyl group, C 1-6 halogenated alkyl group, C 1-6 alkoxy group, C 1-6 halogenated alkoxy group, C 1-6 hydroxyalkyl group, cyano-substituted C 1-6 alkyl group, C 3-12 cycloalkyl group, 3- to 12-membered heterocyclyl group, C 6-12 aryl group, and 5- to 12-membered heteroaryl group, and the alkyl group, the C 3-12 cycloalkyl group, the 3- to 12-membered heterocyclyl group, the C 6-12 aryl group and the 5- to 12-membered heteroaryl group are optionally substituted by one or more substituents selected from the group consisting of deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-6 alkyl group, C 2-6 alkenyl group, C 2-6 alkynyl group, oxo group, thio group, C 1-6 deuterated alkyl group, C 1-6 halogenated alkyl group, C 1-6 alkoxy group, C 1-6 halogenated alkoxy group, C 1-6 hydroxyalkyl group, cyano-substituted C 1-6 alkyl group, C 3-12 cycloalkyl group, the 3- to 12-membered heterocyclyl group, the C 6-12 aryl group and the 5- to 12-membered heteroaryl group; Preferably, the alkyl group is selected from hydrogen, deuterium, halogen, a C 1-3 alkyl group, a C 1-3 deuterated alkyl group, a C 1-3 halogenated alkyl group, a C 1-3 alkoxy group, a C 1-3 hydroxyalkyl group, a 3- to 12-membered heterocyclyl group, or a 5- to 12-membered heteroaryl group, wherein the C 1-3 alkyl group, C 1-3 alkoxy group, C 1-3 hydroxyalkyl group, a 3- to 12-membered heterocyclyl group, or a 5- to 12-membered heteroaryl group may optionally further comprise deuterium, halogen, amino group, nitro group, hydroxy group, cyano group, oxo group, a C 1-3 alkyl group, a C 1-3 deuterated alkyl group, a C 1-3 halogenated alkyl group, a C 1-3 alkoxy group, a C 1-3 hydroxyalkyl group, a C 1-3 halogenated alkoxy group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 3-8 substituted by one or more substituents selected from the group consisting of a cycloalkyl group, a 3- to 12-membered heterocyclyl group, a C 6-12 aryl group and a 5- to 12-membered heteroaryl group; More preferably, it is hydrogen, deuterium, fluorine, chlorine, bromine, a methyl group, an ethyl group, or a trifluoromethyl group. R ４ are independently hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, alkyl group, alkenyl group, alkynyl group, oxo group, thio group, deuterated alkyl group, halogenated alkyl group, alkoxy group, halogenated alkoxy group, hydroxyalkyl group, cyano-substituted alkyl group, cycloalkyl group, heterocyclyl group, aryl group, heteroaryl group, -CR ３３ =CR ４４ (CH ２ ) ｐ R １１ , -CR ３３ =CR ４４ (CH ２ ) ｐ NR １１ R ２２ , -CR ３３ =CR ４４ (CH ２ ) ｐ NR ５５ C(O)R １１ , -CR ３３ =CR ４４ (CH ２ ) ｐ NR ５５ C(O)NR １１ R ２２ , -O(CH ２ ) ｐ R ３３ , -OC(R １１ R ２２ ) ｑ (CH ２ ) ｐ R ３３ , -NR ５５ (CH ２ ) ｐ R ３３ , -(CH ２ ) ｐ -, -(CH ２ ) ｐ R ３３ , -(CH ２ ) ｐ OR ３３ , -(CH ２ ) ｐ SR ３３ , -(CH ２ ) ｐ C(O)R ３３ , -(CH ２ ) ｐ C (=NR ５５ ) R ３３ , -(CH ２ ) ｐ C(O)OR ３３ , -(CH ２ ) ｐ S (O) ｑ R ３３ , -(CH ２ ) ｐ NR １１ R ２２ , -(CH ２ ) ｐ C(O)NR １１ R ２２ , -(CH ２ ) ｐ NR ５５ C(O)R ３３ or -(CH ２ ) ｐ NR ５５ S (O) ｑ R ３３ wherein the alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl groups may optionally be further substituted; Or, any two adjacent or non-adjacent R ４ are linked to adjacent atoms to form a cycloalkyl, heterocyclyl, aryl or heteroaryl group, wherein the cycloalkyl, heterocyclyl, aryl or heteroaryl group is optionally further substituted; R ａａ and R ｂｂ are each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups, and the amino, alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups may optionally be further substituted; Or, R ａａ and R ｂｂ together with the adjacent atom(s) form a cycloalkyl group, a heterocyclyl group, an aryl group, or a heteroaryl group, which cycloalkyl group, heterocyclyl group, aryl group, and heteroaryl group may optionally be further substituted; R ｃｃ , R ｄｄ and R ｅｅ are each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups, and the amino, alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups may optionally be further substituted; R １１ and R ２２ are each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups, and the amino, alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups may optionally be further substituted; Or, R １１ and R ２２ together with the adjacent atom(s) form a cycloalkyl group, a heterocyclyl group, an aryl group, or a heteroaryl group, which cycloalkyl group, heterocyclyl group, aryl group, and heteroaryl group may optionally be further substituted; R ３３ , R ４４ and R ５５ are each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups, and the amino, alkyl, alkenyl, alkynyl, deuterated alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups may optionally be further substituted; m is 0, 1, 2 or 3; n is 0, 1, 2 or 3; p is 0, 1, 2 or 3; q is 0, 1, 2 or 3; x is 0, 1, 2, 3 or 4, and A compound, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein y is an integer from 0 to 6.

2. Furthermore, it is as shown in general formula (IA), 【Transformation 7】 where: Ring B is C ３－１２ Cycloalkyl group, 3- to 14-membered heterocyclyl group, C ６－１４ selected from an aryl group or a 5- to 14-membered heteroaryl group; Preferably, ring B is C ６－１２ an aryl group or a 5- to 14-membered heteroaryl group containing 1 to 3 nitrogen, oxygen and / or sulfur atoms; More preferably, Ring B is selected from a phenyl group, a 5- to 7-membered nitrogen-containing heteroaryl group, a benzo 5- to 7-membered nitrogen-containing heteroaryl group, a 5- to 7-membered nitrogen-containing heteroarylphenyl group, a 5- to 7-membered heteroaryl-fused 5- to 7-membered heteroaryl group, or a tricyclic heteroaryl group; Even more preferably, Ring B is selected from a phenyl group, a pyridyl group, or a pyridazinyl group; Ring C is C ３－６ selected from a cycloalkyl group, a 3- to 8-membered heterocyclyl group, or a 5- to 8-membered heteroaryl group; Preferably, C ５－６ a cycloalkyl group or a 5- or 6-membered heterocyclyl group; More preferably, it is a cyclopentyl group, a cyclohexyl group, a 5-membered heterocyclyl group containing 1 to 3 nitrogen atoms, oxygen atoms and / or sulfur atoms, or a 6-membered heterocyclyl group containing 1 to 3 nitrogen atoms, oxygen atoms and / or sulfur atoms. Ring F is C ３－６ Cycloalkyl group, 3- to 8-membered heterocyclyl group, C ６－１２ selected from an aryl group or a 5- to 12-membered heteroaryl group; Preferably, C ５－６ Cycloalkyl groups, 5-6 membered heterocyclyl groups, C ６－８ an aryl group or a 5- to 8-membered heteroaryl group; Ring Q is C ３－６ Cycloalkyl group, 3- to 8-membered heterocyclyl group, C ６－１２ selected from an aryl group or a 5- to 12-membered heteroaryl group; Preferably, C ５－６ Cycloalkyl groups, 5-6 membered heterocyclyl groups, C ６－８ an aryl group or a 5- to 8-membered heteroaryl group; R １ are independently hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, cyano-substituted C １－６ Alkyl group, C ３－１２ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ an aryl group, a 5- to 12-membered heteroaryl group, —CR ｃｃ =CR ｄｄ (CH ２ ) ｎ R ａａ , -CR ｃｃ =CR ｄｄ (CH ２ ) ｎ NR ａａ R ｂｂ , -CR ｃｃ =CR ｄｄ (CH ２ ) ｎ NR ｅｅ C(O)R ａａ , -CR ｃｃ =CR ｄｄ (CH ２ ) ｎ NR ｅｅ C(O)NR ａａ R ｂｂ , -O(CH ２ ) ｎ R ｃｃ , -OC(R ａａ R ｂｂ ) ｎ (CH ２ ) ｍ R ｃｃ , -NR ｅｅ (CH ２ ) ｎ R ｃｃ , -(CH ２ ) ｎ -, -(CH ２ ) ｎ R ｃｃ , -(CH ２ ) ｎ OR ｃｃ , -(CH ２ ) ｎ SR ｃｃ , -(CH ２ ) ｎ C(O)R ｃｃ , -(CH ２ ) ｎ C (=NR ｅｅ ) R ｃｃ , -(CH ２ ) ｎ C(O)OR ｃｃ , -(CH ２ ) ｎ S (O) ｍ R ｃｃ , -(CH ２ ) ｎ NR ａａ R ｂｂ , -(CH ２ ) ｎ C(O)NR ａａ R ｂｂ , -(CH ２ ) ｎ NR ｅｅ C(O)R ｃｃ , -(CH ２ ) ｎ N=S(O)R ｃｃ R ｅｅ or -(CH ２ ) ｎ NR ｅｅ S (O) ｍ R ｃｃ wherein the amino group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, cyano-substituted C １－６ Alkyl group, C ３－１２ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ The aryl and 5- to 12-membered heteroaryl groups may optionally be substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, oxo group, thio group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, cyano-substituted C １－６ Alkyl group, C ３－１２ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ substituted with one or more substituents selected from aryl and 5- to 12-membered heteroaryl groups; R ２ represents hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, C ３－８ Cycloalkyl group, 3- to 14-membered heterocyclyl group, C ６－１４ selected from an aryl group or a 5- to 14-membered heteroaryl group; R ３ represents hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, C ３－８ Cycloalkyl group, 3- to 14-membered heterocyclyl group, C ６－１４ selected from an aryl group or a 5- to 14-membered heteroaryl group; R ５ represents hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, oxo group, thio group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, cyano-substituted C １－６ Alkyl group, C ３－８ Cycloalkyl group, 3- to 14-membered heterocyclyl group, C ６－１４ an aryl group, a 5- to 14-membered heteroaryl group, —(CH ２ ) ｎ２ C(O)R ａ , -(CH ２ ) ｎ２ C(O)OR ａ , -(CH ２ ) ｎ２ OR ａ , -(CH ２ ) ｎ２ R ａ or -(CH ２ ) ｎ２ S (O) ｍ２ R ａ wherein the amino group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, cyano-substituted C １－６ Alkyl group, C ３－８ Cycloalkyl group, 3- to 14-membered heterocyclyl group, C ６－１４ The aryl and 5- to 14-membered heteroaryl groups may optionally be substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, oxo group, thio group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, cyano-substituted C １－６ Alkyl group, C ３－８ Cycloalkyl group, 3- to 14-membered heterocyclyl group, C ６－１４ substituted with one or more substituents selected from aryl and 5- to 14-membered heteroaryl groups; Preferably R ５ represents hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C １－３ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, oxo group, thio group, C １－３ Deuterated alkyl groups, C １－３ Halogenated alkyl group, C １－３ Alkoxy group, C １－３ Halogenated alkoxy group, C １－３ Hydroxyalkyl group, cyano-substituted C １－３ Alkyl group, C ３－６ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ an aryl group, a 5- to 12-membered heteroaryl group, —(CH ２ ) ｎ２ C(O)R ａ , -(CH ２ ) ｎ２ C(O)OR ａ , -(CH ２ ) ｎ２ OR ａ , -(CH ２ ) ｎ２ R ａ or -(CH ２ ) ｎ２ S (O) ｍ２ R ａ wherein the amino group, C １－３ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C １－３ Deuterated alkyl groups, C １－３ Halogenated alkyl group, C １－３ Alkoxy group, C １－３ Halogenated alkoxy group, C １－３ Hydroxyalkyl group, cyano-substituted C １－３ Alkyl group, C ３－６ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ The aryl and 5- to 12-membered heteroaryl groups may optionally be substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C １－３ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, oxo group, thio group, C １－３ Deuterated alkyl groups, C １－３ Halogenated alkyl group, C １－３ Alkoxy group, C １－３ Halogenated alkoxy group, C １－３ Hydroxyalkyl group, cyano-substituted C １－３ Alkyl group, C ３－６ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ substituted with one or more substituents selected from aryl and 5- to 12-membered heteroaryl groups; R ａ represents hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C １－３ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C １－３ Deuterated alkyl groups, C １－３ Halogenated alkyl group, C １－３ Alkoxy group, C １－３ Halogenated alkoxy group, C １－３ Hydroxyalkyl group, cyano-substituted C １－３ Alkyl group, C ３－６ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ an aryl group or a 5- to 12-membered heteroaryl group, １－３ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C １－３ Deuterated alkyl groups, C １－３ Halogenated alkyl group, C １－３ Alkoxy group, C １－３ Halogenated alkoxy group, C １－３ Hydroxyalkyl group, cyano-substituted C １－３ Alkyl group, C ３－６ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ The aryl and 5- to 12-membered heteroaryl groups may optionally be substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C １－３ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, oxo group, thio group, C １－３ Deuterated alkyl groups, C １－３ Halogenated alkyl group, C １－３ Alkoxy group, C １－３ Halogenated alkoxy group, C １－３ Hydroxyalkyl group, cyano-substituted C １－３ Alkyl group, C ３－６ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ substituted with one or more substituents selected from aryl and 5- to 12-membered heteroaryl groups; R ａａ and R ｂｂ are each independently hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, cyano-substituted C １－６ Alkyl group, C ３－１２ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ aryl or 5- to 12-membered heteroaryl groups, optionally containing deuterium, halogen, amino, hydroxy, cyano, nitro, C １－６ Alkyl group, C ３－１２ cycloalkyl groups, —O(CH ２ ) ｎ１ R ｃ１ , -OC(R ａ１ R ｂ１ ) ｍ１ (CH ２ ) ｎ１ R ｃ１ , -NR ａ１ (CH ２ ) ｎ１ R ｃ１ , -(CH ２ ) ｎ１ -, -(CH ２ ) ｎ１ R ｃ１ , -(CH ２ ) ｎ１ OR ｃ１ , -(CH ２ ) ｎ１ SR ｃ１ , -(CH ２ ) ｎ１ C(O)R ｃ１ , -(CH ２ ) ｎ１ C(O)OR ｃ１ , -(CH ２ ) ｎ１ S (O) ｍ１ R ｃ１ , -(CH ２ ) ｎ１ NR ａ１ R ｂ１ , -(CH ２ ) ｎ１ C(O)NR ａ１ R ｂ１ , -(CH ２ ) ｎ１ NR ａ１ C(O)R ｃ１ and-(CH ２ ) ｎ１ NR ａ１ S (O) ｍ１ R ｃ１ and substituted with one or more substituents of Or, R ａａ and R ｂｂ together with the adjacent atoms, C ３－１２ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ an aryl group or a 5- to 12-membered heteroaryl group, ３－１２ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ and an aryl group to form a 5- to 12-membered heteroaryl group, optionally containing deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, cyano-substituted C １－６ Alkyl group, C ３－１２ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ an aryl group, a 5- to 12-membered heteroaryl group, —O(CH ２ ) ｎ１ R ｃ１ , -OC(R ａ１ R ｂ１ ) ｎ１ (CH ２ ) ｍ１ R ｃ１ , -NR ａ１ (CH ２ ) ｎ１ R ｃ１ , -(CH ２ ) ｎ１ -, -(CH ２ ) ｎ１ R ｃ１ , -(CH ２ ) ｎ１ OR ｃ１ , -(CH ２ ) ｎ１ SR ｃ１ , -(CH ２ ) ｎ１ C(O)R ｃ１ , -(CH ２ ) ｎ１ C(O)OR ｃ１ , -(CH ２ ) ｎ１ S (O) ｍ R ｃ１ , -(CH ２ ) ｎ１ NR ａ１ R ｂ１ , -(CH ２ ) ｎ１ C(O)NR ａ１ R ｂ１ , -(CH ２ ) ｎ１ NR ａ１ C(O)R ｃ１ and-(CH ２ ) ｎ１ NR ａ１ S (O) ｍ１ R ｃ１ and is substituted with one or more substituents selected from the group consisting of R ｃｃ represents hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, cyano-substituted C １－６ Alkyl group, C ３－１２ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ aryl or 5- to 12-membered heteroaryl groups, optionally containing deuterium, halogen, amino, hydroxy, cyano, nitro, C １－６ Alkyl group, C ３－１２ cycloalkyl groups, —O(CH ２ ) ｎ１ R ｃ１ , -OC(R ａ１ R ｂ１ ) ｎ１ (CH ２ ) ｍ R ｃ１ , -NR ａ１ (CH ２ ) ｎ１ R ｃ１ , -(CH ２ ) ｎ１ -, -(CH ２ ) ｎ１ R ｃ１ , -(CH ２ ) ｎ１ OR ｃ１ , -(CH ２ ) ｎ１ SR ｃ１ , -(CH ２ ) ｎ１ C(O)R ｃ１ , -(CH ２ ) ｎ１ C(O)OR ｃ１ , -(CH ２ ) ｎ１ S (O) ｍ R ｃ１ , -(CH ２ ) ｎ１ NR ａ１ R ｂ１ , -(CH ２ ) ｎ１ C(O)NR ａ１ R ｂ１ , -(CH ２ ) ｎ１ NR ａ１ C(O)R ｃ１ and-(CH ２ ) ｎ１ NR ａ１ S (O) ｍ１ R ｃ１ and substituted with one or more substituents of R ａ１ , R ｂ１ and R ｃ１ are each independently hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, cyano-substituted C １－６ Alkyl group, C ３－１２ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ aryl or 5- to 12-membered heteroaryl groups, optionally containing deuterium, halogen, amino, hydroxy, cyano, nitro, C １－６ Alkyl group and C ３－１２ substituted with one or more substituents of a cycloalkyl group; m is 0, 1, 2 or 3; m1 is 0, 1, 2 or 3; m2 is selected from 1 or 2; n is 0, 1, 2 or 3; n1 is 0, 1, 2 or 3; n2 is selected from 0, 1, 2 or 3; x is selected from 0, 1, 2, 3 or 4, and z is selected from 0, 1, 2 or 3; Preferably, Further, as shown in general formula (III), 【Transformation 8】 where: M a , M b , M c or M d are each independently selected from —N—, —NH— or —CH—; Ring C is selected from a phenyl group, a C 3-6 cycloalkyl group, a 5- to 7-membered heterocyclyl group, or a 5- to 7-membered heteroaryl group; Preferably, it is a 5-membered heterocyclyl group containing 1 to 3 nitrogen atoms and / or 1 to 2 oxygen atoms, a 6-membered heterocyclyl group containing 1 to 3 nitrogen atoms and / or 1 to 2 oxygen atoms, a 5-membered heteroaryl group containing 1 to 3 nitrogen atoms, or a 6-membered heteroaryl group containing 1 to 3 nitrogen atoms; R 2 is selected from hydrogen, deuterium, halogen, an amino group, a hydroxy group, a cyano group, a nitro group, a C 1-3 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 1-3 deuterated alkyl group, a C 1-3 halogenated alkyl group, a C 1-3 alkoxy group, a C 1-3 halogenated alkoxy group, a C 1-3 hydroxyalkyl group, a C 3-6 cycloalkyl group, a 3- to 12-membered heterocyclyl group, a C 6-12 aryl group or a 5- to 12-membered heteroaryl group; R 5 is selected from hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-3 alkyl group, C 2-6 alkenyl group, C 2-6 alkynyl group, oxo group, thio group, C 1-3 deuterated alkyl group, C 1-3 halogenated alkyl group, C 1-3 alkoxy group, C 1-3 halogenated alkoxy group, C 1-3 hydroxyalkyl group, cyano-substituted C 1-3 alkyl group, C 3-6 cycloalkyl group, 3- to 12-membered heterocyclyl group, C 6-12 aryl group or 5- to 12-membered heteroaryl group, and the amino group, C 1-3 alkyl group, C 2-6 alkenyl group, C 2-6 alkynyl group, C 1-3 deuterated alkyl group, C 1-3 halogenated alkyl group, C 1-3 alkoxy group, C 1-3 halogenated alkoxy group, C 1-3 hydroxyalkyl group, cyano-substituted C 1-3 alkyl group, C 3-6 cycloalkyl group, 3- to 12-membered heterocyclyl group, C 6-12 aryl group or 5- to 12-membered heteroaryl group. the hydroxyalkyl group, cyano-substituted C 1-3 alkyl group, C 3-6 cycloalkyl group, 3- to 12-membered heterocyclyl group, C 6-12 aryl group and 5- to 12-membered heteroaryl group are optionally substituted by one or more substituents selected from the group consisting of deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C 1-3 alkyl group, C 2-6 alkenyl group, C 2-6 alkynyl group, oxo group, thio group, C 1-3 deuterated alkyl group, C 1-3 halogenated alkyl group, C 1-3 alkoxy group, C 1-3 halogenated alkoxy group, C 1-3 hydroxyalkyl group, cyano-substituted C 1-3 alkyl group, C 3-6 cycloalkyl group, 3- to 12-membered heterocyclyl group, C 6-12 aryl group and 5- to 12-membered heteroaryl group; R 5 is preferably selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxy, cyano, nitro, methyl, ethyl, propyl, isopropyl, oxo, methoxy, ethoxy, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, cyclopropyl or cyclobutyl; 2. The compound of claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, wherein z is selected from 0, 1, 2 or 3.

3. Ring B is C ３－１２ Cycloalkyl group, 3- to 14-membered heterocyclyl group, C ６－１４ selected from an aryl group or a 5- to 14-membered heteroaryl group; Preferably, ring B is C ６－１２ an aryl group, or a 5- to 14-membered heteroaryl group containing 1 to 3 nitrogen atoms, 1 oxygen atom, and / or 1 sulfur atom; More preferably, Ring B is selected from a phenyl group, a 5- to 7-membered nitrogen-containing heteroaryl group, a benzo 5- to 7-membered nitrogen-containing heteroaryl group, a 5- to 7-membered nitrogen-containing heteroarylphenyl group, a 5- to 7-membered heteroaryl-fused 5- to 7-membered heteroaryl group, or a tricyclic heteroaryl group; Even more preferably, the compound, its stereoisomer or its pharmaceutically acceptable salt according to claim 1, wherein ring B is selected from a phenyl group, a pyridyl group or a pyridazinyl group.

4. Further, as shown in general formula (IV) or (V), 【Chemistry 9】 Ring D is selected from a phenyl group, a 5-membered heteroaryl group, or a 6-membered heteroaryl group; Preferably, it is a phenyl group, a 5-membered heteroaryl group containing 1 to 3 nitrogen atoms, or a 6-membered heteroaryl group containing 1 to 3 nitrogen atoms; More preferably, it is a phenyl group, a pyridyl group, a pyrimidinyl group, or a pyridazinyl group. Ring E is a phenyl group, C ３－６ selected from a cycloalkyl group, a 5- to 7-membered heterocyclyl group, or a 5- to 7-membered heteroaryl group; Preferably, a phenyl group, C ５－６ a cycloalkyl group, a 5-membered heterocyclyl group containing 1 to 3 nitrogen atoms and / or 1 to 2 oxygen atoms, a 6-membered heterocyclyl group containing 1 to 3 nitrogen atoms and / or 1 to 2 oxygen atoms, a 5-membered heteroaryl group containing 1 to 3 nitrogen atoms, or a 6-membered heteroaryl group containing 1 to 3 nitrogen atoms; More preferably, it is a phenyl group, a cyclopentyl group, a cyclohexyl group, a pyrrolyl group, a pyrazolyl group, an imidazolyl group, a triazolyl group, a pyridyl group, a pyrimidinyl group, a pyridazinyl group, or a pyrazinyl group, Preferably, Further, it is as shown in general formula (IV-A) or (VA), 【Chemistry 10】 where: The compound, its stereoisomer or pharmaceutically acceptable salt thereof according to claim 2, wherein M a , M c , M e , M f or M g is each independently selected from -N- or -CH-.

5. Further, it is as shown in general formula (IV-B) or (IV-C), 【Chemistry 11】 where: M ａ is selected from —N— or —CH—; M ｃ is selected from —N— or —CH—; R ６ is selected from a 3- to 7-membered heterocyclyl group or a 5- to 7-membered heteroaryl group, and the 3- to 7-membered heterocyclyl group and the 5- to 7-membered heteroaryl group may optionally further comprise deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, oxo group, thio group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, cyano-substituted C １－６ Alkyl group, C ３－１２ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ substituted with one or more substituents selected from aryl and 5- to 12-membered heteroaryl groups; Preferably, R ６ is selected from a 4-membered heterocyclyl group, a 5-membered heterocyclyl group, a 6-membered heterocyclyl group, or a 5-membered heteroaryl group, and the 4-membered heterocyclyl group, the 5-membered heterocyclyl group, the 6-membered heterocyclyl group, and the 5-membered heteroaryl group may optionally further comprise deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C １－３ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, oxo group, thio group, C １－３ Deuterated alkyl groups, C １－３ Halogenated alkyl group, C １－３ Alkoxy group, C １－３ Halogenated alkoxy group, C １－３ Hydroxyalkyl group, cyano-substituted C １－３ Alkyl group, C ３－６ Cycloalkyl group, 3- to 8-membered heterocyclyl group, C ６－１０ substituted with one or more substituents selected from aryl and 5- to 8-membered heteroaryl groups; More preferably, R ６ teeth, 【Chemistry 12】 3. The compound according to claim 2, its stereoisomer or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of: optionally further substituted with one or more substituents selected from the group consisting of deuterium, fluorine, chlorine, bromine, amino, hydroxy, cyano, nitro, methyl, ethyl, oxo, thio, difluoromethyl, trifluoromethyl, methoxy, ethoxy and trifluoromethoxy.

6. Ring C is 【Chemistry 13】 is selected from Preferably, ring C is 【Chemistry 14】 3. The compound according to claim 2, its stereoisomer or a pharmaceutically acceptable salt thereof, selected from:

7. The compound is further represented by general formula (VI): 【Chemistry 15】 R ７ represents hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C １－３ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C １－３ Deuterated alkyl groups, C １－３ Halogenated alkyl group, C １－３ Alkoxy group, C １－３ Halogenated alkoxy group, C １－３ Hydroxyalkyl group, cyano-substituted C １－３ Alkyl group, C ３－６ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ an aryl group, a 5- to 12-membered heteroaryl group, —(CH ２ ) ｎ２ C(O)R ａ , -(CH ２ ) ｎ２ C(O)OR ａ , -(CH ２ ) ｎ２ OR ａ , -(CH ２ ) ｎ２ R ａ or -(CH ２ ) ｎ２ S (O) ｍ２ R ａ wherein the amino group, C １－３ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C １－３ Deuterated alkyl groups, C １－３ Halogenated alkyl group, C １－３ Alkoxy group, C １－３ Halogenated alkoxy group, C １－３ Hydroxyalkyl group, cyano-substituted C １－３ Alkyl group, C ３－６ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ The aryl and 5- to 12-membered heteroaryl groups may optionally be substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C １－３ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, oxo group, thio group, C １－３ Deuterated alkyl groups, C １－３ Halogenated alkyl group, C １－３ Alkoxy group, C １－３ Halogenated alkoxy group, C １－３ Hydroxyalkyl group, cyano-substituted C １－３ Alkyl group, C ３－６ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ substituted with one or more substituents selected from aryl and 5- to 12-membered heteroaryl groups; R ７ is preferably selected from hydrogen, deuterium, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, cyclopropyl, cyclobutyl, benzyl or p-methoxybenzyl; R ａ represents hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C １－３ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C １－３ Deuterated alkyl groups, C １－３ Halogenated alkyl group, C １－３ Alkoxy group, C １－３ Halogenated alkoxy group, C １－３ Hydroxyalkyl group, cyano-substituted C １－３ Alkyl group, C ３－６ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ an aryl group or a 5- to 12-membered heteroaryl group, １－３ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C １－３ Deuterated alkyl groups, C １－３ Halogenated alkyl group, C １－３ Alkoxy group, C １－３ Halogenated alkoxy group, C １－３ Hydroxyalkyl group, cyano-substituted C １－３ Alkyl group, C ３－６ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ The aryl and 5- to 12-membered heteroaryl groups may optionally be substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C １－３ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, oxo group, thio group, C １－３ Deuterated alkyl groups, C １－３ Halogenated alkyl group, C １－３ Alkoxy group, C １－３ Halogenated alkoxy group, C １－３ Hydroxyalkyl group, cyano-substituted C １－３ Alkyl group, C ３－６ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ substituted with one or more substituents selected from aryl and 5- to 12-membered heteroaryl groups; n2 is selected from 0, 1, 2 or 3; 3. The compound according to claim 2, its stereoisomer or a pharmaceutically acceptable salt thereof, wherein m2 is selected from 1 or 2.

8. The compounds may further be represented by the general formula (VI-A), (VI-B), (VI-C), (VI-D), (VI-E), (VI-F) or (VI-G): 【Chemistry 16】 3. The compound according to claim 2, its stereoisomer or a pharmaceutically acceptable salt thereof, wherein:

9. R １ are independently hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, cyano-substituted C １－６ Alkyl group, C ３－１２ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ an aryl group, a 5- to 12-membered heteroaryl group, —CR ｃｃ =CR ｄｄ (CH ２ ) ｎ R ａａ , -CR ｃｃ =CR ｄｄ (CH ２ ) ｎ NR ａａ R ｂｂ , -CR ｃｃ =CR ｄｄ (CH ２ ) ｎ NR ｅｅ C(O)R ａａ , -CR ｃｃ =CR ｄｄ (CH ２ ) ｎ NR ｅｅ C(O)NR ａａ R ｂｂ , -O(CH ２ ) ｎ R ｃｃ , -OC(R ａａ R ｂｂ ) ｎ (CH ２ ) ｍ R ｃｃ , -NR ｅｅ (CH ２ ) ｎ R ｃｃ , -(CH ２ ) ｎ -, -(CH ２ ) ｎ R ｃｃ , -(CH ２ ) ｎ OR ｃｃ , -(CH ２ ) ｎ SR ｃｃ , -(CH ２ ) ｎ C(O)R ｃｃ , -(CH ２ ) ｎ C (=NR ｅｅ ) R ｃｃ , -(CH ２ ) ｎ C(O)OR ｃｃ , -(CH ２ ) ｎ S (O) ｍ R ｃｃ , -(CH ２ ) ｎ NR ａａ R ｂｂ , -(CH ２ ) ｎ C(O)NR ａａ R ｂｂ , -(CH ２ ) ｎ NR ｅｅ C(O)R ｃｃ , -(CH ２ ) ｎ N=S(O)R ｃｃ R ｅｅ or -(CH ２ ) ｎ NR ｅｅ S (O) ｍ R ｃｃ wherein the amino group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, cyano-substituted C １－６ Alkyl group, C ３－１２ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ The aryl and 5- to 12-membered heteroaryl groups may optionally be substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, oxo group, thio group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, cyano-substituted C １－６ Alkyl group, C ３－１２ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ substituted with one or more substituents selected from aryl and 5- to 12-membered heteroaryl groups; R １ are independently preferably hydrogen, deuterium, halogen, an amino group, a hydroxy group, a cyano group, a nitro group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, cyano-substituted C １－６ Alkyl group, C ３－１２ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ an aryl group, a 5- to 12-membered heteroaryl group, —CR ｃｃ =CR ｄｄ (CH ２ ) ｎ R ａａ , -CR ｃｃ =CR ｄｄ (CH ２ ) ｎ NR ａａ R ｂｂ , -CR ｃｃ =CR ｄｄ (CH ２ ) ｎ NR ｅｅ C(O)R ａａ , -CR ｃｃ =CR ｄｄ (CH ２ ) ｎ NR ｅｅ C(O)NR ａａ R ｂｂ , -O(CH ２ ) ｎ R ｃｃ , -OC(R ａａ R ｂｂ ) ｎ (CH ２ ) ｍ R ｃｃ , -NR ｅｅ (CH ２ ) ｎ R ｃｃ , -(CH ２ ) ｎ -, -(CH ２ ) ｎ R ｃｃ , -(CH ２ ) ｎ OR ｃｃ , -(CH ２ ) ｎ SR ｃｃ , -(CH ２ ) ｎ C(O)R ｃｃ , -(CH ２ ) ｎ C (=NR ｅｅ ) R ｃｃ , -(CH ２ ) ｎ C(O)OR ｃｃ , -(CH ２ ) ｎ S (O) ｍ R ｃｃ , -(CH ２ ) ｎ NR ａａ R ｂｂ , -(CH ２ ) ｎ C(O)NR ａａ R ｂｂ , -(CH ２ ) ｎ NR ｅｅ C(O)R ｃｃ or -(CH ２ ) ｎ NR ｅｅ S (O) ｍ R ｃｃ wherein the amino group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, cyano-substituted C １－６ Alkyl group, C ３－１２ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ The aryl and 5- to 12-membered heteroaryl groups may optionally be substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, oxo group, thio group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, cyano-substituted C １－６ Alkyl group, C ３－１２ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ substituted with one or more substituents selected from aryl and 5- to 12-membered heteroaryl groups; R １ is more preferably hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C １－３ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C １－３ Deuterated alkyl groups, C １－３ Halogenated alkyl group, C １－３ Alkoxy group, C １－３ Halogenated alkoxy group, C １－３ Hydroxyalkyl group, cyano-substituted C １－３ Alkyl group, C ３－６ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ an aryl group, a 5- to 12-membered heteroaryl group, —O(CH ２ ) ｎ R ｃｃ , -OC(R ａａ R ｂｂ ) ｎ (CH ２ ) ｍ R ｃｃ , -(CH ２ ) ｎ -, -(CH ２ ) ｎ R ｃｃ or -(CH ２ ) ｎ OR ｃｃ wherein the amino group, C １－３ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C １－３ Deuterated alkyl groups, C １－３ Halogenated alkyl group, C １－３ Alkoxy group, C １－３ Halogenated alkoxy group, C １－３ Hydroxyalkyl group, cyano-substituted C １－３ Alkyl group, C ３－６ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ The aryl and 5- to 12-membered heteroaryl groups may optionally be substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C １－３ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, oxo group, thio group, C １－３ Deuterated alkyl groups, C １－３ Halogenated alkyl group, C １－３ Alkoxy group, C １－３ Halogenated alkoxy group, C １－３ Hydroxyalkyl group, cyano-substituted C １－３ Alkyl group, C ３－６ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ substituted with one or more substituents selected from aryl and 5- to 12-membered heteroaryl groups; R ａａ and R ｂｂ are each independently hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, cyano-substituted C １－６ Alkyl group, C ３－１２ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ aryl or 5- to 12-membered heteroaryl groups, optionally containing deuterium, halogen, amino, hydroxy, cyano, nitro, C １－６ Alkyl group, C ３－１２ cycloalkyl groups, —O(CH ２ ) ｎ１ R ｃ１ , -OC(R ａ１ R ｂ１ ) ｍ１ (CH ２ ) ｎ１ R ｃ１ , -NR ａ１ (CH ２ ) ｎ１ R ｃ１ , -(CH ２ ) ｎ１ -, -(CH ２ ) ｎ１ R ｃ１ , -(CH ２ ) ｎ１ OR ｃ１ , -(CH ２ ) ｎ１ SR ｃ１ , -(CH ２ ) ｎ１ C(O)R ｃ１ , -(CH ２ ) ｎ１ C(O)OR ｃ１ , -(CH ２ ) ｎ１ S (O) ｍ１ R ｃ１ , -(CH ２ ) ｎ１ NR ａ１ R ｂ１ , -(CH ２ ) ｎ１ C(O)NR ａ１ R ｂ１ , -(CH ２ ) ｎ１ NR ａ１ C(O)R ｃ１ and-(CH ２ ) ｎ１ NR ａ１ S (O) ｍ１ R ｃ１ and substituted with one or more substituents of Or, R ａａ and R ｂｂ forms, together with the adjacent atoms, C ３－１２ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ an aryl group or a 5- to 12-membered heteroaryl group, ３－１２ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ The aryl and 5- to 12-membered heteroaryl groups may optionally be substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, cyano-substituted C １－６ Alkyl group, C ３－１２ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ an aryl group, a 5- to 12-membered heteroaryl group, —O(CH ２ ) ｎ１ R ｃ１ , -OC(R ａ１ R ｂ１ ) ｎ１ (CH ２ ) ｍ R ｃ１ , -NR ａ１ (CH ２ ) ｎ１ R ｃ１ , -(CH ２ ) ｎ１ -, -(CH ２ ) ｎ１ R ｃ１ , -(CH ２ ) ｎ１ OR ｃ１ , -(CH ２ ) ｎ１ SR ｃ１ , -(CH ２ ) ｎ１ C(O)R ｃ１ , -(CH ２ ) ｎ１ C(O)OR ｃ１ , -(CH ２ ) ｎ１ S (O) ｍ R ｃ１ , -(CH ２ ) ｎ１ NR ａ１ R ｂ１ , -(CH ２ ) ｎ１ C(O)NR ａ１ R ｂ１ , -(CH ２ ) ｎ１ NR ａ１ C(O)R ｃ１ and-(CH ２ ) ｎ１ NR ａ１ S (O) ｍ１ R ｃ１ and is substituted with one or more substituents selected from the group consisting of R ｃｃ represents hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, cyano-substituted C １－６ Alkyl group, C ３－１２ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ aryl or 5- to 12-membered heteroaryl groups, optionally containing deuterium, halogen, amino, hydroxy, cyano, nitro, C １－６ Alkyl group, C ３－１２ cycloalkyl groups, —O(CH ２ ) ｎ１ R ｃ１ , -OC(R ａ１ R ｂ１ ) ｎ１ (CH ２ ) ｍ R ｃ１ , -NR ａ１ (CH ２ ) ｎ１ R ｃ１ , -(CH ２ ) ｎ１ -, -(CH ２ ) ｎ１ R ｃ１ , -(CH ２ ) ｎ１ OR ｃ１ , -(CH ２ ) ｎ１ SR ｃ１ , -(CH ２ ) ｎ１ C(O)R ｃ１ , -(CH ２ ) ｎ１ C(O)OR ｃ１ , -(CH ２ ) ｎ１ S (O) ｍ R ｃ１ , -(CH ２ ) ｎ１ NR ａ１ R ｂ１ , -(CH ２ ) ｎ１ C(O)NR ａ１ R ｂ１ , -(CH ２ ) ｎ１ NR ａ１ C(O)R ｃ１ and-(CH ２ ) ｎ１ NR ａ１ S (O) ｍ１ R ｃ１ and substituted with one or more substituents of R ａ１ , R ｂ１ and R ｃ１ are each independently hydrogen, deuterium, halogen, amino group, hydroxy group, cyano group, nitro group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C １－６ Deuterated alkyl groups, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C １－６ Hydroxyalkyl group, cyano-substituted C １－６ Alkyl group, C ３－１２ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ aryl or 5- to 12-membered heteroaryl groups, optionally containing deuterium, halogen, amino, hydroxy, cyano, nitro, C １－６ Alkyl group and C ３－１２ substituted with one or more substituents of a cycloalkyl group; m １ is 0, 1, 2 or 3, and n １ is 0, 1, 2 or 3, More preferably, R 1 is selected from hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxy, cyano, nitro, methyl, ethyl, propyl, isopropyl, oxo, methoxy, ethoxy, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, cyclopropyl, cyclobutyl, oxetanyl, azetidinyl, triazolyl, oxazolyl, isoxazolyl, pyrazolyl, pyrrolyl or thiazolyl, wherein the cyclopropyl, cyclobutyl, oxetanyl, azetidinyl, triazolyl, oxazolyl, isoxazolyl, pyrazolyl, pyrrolyl and thiazolyl groups optionally contain deuterium, fluorine, chlorine, bromine, amino, hydroxy, cyano, nitro, C 1-3 alkyl, oxo, thio, C 1-3 deuterated alkyl, C The compound, its stereoisomer or pharmaceutically acceptable salt thereof according to claim 1, characterized in that it is substituted with one or more substituents selected from the group consisting of a C 1-3 halogenated alkyl group, a C 1-3 alkoxy group, a C 1-3 halogenated alkoxy group, a C 1-3 hydroxyalkyl group and a cyano-substituted C 1-3 alkyl group.

10. The structure of the compound is 【Chemistry 17】 [Chemistry 18] 【Chemistry 19】 【Chemistry 20】 2. The compound according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, wherein:

11. A compound represented by general formula (X-B), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, 【Chemistry 21】 where: R ８ is hydrogen, deuterium, C １－３ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C １－３ Deuterated alkyl groups, C １－３ Halogenated alkyl group, C １－３ Alkoxy group, C １－３ Halogenated alkoxy group, C １－３ Hydroxyalkyl group, cyano-substituted C １－３ Alkyl group, C ３－６ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ an aryl group or a 5- to 12-membered heteroaryl group, １－３ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C １－３ Deuterated alkyl groups, C １－３ Halogenated alkyl group, C １－３ Alkoxy group, C １－３ Halogenated alkoxy group, C １－３ Hydroxyalkyl group, cyano-substituted C １－３ Alkyl group, C ３－６ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ The aryl and 5- to 12-membered heteroaryl groups may optionally be substituted with deuterium, halogen, amino, hydroxy, cyano, nitro, C １－３ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, oxo group, thio group, C １－３ Deuterated alkyl groups, C １－３ Halogenated alkyl group, C １－３ Alkoxy group, C １－３ Halogenated alkoxy group, C １－３ Hydroxyalkyl group, cyano-substituted C １－３ Alkyl group, C ３－６ Cycloalkyl groups, 3- to 12-membered heterocyclyl groups, C ６－１２ substituted with one or more substituents selected from aryl and 5- to 12-membered heteroaryl groups; Preferably, R ８ is hydrogen, deuterium, C １－３ alkyl groups, M ａ , M ｂ , M ｃ , M ｄ , R ２ , R ５ 10. A compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof, wherein ring C and z are as defined in claim 2.

12. A method for producing a compound represented by general formula (X-B), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, comprising: 【Chemistry 22】 a compound of general formula (X-E); 【Chemistry 23】 to obtain a compound of general formula (X-B), M ａ , M ｂ , M ｃ , M ｄ , R ２ , R ５ , R ８ , wherein rings C and z are as defined in claim 2.

13. A method for preparing the compound of claim 2, its stereoisomer or its pharmaceutically acceptable salt, comprising: 【Chemistry 24】 A method for producing a compound of general formula (III) by amide condensation of a compound of general formula (X-F) in the presence of a condensing agent, the condensing agent is selected from phosphorus oxychloride, thionyl chloride, oxalyl chloride, diisopropyl azodicarboxylate, diethyl azodicarboxylate, carbodiimide hydrochloride, N,N'-diisopropylcarbodiimide, dicyclohexylcarbodiimide, HATU, HBTU, HOBT, TCFH, PyBop or PyClock; M ａ , M ｂ , M ｃ , M ｄ , R ２ , R ５ , R １ , Ring B, Ring C, x and z are as defined in claim 2.

14. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, diluents or excipients.

15. 16. The use of the compound according to any one of claims 1 to 10, its stereoisomer or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 14 in the manufacture of a MALT1 inhibitor drug.

16. 16. The use of the compound according to any one of claims 1 to 10, its stereoisomer or pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 14 in the manufacture of a medicament for treating cancer or an autoimmune disease, wherein the cancer or autoimmune disease is selected from B-cell lymphoma, non-Hodgkin's lymphoma, mantle cell lymphoma, follicular lymphoma, mucosa-associated lymphoid tissue lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, psoriatic arthritis, psoriasis, ulcerative colitis, Crohn's disease, systemic lupus erythematosus, asthma and chronic obstructive pulmonary disease.

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