Tricyclic heterocyclic derivatives, their compositions, and applications

Abstract

The present invention relates to a tricyclic heterocyclic derivative represented by formula (I), a pharmaceutical composition thereof, a method for producing it, and its use as a therapeutic agent. [Formula 1] TIFF2026516841000225.tif30170

Description

[Technical Field]

[0001] Cross-reference of related applications This invention claims the benefits of International Application No. PCT / CN2023 / 091391, filed on 27 April 2023, International Application No. PCT / CN2023 / 101168, filed on 19 June 2023, and International Application No. PCT / CN2023 / 126326, filed on 25 October 2023, the contents of which are incorporated collectively by reference.

[0002] Technical field This invention relates to a tricyclic heterocyclic derivative as a PARG inhibitor. The invention also relates to a method for producing the above tricyclic heterocyclic derivative, a pharmaceutical composition, and applications for treating PARG-mediated diseases such as cancer and other diseases. [Background technology]

[0003] DNA damage repair (DDR) is a set of processes by which cells recognize and repair damage to the DNA molecules that encode their genome. However, when cancer develops, the DNA repair pathway becomes a double-edged sword, as cancer cells use chemotherapy and radiation therapy to repair DNA damage and promote cell survival. Therefore, cancer with impaired DNA repair is more susceptible to DNA damage and relies on other complementary repair pathways, which can be developed as strategies for treating cancer.

[0004] Abnormal DNA repair deficiencies (DDRs) typically make cancer cells sensitive to specific types of DNA damage, so DDR-deficient DDRs can be developed as a therapy for targeted cancers. Targeting DNA repair deficiencies has been a validated and effective strategy in cancer treatment. For example, poly(ADP-ribose) polymerase (PARP) has been successful in treating BRCA-deficient breast, ovarian, prostate, and pancreatic cancers (Audeh MW et al., 2010).

[0005] Poly(ADP-ribosyl)ation (PARylation) is a unique post-translational modification that maintains genomic stability through different molecular pathways, particularly DNA repair (Kraus WL et al., 2015). The binding of PARP to cleaved DNA and the rapid synthesis of polyADP-ribose (PAR) by PARP itself are among the earliest events in single-strand and DNA repair processes. Currently, PARP inhibitors inhibit PARP1 / 2-dependent DNA repair, primarily by inhibiting PARP1 and PARP2 enzyme activity. Recently, clinical drug resistance to PARP inhibitors has been reported (Drost and Jonkers, 2014) (Barber LJ et al., 2013) (Tobalina L et al., 2021), necessitating alternative inhibitors for DNA damage repair mechanisms.

[0006] PARylation is a transient post-translational modification that can be rapidly degraded by PAR glycohydrolase (PARG) (Barkauskaite E et al., 2015). Since the catalytic activity of PARP is reduced when it binds to PAR, PARG activity contributes to returning PARP to its catalytically active form (Curtin and Szabo, 2013). Similar to PARPs, PARG also promotes DNA double-strand break (DSB) and single-strand break (SSB) repair (Mortusewicz O et al., 2011). In addition to its main role in DNA repair, PARG also influences PAR signaling in RNA splicing, transcription, and epigenetic regulation (Ji and Tulin 2009) (Le May N et al., 2012) (Dahl M et al., 2014) (Guastafierro T et al., 2013) (Caiafa P et al., 2009). Several pieces of evidence suggest that PARG deletion inhibits SSB repair and reduces the viability of BRCA2-deficient cells (Fathers C et al., 2012). However, other tumor mutations may cause deficiencies in the DSB repair mechanism (so-called "BRCA-ness"), which could make tumor cells more sensitive to PARG inhibition.

[0007] However, not all drugs (e.g., gemcitabine, camptothecin) are sensitive to PARG deletion, indicating that PARG function has specificity for several pathways of DDR, chemotherapy, and radiotherapy (Fujihara H et al., 2009) (Shirai H et al., 2013) (Zhou Y et al., 2011). In humans, PARG knockout or deletion makes lung cancer, cervical cancer, and pancreatic cancer cells sensitive to radiation or experimental DNA damaging agents (e.g., hydrogen peroxide, methyl methanesulfonate) (Ame JC et al., 2009) (Nakadate Y et al., 2013) (Shirai H et al., 2013).

[0008] Several studies have shown that PARG inhibition may offer therapeutic benefits to PARP inhibitor-resistant cells (Fisher AE et al., 2007). Furthermore, it has been reported that gene expression patterns induced by PARG deletion and those induced by PARP deletion are distinctly different in breast cancer cells (Frizzell KM et al., 2009). Ovarian cancer cells respond differently to PARP inhibitors and PARG inhibitors, with the latter being more sensitive due to persistent replication fork stagnation and replication disaster (Pillay N et al., 2019) (Coulson-Gilmer C et al., 2021).

[0009] Furthermore, recent studies have shown that there are differences in the mechanisms of PARG inhibition and PARP inhibition. Compared to PARP deletion, the toxicity of PARG gene deletion leads to a reduction in NAD levels, which can lead to lung cancer cell death, possibly caused by energy deficiency (Erdelyi K et al., 2009). PARG inhibition can also consume NAD+, thereby enhancing the metabolic lethality of alkylating chemotherapy in IDH-mutated tumor cells (Nagashima H et al., 2020).

[0010] Currently, there are very few known PARG inhibitors with cell permeability. For example, Tannic acid, Gallotannin, or PDD00017273 have relatively low specificity for PARG and limited bioavailability (Sun Y et al., 2012)(Fathers C et al., 2012)(Blenn C et al., 2011)(James DI et al., 2016).

[0011] The present invention provides a PARG inhibitor with cell permeability.

Summary of the Invention

[0012] The present invention provides a compound represented by formula (I)

Chemical formula

Chemical formula

[0013] The present invention further provides a pharmaceutical composition comprising a compound represented by formula (I), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuteride thereof, and a pharmaceutically acceptable carrier.

[0014] In another embodiment, the present invention provides a method for inhibiting PARG, comprising contacting PARG with a compound represented by formula (I), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuteride.

[0015] In another embodiment, the present invention provides a method for treating cancer / disease, comprising administering to a subject a therapeutically effective amount of a compound represented by formula (I), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound represented by formula (I). [Modes for carrying out the invention]

[0016] The present invention can be better understood by referring to the following description, which includes the definitions and examples below. Some features of the compositions and methods of the present invention described in different contexts may be provided in combination in a single embodiment. Alternatively, for the sake of brevity, various features of the compositions and methods of the present invention described in the context of a single embodiment may be provided individually or in any sub-combination.

[0017] Before further describing the present invention, it should be understood that the present invention is not limited to the specific embodiments described herein, and that the terms used in the present invention are used solely for the purpose of describing specific embodiments and do not limit the scope of the present invention.

[0018] In some embodiments, the present invention relates to a compound represented by formula (I), [ka] Or, providing pharmaceutically acceptable salts, stereoisomers, solvates, N-oxides, tautomers, isotopic variants, prodrugs, or deuterated products thereof, among, [ka] It is either a single bond or a double bond. X is O or NR 4 And, X 1 is C or N, X 2 is C or N, X 3 is C or N, X 4 is C or N, X 5 is C or N, [ka] teeth, [ka] And, [ka] teeth [ka] And, Y 1 and Y 3 These are independently N or CR 5 Selected from, Y 2 is N or CR 6 And, Y 4 is S, O or NR 7 And, Y 5 , Y 7 and Y 8 These are independently N or CR 8 Selected from, Y 6 is S, O or NR 9 And, Z 1 It is a 5-10 member heteroaryl group, and R can be optionally selected. 10 Substituted with 1, 2, 3, 4, or 5 substituents independently selected from, Z 2H, D, halogen, CN, NO2, SF5, C1-C8 alkyl group, C2-C8 alkenyl group, C2-C8 alkynyl group, C6-C 10 Aryl group, C3-C 10 Cycloalkyl groups, 5-10 membered heteroaryl groups, 4-14 membered heterocycloalkyl groups, NR C R D , OR A , SR A NHOR A , C(O)R B , C(O)OR A , C(O)NR C R D , OC(O)NR C R D , NR C C(O)R B , NR C C(O)NR C R D , NR C C(O)OR A , NR C S(O)2R B , S(O)R B , S(O)NR C R D S(O)2R B , S(O)2NR C R D , or NR C S(O)2NR C R D These include the above C1-C8 alkyl group, C2-C8 alkenyl group, C2-C8 alkynyl group, and C6-C 10 Aryl group, C3-C 10 Cycloalkyl groups, 5-10 membered heteroaryl groups, or 4-14 membered heterocycloalkyl groups are optionally used in R 11 Substituted with 1, 2, 3, 4, or 5 substituents independently selected from, R 1 , R 2 and R 3Each of these is independently selected from H, D, CN, C1-C3 alkyl groups, C2-C3 alkenyl groups, C2-C3 alkynyl groups, C3-C7 cycloalkyl groups, or 4- to 7-membered heterocycloalkyl groups, and of these, the above C1-C3 alkyl groups, C2-C3 alkenyl groups, C2-C3 alkynyl groups, C3-C7 cycloalkyl groups, or 4- to 7-membered heterocycloalkyl groups are optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from D, halogens, CN, OH, C1-C6 alkyl groups, C1-C6 haloalkyl groups, -O-C1-C6 alkyl groups, or -OC1-C6 haloalkyl groups. Alternatively, R 2 and R 3 These, together with the carbon atoms linked to them, form a C3-C7 cycloalkyl group or a 4-7 member heterocycloalkyl group, and the above C3-C7 cycloalkyl group or 4-7 member heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, NO2, oxo, OH, C1-C6 alkyl group, C1-C6 haloalkyl group, -O-C1-C6 alkyl group, or -OC1-C6 haloalkyl group. R 4 H, D, CN, OR B , or a C1-C4 alkyl group, optionally R 4A It is replaced by, and of which, each R 4A The substituents are independently selected from D, F, Cl, CN, NH2, OH, -O-C1-C6 alkyl groups, -OC1-C6 haloalkyl groups, selectively substituted C3-C7 cycloalkyl groups, or selectively substituted 4- to 7-membered heterocycloalkyl groups, of which the selectively substituted substituents are selected from D, halogens, CN, OH, C1-C4 alkyl groups, C1-C4 haloalkyl groups, -O-C1-C4 alkyl groups, and -OC1-C4 haloalkyl groups. Alternatively, R 1 and R 4forms, together with the atoms to which they are attached, a 5- to 7-membered partially unsaturated cycloalkyl group, optionally substituted with 1, 2, 3 or 4 substituents independently selected from D, halogen, CN, CF3, NO2, oxo, OH, C1-C6 alkyl group, C1-C6 haloalkyl group, -O-C1-C6 alkyl group, -OC1-C6 haloalkyl group, R 5 is H, D, CN, halogen, SF5, OH, NH2, CHO, COOH, C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C1-C3 haloalkyl group, C1-C3 cyanoalkyl group, OR A NR C R D or C(O)R B and R 6 is H, D, CN, halogen, OH, NH2, SF5, C1-C3 alkyl group, C1-C3 haloalkyl group, -O-C1-C3 alkyl group, -OC1-C3 haloalkyl group, C1-C3 cyanoalkyl group, R 7 and R 9 are each independently H, D, C1-C6 alkyl group, C1-C6 haloalkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkyl-OR A C1-C6 alkyl-CN, C1-C6 alkyl-NR C R D C(O)R B C(O)NR C R D selected from each R 8 is each independently H, D, halogen, CN, NO2, C1-C6 alkyl group, C1-C6 haloalkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, OR A SR A SF5, NHOR A C(O)OR A C(O)R B C(O)NR C R D OC(O)NR C R D NR C R D NRC C(O)R B , NR C C(O)NR C R D , NR C C(O)OR A , NR C S(O)2R B , B(OR C )(OR D ), C(=NR C )NR C R D , NR D C(=NR C )NR C R D , NR D C(=NR C )R B P(O)R E R F , P(O)OR E Ure F , OP(O)OR E Ure F , S(O)(=NR B )R B , S(O)R B , S(O)NR C R D S(O)2R B , S(O)2NR C R D , NR C S(O)2NR C R D , or NR C S(O)(=NR B )R B Selected from these, of which the above C1-C6 alkyl group, C2-C6 alkenyl group, or C2-C6 alkynyl group is optionally selected as R 12 Substituted with one, two, or three substituents independently selected from, Each R 10Each is independently selected from H, D, halogen, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl group, OC1-C6 alkyl group, OC1-C6 haloalkyl group, OC3-C7 cycloalkyl group, C3-C7 cycloalkyl group, CN, NO2, N3, or SF5, of which the above C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, or C3-C7 cycloalkyl group is optionally selected from R 12 Substituted with one, two, or three substituents independently selected from, Two R's 10 These, along with the atoms linked to them, are oxo, C 3- C 10 Forms a cycloalkyl group or a 4-10 member heterocycloalkyl group, of which the above C 3- C 10 Cycloalkyl groups or 4-10 member heterocycloalkyl groups can optionally include D, halogen, C1-C6 alkyl, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl group, C1-C6 cyanoalkyl group, CN, NO2, oxo, OR a , SR a SF5, NHOR a , C(O)R b , C(O)NR c R d , C(O)OR a ,OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R b , NR c C(O)NR c R d , NR c C(O)OR a , B(OR c )(OR d ), C(=NR c )NR c R d , NR d C(=NR c )NR c R d , NR dC(=NR c )R b , OP(O)OR e Ure f , P(O)OR e Ure f , S(O)(=NR b )R b , S(O)R b , S(O)NR c R d S(O)2R b , NR c S(O)2R b , S(O)2NR c R d , NR c S(O)2NR c R d , NR c S(O)(=NR b )R b Cy 4 Substituted with one, two, or three substituents independently selected from, of which Cy 4 is C6-C 10 Aryl group, C3-C 10 The group consists of a cycloalkyl group, a 5-10 membered heteroaryl group, and a 4-10 membered heterocycloalkyl group, among which Cy 4 It is optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, NO2, OH, oxo, NH2, NHC1-C4 alkyl, N(C1-C4 alkyl)2, C1-C3 alkyl, C1-C3 haloalkyl, OC1-C3 alkyl, OC1-C3 haloalkyl, OC2-C3 alkylOH, OC2-C3 alkyl-O-C1-C6 alkyl, or SF5. Each R 11 These are, independently, H, D, halogen, CN, NO2, N3, oxo, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, OR A , SR A SF5, NR C Ure A , C(O)R B , C(=S)R B , C(O)NR C R D , C(O)N(R C )ORA 、 C(O)OR A 、 OC(O)R B 、 OC(O)NR C R D 、 NR C R D 、 NR C C(O)R D 、 NR C C(O)NR C R D 、 NR C C(O)OR A 、 B(OR C )(OR D )、 C(=NR C )NR C R D 、 NR D C(=NR C )NR C R D 、 NR D C(=NR C )R B 、 SiR G R H R I 、 P(O)R E R F 、 P(O)OR E OR F 、 OP(O)OR E OR F 、 S(O)(=NR B )R B 、 S(O)R B 、 S(O)NR C R D 、 S(O)2R B )、 NR C S(O)2R B 、 S(O)2NR C R D 、 NR C S(O)2NR C R D 、 NR C S(O)(=NR B )R B 、 Cy 3 、 C1-C6 alkyl-Cy 3 、 OCy 3 、 or O-C1-C6 alkyl-Cy 3From which the above C1-C6 alkyl group, C2-C6 alkenyl group, and C2-C6 alkynyl group are optionally selected as R 12 Substituted with 1, 2, 3, 4, or 5 substituents independently selected from, Each R 12 These are, independently, H, D, halogen, CN, NO2, N3, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl group, OC1-C6 alkylOH, OC1-C6 alkyl-O-C1-C6 alkyl group, OR a1 , SR a1 SF5, NHOR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)OR a1 ,OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)NR c1 R d1 , NR c1 C(O)OR a1 , B(OR c1 )(OR d1 ), C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )R b1 , P(O)OR e1 Ure f1 , OP(O)OR e1 Ure f1 , S(O)(=NR b1 )R b1 , S(O)R b1 , S(O)NR c1 R d1 S(O)2R b1 , NR c1 S(O)2Rb1 , S(O)2NR c1 R d1 , NR c1 S(O)2NR c1 R d1 , NR c1 S(O)(=NR b1 )R b1 , C6-C 10 Aryl group, C3-C 10 Selected from cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups, among which the above C6-C 10 Aryl group, C3-C 10 Cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups are optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from D, halogens, CN, NO2, NH2, NHC1-C4 alkyl groups, N(C1-C4 alkyl)2, C1-C3 alkyl groups, C1-C3 haloalkyl groups, OC1-C3 alkyl groups, OC1-C3 haloalkyl groups, OC2-C3 alkylOH, OC2-C3 alkyl-O-C1-C6 alkyl groups, or SF5. Cy 3 C6-C 10 Aryl group, C3-C 10 Selected from cycloalkyl groups, 5-10 membered heteroaryl groups, or 4-10 membered heterocycloalkyl groups, among which Cy 3 R is chosen at will. 13 Substituted with 1, 2, 3, 4, or 5 substituents independently selected from, Each R 13 These are, independently, D, halogen, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl group, C1-C6 alkylOH, C1-C6 alkyl-O-C1-C6 alkyl group, CN, NO2, N3, OR a1 , SR a1 SF5, NHOR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 ,OC(O)R b1 , OC(O)NR c1 Rd1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)NR c1 R d1 , NR c1 C(O)OR a1 , B(OR c1 )(OR d1 ), C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )R b1 P(O)R e1 R f1 , P(O)OR e1 Ure f1 , OP(O)OR e1 Ure f1 , S(O)(=NR b1 )R b1 , S(O)R b1 , S(O)NR c1 R d1 S(O)2R b1 , NR c1 S(O)2R b1 , S(O)2NR c1 R d1 , NR c1 S(O)2NR c1 R d1 , NR c1 S(O)(=NR b1 )R b1 , C6-C 10 Aryl group, C3-C 10 Selected from cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups, among which the above C6-C 10 Aryl group, C3-C 10Cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups are optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from D, halogens, CN, NO2, NH2, NHC1-C4 alkyl groups, N(C1-C4 alkyl)2, C1-C3 alkyl groups, C1-C3 haloalkyl groups, OC1-C3 alkyl groups, OC1-C3 haloalkyl groups, OC2-C3 alkylOH, OC2-C3 alkyl-O-C1-C6 alkyl groups, or SF5. Each R 14 These are, independently, H, D, NO2, CN, halogen, oxo, SF5, C1-C8 alkyl group, C2-C8 alkenyl group, C2-C8 alkynyl group, and C6-C 14 Aryl group, C3-C 14 Cycloalkyl groups, 5-14 member heteroaryl groups, or 4-14 member heterocycloalkyl groups, OR a , SR a SF5, NHOR a , C(O)R b , C(O)NR c R d , C(O)OR a ,OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R b , NR c C(O)NR c R d , NR c C(O)OR a , B(OR c )(OR d ), C(=NR c )NR c R d , NR d C(=NR c )NR c R d , NR d C(=NR c )R b P(O)R e R f , P(O)OR e Ure f , OP(O)ORe Ure f , S(O)R b , S(O)NR c R d S(O)2R b , NR c S(O)2R b , S(O)2NR c R d , NR c S(O)2NR c R d , or NR c S(O)(=NR b )R b Selected from among, of which the above C1-C8 alkyl group, C2-C8 alkenyl group, C2-C8 alkynyl group, C6-C 14 Aryl group, C3-C 14 Cycloalkyl groups, 5-14 membered heteroaryl groups, or 4-14 membered heterocycloalkyl groups are optionally D, NO2, CN, halogen, oxo, SF5, C1-C6 alkyl groups, C2-C6 alkenyl groups, C2-C6 alkynyl groups, C1-C6 haloalkyl groups, C1-C6 alkylOH, C1-C6 alkyl-O-C1-C6 alkyl groups, CN, NO2, N3, OR a1 , SR a1 SF5, NHOR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 ,OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)NR c1 R d1 , NR c1 C(O)OR a1 , B(OR c1 )(OR d1 ), C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )NR c1 R d1, NR d1 C(=NR c1 )R b1 P(O)R e1 R f1 , P(O)OR e1 Ure f1 , OP(O)OR e1 Ure f1 , S(O)(=NR b1 )R b1 , S(O)R b1 , S(O)NR c1 R d1 S(O)2R b1 , NR c1 S(O)2R b1 , S(O)2NR c1 R d1 , NR c1 S(O)2NR c1 R d1 , NR c1 S(O)(=NR b1 )R b1 , C6-C 10 Aryl group, C3-C 10 Substituted with 1, 2, 3, 4, or 5 substituents independently selected from cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups, Each R A These are, independently, H, D, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Selected from cycloalkyl-C1-C6 alkyl groups or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, of which the above C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, are optionally R 14 Substituted with 1, 2, 3, 4, or 5 substituents independently selected from, Each R B These are, independently, H, D, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Selected from cycloalkyl-C1-C6 alkyl groups or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, of which the above C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, are optionally R 14 Substituted with 1, 2, 3, 4, or 5 substituents independently selected from, R C and R D These are, independently, H, D, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10Selected from cycloalkyl-C1-C6 alkyl groups or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, of which the above C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, are optionally R 14 Substituted with 1, 2, 3, 4, or 5 substituents independently selected from, or R C and R D These, together with the N atoms linked to them, form 4-7 member heterocycloalkyl groups, optionally consisting of D, halogen, oxo, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkyl-CN, OR a , SR a , C(O)R b , NR c R d Substituted with 1, 2, 3, 4, or 5 substituents independently selected from, R a and R a1 Each is independently selected from H, D, C1-C4 alkyl groups, C2-C4 alkenyl groups, C2-C4 alkynyl groups, phenyl groups, C3-C7 cycloalkyl groups, 5-6 membered heteroaryl groups, or 4-7 membered heterocycloalkyl groups, of which the above C1-C4 alkyl groups, C2-C4 alkenyl groups, C2-C4 alkynyl groups, phenyl groups, and C 3- A C7 cycloalkyl group, a 5-6 membered heteroaryl group, or a 4-7 membered heterocycloalkyl group may be optionally substituted with one, two, or three substituents independently selected from D, OH, CN, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, halogen, C1-C4 alkyl group, C1-C4 alkoxy group, C1-C4 haloalkyl group, or C1-C4 haloalkoxy group. Rb and R b1 These are, independently, H, D, C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, and C 6- C 10 Aryl group, 5-10 membered heteroaryl group, C 3- C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C 6- C 10 Aryl-C1-C4 alkyl group, 5-10 member heteroaryl-C1-C4 alkyl group, C3-C 10 Selected from cycloalkyl-C1-C4 alkyl groups or 4-10 member heterocycloalkyl-C1-C4 alkyl groups, among which the above C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, C 6- C 10 Aryl group, 5-10 membered heteroaryl group, C 3- C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C 6- C 10 Aryl-C1-C4 alkyl group, 5-10 member heteroaryl-C1-C4 alkyl group, C3-C 10 Cycloalkyl-C1-C4 alkyl groups, or 4-10 member heterocycloalkyl-C1-C4 alkyl groups, can optionally include D, OH, halogen, CN, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, C1-C4 alkyl, C1-C4 haloalkyl, -OC1-C4 alkyl, -OC1-C4 haloalkyl, and C6-C 10 Aryl group, C3-C 10 Substituted with 1, 2, 3, 4, or 5 substituents independently selected from cycloalkyl groups, 5-10 membered heteroaryl groups, or 4-10 membered heterocycloalkyl groups, R c , R d , R c1 and R d1 These are, independently, H, D, C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, and C 6- C 10 Aryl group, 5-10 membered heteroaryl group, C 3- C10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C 6- C 10 Aryl-C1-C4 alkyl group, 5-10 member heteroaryl-C1-C4 alkyl group, C 3- C 10 Cycloalkyl-C1-C4 alkyl group, 4-10 member heterocycloalkyl-C1-C4 alkyl group, C 6- C 10 Aryl-C 3- C 10 Cycloalkyl groups, C 6- C 10 Aryl-4 to 10-membered heterocycloalkyl groups, C 6- C 10 Aryl-5 to 10-membered heteroaryl group, bis(C) 6- C 10 aryl), 5-10 member heteroaryl-C 3- C 10 Cycloalkyl groups, 5-10 member heteroaryl groups - 4-10 member heterocycloalkyl groups, 5-10 member heteroaryl groups - C 6- C 10 Selected from aryl groups or bis(5-10 membered heteroaryl), among which the above C1-C4 alkyl groups, C2-C4 alkenyl groups, C2-C4 alkynyl groups, C 6- C 10 Aryl group, 5-10 membered heteroaryl group, C 3- C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C 6- C 10 Aryl-C1-C4 alkyl group, 5-10 member heteroaryl-C1-C4 alkyl group, C 3- C 10 Cycloalkyl-C1-C4 alkyl group, 4-10 member heterocycloalkyl-C1-C4 alkyl group, C 6- C 10 Aryl-C 3- C 10 Cycloalkyl groups, C 6- C 10 Aryl-4 to 10-membered heterocycloalkyl groups, C 6- C 10 Aryl-5~10 member heteroaryl group, bis(C6-C10 aryl), 5-10 member heteroaryl-C 3- C 10 Cycloalkyl groups, 5-10 member heteroaryl groups - 4-10 member heterocycloalkyl groups, 5-10 member heteroaryl groups - C 6- C 10 The aryl group, or bis(5-10 membered heteroaryl), can be optionally D, halogen, OH, CN, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, C1-C4 alkyl, -O-C1-C4 alkyl, C1-C4 haloalkyl, -O-C1-C4 haloalkyl, C1-C4 alkyl-OH, C1-C4 alkyl-CN, C6-C 10 Aryl group, 5-10 membered heteroaryl group, -C(O)OR a1 , -C(O)R b1 -S(O)2R b1 , substituted with 1, 2, 3, 4, or 5 substituents independently selected from -C1-C4alkyl-O-C1-C4alkyl and -C1-C4alkyl-O-C1-C4alkyl-O-, Alternatively, R c and R d These, together with the N atoms linked to them, form 4-7 member heterocycloalkyl groups, and optionally D, OH, CN, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, halogen, C1-C4 alkyl, C1-C4 alkoxy group, C1-C4 haloalkyl, C1-C4 haloalkoxy group, C1-C4 hydroxyalkyl, C1-C4 cyanoalkyl, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C(O)OR a1 , C(O)R b1 S(O)2R b1 , substituted with 1, 2, or 3 substituents independently selected from C1-C4 alkoxy-C1-C4 alkyl groups and C1-C4 alkoxy-C1-C4 alkoxy groups, Alternatively, R c1 and R d1These, together with the N atoms linked to them, form 4-7 member heterocycloalkyl groups, and optionally D, OH, CN, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, halogen, C1-C4 alkyl, C1-C4 alkoxy group, C1-C4 haloalkyl, C1-C4 haloalkoxy group, C1-C4 hydroxyalkyl, C1-C4 cyanoalkyl, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C(O)OR a1 , C(O)R b1 S(O)2R b1 , substituted with 1, 2, or 3 substituents independently selected from C1-C4 alkoxy-C1-C4 alkyl groups and C1-C4 alkoxy-C1-C4 alkoxy groups, R E , R e and R e1 These are, independently, H, D, C1-C4 alkyl group, C1-C4 haloalkyl group, C2-C4 alkenyl group, (C1-C4 alkoxy)-C1-C4 alkyl group, C2-C4 alkynyl group, and C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl-C1-C4 alkyl groups, C3-C 10 Selected from cycloalkyl-C1-C4 alkyl groups, 5-10 member heteroaryl-C1-C4 alkyl groups, or 4-10 member heterocycloalkyl-C1-C4 alkyl groups, R F , R f and R f1 These are, independently, H, D, C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, and C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 Selected from cycloalkyl groups or 4-10 member heterocycloalkyl groups, R G , R H and R I Each of these is independently selected from a C1-C4 alkyl group or a phenyl group.

[0019] In some other embodiments, the present invention relates to the compound represented by formula (I'). [ka] Or further, provide a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated thereof. Eventually, [ka] Ring A, Ring B, R 1 , R 2 , R 3 , X, X 1 , X 2 , X 3 , X 4 , Z 1 and Z 2 This is as defined in the present invention.

[0020] In some other embodiments, the present invention relates to compounds represented by formulas (IA), (IB), (IC), (ID), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), [ka] Or provide a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated thereof. Among them, ring B, R 1 , R 2 , R 3 , X, X 3 , X 4 , Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , Y 7 , Y 8 , Z 1 , and Z 2 This is as defined in the present invention.

[0021] In some other embodiments, the present invention relates to compounds represented by formulas (IA), (Ib), (Ic), (Id), and (Ie), [ka] Or provide a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated thereof. Among them, ring B, R 1 , R 2 , R 3 , X, X 3 , X 4 , Y, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , Y 8 , Z 1 , and Z 2 This is as defined in the present invention.

[0022] In some other embodiments, the present invention relates to compounds represented by formulas (IB), (If), (Ig), (Ih), (Ii), (Ij), [ka] Or provide a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated thereof. Among them, ring B, R 1 , R 2 , R 3 , X, X 3 , X 4 , Y 1 , Y 4 , Y 5 , Y 6 , Y 7 , Y 8 , Z 1 , and Z 2 This is as defined in the present invention.

[0023] In some embodiments, Y1 is N, and Y 4 S is.

[0024] In some embodiments, Y 1 is N, and Y 4 It is O.

[0025] In some embodiments, Y 1 is N, and Y 4 is NR 7 That is the case.

[0026] In some embodiments, Y 1 CR 5 and Y 4 S is.

[0027] In some embodiments, Y 1 CR 5 and Y 4 It is O.

[0028] In some embodiments, Y 1 CR 5 and Y 4 is NR 7 That is the case.

[0029] In some embodiments, R 7 H, D, C1-C6 alkyl group, C1-C6 haloalkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkyl-OR A , C1-C6 alkyl-CN, C1-C6 alkyl-NR C R D , C(O)R B , C(O)NR C R D That is the case.

[0030] In some embodiments, R 7 H is H. In some embodiments, R 7 It is D.

[0031] In some embodiments, R7 is a C1-C6 alkyl group. In some embodiments, R 7 is a C1-C6 haloalkyl group. In some embodiments, R 7 R is a C2-C6 alkenyl group. In some embodiments, R 7 R is a C2-C6 alkynyl group. In some embodiments, R 7 is C1-C6 alkyl-OR A In some embodiments, R 7 is C1-C6 alkyl-CN. In some embodiments, R 7 is C1-C6 alkyl-NR C R D In some embodiments, R 7 is C(O)R B In some embodiments, R 7 is C(O)NR C R D That is the case.

[0032] In some embodiments, R 7 is H, D, C1-C6 alkyl group. In some embodiments, R 7 These are H, D, and CH3.

[0033] In some other embodiments, the present invention relates to compounds represented by formulas (IC), (Ik), (Il), (Im), and (In). [ka] Or provide a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated thereof. Among them, ring B, R 1 , R 2 , R 3 , X, X 3 , X 4 , Y 1 , Y 3 , Y 5 , Y 6 , Y 7 , Y 8 , Z 1 , and Z2 This is as defined in the present invention.

[0034] In some other embodiments, the present invention relates to compounds represented by formulas (ID), (Io), (Ip), (Iq), and (Ir). [ka] Or provide a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated thereof. Among them, ring B, R 1 , R 2 , R 3 , X, X 3 , X 4 , Y 1 , Y 3 , Y 5 , Y 6 , Y 7 , Y 8 , Z 1 , and Z 2 This is as defined in the present invention.

[0035] In some embodiments, Y 1 is N, and Y 3 It is N.

[0036] In some embodiments, Y 1 is N, and Y 3 CR 5 That is the case.

[0037] In some embodiments, Y 1 CR 5 and Y 3 It is N.

[0038] In some embodiments, Y 1 CR 5 and Y 3 CR 5 That is the case.

[0039] In some embodiments, Y 5 is N, and Y6 S is.

[0040] In some embodiments, Y 5 is N, and Y 6 It is O.

[0041] In some embodiments, Y 5 is N, and Y 6 is NR 9 That is the case.

[0042] In some embodiments, Y 5 CR 8 and Y 6 S is.

[0043] In some embodiments, Y 5 CR 8 and Y 6 It is O.

[0044] In some embodiments, Y 5 CR 8 and Y 6 is NR 9 That is the case.

[0045] In some embodiments, Y 5 is N, and Y 7 It is N.

[0046] In some embodiments, Y 5 is N, and Y 7 CR 8 That is the case.

[0047] In some embodiments, Y 5 CR 8 and Y 7 It is N.

[0048] In some embodiments, Y 5 CR 8 and Y 7 CR 8 That is the case.

[0049] In some embodiments, R 9 H, D, C1-C6 alkyl group, C1-C6 haloalkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkyl-OR A , C1-C6 alkyl-CN, C1-C6 alkyl-NR C R D , C(O)R B , C(O)NR C R D That is the case.

[0050] In some embodiments, R 9 H is H. In some embodiments, R 9 It is D.

[0051] In some embodiments, R 9 is a C1-C6 alkyl group. In some embodiments, R 9 is a C1-C6 haloalkyl group. In some embodiments, R 9 R is a C2-C6 alkenyl group. In some embodiments, R 9 R is a C2-C6 alkynyl group. In some embodiments, R 9 is C1-C6 alkyl-OR A In some embodiments, R 9 is C1-C6 alkyl-CN. In some embodiments, R 9 is C1-C6 alkyl-NR C R D In some embodiments, R 9 is C(O)R B In some embodiments, R 9 is C(O)NR C R D That is the case.

[0052] In some other embodiments, the present invention relates to compounds represented by formula (IA) or (Ie), [ka] Or provide a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated thereof. Among them, ring B, R 1 , R 2 , R 3 , X, X 3 , X 4 , Y 1 , Y 2 , Y 3 , Y 5 , Y 7 , Y 8 , Z 1 , and Z 2 This is as defined in the present invention.

[0053] In some other embodiments, the present invention relates to the compound represented by formula (Ie). [ka] Or provide a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated thereof. Eventually, R 1 , R 2 , R 3 , X, Y 1 , Y 2 , Y 3 , Y 5 , Y 7 , Y 8 , Z 1 , and Z 2 This is as defined in the present invention.

[0054] In some embodiments, X is O or NR 4 That is the case.

[0055] In some embodiments, X is O.

[0056] In some other embodiments, X is NR 4 That is the case.

[0057] In some embodiments, R 4 H, D, CN, ORB , a C1-C4 alkyl group, and optionally at least one R 4A It is replaced by, and of which, each R 4A The substituents are independently selected from D, F, Cl, CN, NH2, OH, -O-C1-C6 alkyl groups, -OC1-C6 haloalkyl groups, selectively substituted C3-C7 cycloalkyl groups, or selectively substituted 4- to 7-membered heterocycloalkyl groups, of which the selectively substituted substituents are D, halogen, CN, OH, C1-C4 alkyl groups, C1-C4 haloalkyl groups, -O-C1-C4 alkyl groups, and -OC1-C4 haloalkyl groups.

[0058] In some embodiments, R 4 H is H. In some embodiments, R 4 In some embodiments, R 4 is CN. In some embodiments, R 4 is OR B That is the case.

[0059] In some embodiments, R 4 is a C1-C4 alkyl group, and R is optionally selected. 4A It is replaced by, and of which, each R 4A The substituents are independently selected from D, F, Cl, CN, NH2, OH, -O-C1-C6 alkyl groups, -OC1-C6 haloalkyl groups, selectively substituted C3-C7 cycloalkyl groups, or selectively substituted 4- to 7-membered heterocycloalkyl groups, of which the selectively substituted substituents are D, halogen, CN, OH, C1-C4 alkyl groups, C1-C4 haloalkyl groups, -O-C1-C4 alkyl groups, and -OC1-C4 haloalkyl groups.

[0060] In some other embodiments, the present invention relates to compounds represented by formulas (IIa) and (IIb), [ka] Or provide pharmaceutically acceptable salts, stereoisomers, solvates, N-oxides, tautomers, isotopic variants, prodrugs, or deuterated compounds, among which R 1 , R2 , R 3 , R 4 , Y 1 , Y 2 , Y 3 , Y 5 , Y 7 , Y 8 , Z 1 , and Z 2 This is as defined in the present invention.

[0061] In some embodiments, Z 1 It is a 5-10 member heteroaryl group, and R can be optionally selected. 10 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from. In some embodiments, Z 1 This is a 5-10 membered heteroaryl group having 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, and the above Z 1 R is chosen at will. 10 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0062] In some embodiments, Z 1 It is a 5-6 member heteroaryl group, and R can be optionally selected. 10 It is substituted with one, two, three, or four substituents independently selected from Z. In some embodiments, Z 1 This is a 5-6 membered heteroaryl group having 1, 2, or 3 heteroatoms independently selected from N, O, and S, and the above Z 1 R is chosen at will. 10 It is substituted with 1, 2, 3, or 4 substituents independently selected from the given molecule.

[0063] In some embodiments, Z 1 It is a 5-membered heteroaryl group, and R can be optionally selected. 10 It is substituted with one, two, or three substituents independently selected from Z. In some embodiments, Z 1 This is a 5-membered heteroaryl group having 1, 2, or 3 heteroatoms independently selected from N, O, and S, and the above Z 1 R is chosen at will. 10is substituted with 1, 2, or 3 substituents independently selected therefrom.

[0064] In some embodiments, Z 1 is

Chemical formula

[0065] In some embodiments, Z 1 is

Chemical formula

[0066] In some embodiments, Z 1 is

Chemical formula

Chemical formula

[0067] In some embodiments, the present invention provides a compound represented by formula (III)

Chemical formula

[0068] In some embodiments, R1 , R 2 and R 3 These are, independently, H, D, CN, C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, and C 3- Selected from C7 cycloalkyl groups or 4-7 membered heterocycloalkyl groups, of which the above C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C 3- C7 cycloalkyl groups and 4- to 7-membered heterocycloalkyl groups are optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from D, halogens, CN, OH, C1-C6 alkyl groups, C1-C6 haloalkyl groups, -O-C1-C6 alkyl groups, and -OC1-C6 haloalkyl groups.

[0069] In some embodiments, R 1 H, D, CN, C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C 3- C7 cycloalkyl group, or 4-7 membered heterocycloalkyl group, of which the above C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C 3- C7 cycloalkyl groups and 4- to 7-membered heterocycloalkyl groups are optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from D, halogens, CN, OH, C1-C6 alkyl groups, C1-C6 haloalkyl groups, -O-C1-C6 alkyl groups, and -OC1-C6 haloalkyl groups.

[0070] In some embodiments, R 1 H, D, CN, C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C 3- C7 cycloalkyl group, or 4-7 membered heterocycloalkyl group, of which the above C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C 3- C7 cycloalkyl groups, or 4- to 7-membered heterocycloalkyl groups, are optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from D, halogens (e.g., F, Cl, Br, or I), CN, OH, Me, CF3, OMe, OCF3, and OEt.

[0071] In some embodiments, R 1 The substituent is H, D, CN, or a C1-C3 alkyl group, which is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from D, halogens (e.g., F, Cl, Br, or I), CN, OH, Me, CF3, OMe, OCF3, or OEt.

[0072] In some embodiments, R 1 These are H, D, CN, CH3, CD3, CH2CH3, CF3, CHF2, CH2F, CH2CH2F, CH2OH, CH2OCH3, or CH2CN.

[0073] In some embodiments, R 1 is CN, CH3, CD3, CF3, CHF2, CD2F, or CH2F. In some embodiments, R 1 CF3 is CF3. In some embodiments, R 1 is CHF2. In some embodiments, R 1 is CH2F. In some embodiments, R 1 It is CD2F. In some embodiments, R 1 is CH3. In some embodiments, R 1 is CN.

[0074] In some embodiments, R 1 and R 4 These atoms, together with the atoms they link to, form a 5-7 membered partially saturated heterocycloalkyl group and are optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, CF3, NO2, oxo, OH, C1-C3 alkyl, C1-C3 haloalkyl, -O-C1-C3 alkyl, and -OC1-C3 haloalkyl groups.

[0075] In some embodiments, R 1 and R 4These atoms, together with the atoms they link to, form a 5-7 membered partially saturated heterocycloalkyl group and are optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, CF3, NO2, oxo, OH, Me, CF3, OMe, OCF3, and OEt.

[0076] In some embodiments, R 2 H, D, CN, C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C 3- C7 cycloalkyl group, or 4-7 membered heterocycloalkyl group, of which the above C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C 3- C7 cycloalkyl groups and 4- to 7-membered heterocycloalkyl groups are optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from D, halogens, CN, OH, C1-C6 alkyl groups, C1-C6 haloalkyl groups, -O-C1-C6 alkyl groups, and -OC1-C6 haloalkyl groups.

[0077] In some embodiments, R 2 H, D, CN, C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C 3- C7 cycloalkyl group, or 4-7 membered heterocycloalkyl group, of which the above C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C 3- A C7 cycloalkyl group or a 4- to 7-membered heterocycloalkyl group may be optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from D, halogens, CN, OH, Me, CF3, OMe, OCF3, and OEt.

[0078] In some embodiments, R 2 C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C 3- C7 cycloalkyl group, or 4-7 membered heterocycloalkyl group, of which the above C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C 3-C7 cycloalkyl groups and 4- to 7-membered heterocycloalkyl groups are optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from D, halogens, CN, OH, C1-C6 alkyl groups, C1-C6 haloalkyl groups, -O-C1-C6 alkyl groups, and -OC1-C6 haloalkyl groups.

[0079] In some embodiments, R 3 H, D, CN, C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C 3- C7 cycloalkyl group, or 4-7 membered heterocycloalkyl group, of which the above C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C 3- C7 cycloalkyl groups and 4- to 7-membered heterocycloalkyl groups are optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from D, halogens, CN, OH, C1-C6 alkyl groups, C1-C6 haloalkyl groups, -O-C1-C6 alkyl groups, and -OC1-C6 haloalkyl groups.

[0080] In some embodiments, R 3 H, D, CN, C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C 3- C7 cycloalkyl group, or 4-7 membered heterocycloalkyl group, of which the above C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C 3- A C7 cycloalkyl group or a 4- to 7-membered heterocycloalkyl group may be optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from D, halogens, CN, OH, Me, CF3, OMe, OCF3, and OEt.

[0081] In some embodiments, R 3 C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C 3- C7 cycloalkyl group, or 4-7 membered heterocycloalkyl group, of which the above C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C 3-C7 cycloalkyl groups and 4- to 7-membered heterocycloalkyl groups are optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from D, halogens, CN, OH, C1-C6 alkyl groups, C1-C6 haloalkyl groups, -O-C1-C6 alkyl groups, and -OC1-C6 haloalkyl groups.

[0082] In some embodiments, R 2 and R 3 These atoms, together with carbon atoms linked to them, form a C3-C7 cycloalkyl group or a 4- to 7-membered heterocycloalkyl group, and the above C3-C7 cycloalkyl group or 4- to 7-membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, NO2, oxo, OH, C1-C6 alkyl group, C1-C6 haloalkyl group, -O-C1-C6 alkyl group, or -OC1-C6 haloalkyl group.

[0083] In some embodiments, R 2 and R 3 These groups, together with carbon atoms linked to them, form a cyclopropyl group, a cyclobutyl group, an oxetanyl group, or a siletanyl group, and each substituent is optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, NO2, oxo, OH, C1-C6 alkyl, C1-C6 haloalkyl, -O-C1-C6 alkyl, or -OC1-C6 haloalkyl.

[0084] In some embodiments, R 2 and R 3 These, together with the carbon atoms linked to them, form a cyclopropyl group. In some embodiments, R 2 and R 3 These, together with the carbon atoms to which they are linked, form a cyclobutyl group. In some embodiments, R 2 and R 3 These, together with the carbon atoms linked to them, form an oxetanyl group. In some embodiments, R 2 and R 3forms a silylanyl group together with the carbon atoms connecting thereto, and is optionally substituted with 1, 2, 3 or 4 substituents independently selected from D, halogen, CN, NO2, oxo, OH, C1-C6 alkyl group, C1-C6 haloalkyl group, -O-C1-C6 alkyl group, -OC1-C6 haloalkyl group.

[0085] In some embodiments, the above

Chemical Formula

Chemical Formula

[0086] In some other embodiments, the present invention provides a compound represented by formula (IV),

Chemical Formula

[0087] In some embodiments, ring C is a 4- to 7-membered heterocycloalkyl group, optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, NO2, oxo, OH, C1-C6 alkyl, C1-C6 haloalkyl, -O-C1-C6 alkyl, or -OC1-C6 haloalkyl group. In some embodiments, ring C is an azetidinyl group, an oxetanyl group, a siletanyl group, a pyrrolidinyl group, or a tetrahydrofuranyl group, each substituent optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, NO2, oxo, OH, C1-C6 alkyl, C1-C6 haloalkyl, -O-C1-C6 alkyl, or -OC1-C6 haloalkyl group. In some embodiments, the C ring is an oxetanyl group, which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, NO2, oxo, OH, C1-C6 alkyl, C1-C6 haloalkyl, -O-C1-C6 alkyl, and -OC1-C6 haloalkyl.

[0088] In some embodiments, ring C is a C3-C7 cycloalkyl group and is optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, NO2, oxo, OH, C1-C6 alkyl, C1-C6 haloalkyl, -O-C1-C6 alkyl, and -OC1-C6 haloalkyl groups.

[0089] In some embodiments, the C ring is a cyclobutyl group and is optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, NO2, oxo, OH, C1-C6 alkyl, C1-C6 haloalkyl, -O-C1-C6 alkyl, and -OC1-C6 haloalkyl.

[0090] In some embodiments, the C ring is a cyclopropyl group and is optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, NO2, oxo, OH, C1-C6 alkyl, C1-C6 haloalkyl, -O-C1-C6 alkyl, and -OC1-C6 haloalkyl.

[0091] In some embodiments, ring C is a cyclobutyl group. In some embodiments, ring C is a cyclopropyl group.

[0092] In some other embodiments, the present invention relates to a compound represented by formula (IVa), [ka] Or provide a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated thereof, among which R 1 , R 10 , X, Y 1 , Y 2 , Y 3 , Y 5 , Y 7 , Y 8 , and Z 2 This is as defined in the present invention.

[0093] In some embodiments, R 1 The substituent is H, D, CN, or a C1-C3 alkyl group, which is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from D, halogen, CN, OH, Me, CF3, OMe, OCF3, or OEt.

[0094] In some embodiments, R 1 These are H, D, CN, CH3, CD3, CH2CH3, CF3, CHF2, CH2F, CD2F, CH2CH2F, CH2OH, CH2OCH3, or CH2CN.

[0095] In some embodiments, R 1 is CN, CH3, CD3, CF3, CHF2, CD2F, or CH2F. In some embodiments, R 1 CF3 is CF3. In some embodiments, R 1 is CHF2. In some embodiments, R 1 is CH2F. In some embodiments, R 1It is CD2F. In some embodiments, R 1 is CH3. In some embodiments, R 1 is CD3. In some embodiments, R 1 is CN.

[0096] In some embodiments, X is NR 4 In some embodiments, X is O.

[0097] In some embodiments, Y 1 is N, and Y 2 is N, and Y 3 CR 5 That is the case.

[0098] In some embodiments, Y 1 is N, and Y 2 is N, and Y 3 It is N.

[0099] In some embodiments, Y 1 is N, and Y 2 CR 6 and Y 3 CR 5 That is the case.

[0100] In some embodiments, Y 1 is N, and Y 2 CR 6 and Y 3 It is N.

[0101] In some embodiments, Y 1 CR 5 Y 2 is N, and Y 3 CR 5 That is the case.

[0102] In some embodiments, Y 1 CR 5 Y 2 is N, and Y 3 It is N.

[0103] In some embodiments, Y 1 CR 5 Y 2 CR 6 and Y 3 It is N.

[0104] In some embodiments, Y 1 CR 5 Y 2 CR 6 and Y 3 CR 5 In some embodiments, Y 1 CH is Y 2 CH is CH, and Y 3 is CH. In some embodiments, Y 1 CH is Y 2 CF is and Y 3 It is CH.

[0105] In some embodiments, each R 5 These are, independently, H, D, CN, halogen, SF5, OH, NH2, CHO, COOH, C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C1-C3 haloalkyl group, C1-C3 cyanoalkyl group, OR A , NR C R D or C(O)R B They are selected from among them.

[0106] In some embodiments, each R 5 Each of these is independently selected from H, D, OH, CN, NO2, SF5, halogen, C1-C3 haloalkyl, and C1-C3 cyanoalkyl.

[0107] In some embodiments, each R 5 Each of these elements is independently selected from H, D, halogens (e.g., F, Cl, Br, or I), and C1-C3 alkyl groups.

[0108] In some embodiments, each R 5Each is independently selected from H, D, F, Cl, or CH3. In some embodiments, each R 5 Each of them is independently selected from H.

[0109] In some embodiments, R 6 These are H, D, CN, halogen, OH, NH2, C1-C3 alkyl (e.g., CH3, CH2CH3, CH2CH2CH3, CH(CH3)2), C1-C3 haloalkyl (e.g., CF3, CHF2, CH2F), -O-C1-C3 alkyl (e.g., OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2), -OC1-C3 haloalkyl, C1-C3 cyanoalkyl, or SF5.

[0110] In some other embodiments, R 6 is H, D, F, Cl, OH, NH2, CN, CH3, CF3, OMe, OCF3, or SF5. In some other embodiments, R 6 is H, D, F, Cl, OH, NH2, or CN.

[0111] In some embodiments, R 6 H is H. In some embodiments, R 6 In some embodiments, R 6 is F. In some embodiments, R 6 is Cl. In some embodiments, R 6 is OH. In some embodiments, R 6 is CN.

[0112] In some other embodiments, R 6 It is H, D, or F.

[0113] In some embodiments, R 6 is a C1-C3 alkyl group, for example, CH3. In some embodiments, R 6 is a C1-C3 haloalkyl group, for example, CHF2, CF3. In some embodiments, R 6R is an -O-C1-C3 alkyl group, for example, OMe. In some embodiments, R 6 is a -OC1-C3 haloalkyl group, for example, OCF3. In some embodiments, R 6 It is SF5.

[0114] In some embodiments, Y 5 CR 8 Y 7 CR 8 and Y 8 CR 8 That is the case.

[0115] In some embodiments, Y 5 CR 8 Y 7 CR 8 and Y 8 It is N.

[0116] In some embodiments, Y 5 CR 8 Y 7 is N, and Y 8 CR 8 That is the case.

[0117] In some embodiments, Y 5 CR 8 Y 7 is N, and Y 8 It is N.

[0118] In some embodiments, Y 5 is N, and Y 7 CR 8 and Y 8 CR 8 That is the case.

[0119] In some embodiments, Y 5 is N, and Y 7 CH is CH, and Y 8 is CH. In some embodiments, Y 5 is N, and Y 7It is CCH3, and Y 8 It is CH.

[0120] In some embodiments, Y 5 is N, and Y 7 CR 8 and Y 8 It is N.

[0121] In some embodiments, Y 5 is N, and Y 7 CH is CH, and Y 8 is N. In some embodiments, Y 5 is N, and Y 7 It is CCH3, and Y 8 It is N.

[0122] In some embodiments, Y 5 is N, and Y 7 is N, and Y 8 CR 8 That is the case.

[0123] In some embodiments, Y 5 is N, and Y 7 is N, and Y 8 It is N.

[0124] In some embodiments, each R 8 These are, independently, H, D, halogen, CN, NO2, C1-C6 alkyl group, C1-C6 haloalkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, OR A , SR A SF5, NHOR A , C(O)OR A , C(O)R B , C(O)NR C R D , OC(O)NR C R D , NR C R D , NR C C(O)R B , NR C C(O)NR C RD , NR C C(O)OR A , NR C S(O)2R B , B(OR C )(OR D ), C(=NR C )NR C R D , NR D C(=NR C )NR C R D , NR D C(=NR C )R B P(O)R E R F , P(O)OR E Ure F , OP(O)OR E Ure F , S(O)(=NR B )R B , S(O)R B , S(O)NR C R D S(O)2R B , S(O)2NR C R D , NR C S(O)2NR C R D , or NR C S(O)(=NR B )R B Selected from, of which the above C1-C6 alkyl group, C2-C6 alkenyl group, or C2-C6 alkynyl group is R 12 It is optionally substituted with one, two, or three substituents independently selected from the given molecule.

[0125] In some embodiments, each R 8 These are H, D, halogen, CN, NO2, and OR, respectively, independently. A , SR A , selected from SF5, C1-C6 alkyl groups or C1-C6 haloalkyl groups. In some embodiments, R 8 H is H. In some embodiments, R 8 In some embodiments, R 8is a halogen. In some embodiments, R 8 is F. In some embodiments, R 8 is Cl. In some embodiments, R 8 is Br. In some embodiments, R 8 is I. In some embodiments, R 8 is CN. In some embodiments, R 8 It is NO2. In some embodiments, R 8 SF5. In some embodiments, R 8 is OR A These are, for example, -OH, -OMe, and -OCF3. In some embodiments, R 8 is SR A For example, -SMe.

[0126] In some embodiments, R 8 is a C1-C6 alkyl group, and R is optionally selected. 12 It is substituted with one, two, or three substituents independently selected from, for example, -CH3, -CH2CH3. In some embodiments, R 6 These are C1-C6 haloalkyl groups, such as -CF3, -CHF2, and -CH2F.

[0127] In some embodiments, R 8 It is a C2-C6 alkenyl group, and R is optionally selected. 12 It is substituted with one, two, or three substituents independently selected from R. In some embodiments, R 8 It is a C2-C6 alkynyl group, and R is optionally selected. 12 It is substituted with one, two, or three substituents independently selected from the given molecule.

[0128] In some embodiments, R 8 is B(OR C )(OR D ) is, for example, B(OH)2. In some embodiments, R 8 NHOR AFor example, NHOH. In some embodiments, R 8 is NR C R D These are, for example, -NH2, -NHCH3, and -N(CH3)2.

[0129] In some embodiments, R 8 is H, D, C1-C6 alkyl group. In some embodiments, R 8 These are H, D, and CH3.

[0130] In some embodiments, R 10 The elements are H, D, halogen, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl group, OC1-C6 alkyl group, OC1-C6 haloalkyl group, OC3-C7 cycloalkyl group, C3-C7 cycloalkyl group, CN, NO2, N3, or SF5, of which the above C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, or C3-C7 cycloalkyl group are optionally R 12 It is substituted with one, two, or three substituents independently selected from the given molecule.

[0131] In some embodiments, R 10 H is H. In some embodiments, R 10 In some embodiments, R 10 is a halogen. In some embodiments, R 10 These are F, Cl, Br, and I. In some embodiments, R 10 is CN. In some embodiments, R 10 It is NO2. In some embodiments, R 10 is N3. In some embodiments, R 10 It is SF5.

[0132] In some other embodiments, R 10The C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C1-C6 haloalkyl group are optionally R 12 It is substituted with one, two, or three substituents independently selected from the given molecule.

[0133] In some other embodiments, R 10 R is a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, or a C1-C6 haloalkyl group. In some embodiments, R 10 is a C1-C6 alkyl group. In some embodiments, R 10 R is a methyl group. In some embodiments, R 10 R is an ethyl group. In some embodiments, R 10 R is an isopropyl group. In some embodiments, R 10 It is a tert-butyl group.

[0134] In some other embodiments, R 10 R is a C2-C6 alkenyl group. In some other embodiments, R 10 is a C2-C6 alkynyl group. In some other embodiments, R 10 is a C1-C6 haloalkyl group. In some embodiments, R 10 CF3 is CF3. In some embodiments, R 10 is CHF2. In some embodiments, R 10 is CH2F. In some embodiments, R 10 This is CDF2.

[0135] In some other embodiments, R 10 is a C3-C7 cycloalkyl group, and R is optionally selected. 12 It is substituted with one, two, or three substituents independently selected from. In some other embodiments, R 10 R is a C3-C7 cycloalkyl group. In some other embodiments, R 10is a cyclobutyl group. In some other embodiments, R 10 It is a cyclopropyl group.

[0136] In some other embodiments, R 10 These are OC1-C6 alkyl groups, OC1-C6 haloalkyl groups, and OC3-C7 cycloalkyl groups, of which the above C1-C6 alkyl group or C3-C7 cycloalkyl group is optionally R 12 It is substituted with one, two, or three substituents independently selected from R. In some embodiments, R 10 is a selectively substituted OC1-C6 alkyl group. In some embodiments, R 10 R is an OC1-C6 haloalkyl group. In some embodiments, R 10 It is an OC3-C7 cycloalkyl group.

[0137] In some embodiments, R 10 is a C1-C6 haloalkyl group. In some embodiments, R 10 It is CHF2.

[0138] In some embodiments, Z 2 H, D, halogen, CN, NO2, SF5, C1-C8 alkyl group, C2-C8 alkenyl group, C2-C8 alkynyl group, C6-C 10 Aryl group, C3-C 10 Cycloalkyl groups, 5-10 membered heteroaryl groups, or 4-14 membered heterocycloalkyl groups, NR C R D , OR A , SR A NHOR A , C(O)R B , C(O)OR A , C(O)NR C R D , OC(O)NR C R D , NR C C(O)R B , NR C C(O)NR C R D , NR CC(O)OR A , NR C S(O)2R B , S(O)R B , S(O)NR C R D S(O)2R B , S(O)2NR C R D , or NR C S(O)2NR C R D These include the above C1-C8 alkyl group, C2-C8 alkenyl group, C2-C8 alkynyl group, and C6-C 10 Aryl group, C3-C 10 Cycloalkyl groups, 5-10 membered heteroaryl groups, or 4-14 membered heterocycloalkyl groups are optionally used in R 11 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0139] In some embodiments, Z 2 is H. In some embodiments, Z 2 In some embodiments, Z 2 is a halogen (e.g., F, Cl, Br, or I). In some embodiments, Z 2 is CN. In some embodiments, Z 2 It is NO2. In some embodiments, Z 2 It is SF5.

[0140] In some embodiments, Z 2 is NR C R D , OR A , SR A , NR C C(O)R B The C1-C8 alkyl group, C2-C8 alkenyl group, and C2-C8 alkynyl group are optionally R 11 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0141] In some embodiments, each R A These are independently H, D, C1-C6 alkyl, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Selected from cycloalkyl-C1-C6 alkyl groups or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, of which the above C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, are optionally R 14 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0142] In some embodiments, each R A These are H, D, C1-C6 alkyl, and C3-C, respectively, independently. 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C3-C 10 Selected from cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, of which the above C1-C6 alkyl group and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C3-C 10 Cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, are optionally R 14 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0143] In some embodiments, R B These are independently C1-C6 alkyl groups and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Selected from cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, of which the above C1-C6 alkyl group and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, are optionally R 14 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0144] In some embodiments, R B These are independently C1-C6 alkyl groups and C3-C 10 Selected from cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, of which the above C1-C6 alkyl group and C3-C 10 Cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, are optionally R 14 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0145] In some embodiments, each R C These are, independently, H, D, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Selected from cycloalkyl-C1-C6 alkyl groups or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, of which the above C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, are optionally R 14 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0146] In some embodiments, each R C These are H, D, C1-C6 alkyl, and C6-C, respectively, independently. 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Selected from cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, among which the above C1-C6 alkyl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, are optionally R 14 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0147] In some embodiments, each R C These are H, D, C1-C6 alkyl, and C6-C, respectively, independently. 10Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Selected from cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, among which the above C1-C6 alkyl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, are optionally R 14 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0148] In some embodiments, each R C Each is independently selected from H, D, and C1-C6 alkyl groups. In some embodiments, each R C Each of these is independently selected from H, D, CH3, CD3, and CH2CH3.

[0149] In some embodiments, R D H, D, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 A cycloalkyl-C1-C6 alkyl group, or a 4-10 member heterocycloalkyl-C1-C6 alkyl group, of which the above C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10Cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, are optionally R 14 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0150] In some embodiments, R D H, D, C1-C6 alkyl, C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 A cycloalkyl-C1-C6 alkyl group, or a 4-10 member heterocycloalkyl-C1-C6 alkyl group, of which the above C1-C6 alkyl group and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, are optionally R 14 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0151] In some embodiments, each R 14 These are, independently, H, D, CN, halogen, oxo, SF5, C1-C8 alkyl group, C2-C8 alkenyl group, C2-C8 alkynyl group, and C6-C 14 Aryl group, C3-C 14 Cycloalkyl groups, 5-14 member heteroaryl groups, or 4-14 member heterocycloalkyl groups, OR a , SR a SF5, NHOR a , C(O)R b , C(O)NR c R d , C(O)OR a, NR c R d , or NR c C(O)R b Selected from among, of which the above C1-C8 alkyl group, C2-C8 alkenyl group, C2-C8 alkynyl group, C6-C 14 Aryl group, C3-C 14 Cycloalkyl groups, 5-14 membered heteroaryl groups, or 4-14 membered heterocycloalkyl groups are optionally D, NO2, CN, halogen, oxo, SF5, C1-C6 alkyl groups, C2-C6 alkenyl groups, C2-C6 alkynyl groups, C1-C6 haloalkyl groups, C1-C6 alkylOH, C1-C6 alkyl-O-C1-C6 alkyl groups, CN, NO2, N3, OR a1 , SR a1 SF5, NHOR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 ,OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0152] In some embodiments, each R 14 These are H, D, CN, halogen, oxo, SF5, C1-C8 alkyl, and C6-C, respectively, independently. 14 Aryl group, C3-C 14 Cycloalkyl groups, 5-14 member heteroaryl groups, or 4-14 member heterocycloalkyl groups, OR a , SR a SF5, NHOR a , C(O)R b , C(O)NR c R d , C(O)OR a , NR c R d , or NR c C(O)R bSelected from among, of which the above C1-C8 alkyl groups and C6-C 14 Aryl group, C3-C 14 Cycloalkyl groups, 5-14 membered heteroaryl groups, or 4-14 membered heterocycloalkyl groups are optionally D, NO2, CN, halogen, oxo, SF5, C1-C6 alkyl groups, C2-C6 alkenyl groups, C2-C6 alkynyl groups, C1-C6 haloalkyl groups, C1-C6 alkylOH, C1-C6 alkyl-O-C1-C6 alkyl groups, CN, NO2, N3, OR a1 , SR a1 SF5, NHOR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 ,OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0153] In some embodiments, each R 14 Each is independently selected from H, D, CN, halogen, oxo, SF5, -CH3, -CD3, -CH2CH3, -OH, -OCH3, -OCH2CH3, -NH2, -N(CH3)2, -N(CH2CH3)2, -C(O)CH(CH3)2, -COOH, -C(O)N(CH3)2, or [ka] They are selected from among them.

[0154] In some embodiments, each R A These are, independently, H, D, -CH3, -CD3, -CH2CH3, -CF3, -CH2CH2OH, -CH2CH2OCH3, and a tetrahydrofuranyl group. [ka] They are selected from among them.

[0155] In some embodiments, R B teeth [ka] That is the case.

[0156] In some embodiments, R D H, D, -CH3, -CD3, -CH2CH3, [ka] That is the case.

[0157] In some embodiments, Z 2 These are C1-C8 alkyl groups, C2-C8 alkenyl groups, and C2-C8 alkynyl groups, of which the above C1-C8 alkyl groups, C2-C8 alkenyl groups, and C2-C8 alkynyl groups are optionally R 11 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0158] In some embodiments, Z 2 is a C1-C8 alkyl group, and R is optionally selected. 11 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0159] In some embodiments, the above Z 2 teeth, [ka] It has the structure of [the object].

[0160] In some embodiments, Z 2 This is a C2-C8 alkenyl group, and R is optionally selected. 11 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0161] In some embodiments, the above Z 2 teeth, [ka] It has the structure of [the object].

[0162] In some embodiments, Z 2 It is a C2-C8 alkynyl group, and R is optionally selected. 11 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0163] In some embodiments, the above Z 2 teeth, [ka] It has the structure of [the object].

[0164] In some embodiments, each R 11 These are H, D, halogen, CN, N3, oxo, and OR, respectively, independently. A , SR A SF5, C(O)R B , C(O)NR C R D , C(O)OR A ,OC(O)R B , OC(O)NR C R D , NR C R D , NR C C(O)R D Cy 3 They are selected from among them.

[0165] In some embodiments, each R 11 Each of these is independently selected from H, D, halogen, CN, -OH, -OCH3, -OCH2CH3, -NH2, -NHCH3, -N(CH3)2, -N(CH2CH3)2, morpholinyl group, or pyrazolyl group.

[0166] In some embodiments, the above Z 2 SH, OCF2CF3, [ka] [ka] It has the structure of [the object].

[0167] In some embodiments, Z 2 NHOR A In some embodiments, Z 2 is C(O)R B In some embodiments, Z 2 is C(O)OR A In some embodiments, Z 2 is C(O)NR C R D In some embodiments, Z 2 is OC(O)NR C R D In some embodiments, Z 2 is NR C C(O)NR C R D In some embodiments, Z 2 is NR C C(O)OR A In some embodiments, Z 2 is NR C S(O)2R B In some embodiments, Z 2 is S(O)R B In some embodiments, Z 2 is S(O)NR C R D In some embodiments, Z 2 is S(O)2R B In some embodiments, Z 2 is S(O)2NR C R D In some embodiments, Z 2 is NR C S(O)2NR C R D That is the case.

[0168] In some embodiments, Z 2 is C6-C 10 Aryl group, C3-C10 The C6-C is a cycloalkyl group, a 5-10 membered heteroaryl group, or a 4-14 membered heterocycloalkyl group, among which the above C6-C 10 Aryl group, C3-C 10 Cycloalkyl groups, 5-10 membered heteroaryl groups, or 4-14 membered heterocycloalkyl groups are optionally used in R 11 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0169] In some embodiments, Z 2 is C 6- C 10 Aryl group, C 3- C 10 The C6-C is a cycloalkyl group, a 5-10 membered heteroaryl group, or a 4-10 membered heterocycloalkyl group, among which the above C6-C 10 Aryl group, C3-C 10 Cycloalkyl groups, 5-10 membered heteroaryl groups, or 4-10 membered heterocycloalkyl groups are optionally used in R 11 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0170] In some embodiments, Z 2 is C 6- C 10 It is an aryl group, and R is optionally selected. 10 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from. In some embodiments, Z 2 R is a phenyl group, and optionally 1, 2, 3, 4, or 5 R groups. 11 It will be replaced with.

[0171] In some embodiments, Z 2 It is a 5-10 member heteroaryl group, and R can be optionally selected. 11 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0172] In some embodiments, for example, Z 2The group is a pyrrolyl group, furanyl group, thienyl group, imidazolyl group, oxazolyl group, thiazolyl group, pyrazolyl group, triazolyl group, thiadiazolyl group, oxadiazolyl group, pyridinyl group, pyrimidinyl group, pyrazinyl group, pyridadinyl group, indolyl group, indazolyl group, benzo[d]imidazolyl group, quinolinyl group, quinoxalinyl group, pyrrolo[3,2-b]pyridinyl group, or indolidinyl group, and each ring is optionally R 11 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0173] In some embodiments, Z 2 is C 3- C 10 It is a cycloalkyl group, and R is optionally selected. 11 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0174] In some embodiments, Z 2 is saturated C 3- C 10 Cycloalkyl groups or partially unsaturated C 5- C 10 It is a cycloalkyl group, and each substituent is optionally R 11 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0175] In some embodiments, Z 2 The group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, or a cycloheptyl group, and each ring is optionally R 11 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0176] In some embodiments, Z 2 R is a saturated 4-14 member heterocycloalkyl group, and R is optionally selected. 11 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from. In some embodiments, Z 2This is a saturated 4-14 member heterocycloalkyl group having 1, 2, 3, or 4 heteroatoms independently selected from N, O, S, P, and Si, wherein the heteroatoms are optionally substituted with one or more oxo or thio atoms (e.g., S(O), S(O)2, or P(O)), and among these, the 4-14 member heterocycloalkyl group is optionally substituted with R 11 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0177] In some embodiments, Z 2 It is a partially unsaturated 5-14 member monoheterocycloalkyl group, and R is optionally selected. 11 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0178] In some embodiments, Z 2 These are piperidinyl group, piperazinyl group, morpholinyl group, octahydropyrrolo[3,4-c]pyrrolyl group, octahydro-1H-pyrrolo[3,2-c]pyridinyl group, 2-azabicyclo[2.2.1]heptyl group, 2,5-diazabicyclo[2.2.1]heptyl group, 5,6,7,8-tetrahydroimidazo[1,5-a]pyradinyl group, 5,6,7,8-te The substituents are trahydroimidazo[1,2-a]pyradinyl group, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyradinyl group, 5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyradinyl group, 4,7-diazaspiro[2.5]octyl group, and 1,8-diazaspiro[4.5]decyl group, and each substituent is optionally R 11 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0179] In some embodiments, each R 11 These are H, D, halogen, CN, N3, oxo, C1-C6 alkyl, and OR, respectively, independently. A , SR A SF5, NR C Ure A , C(O)R B , NR C R DCy 3 From which the above C1-C6 alkyl groups are selected, R is optionally selected. 12 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0180] In some embodiments, each R 11 The group is independently selected from H, D, halogen, CN, N3, oxo, -CH3, -CD3, CH2F, CHF2, CF3, -CH2CH3, -CH(CH3)2, -CH2OH, -CH2OCH3, -CH2NH2, -CH2NHCH3, -CH2N(CH3)2, -OH, -OCH3, -OCH2CH3, -NH2, -NHCH3, -N(CH3)2, -NHCH2CH3, -N(CH2CH3)2, morpholinyl group, pyrazolyl group, or 4,4-difluoro-1-piperidinyl group.

[0181] In some embodiments, the above Z 2 teeth, [ka] It has the structure of [the object].

[0182] In some embodiments, each R 11 These are independently H, D, halogen, CN, NO2, N3, oxo, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, OR A , SR A SF5, NR C Ure A , C(O)R B , C(=S)R B , C(O)NR C R D , C(O)NR C Ure A , C(O)OR A , C(=NR C )NR C R D ,OC(O)R B , OC(O)NR C R D , NR C R D , NR CC(O)R D , NR C C(O)NR C R D , NR C C(O)OR A , B(OR C )(OR D ), NR D C(=NR C )NR C R D , NR D C(=NR C )R B , SiR G R H R I P(O)R E R F , P(O)OR E Ure F , OP(O)OR E Ure F , S(O)(=NR B )R B , S(O)R B , S(O)NR C R D S(O)2R B , NR C S(O)2R B , S(O)2NR C R D , NR C S(O)2NR C R D , NR C S(O)(=NR B )R B Cy 3 , C1-C6 alkyl-Cy 3 OCy 3 O-C1-C6 alkyl-Cy 3 Selected from these, of which the above C1-C6 alkyl group, C2-C6 alkenyl group, and C2-C6 alkynyl group optionally have 1, 2, 3, 4, or 5 R 12 It will be replaced with.

[0183] In some embodiments, each R 11 R is independently selected from H, D, halogen, CN, NO2, N3, oxo, and SF5. In some embodiments, each R 11R is independently selected from H. In some embodiments, each R 11 R is independently selected from D. In some embodiments, each R 11 R is independently selected from halogens (e.g., F, Cl, Br, I). In some embodiments, each R 11 R is independently selected from CN. In some embodiments, each R 11 It is independently selected from NO2. In some embodiments, each R 11 R is independently selected from N3. In some embodiments, each R 11 R is independently selected from oxos, for example, carbon atoms and heteroatoms are optionally substituted with one or more oxos or thios (e.g., C(O), S(O), C(S), or S(O)2, or P(O), etc.). In some embodiments, each R 11 They are selected independently from SF5.

[0184] In some embodiments, each R 11 OR A Selected from. In some embodiments, for example, each R 11 These are independently selected from OH, OCH3, OCH2CH3, OCF3, and OCH2CF3.

[0185] In some embodiments, each R 11 SR is independently A Selected from. In some embodiments, each R 11 NHOR A Selected from among, for example, NHOH.

[0186] In some embodiments, each R 11 C(O)R B Selected from. In some embodiments, each R 11 C(O)R B Selected from, and R B is H, D. In some embodiments, each R 11 He is the CHO.

[0187] In some embodiments, each R 11 C(O)R B Selected from, and R B C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 The substituents are an aryl group, a 5-10 membered heteroaryl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, or a heterocycloalkylalkyl group, and each substituent is optionally R 14 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0188] In some embodiments, each R 11 C(O)R B Selected from, and R B C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 A cycloalkyl-C1-C6 alkyl group, or a 4-10 member heterocycloalkyl-C1-C6 alkyl group, where each substituent is optionally R 14 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0189] In some embodiments, each R 11 Independently, C(=S)R B Selected from. In some embodiments, each R 11 These are independently selected from C(=S)CH3, C(=S)CH2CH3, C(=S)CH2CH2CH3, C(=S)CH(CH3)2, and C(=S)C(CH3)3.

[0190] In some embodiments, each R 11 Independently, C(O)NRC R D Selected from. In some embodiments, each R 11 Independently, C(O)NR C Ure A Selected from. In some embodiments, each R 11 C(O)OR A They are selected from among them.

[0191] In some embodiments, each R 11 Independently, C(=NR) C )NR C R D Selected from. In some other embodiments, each R 11 O(O)R is independently B Selected from. In some other embodiments, each R 11 Independently, OC(O)NR C R D They are selected from among them.

[0192] In some other embodiments, each R 11 Independently, NR C R D Selected from, and R C and R D These are independently H, D, C1-C6 alkyl, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Selected from cycloalkyl-C1-C6 alkyl groups or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, of which the above C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, are optionally R 14 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from R. In some other embodiments, each R 11 These are independently selected from NH2, NHCH3, N(CH3)2, NHCH2CH3, N(CH2CH3)2, NHCH2CH2CH3, N(CH2CH2CH3)2, NHCH(CH3)2, NHCH2CH2OH, N(CH3)CH2CH2OH, NHCH2CH2OCH3, and N(CH3)CH2CH2OCH3.

[0193] In some other embodiments, each R 11 Independently, NR C C(O)R D Selected from. In some other embodiments, each R 11 Independently, NR C C(O)NR C R D Selected from. In some other embodiments, each R 11 Independently, NR C C(O)OR A Selected from. In some other embodiments, each R 11 Independently, NR D C(=NR C )NR C R D Selected from. In some other embodiments, each R 11 Independently, NR D C(=NR C )R B They are selected from among them.

[0194] In some other embodiments, each R 11 B(OR) is independent C )(OR D ) are selected from. In some other embodiments, each R 11 Independently, SiR G R H RI Selected from, for example, each R 11 R is independently selected from Si(CH3)3. In some other embodiments, each R 11 Independently, P(O)R E R F Selected from, for example, each R 11 R is independently selected from P(O)(CH3)2. In some other embodiments, each R 11 P(O)OR E Ure F Selected from. In some other embodiments, each R 11 OP(O)OR E Ure F Selected from. In some other embodiments, each R 11 S(O)(=NR) B )R B They are selected from among them.

[0195] In some other embodiments, each R 11 S(O)R B Selected from. In some other embodiments, each R 11 S(O)NR is independent C R D Selected from. In some other embodiments, each R 11 This is independently S(O)2R B Selected from. In some other embodiments, each R 11 Independently, NR C S(O)2R B Selected from. In some other embodiments, each R 11 This is independently S(O)2NR C R D Selected from. In some other embodiments, each R 11 Independently, NR C S(O)2NR C R D Selected from. In some other embodiments, each R 11 Independently, NR C S(O)(=NR B )R B They are selected from among them.

[0196] In some other embodiments, each R 11 Cy 3 Selected from, Cy 3phenyl group, naphthyl group, pyrrolyl group, furanyl group, thienyl group, imidazolyl group, oxazolyl group, thiazolyl group, tetrazolyl group, pyrazolyl group, triazolyl group, thiadiazolyl group, oxadiazolyl group, pyridinyl group, pyrimidinyl group, pyrazinyl group, pyridadinyl group, indolyl group, isoindolyl group, indolidinyl group, benzofuranyl group, isobenzofuranyl group, benzo[b]thienyl group, benzo[c]thienyl group, indazolyl group, benzo[d]imidazolyl group, pyrrolyl[3, 2-b]pyridinyl group, pyrrolo[3,2-c]pyridinyl group, pyrrolo[2,3-c]pyridinyl group, pyrrolo[2,3-b]pyridinyl group, pyrrolo[3,4-b]pyridinyl group, pyrrolo[3,4-c]pyridinyl group, benzo[d]isoxazolyl group, benzo[d]oxazolyl group, flou[3,2-b]pyridinyl group, flou[3,2-c]pyridinyl group, flou[2,3-c]pyridinyl group, flou[2,3-b]pyridinyl group, benzo[c]isoxazolyl group, flou[3,4-b]pyridinyl group, flou [3,4-c]pyridinyl group, benzo[d]isothiazolyl group, benzo[d]thiazolyl group, thieno[3,2-b]pyridinyl group, thieno[3,4-c]pyridinyl group, benzo[d][1,2,3]triazolyl group, pyrazolo[4,3-b]pyridinyl group, pyrazolo[4,3-c]pyridinyl group, pyrazolo[3,4-c]pyridinyl group, pyrazolo[3,4-b]pyridinyl group, imidazo[4,5-b]pyridinyl group, imidazo[4,5-c]pyridinyl group, imidazo[4,5-c]pyridinyl group , imidazo[4,5-b]pyridinyl group, pyrrolo[3,2-c]pyridazinyl group, pyrrolo[3,2-d]pyridazinyl group, pyrrolo[2,3-b]pyridazinyl group, pyrrolo[2,3-d]pyridazinyl group, pyrrolo[2,3-c]pyridazinyl group, pyrrolo[3,4-c]pyridazinyl group, pyrrolo[3,4-d]pyridazinyl group, pyrrolo[3,4-b]pyridazinyl group, pyrrolo[3,4-d]pyridazinyl group, pyrrolo[3,4-d]pyridazinyl group, 6H-pyrrolo[3,4-c] Pyridazinyl group, azetidinyl group, oxetanyl group, thietanyl group, pyrrolidinyl group, tetrahydrofuranyl group, tetrahydrothienyl group, piperidinyl group, dioxanyl group, tetrahydropyranyl group, tetrahydrothiopyranyl group, piperazinyl group, morpholinyl group, azepanyl group, diazepanyl group, diazokanyl group, azepanyl group, cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, and each ring optionally has 1, 2, 3, 4 or 5 R, 13 It will be replaced with.

[0197] In some other embodiments, each R 11 These are independently C1-C6 alkyl-Cy 3 Selected from. In some other embodiments, each R 11 These are independently C1 alkyl-Cy 3 Selected from. In some other embodiments, each R 11 These are independently C2 alkyl-Cy 3 Selected from. In some other embodiments, each R 11 These are independently C3 alkyl-Cy 3 Selected from. In some other embodiments, each R 11 These are independently C4 alkyl-Cy 3 Selected from. In some other embodiments, each R 11 These are independently C5 alkyl-Cy 3 Selected from. In some other embodiments, each R 11 This is independently C6 alkyl-Cy 3 They are selected from among them.

[0198] In some other embodiments, each R 11 OCy 3 Selected from. In some other embodiments, each R 11 Independently, OC6-C 10 Selected from aryl groups. In some other embodiments, each R 11 Independently, OC3-C 10Selected from cycloalkyl groups. In some other embodiments, each R 11 R is independently selected from O-5 to 10-membered heteroaryl groups. In some other embodiments, each R 11 These are independently selected from O-4 to 10-membered heterocycloalkyl groups.

[0199] In some other embodiments, each R 11 These are independently O-C1-C6 alkyl-Cy 3 Selected from. In some other embodiments, each R 11 These are independently O-C1 alkyl-Cy 3 Selected from. In some other embodiments, each R 11 These are independently O-C2 alkyl-Cy 3 Selected from. In some other embodiments, each R 11 These are independently O-C3 alkyl-Cy 3 Selected from. In some other embodiments, each R 11 These are independently O-C4 alkyl-Cy 3 Selected from. In some other embodiments, each R 11 These are independently O-C5 alkyl-Cy 3 Selected from. In some other embodiments, each R 11 These are independently O-C6 alkyl-Cy 3 They are selected from among them.

[0200] In some embodiments, each R 11 The R group is independently selected from C1-C6 alkyl groups (e.g., C1-C6 alkyl groups, C1-C5 alkyl groups, C1-C4 alkyl groups, C1-C3 alkyl groups, C1-C2 alkyl groups) and optionally has 1, 2, 3, 4, or 5 R groups. 12 It is replaced by. In some embodiments, each R 11These are independently selected from CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2CH2CH2CH3, CH2CH(CH3)2, C(CH3)3, CH2F, CHF2, CF3, CH2CH2F, CH2CHF2, CH2CF3, CF2CH3, CF2CF3, CF2CH2CH3, CH2OH, CH2CH2OH, CH(OH)CH3, CH2CH2CH2OH, CH(OH)CH2CH2OH, CH2NH2, CH2CH2NH2, CH2NH2, CH2CH2NHCH3, CH2CH2N(CH3)2, CH2CN, CH2CH2CN, and CH2CH2CH2CN.

[0201] In some embodiments, each R 11 R is independently selected from C2-C6 alkenyl groups (e.g., C2-C6 alkenyl group, C2-C5 alkenyl group, C2-C4 alkenyl group, C2-C3 alkenyl group), and 1, 2, 3, 4, or 5 R are optionally selected. 12 It will be replaced with.

[0202] In some embodiments, each R 11 R is independently selected from C2-C6 alkynyl groups (e.g., C2-C6 alkynyl group, C2-C5 alkynyl group, C2-C4 alkynyl group, C2-C3 alkynyl group), and R is optionally selected. 12 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0203] In some embodiments, each R 11 These are independently H, D, halogen, CN, OR A , NR C R D Cy 3 , selected from C1-C6 alkyl groups, and R is optionally selected 12 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0204] In some embodiments, each R 11These are independently selected from H, D, halogen, CN, OH, OCH3, OCH2CH3, NH2, NHCH3, N(CH3)2, NCH2CH3, N(CH2CH3)2, CH3, CH2F, CHF2, CF3, CH2CH3, CH2OH, CH2N(CH3)2, morpholinyl group, and 4,4-difluoro-1-piperidinyl group.

[0205] In some embodiments, two R 11 These atoms, along with the atoms they bond to, form an oxo molecule.

[0206] In some embodiments, two adjacent R 11 C 3- C 10 Forms a cycloalkyl group or a 4-10 member heterocycloalkyl group, of which the above C 3- C 10 Cycloalkyl groups or 4-10 member heterocycloalkyl groups can optionally include D, halogen, C1-C6 alkyl, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl group, C1-C6 cyanoalkyl group, CN, NO2, oxo, OR a , SR a SF5, NHOR a , C(O)R b , C(O)NR c R d , C(O)OR a ,OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R b , NR c C(O)NR c R d , NR c C(O)OR a , B(OR c )(OR d ), C(=NR c )NR c R d , NR d C(=NR c )NR cR d , NR d C(=NR c )R b , OP(O)OR e Ure f , P(O)OR e Ure f , S(O)(=NR b )R b , S(O)R b , S(O)NR c R d S(O)2R b , NR c S(O)2R b , S(O)2NR c R d , NR c S(O)2NR c R d , NR c S(O)(=NR b )R b , C6-C 10 Aryl group, C3-C 10 Substituted with 1, 2, or 3 substituents independently selected from cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups, of which the above C6-C 10 Aryl group, C3-C 10 Cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups are optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogens, CN, NO2, NH2, NHC1-C4 alkyl groups, N(C1-C4 alkyl)2, C1-C3 alkyl groups, C1-C3 haloalkyl groups, OC1-C3 alkyl groups, OC1-C3 haloalkyl groups, OC2-C3 alkylOH, OC2-C3 alkyl-O-C1-C6 alkyl groups, or SF5.

[0207] In some embodiments, two adjacent R 11 C 3- C 10Forms cycloalkyl groups, optionally including D, halogen, C1-C6 alkyl, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl group, C1-C6 cyanoalkyl group, CN, NO2, oxo, OR a , SR a SF5, NHOR a , C(O)R b , C(O)NR c R d , C(O)OR a ,OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R b , NR c C(O)NR c R d , NR c C(O)OR a , B(OR c )(OR d ), C(=NR c )NR c R d , NR d C(=NR c )NR c R d , NR d C(=NR c )R b , OP(O)OR e Ure f , P(O)OR e Ure f , S(O)(=NR b )R b , S(O)R b , S(O)NR c R d S(O)2R b , NR c S(O)2R b , S(O)2NR c R d , NR c S(O)2NR c R d , NR c S(O)(=NR b )R b Cy 4Substituted with one, two, or three substituents independently selected from, of which Cy 4 is C6-C 10 Aryl group, C3-C 10 The group consists of a cycloalkyl group, a 5-10 membered heteroaryl group, and a 4-10 membered heterocycloalkyl group, among which Cy 4 It is optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, NO2, OH, oxo, NH2, NHC1-C4 alkyl, N(C1-C4 alkyl)2, C1-C3 alkyl, C1-C3 haloalkyl, OC1-C3 alkyl, OC1-C3 haloalkyl, OC2-C3 alkylOH, OC2-C3 alkyl-O-C1-C6 alkyl, or SF5.

[0208] In some embodiments, two adjacent R 11 These, together with the atoms linked to them, form 4-10 membered heterocycloalkyl groups, optionally consisting of D, halogen, C1-C6 alkyl, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl group, C1-C6 cyanoalkyl group, CN, NO2, oxo, OR a , SR a SF5, NHOR a , C(O)R b , C(O)NR c R d , C(O)OR a ,OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R b , NR c C(O)NR c R d , NR c C(O)OR a , B(OR c )(OR d ), C(=NR c )NR c R d , NR d C(=NR c )NR c Rd , NR d C(=NR c )R b , OP(O)OR e Ure f , P(O)OR e Ure f , S(O)(=NR b )R b , S(O)R b , S(O)NR c R d S(O)2R b , NR c S(O)2R b , S(O)2NR c R d , NR c S(O)2NR c R d , NR c S(O)(=NR b )R b Cy 4 Substituted with one, two, or three substituents independently selected from, of which Cy 4 is C6-C 10 Aryl group, C3-C 10 The group consists of a cycloalkyl group, a 5-10 membered heteroaryl group, and a 4-10 membered heterocycloalkyl group, among which Cy 4 It is optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, NO2, OH, oxo, NH2, NHC1-C4 alkyl, N(C1-C4 alkyl)2, C1-C3 alkyl, C1-C3 haloalkyl, OC1-C3 alkyl, OC1-C3 haloalkyl, OC2-C3 alkylOH, OC2-C3 alkyl-O-C1-C6 alkyl, or SF5.

[0209] In some embodiments, each Cy 3 These are each independently selective substitutions of C6-C 10 Aryl group, C3-C 10 Selected from cycloalkyl groups, 5-10 membered heteroaryl groups, or 4-10 membered heterocycloalkyl groups, each Cy 3 R is chosen at will. 13It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0210] In some embodiments, Cy 3 is C6-C 10 It is an aryl group, and R is optionally selected. 12 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from. In some embodiments, Cy 3 R is a phenyl group or a naphthyl group, and R is optionally selected. 12 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from. In some embodiments, Cy 3 is a phenyl group, and R is optionally selected. 13 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0211] In some embodiments, Cy 3 It is a 5-10 member heteroaryl group, and R can be optionally selected. 13 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0212] In some embodiments, Cy 3The pyrrolyl group, furanyl group, thienyl group, imidazolyl group, oxazolyl group, thiazolyl group, tetrazolyl group, pyrazolyl group, triazolyl group, thiadiazolyl group, oxadiazolyl group, pyridinyl group, pyrimidinyl group, pyrazinyl group, pyridadinyl group, indolyl group, isoindolyl group, indolidinyl group, benzofuranyl group, isobenzofuranyl group, benzo[b]thienyl group, benzo[c]thienyl group, indazolyl group, benzo[d]imidazolyl group, pyrrolo[3,2-b]pyridinyl group, pyrrolo[ 3,2-c]pyridinyl group, pyrrolo[2,3-c]pyridinyl group, pyrrolo[2,3-b]pyridinyl group, pyrrolo[3,4-b]pyridinyl group, pyrrolo[3,4-c]pyridinyl group, benzo[d]isoxazolyl group, benzo[d]oxazolyl group, flou[3,2-b]pyridinyl group, flou[3,2-c]pyridinyl group, flou[2,3-c]pyridinyl group, flou[2,3-b]pyridinyl group, benzo[c]isoxazolyl group, flou[3,4-b]pyridinyl group, flou[3,4-c]pyridinyl group, benzo[ d] isothiazolyl group, benzo[d]thiazolyl group, thieno[3,2-b]pyridinyl group, thieno[3,4-c]pyridinyl group, benzo[d][1,2,3]triazolyl group, pyrazolo[4,3-b]pyridinyl group, pyrazolo[4,3-c]pyridinyl group, pyrazolo[3,4-c]pyridinyl group, pyrazolo[3,4-b]pyridinyl group, imidazo[4,5-b]pyridinyl group, imidazo[4,5-c]pyridinyl group, imidazo[4,5-b]pyridinyl group, pyrrolo[ The group consists of a 3,2-c]pyridazinyl group, a pyrrolo[3,2-d]pyrimidinyl group, a pyrrolo[2,3-b]pyridazinyl group, a pyrrolo[2,3-d]pyrimidinyl group, a pyrrolo[2,3-c]pyridazinyl group, a pyrrolo[3,4-c]pyridazinyl group, a pyrrolo[3,4-d]pyrimidinyl group, a pyrrolo[3,4-b]pyridazinyl group, a pyrrolo[3,4-d]pyridazinyl group, a pyrrolo[3,4-d]pyrimidinyl group, and a 6H-pyrrolo[3,4-c]pyridazinyl group, and each ring is optionally R 13 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0213] In some embodiments, Cy 3 is a pyrimidinyl group, and R is optionally selected. 13 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from. In some embodiments, Cy 3 is a pyridazinyl group, and R is optionally selected. 13 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from. In some embodiments, Cy 3 is a pyrazinyl group, and R is optionally selected. 13 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from. In some other embodiments, Cy 3 It is a pyrazolyl group, and R is optionally selected. 13 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0214] In some other embodiments, Cy 3 is C3-C 10 It is a cycloalkyl group, and R is optionally selected. 13 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0215] In some other embodiments, Cy 3 R is a 4-10 member heterocycloalkyl group, and R is optionally selected. 13 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0216] In some embodiments, Cy 3 The group is an azetidinyl group, an oxetanyl group, a thiocyclobutyl group, a pyrrolidinyl group, a tetrahydrofuranyl group, a tetrahydrothienyl group, a piperidinyl group, a dioxanyl group, a tetrahydropyranyl group, a tetrahydrothiopyranyl group, a piperazinyl group, a morpholinyl group, an azepanyl group, a diazokanyl group, a diazepanyl group, or an azepanyl group, and each ring can optionally have 1, 2, 3, 4, or 5 R groups. 13 It will be replaced with.

[0217] In some other embodiments, each R 12These are, independently, H, D, halogen, CN, NO2, N3, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl group, C1-C6 alkylOH, C1-C6 alkyl-O-C1-C6 alkyl group, OR a1 , SR a1 SF5, NHOR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)OR a1 ,OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)NR c1 R d1 , NR c1 C(O)OR a1 , B(OR c1 )(OR d1 ), C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )R b1 , P(O)OR e1 Ure f1 , OP(O)OR e1 Ure f1 , S(O)(=NR b1 )R b1 , S(O)R b1 , S(O)NR c1 R d1 S(O)2R b1 , NR c1 S(O)2R b1 , S(O)2NR c1 R d1 , NR c1 S(O)2NR c1 R d1 , NR c1 S(O)(=NR b1 )Rb1 , C6-C 10 Aryl group, C3-C 10 Selected from cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups.

[0218] In some embodiments, each R 12 These are, independently, H, D, halogen, CN, NO2, N3, SF5, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl group, OC1-C6 alkylOH, OC1-C6 alkyl-O-C1-C6 alkyl group, OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 S(O)2R b1 , C6-C 10 Aryl group, C3-C 10 Selected from cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups, among which the above C6-C 10 Aryl group, C3-C 10 The cycloalkyl group, 5-10 membered heteroaryl group, or 4-10 membered heterocycloalkyl group may be unsubstituted or substituted with substituents independently selected from D, halogen, CN, NO2, NH2, NHC1-C4 alkyl, N(C1-C4 alkyl)2, C1-C3 alkyl, C1-C3 haloalkyl, OC1-C3 alkyl, OC1-C3 haloalkyl, OC2-C3 alkylOH, OC2-C3 alkyl-O-C1-C6 alkyl, or SF5.

[0219] In some embodiments, each R 12 Each is independently selected from H, D, halogen, CN, NO2, N3, and SF5. In some embodiments, each R 12 Each is independently selected from H. In some embodiments, each R 12 Each is independently selected from D. In some embodiments, each R 12Each is independently selected from halogens (e.g., F, Cl, Br, I). In some embodiments, each R 12 Each is independently selected from CN. In some embodiments, each R 12 Each is independently selected from NO2. In some embodiments, each R 12 Each is independently selected from N3. In some embodiments, each R 12 Each of them is independently selected from SF5.

[0220] In some embodiments, each R 12 Each of these is independently selected from C1-C6 alkyl groups, C2-C6 alkenyl groups, C2-C6 alkynyl groups, C1-C6 haloalkyl groups, OC1-C6 alkylOH groups, and OC1-C6 alkyl-O-C1-C6 alkyl groups.

[0221] In some embodiments, each R 12 Each of these is an OR a1 They are selected from among them.

[0222] In some embodiments, each R 12 Each of them is independently SR a1 They are selected from among them.

[0223] In some embodiments, each R 12 Each of them independently operates under NHOR a1 Selected from. In some embodiments, each R 12 Each of these is independently C(O)R b1 Selected from. In some embodiments, each R 12 Each of these is independently C(O)NR c1 R d1 Selected from. In some embodiments, each R 12 Each of these is independently C(O)OR a1 Selected from. In some embodiments, each R 12 Each of these is independently OC(O)OR a1 Selected from. In some embodiments, each R 12Each of these is independently OC(O)R b1 Selected from. In some embodiments, each R 12 These are each independently OC(O)NR c1 R d1 They are selected from among them.

[0224] In some embodiments, each R 12 Each of them is independently NR c1 R d1 Selected from. In some embodiments, each R 12 Each of them is independently NR c1 C(O)R b1 Selected from. In some embodiments, each R 12 Each of them is independently NR c1 C(O)NR c1 R d1 Selected from. In some embodiments, each R 12 Each of them is independently NR c1 C(O)OR a1 They are selected from among them.

[0225] In some embodiments, each R 12 Each of these is independently B(OR c1 )(OR d1 ) are selected from. In some embodiments, each R 12 Each of these is independently C(=NR c1 )NR c1 R d1 Selected from. In some embodiments, each R 12 Each of them is independently NR d1 C(=NR c1 )NR c1 R d1 Selected from. In some embodiments, each R 12 Each of them is independently NR d1 C(=NR c1 )R b1 They are selected from among them.

[0226] In some embodiments, each R 12 Each of these is independently P(O)OR e1 Ure f1Selected from. In some embodiments, each R 12 These are OP(O)OR, each independently. e1 Ure f1 They are selected from among them.

[0227] In some embodiments, each R 12 These are S(O)(=NR) independently of each other. b1 )R b1 Selected from. In some embodiments, each R 12 These are S(O)R, each independently. b1 Selected from. In some embodiments, each R 12 These are S(O)NR, each independently. c1 R d1 They are selected from among them.

[0228] In some embodiments, each R 12 These are S(O)2R, each independently. b1 Selected from. In some embodiments, each R 12 Each of them is independently NR c1 S(O)2R b1 Selected from. In some embodiments, each R 12 These are S(O)2NR, each independently. c1 R d1 Selected from. In some embodiments, each R 12 Each of them is independently NR c1 S(O)2NR c1 R d1 Selected from. In some embodiments, each R 12 Each of them is independently NR c1 S(O)(=NR b1 )R b1 They are selected from among them.

[0229] In some embodiments, each R 12 These are each independently C6-C 10 Aryl group, C3-C 10 Selected from cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups, among which the above C6-C 10 Aryl group, C3-C10 The cycloalkyl group, 5-10 membered heteroaryl group, or 4-10 membered heterocycloalkyl group may be unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents independently selected from D, halogen, CN, NO2, NH2, NHC1-C4 alkyl, N(C1-C4 alkyl)2, C1-C3 alkyl, C1-C3 haloalkyl, OC1-C3 alkyl, OC1-C3 haloalkyl, OC2-C3 alkylOH, OC2-C3 alkyl-O-C1-C6 alkyl, or SF5.

[0230] In some embodiments, each R 13 These are, independently, D, halogen, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl group, C1-C6 alkylOH, C1-C6 alkyl-O-C1-C6 alkyl group, CN, NO2, N3, OR a1 , SR a1 SF5, NHOR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 ,OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)NR c1 R d1 , NR c1 C(O)OR a1 , B(OR c1 )(OR d1 ), C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )R b1 P(O)R e1 R f1 , P(O)OR e1 Ure f1, OP(O)OR e1 Ure f1 , S(O)(=NR b1 )R b1 , S(O)R b1 , S(O)NR c1 R d1 S(O)2R b1 , NR c1 S(O)2R b1 , S(O)2NR c1 R d1 , NR c1 S(O)2NR c1 R d1 , NR c1 S(O)(=NR b1 )R b1 , C6-C 10 Aryl group, C3-C 10 Selected from cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups, among which the above C6-C 10 Aryl group, C3-C 10 The cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups may be unsubstituted or substituted with substituents selected from D, halogen, CN, NO2, NH2, NHC1-C4 alkyl groups, N(C1-C4 alkyl)2, C1-C3 alkyl groups, C1-C3 haloalkyl groups, OC1-C3 alkyl groups, OC1-C3 haloalkyl groups, OC2-C3 alkylOH, OC2-C3 alkyl-O-C1-C6 alkyl groups, or SF5.

[0231] In some embodiments, each R 13 These are D, halogen, CN, NO2, N3, and OR, respectively, independently. a1 , SR a1 , SF5, or NHOR a1 Selected from. In some embodiments, each R 13 Each is independently selected from D. In some embodiments, each R 13 R is independently selected from halogens (e.g., F, Cl, Br, I). In some embodiments, each R 13 Each is independently selected from CN. In some embodiments, each R 13Each is independently selected from NO2. In some embodiments, each R 13 R is independently selected from N3. In some embodiments, each R 13 Each of these is an OR a1 (For example, selected from OH, OCH3, OCH2CH3, OCH2F, OCHF2, OCF3). In some embodiments, each R 13 Each of them is independently SR a1 (For example, SCH3) is selected. In some embodiments, each R 13 Each is independently selected from SF5. In some embodiments, each R 13 Each of them independently operates under NHOR a1 They are selected from among them.

[0232] In some embodiments, each R 13 Each of these is independently C(O)R b1 Selected from. In some embodiments, each R 13 Each of these is independently C(O)NR c1 R d1 Selected from. In some embodiments, each R 13 Each of these is independently C(O)OR a1 They are selected from among them.

[0233] In some embodiments, each R 13 Each of these is independently OC(O)R b1 Selected from. In some embodiments, each R 13 These are each independently OC(O)NR c1 R d1 They are selected from among them.

[0234] In some embodiments, each R 13 Each of them is independently NR c1 R d1 (For example, selected from NH2, NHCH3, N(CH3)2). In some embodiments, each R 13 Each of them is independently NR c1 C(O)R b1 Selected from. In some embodiments, each R13 Each of them is independently NR c1 C(O)NR c1 R d1 Selected from. In some embodiments, each R 13 Each of them is independently NR c1 C(O)OR a1 They are selected from among them.

[0235] In some embodiments, each R 13 Each of these is independently B(OR c1 )(OR d1 ) are selected from. In some embodiments, each R 13 Each of these is independently C(=NR c1 )NR c1 R d1 Selected from. In some embodiments, each R 13 Each of them is independently NR d1 C(=NR c1 )NR c1 R d1 Selected from. In some embodiments, each R 13 Each of them is independently NR d1 C(=NR c1 )R b1 They are selected from among them.

[0236] In some embodiments, each R 13 Independently, P(O)R e1 R f1 Selected from. In some embodiments, each R 13 P(O)OR e1 Ure f1 Selected from. In some embodiments, each R 13 OP(O)OR e1 Ure f1 They are selected from among them.

[0237] In some embodiments, each R 13 S(O)(=NR) b1 )R b1 Selected from. In some embodiments, each R 13 S(O)R b1Selected from. In some embodiments, each R 13 S(O)NR is independent c1 R d1 They are selected from among them.

[0238] In some embodiments, each R 13 This is independently S(O)2R b1 Selected from. In some embodiments, each R 13 Independently, NR c1 S(O)2R b1 Selected from. In some embodiments, each R 13 This is independently S(O)2NR c1 R d1 Selected from. In some embodiments, each R 13 Independently, NR c1 S(O)2NR c1 R d1 Selected from. In some embodiments, each R 13 Independently, NR c1 S(O)(=NR b1 )R b1 They are selected from among them.

[0239] In some other embodiments, each R 13 These are independently selected from C1-C6 alkyl groups, C2-C6 alkenyl groups, C2-C6 alkynyl groups, C1-C6 haloalkyl groups, C1-C6 alkylOH groups, and C1-C6 alkyl-O-C1-C6 alkyl groups.

[0240] In some other embodiments, each R 13 It is independently C6-C 10 Aryl group, C3-C 10 Selected from cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups, among which the above C6-C 10 Aryl group, C3-C 10The cycloalkyl group, 5-10 membered heteroaryl group, or 4-10 membered heterocycloalkyl group may be unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents independently selected from D, halogen, CN, NO2, NH2, NHC1-C4 alkyl, N(C1-C4 alkyl)2, C1-C3 alkyl, C1-C3 haloalkyl, OC1-C3 alkyl, OC1-C3 haloalkyl, OC2-C3 alkylOH, OC2-C3 alkyl-O-C1-C6 alkyl, or SF5.

[0241] In some embodiments, each R 14 These are, independently, H, D, NO2, CN, halogen, oxo, SF5, C1-C8 alkyl group, C2-C8 alkenyl group, C2-C8 alkynyl group, and C6-C 14 Aryl group, C3-C 14 Cycloalkyl groups, 5-14 member heteroaryl groups, or 4-14 member heterocycloalkyl groups, OR a , SR a SF5, NHOR a , C(O)R b , C(O)NR c R d , C(O)OR a ,OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R b , NR c C(O)NR c R d , NR c C(O)OR a , B(OR c )(OR d ), C(=NR c )NR c R d , NR d C(=NR c )NR c R d , NR d C(=NR c )R b P(O)R e R f, P(O)OR e Ure f , OP(O)OR e Ure f , S(O)R b , S(O)NR c R d S(O)2R b , NR c S(O)2R b , S(O)2NR c R d , NR c S(O)2NR c R d , or NR c S(O)(=NR b )R b Selected from among, of which the above C1-C8 alkyl group, C2-C8 alkenyl group, C2-C8 alkynyl group, C6-C 14 Aryl group, C3-C 14 Cycloalkyl groups, 5-14 membered heteroaryl groups, or 4-14 membered heterocycloalkyl groups are optionally D, NO2, CN, halogen, oxo, SF5, C1-C6 alkyl groups, C2-C6 alkenyl groups, C2-C6 alkynyl groups, C1-C6 haloalkyl groups, C1-C6 alkylOH, C1-C6 alkyl-O-C1-C6 alkyl groups, CN, NO2, N3, OR a1 , SR a1 SF5, NHOR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 ,OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)NR c1 R d1 , NR c1 C(O)OR a1 , B(OR c1 )(OR d1 ), C(=NR c1 )NR c1 R d1 , NR d1C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )R b1 P(O)R e1 R f1 , P(O)OR e1 Ure f1 , OP(O)OR e1 Ure f1 , S(O)(=NR b1 )R b1 , S(O)R b1 , S(O)NR c1 R d1 S(O)2R b1 , NR c1 S(O)2R b1 , S(O)2NR c1 R d1 , NR c1 S(O)2NR c1 R d1 , NR c1 S(O)(=NR b1 )R b1 , C6-C 10 Aryl group, C3-C 10 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from cycloalkyl groups, 5- to 10-membered heteroaryl groups, and 4- to 10-membered heterocycloalkyl groups.

[0242] In some embodiments, each R 14 R is independently selected from H. In some embodiments, each R 14 R is independently selected from D. In some embodiments, each R 14 It is independently selected from NO2. In some embodiments, each R 14 R is independently selected from CN. In some embodiments, each R 14 R is independently selected from halogens (e.g., F, Cl, Br, or I). In some embodiments, each R 14 R is independently selected from the oxo. In some embodiments, each R 14 They are selected independently from SF5.

[0243] In some embodiments, each R 14 The group is independently selected from C1-C8 alkyl groups, and optionally selected from D, NO2, CN, halogen, oxo, SF5, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl group, C1-C6 alkylOH, C1-C6 alkyl-O-C1-C6 alkyl group, CN, NO2, N3, OR a1 , SR a1 SF5, NHOR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 ,OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)NR c1 R d1 , NR c1 C(O)OR a1 , B(OR c1 )(OR d1 ), C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )R b1 P(O)R e1 R f1 , P(O)OR e1 Ure f1 , OP(O)OR e1 Ure f1 , S(O)(=NR b1 )R b1 , S(O)R b1 , S(O)NR c1 R d1 S(O)2R b1 , NR c1 S(O)2R b1 , S(O)2NR c1 R d1 , NR c1S(O)2NR c1 R d1 , NR c1 S(O)(=NR b1 )R b1 , C6-C 10 Aryl group, C3-C 10 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from cycloalkyl groups, 5- to 10-membered heteroaryl groups, and 4- to 10-membered heterocycloalkyl groups.

[0244] In some embodiments, each R 14 The group is independently selected from C2-C8 alkenyl groups, and optionally selected from D, NO2, CN, halogen, oxo, SF5, C1-C6 alkyl, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl, C1-C6 alkylOH, C1-C6 alkyl-O-C1-C6 alkyl, CN, NO2, N3, OR a1 , SR a1 SF5, NHOR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 ,OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)NR c1 R d1 , NR c1 C(O)OR a1 , B(OR c1 )(OR d1 ), C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )R b1 P(O)R e1 R f1 , P(O)OR e1 Uref1 , OP(O)OR e1 Ure f1 , S(O)(=NR b1 )R b1 , S(O)R b1 , S(O)NR c1 R d1 S(O)2R b1 , NR c1 S(O)2R b1 , S(O)2NR c1 R d1 , NR c1 S(O)2NR c1 R d1 , NR c1 S(O)(=NR b1 )R b1 , C6-C 10 Aryl group, C3-C 10 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from cycloalkyl groups, 5- to 10-membered heteroaryl groups, and 4- to 10-membered heterocycloalkyl groups.

[0245] In some embodiments, each R 14 The group is independently selected from C2-C8 alkynyl groups, and optionally selected from D, NO2, CN, halogen, oxo, SF5, C1-C6 alkyl, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl, C1-C6 alkylOH, C1-C6 alkyl-O-C1-C6 alkyl, CN, NO2, N3, OR a1 , SR a1 SF5, NHOR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 ,OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)NR c1 R d1 , NR c1 C(O)OR a1 , B(OR c1)(OR d1 ), C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )R b1 P(O)R e1 R f1 , P(O)OR e1 Ure f1 , OP(O)OR e1 Ure f1 , S(O)(=NR b1 )R b1 , S(O)R b1 , S(O)NR c1 R d1 S(O)2R b1 , NR c1 S(O)2R b1 , S(O)2NR c1 R d1 , NR c1 S(O)2NR c1 R d1 , NR c1 S(O)(=NR b1 )R b1 , C6-C 10 Aryl group, C3-C 10 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from cycloalkyl groups, 5- to 10-membered heteroaryl groups, and 4- to 10-membered heterocycloalkyl groups.

[0246] In some embodiments, each R 14 It is independently C6-C 14 Selected from aryl groups, optionally D, NO2, CN, halogen, oxo, SF5, C1-C6 alkyl, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl, C1-C6 alkylOH, C1-C6 alkyl-O-C1-C6 alkyl, CN, NO2, N3, OR a1 , SR a1 SF5, NHOR a1 , C(O)R b1 , C(O)NR c1 Rd1 , C(O)OR a1 ,OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)NR c1 R d1 , NR c1 C(O)OR a1 , B(OR c1 )(OR d1 ), C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )R b1 P(O)R e1 R f1 , P(O)OR e1 Ure f1 , OP(O)OR e1 Ure f1 , S(O)(=NR b1 )R b1 , S(O)R b1 , S(O)NR c1 R d1 S(O)2R b1 , NR c1 S(O)2R b1 , S(O)2NR c1 R d1 , NR c1 S(O)2NR c1 R d1 , NR c1 S(O)(=NR b1 )R b1 , C6-C 10 Aryl group, C3-C 10 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from cycloalkyl groups, 5- to 10-membered heteroaryl groups, and 4- to 10-membered heterocycloalkyl groups.

[0247] In some embodiments, each R 14It is independently C3-C 14 Selected from cycloalkyl groups, optionally D, NO2, CN, halogen, oxo, SF5, C1-C6 alkyl, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl, C1-C6 alkylOH, C1-C6 alkyl-O-C1-C6 alkyl, CN, NO2, N3, OR a1 , SR a1 SF5, NHOR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 ,OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)NR c1 R d1 , NR c1 C(O)OR a1 , B(OR c1 )(OR d1 ), C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )R b1 P(O)R e1 R f1 , P(O)OR e1 Ure f1 , OP(O)OR e1 Ure f1 , S(O)(=NR b1 )R b1 , S(O)R b1 , S(O)NR c1 R d1 S(O)2R b1 , NR c1 S(O)2R b1 , S(O)2NR c1 R d1 , NR c1 S(O)2NRc1 R d1 , NR c1 S(O)(=NR b1 )R b1 , C6-C 10 Aryl group, C3-C 10 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from cycloalkyl groups, 5- to 10-membered heteroaryl groups, and 4- to 10-membered heterocycloalkyl groups.

[0248] In some embodiments, each R 14 The group is independently selected from 5-14 member heteroaryl groups, and optionally selected from D, NO2, CN, halogen, oxo, SF5, C1-C6 alkyl, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl, C1-C6 alkylOH, C1-C6 alkyl-O-C1-C6 alkyl, CN, NO2, N3, OR a1 , SR a1 SF5, NHOR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 ,OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)NR c1 R d1 , NR c1 C(O)OR a1 , B(OR c1 )(OR d1 ), C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )R b1 P(O)R e1 R f1 , P(O)OR e1 Ure f1, OP(O)OR e1 Ure f1 , S(O)(=NR b1 )R b1 , S(O)R b1 , S(O)NR c1 R d1 S(O)2R b1 , NR c1 S(O)2R b1 , S(O)2NR c1 R d1 , NR c1 S(O)2NR c1 R d1 , NR c1 S(O)(=NR b1 )R b1 , C6-C 10 Aryl group, C3-C 10 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from cycloalkyl groups, 5- to 10-membered heteroaryl groups, and 4- to 10-membered heterocycloalkyl groups.

[0249] In some embodiments, each R 14 The group is independently selected from 4-14 member heterocycloalkyl groups, and optionally selected from D, NO2, CN, halogen, oxo, SF5, C1-C6 alkyl, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl, C1-C6 alkylOH, C1-C6 alkyl-O-C1-C6 alkyl, CN, NO2, N3, OR a1 , SR a1 SF5, NHOR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 ,OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)NR c1 R d1 , NR c1 C(O)OR a1 , B(OR c1 )(ORd1 ), C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )NR c1 R d1 , NR d1 C(=NR c1 )R b1 P(O)R e1 R f1 , P(O)OR e1 Ure f1 , OP(O)OR e1 Ure f1 , S(O)(=NR b1 )R b1 , S(O)R b1 , S(O)NR c1 R d1 S(O)2R b1 , NR c1 S(O)2R b1 , S(O)2NR c1 R d1 , NR c1 S(O)2NR c1 R d1 , NR c1 S(O)(=NR b1 )R b1 , C6-C 10 Aryl group, C3-C 10 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from cycloalkyl groups, 5- to 10-membered heteroaryl groups, and 4- to 10-membered heterocycloalkyl groups.

[0250] In some embodiments, each R 14 OR a Selected from. In some embodiments, each R 14 SR is independently a Selected from. In some embodiments, each R 14 R is independently selected from SF5. In some embodiments, each R 14 NHOR a They are selected from among them.

[0251] In some embodiments, each R 14C(O)R b Selected from. In some embodiments, each R 14 Independently, C(O)NR c R d Selected from. In some embodiments, each R 14 C(O)OR a Selected from. In some embodiments, each R 14 O(O)R is independently b Selected from. In some embodiments, each R 14 Independently, OC(O)NR c R d They are selected from among them.

[0252] In some embodiments, each R 14 Independently, NR c R d Selected from. In some embodiments, each R 14 Independently, NR c C(O)R b Selected from. In some embodiments, each R 14 Independently, NR c C(O)NR c R d Selected from. In some embodiments, each R 14 Independently, NR c C(O)OR a They are selected from among them.

[0253] In some embodiments, each R 14 B(OR) is independent c )(OR d ) are selected from. In some embodiments, each R 14 Independently, C(=NR) c )NR c R d Selected from. In some embodiments, each R 14 Independently, NR d C(=NR c )NR c R d Selected from. In some embodiments, each R 14 Independently, NRd C(=NR c )R b They are selected from among them.

[0254] In some embodiments, each R 14 Independently, P(O)R e R f Selected from. In some embodiments, each R 14 P(O)OR e Ure f Selected from. In some embodiments, each R 14 OP(O)OR e Ure f Selected from, In some embodiments, each R 14 S(O)R b Selected from. In some embodiments, each R 14 S(O)NR is independent c R d Selected from. In some embodiments, each R 14 This is independently S(O)2R b Selected from. In some embodiments, each R 14 Independently, NR c S(O)2R b Selected from. In some embodiments, each R 14 This is independently S(O)2NR c R d Selected from. In some embodiments, each R 14 Independently, NR c S(O)2NR c R d Selected from. In some embodiments, each R 14 Independently, NR c S(O)(=NR b )R b They are selected from among them.

[0255] In the compound shown in formula I, each R A These are, independently, H, D, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Selected from cycloalkyl-C1-C6 alkyl groups or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, of which the above C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, are optionally R 14 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0256] In some embodiments, each R A R is independently selected from H. In some embodiments, each R A It is selected independently from D.

[0257] In some other embodiments, each R A These are independently C1-C6 alkyl groups, C2-C6 alkenyl groups, C2-C6 alkynyl groups, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Selected from cycloalkyl-C1-C6 alkyl groups or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, of which the above C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, are optionally R 14 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0258] In the compound shown in formula I, each R B These are, independently, H, D, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Selected from cycloalkyl-C1-C6 alkyl groups or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, of which the above C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, are optionally R 14 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0259] In some embodiments, each R B R is independently selected from H. In some embodiments, each R B It is selected independently from D.

[0260] In some embodiments, each R B These are independently C1-C6 alkyl groups, C2-C6 alkenyl groups, C2-C6 alkynyl groups, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Selected from cycloalkyl-C1-C6 alkyl groups or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, of which the above C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, are optionally R 14 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0261] In some embodiments, each R C These are, independently, H, D, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Selected from cycloalkyl-C1-C6 alkyl groups or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, of which the above C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, are optionally R 14 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0262] In some embodiments, each R C R is independently selected from H. In some embodiments, each R C It is selected independently from D.

[0263] In some embodiments, each R C These are independently C1-C6 alkyl groups, C2-C6 alkenyl groups, C2-C6 alkynyl groups, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Selected from cycloalkyl-C1-C6 alkyl groups or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, of which the above C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, are optionally R 14 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0264] In some embodiments, each R D These are, independently, H, D, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Selected from cycloalkyl-C1-C6 alkyl groups or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, of which the above C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, are optionally R 14 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0265] In some embodiments, each R D R is independently selected from H. In some embodiments, each R D It is selected independently from D.

[0266] In some embodiments, each R D These are independently C1-C6 alkyl groups, C2-C6 alkenyl groups, C2-C6 alkynyl groups, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10Selected from cycloalkyl-C1-C6 alkyl groups or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, of which the above C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, and C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 member heteroaryl-C1-C6 alkyl group, C3-C 10 Cycloalkyl-C1-C6 alkyl groups, or 4-10 member heterocycloalkyl-C1-C6 alkyl groups, are optionally R 14 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0267] In some other embodiments, R C and R D These, together with the N atoms linked to them, form 4-7 member heterocycloalkyl groups, optionally consisting of D, halogen, oxo, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkyl-CN, OR a , SR a , C(O)R b , NR c R d It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the given molecule.

[0268] In some embodiments, each R E These are, independently, H, D, C1-C4 alkyl group, C1-C4 haloalkyl group, C2-C4 alkenyl group, (C1-C4 alkoxy)-C1-C4 alkyl group, C2-C4 alkynyl group, and C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl-C1-C4 alkyl groups, C3-C 10 Selected from cycloalkyl-C1-C4 alkyl groups, 5-10 member heteroaryl-C1-C4 alkyl groups, or 4-10 member heterocycloalkyl-C1-C4 alkyl groups.

[0269] In some embodiments, each R F These are, independently, H, D, C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, and C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 Selected from cycloalkyl groups and 4- to 10-membered heterocycloalkyl groups.

[0270] In some embodiments, each R a Each of these is independently selected from H, D, C1-C4 alkyl groups, C2-C4 alkenyl groups, C2-C4 alkynyl groups, phenyl groups, C3-C7 cycloalkyl groups, 5-6 membered heteroaryl groups, or 4-7 membered heterocycloalkyl groups, and of these, the above C1-C4 alkyl groups, C2-C4 alkenyl groups, C2-C4 alkynyl groups, phenyl groups, C3-C7 cycloalkyl groups, 5-6 membered heteroaryl groups, or 4-7 membered heterocycloalkyl groups are optionally substituted with 1, 2, or 3 substituents independently selected from D, OH, CN, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, halogens, C1-C4 alkyl groups, C1-C4 alkoxy groups, C1-C4 haloalkyl groups, or C1-C4 haloalkoxy groups.

[0271] In some embodiments, each R a They are selected independently from H and D.

[0272] In some embodiments, each R aThe C1-C4 alkyl group is independently selected from a C1-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a phenyl group, a C3-C7 cycloalkyl group, a 5-6 member heteroaryl group, or a 4-7 member heterocycloalkyl group. Of these, the C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, phenyl group, C3-C7 cycloalkyl group, a 5-6 member heteroaryl group, or a 4-7 member heterocycloalkyl group is optionally substituted with one, two, or three substituents independently selected from D, OH, CN, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, halogen, C1-C4 alkyl group, C1-C4 alkoxy group, C1-C4 haloalkyl group, or C1-C4 haloalkoxy group.

[0273] In some embodiments, each R b These are, independently, H, D, C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, and C 6- C 10 Aryl group, 5-10 membered heteroaryl group, C 3- C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C 6- C 10 Aryl-C1-C4 alkyl group, 5-10 member heteroaryl-C1-C4 alkyl group, C3-C 10 Selected from cycloalkyl-C1-C4 alkyl groups or 4-10 member heterocycloalkyl-C1-C4 alkyl groups, among which the above C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, phenyl group, C 3- C7 cycloalkyl group, 5-6 membered heteroaryl group, or 4-7 membered heterocycloalkyl group, C 6- C 10 Aryl-C1-C4 alkyl group, 5-10 member heteroaryl-C1-C4 alkyl group, C3-C 10Cycloalkyl-C1-C4 alkyl groups, or 4-10 member heterocycloalkyl-C1-C4 alkyl groups, can optionally include D, OH, halogen, CN, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, C1-C4 alkyl groups, C1-C4 haloalkyl groups, -OC1-C4 alkyl groups, or -OC1-C4 haloalkyl groups, C 6- C 10 Aryl group, C3-C 10 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from cycloalkyl groups, 5-10 membered heteroaryl groups, or 4-10 membered heterocycloalkyl groups.

[0274] In some embodiments, each R b They are selected independently from H and D.

[0275] In some embodiments, each R b These are independently C1-C4 alkyl groups, C2-C4 alkenyl groups, C2-C4 alkynyl groups, and C 6- C 10 Aryl group, 5-10 membered heteroaryl group, C 3- C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C 6- C 10 Aryl-C1-C4 alkyl group, 5-10 member heteroaryl-C1-C4 alkyl group, C3-C 10 Selected from cycloalkyl-C1-C4 alkyl groups or 4-10 member heterocycloalkyl-C1-C4 alkyl groups, among which the above C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, phenyl group, C 3- C7 cycloalkyl group, 5-6 membered heteroaryl group, or 4-7 membered heterocycloalkyl group, C 6- C 10 Aryl-C1-C4 alkyl group, 5-10 member heteroaryl-C1-C4 alkyl group, C3-C 10Cycloalkyl-C1-C4 alkyl groups, or 4-10 member heterocycloalkyl-C1-C4 alkyl groups, can optionally include D, OH, halogen, CN, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, C1-C4 alkyl groups, C1-C4 haloalkyl groups, -OC1-C4 alkyl groups, or -OC1-C4 haloalkyl groups, C 6- C 10 Aryl group, C3-C 10 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from cycloalkyl groups, 5-10 membered heteroaryl groups, or 4-10 membered heterocycloalkyl groups.

[0276] In some embodiments, R c and R d These are, independently, H, D, C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, and C 6- C 10 Aryl group, 5-10 membered heteroaryl group, C 3- C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C 6- C 10 Aryl-C1-C4 alkyl group, 5-10 member heteroaryl-C1-C4 alkyl group, C 3- C 10 Cycloalkyl-C1-C4 alkyl group, 4-10 member heterocycloalkyl-C1-C4 alkyl group, C 6- C 10 Aryl-C 3- C 10 Cycloalkyl groups, C 6- C 10 Aryl-4 to 10-membered heterocycloalkyl groups, C 6- C 10 Aryl-5~10 member heteroaryl group, bis(C6-C 10 aryl), 5-10 member heteroaryl-C 3- C 10 Cycloalkyl groups, 5-10 member heteroaryl groups - 4-10 member heterocycloalkyl groups, 5-10 member heteroaryl groups - C 6- C 10Selected from aryl groups or bis(5-10 membered heteroaryls), of which the above C 1-4 Alkyl alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 6- C 10 Aryl group, 5-10 membered heteroaryl group, C 3- C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C 6- C 10 Aryl-C1-C4 alkyl group, 5-10 member heteroaryl-C1-C4 alkyl group, C 3- C 10 Cycloalkyl-C1-C4 alkyl group, 4-10 member heterocycloalkyl-C1-C4 alkyl group, C 6- C 10 Aryl-C 3- C 10 Cycloalkyl groups, C 6- C 10 Aryl-4 to 10-membered heterocycloalkyl groups, C 6- C 10 Aryl-5~10 member heteroaryl group, bis(C6-C 10 aryl), 5-10 member heteroaryl-C 3- C 10 Cycloalkyl groups, 5-10 member heteroaryl groups - 4-10 member heterocycloalkyl groups, 5-10 member heteroaryl groups - C 6- C 10 The aryl group, or bis(5-10 membered heteroaryl), can be optionally D, halogen, OH, CN, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, C1-C4 alkyl, O-C1-C4 alkyl, C1-C4 haloalkyl, O-C1-C4 haloalkyl, C1-C4 alkyl-OH, C1-C4 alkyl-CN, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C(O)OR a1 , C(O)R b1 S(O)2R b1 The molecule is substituted with 1, 2, 3, 4, or 5 substituents independently selected from C1-C4alkyl-O-C1-C4alkyl groups and C1-C4alkyl-O-C1-C4alkyl-O- groups.

[0277] In some embodiments, R c and R d These, together with the N atoms linked to them, form 4- to 7-membered heterocycloalkyl groups (e.g., 4-membered heterocycloalkyl groups, 5-membered heterocycloalkyl groups, 6-membered heterocycloalkyl groups, 7-membered heterocycloalkyl groups), and optionally form D, OH, CN, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, halogen, C1-C4 alkyl group, C1-C4 alkoxy group, C1-C4 haloalkyl group, C1-C4 haloalkoxy group, C1-C4 hydroxyalkyl group, C1-C4 cyanoalkyl group, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C(O)OR a1 , C(O)R b1 S(O)2R b1 The molecule is substituted with one, two, or three substituents independently selected from a C1-C4 alkoxy-C1-C4 alkyl group and a C1-C4 alkoxy-C1-C4 alkoxy group.

[0278] In some embodiments, each R e R is independently selected from H. In some embodiments, each R e It is selected independently from D.

[0279] In some embodiments, each R e R is independently selected from C1-C4 alkyl groups. In some embodiments, each R e R is independently selected from C1-C4 haloalkyl groups. In some embodiments, each R e These are independently selected from C2-C4 alkenyl groups.

[0280] In some embodiments, each R e R is independently selected from (C1-C4 alkoxy)-C1-C4 alkyl groups. In some embodiments, each R e These are independently selected from the C2-C4 alkynyl groups.

[0281] In some embodiments, each R e It is independently C6-C 10 Selected from aryl groups. In some embodiments, each R e R is independently selected from 5-10 membered heteroaryl groups. In some embodiments, each R e It is independently C3-C 10 Selected from cycloalkyl groups. In some embodiments, each R e These are independently selected from 4- to 10-membered heterocycloalkyl groups.

[0282] In some embodiments, each R e It is independently C6-C 10 Selected from aryl-C1-C4 alkyl groups. In some embodiments, each R e It is independently C3-C 10 Selected from cycloalkyl-C1-C4 alkyl groups. In some embodiments, each R e R is independently selected from 5-10 member heteroaryl-C1-C4 alkyl groups. In some embodiments, each R e These are independently selected from 4-10 member heterocycloalkyl-C1-C4 alkyl groups.

[0283] In some embodiments, each R f They are selected independently from H and D.

[0284] In some embodiments, each R f These are independently C1-C4 alkyl groups, C2-C4 alkenyl groups, C2-C4 alkynyl groups, and C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 Selected from cycloalkyl groups and 4- to 10-membered heterocycloalkyl groups.

[0285] In some embodiments, each R a1 They are selected independently from H and D.

[0286] In some embodiments, each R a1Each is independently selected from C1-C4 alkyl groups, C2-C4 alkenyl groups, C2-C4 alkynyl groups, phenyl groups, C3-C7 cycloalkyl groups, 5-6 membered heteroaryl groups, or 4-7 membered heterocycloalkyl groups, of which the above C1-C4 alkyl groups, C2-C4 alkenyl groups, C2-C4 alkynyl groups, phenyl groups, C 3- The C7 cycloalkyl group, 5-6 membered heteroaryl group, or 4-7 membered heterocycloalkyl group may be optionally substituted with one, two, or three substituents independently selected from D, OH, CN, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, halogen, C1-C4 alkyl group, C1-C4 alkoxy group, C1-C4 haloalkyl group, or C1-C4 haloalkoxy group.

[0287] In some embodiments, each R b1 These are, independently, H, D, C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, and C 6- C 10 Aryl group, 5-10 membered heteroaryl group, C 3- C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C 6- C 10 Aryl-C1-C4 alkyl group, 5-10 member heteroaryl-C1-C4 alkyl group, C3-C 10 Selected from cycloalkyl-C1-C4 alkyl groups or 4-10 member heterocycloalkyl-C1-C4 alkyl groups, among which the above C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, C 6- C 10 Aryl group, 5-10 membered heteroaryl group, C 3- C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C 6- C 10 Aryl-C1-C4 alkyl group, 5-10 member heteroaryl-C1-C4 alkyl group, C3-C 10Cycloalkyl-C1-C4 alkyl groups, or 4-10 member heterocycloalkyl-C1-C4 alkyl groups, can optionally include D, OH, halogen, CN, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, C1-C4 alkyl groups, C1-C4 haloalkyl groups, -OC1-C4 alkyl groups, or -OC1-C4 haloalkyl groups, C 6- C 10 Aryl group, C 3- C 10 It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from cycloalkyl groups, 5-10 membered heteroaryl groups, or 4-10 membered heterocycloalkyl groups.

[0288] In some embodiments, R c1 and R d1 These are, independently, H, D, C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, and C 6- C 10 Aryl group, 5-10 membered heteroaryl group, C 3- C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C 6- C 10 Aryl-C1-C4 alkyl group, 5-10 member heteroaryl-C1-C4 alkyl group, C 3- C 10 Cycloalkyl-C1-C4 alkyl group, 4-10 member heterocycloalkyl-C1-C4 alkyl group, C 6- C 10 Aryl-C 3- C 10 Cycloalkyl groups, C 6- C 10 Aryl-4 to 10-membered heterocycloalkyl groups, C 6- C 10 Aryl-5~10 member heteroaryl group, bis(C6-C 10 aryl), 5-10 member heteroaryl-C 3- C 10 Cycloalkyl groups, 5-10 member heteroaryl groups - 4-10 member heterocycloalkyl groups, 5-10 member heteroaryl groups - C 6- C 10Selected from aryl groups or bis(5-10 membered heteroaryls), of which the above C 1-4 Alkyl alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 6- C 10 Aryl group, 5-10 membered heteroaryl group, C 3- C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C 6- C 10 Aryl-C1-C4 alkyl group, 5-10 member heteroaryl-C1-C4 alkyl group, C 3- C 10 Cycloalkyl-C1-C4 alkyl group, 4-10 member heterocycloalkyl-C1-C4 alkyl group, C 6- C 10 Aryl-C 3- C 10 Cycloalkyl groups, C 6- C 10 Aryl-4 to 10-membered heterocycloalkyl groups, C 6- C 10 Aryl-5 to 10-membered heteroaryl group, bis(C) 6- C 10 aryl), 5-10 member heteroaryl-C 3- C 10 Cycloalkyl groups, 5-10 member heteroaryl groups - 4-10 member heterocycloalkyl groups, 5-10 member heteroaryl groups - C 6- C 10 The aryl group, or bis(5-10 membered heteroaryl), can be optionally D, halogen, OH, CN, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, C1-C4 alkyl, O-C1-C4 alkyl, C1-C4 haloalkyl, O-C1-C4 haloalkyl, C1-C4 alkyl-OH, C1-C4 alkyl-CN, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C(O)OR a1 , C(O)R b1 S(O)2R b1The molecule is substituted with 1, 2, 3, 4, or 5 substituents independently selected from C1-C4alkyl-O-C1-C4alkyl groups and C1-C4alkyl-O-C1-C4alkyl-O- groups.

[0289] In some embodiments, R c1 and R d1 These, together with the N atoms linked to them, form 4-7 member heterocycloalkyl groups, and optionally D, OH, CN, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, halogen, C1-C4 alkyl, C1-C4 alkoxy group, C1-C4 haloalkyl, C1-C4 haloalkoxy group, C1-C4 hydroxyalkyl, C1-C4 cyanoalkyl, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C(O)OR a1 , C(O)R b1 S(O)2R b1 The molecule is substituted with one, two, or three substituents independently selected from a C1-C4 alkoxy-C1-C4 alkyl group and a C1-C4 alkoxy-C1-C4 alkoxy group.

[0290] In some embodiments, each R e1 They are selected independently from H and D.

[0291] In some embodiments, each R e1 These are independently C1-C4 alkyl groups, C1-C4 haloalkyl groups, C2-C4 alkenyl groups, (C1-C4 alkoxy)-C1-C4 alkyl groups, C2-C4 alkynyl groups, and C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C6-C 10 Aryl-C1-C4 alkyl groups, C3-C 10 Selected from cycloalkyl-C1-C4 alkyl groups, 5-10 member heteroaryl-C1-C4 alkyl groups, or 4-10 member heterocycloalkyl-C1-C4 alkyl groups.

[0292] In some embodiments, each Rf1 They are selected independently from H and D.

[0293] In some embodiments, each R f1 These are independently C1-C4 alkyl groups, C2-C4 alkenyl groups, C2-C4 alkynyl groups, and C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 Selected from cycloalkyl groups and 4- to 10-membered heterocycloalkyl groups.

[0294] In some embodiments, R G , R H and R I These are independently selected from C1-C4 alkyl groups or phenyl groups.

[0295] In some embodiments, R G is a C1-C4 alkyl group or a phenyl group. In some embodiments, R G These are a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an i-butyl group, a tert-butyl group, or a phenyl group.

[0296] In some embodiments, R H is a C1-C4 alkyl group or a phenyl group. In some embodiments, R G These are a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an i-butyl group, a tert-butyl group, or a phenyl group.

[0297] In some embodiments, R I is a C1-C4 alkyl group or a phenyl group. In some embodiments, R G These are a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an i-butyl group, a tert-butyl group, or a phenyl group.

[0298] In some embodiments, the compound represented by formula (I) is a pharmaceutically acceptable salt. In some embodiments, the compound represented by formula (I) is a stereoisomer. In some embodiments, the compound represented by formula (I) is a solvate. In some embodiments, the compound represented by formula (I) is the N-oxide of the compound represented by formula (I).

[0299] The present invention also considers, describes, and incorporates stereoisomers, pharmaceutically acceptable salts, and solvates of the compound represented by Formula I above. The present invention also describes the use of the compound represented by Formula I above and its pharmaceutical compositions.

[0300] In some embodiments, the compound represented by formula (I) provided by the present invention is [ka] [ka] [ka] [ka] [ka] [ka] [ka] Alternatively, it may be selected from its pharmaceutically acceptable salts.

[0301] In some other embodiments, the compound represented by formula (I) provided by the present invention is [ka] [ka] [ka] [ka] Alternatively, it may be selected from its pharmaceutically acceptable salts.

[0302] In some other embodiments, the compound represented by formula (I) provided by the present invention is [ka] [ka] [ka] [ka] Alternatively, it may be selected from its pharmaceutically acceptable salts.

[0303] Clearly, the compounds represented by Formula I described in the present invention include all the subgenera described herein and may have multiple stereocenters. Therefore, the compounds represented by Formula I (subgenera described in the present invention) have multiple stereoisomers (enantiomers and diastereomers). The present invention considers and encompasses any one stereoisomer of the compounds represented by Formula I (subgenera described in the present invention), and mixtures of the above stereoisomers.

[0304] The pharmaceutically acceptable salts and solvates of the compounds represented by Formula I above (subgenus described in this invention) are also included within the scope of this invention.

[0305] Isotope variants of the compound shown in formula I above (subgenus described in the present invention) are also included in the scope described in the present invention.

[0306] The present invention further provides a pharmaceutical composition comprising a compound described in the present invention, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[0307] The present invention further provides the use of the compounds described in the present invention or pharmaceutically acceptable salts thereof in any one of the methods described in the present invention. The present invention further provides the application of the compounds of the present invention or pharmaceutically acceptable salts thereof in the manufacture of therapeutic drugs, wherein the drug is used in any one of the methods described in the present invention.

[0308] The PARG inhibitors described in the present invention can be used to treat various cancers, including, but not limited to, breast cancer, ovarian cancer, gastric cancer, prostate cancer, pancreatic cancer, uterine cancer, cervical cancer, endometrial cancer, lung cancer, brain cancer, bile duct cancer, and hematological cancers.

[0309] The routes of administration of the compounds described in the present invention include, but are not limited to, oral, injection, topical, and inhalation.

[0310] The compounds described in the present invention can be used alone or in combination with other therapeutic methods. Such therapeutic methods may include, for example, one or more of the above-mentioned cancer treatment methods, such as surgery, chemotherapy, radiotherapy, targeted therapy (e.g., kinase inhibitors, growth factor inhibitors, cyclin-dependent kinase inhibitors, etc.), other DDR modulators (e.g., DNA-PK inhibitors, ATM inhibitors, ATR inhibitors, CHK1 inhibitors, WEE1 inhibitors, CDK1 inhibitors, LIG4 inhibitors, HIF-1 inhibitors, HDAC inhibitors, RAD51 inhibitors, Polθ inhibitors, WRN inhibitors, PRMT5 inhibitors, MAT2A inhibitors, and PKMYT1 inhibitors, etc.), immunotherapy, and gene and cell therapies.

[0311] In some embodiments, the present invention provides an intermediate compound represented by formula (A), [ka] W 1The leaving group is (for example, a halogen (e.g., Cl, Br, or I), a pseudohalogen (e.g., C1-C3 alkyl-SO2-, phenyl-SO2- (e.g., OTf, OTs, or OMs), -SC1-C4 alkyl group (e.g., -SCH3, -SCH2CH3), -S-phenyl group, -OC1-C4 alkyl group, -OC1-C4 haloalkyl group (e.g., -OCF2CF3), of which the above C1-C4 alkyl group and phenyl group are optionally substituted with halogen, CN, NO2, SF5, OH, C1-C4 alkyl group, C1-C4 haloalkyl group, -O-C1-C4 alkyl group, or -OC1-C4 haloalkyl group)). Eventually, R 1 , R 2 , R 3 , X, Y 1 , Y 2 , Y 3 , Y 5 , Y 7 , Y 8 , and Z 1 This is as defined in the present invention.

[0312] In some embodiments, W 1 The group is a halogen, a C1-C3 alkyl-SO2-, a phenyl-SO2-, an -SC1-C4 alkyl group, an -S-phenyl group, an -OC1-C4 alkyl group, or an -OC1-C4 haloalkyl group. Of these, the C1-C4 alkyl group and the phenyl group can be optionally substituted with a halogen, CN, NO2, SF5, OH, a C1-C4 alkyl group, a C1-C4 haloalkyl group, an -O-C1-C4 alkyl group, or an -OC1-C4 haloalkyl group.

[0313] In some embodiments, W 1 These are F, Cl, Br, I, OTf, OTs, OMs, -SCH3, -SCH2CH3, -S-phenyl group, and -OCF2CF3.

[0314] In some other embodiments, the present invention provides an intermediate compound represented by formula (Aa), [ka] Eventually, W 1 , R 1 , R 2 , R 3 , R 10 , X, Y 1 , Y 2 , Y 3 , Y 5 , Y 7 , Y 8 , and Z 1 This is as defined in the present invention.

[0315] In some other embodiments, the present invention provides an intermediate compound represented by formula (Ab), [ka] Eventually, W 1 , ring C, R 1 , R 10 , X, Y 1 , Y 2 , Y 3 , Y 5 , Y 7 , Y 8 , and Z 1 This is as defined in the present invention.

[0316] In some embodiments, the intermediate compounds provided by the present invention are [ka] Or it is selected from that salt.

[0317] In some embodiments, the present invention provides an intermediate compound represented by formula (B), [ka] W 2The leaving group is (for example, -SC1-C4 alkyl group (e.g., -SCH3, -SCH2CH3), -S-phenyl group, -OC1-C4 alkyl group, -OC1-C4 haloalkyl group (e.g., -OCF2CF3), of which the above C1-C4 alkyl group and phenyl group can be optionally substituted with halogen, CN, NO2, SF5, OH, C1-C4 alkyl group, C1-C4 haloalkyl group, -O-C1-C4 alkyl group, or -OC1-C4 haloalkyl group), Eventually, R 1 , R 2 , R 3 , X, Y 1 , Y 2 , Y 3 , Y 5 , Y 7 , and Y 8 This is as defined in the present invention.

[0318] In some embodiments, W 2 The group is a -SC1-C4 alkyl group, an -S-phenyl group, an -OC1-C4 alkyl group, or an -OC1-C4 haloalkyl group, of which the C1-C4 alkyl group and phenyl group may be optionally substituted with a halogen, CN, NO2, SF5, OH, a C1-C4 alkyl group, a C1-C4 haloalkyl group, an -O-C1-C4 alkyl group, or an -OC1-C4 haloalkyl group.

[0319] In some embodiments, W 2 The group is -SCH3, -SCH2CH3, -S-phenyl group, or -OCF2CF3.

[0320] In some other embodiments, the present invention provides an intermediate compound represented by formula (Ba), [ka] Eventually, W 2 , ring C, R 1 , X, Y 1 , Y 2 , Y 3 , Y 5 , Y 7 , and Y 8These are as defined in the present invention.

[0321] In some embodiments, the intermediate compounds provided by the present invention are [ka] Or it is selected from that salt.

[0322] definition Unless otherwise specified, the following terms have the meanings set forth below. Other terms are defined elsewhere in this specification.

[0323] Unless otherwise specified in the context, the singular forms “1(a),” “an,” and “the” as used herein include multiple subjects. It should also be noted that claims can be drafted to exclude any optional element. Accordingly, this description aims to provide a prior basis relating to the use of such exclusive terms, such as “only,” “only,” etc., in reference to claim elements or “negative” restrictions.

[0324] In different parts of this specification, variables defining divalent linking groups are described. Specifically, each linking substituent includes both forward and reverse forms of the linking substituent. For example, -NR(CR'R'')- includes -NR(CR'R'')- and -(CR'R'')NR-, and the purpose is to disclose each form separately. Where a structure requires a linking group, the Markousch variables listed for that group are understood as linking groups. For example, if a structure requires a linking group and the Markousch group definition for that variable lists "alkyl group" or "aryl group," it should be understood that "alkyl group" or "aryl group" represents a linked alkyl group or aryl group, respectively.

[0325] The term "substituted" means that one atom or group of atoms formally replaces a hydrogen atom and is linked to another group as a "substituent." Unless otherwise specified, the term "substitution" refers to any number of substitutions, such as mono-, di-, tri-, tetra-, or penta-substitutions, where such substitutions are permitted. Substituents are independently selected and may be substituted at any chemically accessible position. It should be understood that substitutions at a particular atom are limited by its valence. The term "optionally substituted" means either unsubstituted or substituted. The term "substituted" means that a hydrogen atom is removed and replaced with a substituent. A single divalent substituent, e.g., oxo, can substitute two hydrogen atoms.

[0326] The term "Cn-Cm" represents a range including the endpoints mentioned above, where n and m are integers representing the number of carbon atoms. For example, the term "C1-C6 alkyl group" specifically refers to methyl, ethyl, C3, C4, C5, and C6 alkyl groups. "C0 alkyl group" refers to a covalent bond.

[0327] The compounds of the present invention are stable. As used herein, “stable” means that the compound is sufficiently stable during the process of being separated from the reaction mixture to a useful purity, and preferably, that the compound can be prepared into an effective therapeutic agent.

[0328] It should also be understood that, for clarity, some features of the present invention described in the context of a single embodiment may be provided in combination with a single embodiment. Conversely, for brevity, various features of the present invention described in the context of a single embodiment may be provided individually or in any suitable sub-combination.

[0329] As used herein, unless otherwise specified, the term “alkyl group” refers to a linear or branched saturated hydrocarbon group, either by itself or as part of another substituent. Alkyl groups may contain 1 to about 20, 2 to about 20, 1 to about 10, 1 to about 8, 1 to about 6, 1 to about 4, or 1 to about 3 carbon atoms. Similarly, C 1-8 , C 1-8 Alkyl groups are defined as groups arranged in a linear or branched chain and having 1, 2, 3, 4, 5, 6, 7, or 8 carbon atoms. Exemplary alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), propyl (e.g., n-propyl and isopropyl), butyl (e.g., n-butyl, isobutyl, and tert-butyl), and pentyl (e.g., n-pentyl, isopentyl, and neopentyl) groups.

[0330] As used herein, unless otherwise specified, “alkenyl group” refers to an alkyl group having one or more carbon-carbon double bonds. Exemplary alkenyl groups include, but are not limited to, vinyl groups and propenyl groups.

[0331] As used herein, unless otherwise specified, “alkynyl group” refers to an alkyl group having one or more carbon-carbon triple bonds. Exemplary alkynyl groups include, but are not limited to, ethynyl and propynyl groups.

[0332] As used herein, unless otherwise specified, “haloalkyl group” refers to an alkyl group having one or more halogen substituents. Exemplary haloalkyl groups include, but are not limited to, CF3, C2F5, CHF2, CH2F, CCl3, CHCl2, C2Cl5, and the like.

[0333] As used herein, unless otherwise specified, “aryl group” refers to an unsubstituted or substituted monocyclic or polycyclic (e.g., having two, three, or four fused rings) aromatic hydrocarbon. In some embodiments, the aryl group has 6 to about 20 carbon atoms. In some embodiments, the aryl group has 6 to about 14 carbon atoms. In some embodiments, the aryl group has 6 to about 10 carbon atoms. Exemplary aryl groups include, but are not limited to, phenyl, naphthyl, anthracenyl, phenantrenyl, indanyl, and indenyl groups.

[0334] As used herein, unless otherwise specified, “cycloalkyl group” refers to an unsubstituted or substituted non-aromatic carbon ring (saturated or partially unsaturated ring), and includes cyclized alkyl groups, alkenyl groups, and alkynyl groups. Cycloalkyl groups include monocyclic- or polycyclic (e.g., having 2, 3, or 4 fused rings) ring systems, and include fused carbon rings, spiro-carbon rings, and crosslinked-carbon rings (e.g., crosslinked-bicycloalkyl groups). In some embodiments, cycloalkyl groups may have 3 to about 20 carbon atoms, 3 to about 14 carbon atoms, 3 to about 10 carbon atoms, or 3 to about 7 carbon atoms. Cycloalkyl groups may further have 0, 1, 2, or 3 double bonds and / or 0, 1, or 2 triple bonds. Cycloalkyl groups may optionally be substituted with oxo or thio (e.g., -C(O)- or -C(S)-). The definition of a cycloalkyl group further includes a group having one or more aromatic rings condensed with (i.e., having a common bond with) the cycloalkyl group, such as benzo derivatives of cyclopentyl, cyclopentenyl, and cyclohexyl groups. A cycloalkyl group having one or more condensed aromatic rings can be linked via an aromatic ring moiety or a non-aromatic ring moiety. One or more ring-forming carbon atoms of the cycloalkyl group may be oxidized to form, for example, oxo or thio substituents. In some embodiments, the cycloalkyl group is selected from C3-C7 monocyclic cycloalkyl groups. In some embodiments, the cycloalkyl group is C4-C10 The cycloalkyl group is selected from a spiro ring or a crosslinked ring cycloalkyl group. Exemplary cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexadienyl, cycloheptatrienyl, norbornyl, norpinyl, norcarel, cubanyl, adamantyl, bicyclo[1.1.1]pentyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[3.1.1]heptyl, bicyclo[2.2.2]octyl, and spiro[3.3]heptyl groups. In some embodiments, the cycloalkyl group is selected from a cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl group. In some embodiments, the cycloalkyl group is a non-aromatic hydrocarbon group containing a ring, with 3 to 12 carbon atoms ("C3-C"). 12 It has a cycloalkyl group, preferably having 3 to 6 carbon atoms ("C3-C6"). Examples of cycloalkyl groups include, for example, a cyclopropyl group (C3, 3-membered), a cyclobutyl group (C4, 4-membered), a cyclopropylmethyl group (C4), a cyclopentyl group (C5), a cyclohexyl group (C6), a 1-methylcyclopropyl group (C4), a 2-methylcyclopentyl group (C4), and an adamantyl group (C 10 ) and others.

[0335] The term "spirocycloalkyl group," when used alone or as part of a substituent, refers to a non-aromatic cyclic hydrocarbon group containing two cycloalkyl groups, of which typically the two cycloalkyl groups share one carbon atom.

[0336] As used herein, unless otherwise specified, “heteroaryl group” refers to an unsubstituted or substituted aromatic heterocycle having at least one heteroatom ring member, e.g., boron, sulfur, oxygen, or nitrogen. Heteroaryl groups include monocyclic and polycyclic (e.g., having two, three, or four fused rings) systems. Any ring-forming N atom of a heteroaryl group can be oxidized to form an N-oxide. Exemplary heteroaryl groups include, but are not limited to, pyridinyl, N-oxopyridinyl, pyrimidinyl, pyrazinyl, pyridadinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 1,2,4-thiadiazolyl, isothiazolyl, benzothienyl, prinyl, carbazolyl, benzimidazolyl, and indolinyl groups. In some embodiments, the heteroaryl groups have 1 to about 20 carbon atoms, and in some further embodiments, they have 3 to about 20 carbon atoms. In some embodiments, the heteroaryl group contains 3 to about 14, 3 to about 7, or 5 to 6 ring atoms. In some embodiments, the heteroaryl group has 1 to about 4, 1 to about 3, or 1 to 2 heteroatoms.

[0337] As used herein, unless otherwise specified, “heterocycloalkyl group” means an unsubstituted or substituted monocyclic (saturated or partially unsaturated) or polycyclic heterocyclic group having at least one non-aromatic ring (saturated or partially unsaturated), of which one or more ring-forming carbon atoms may be substituted with heteroatoms selected from N, O, S, Si, P, and B, and the ring-forming carbon atoms and heteroatoms of the heterocycloalkyl group may be optionally substituted with one or more oxo or thio atoms (e.g., C(O), S(O), C(S), S(O)2, or P(O)). Heterocycloalkyl groups include monocyclic and polycyclic (e.g., having two fused rings) systems. Heterocycloalkyl groups include monocyclic and polycyclic 3-10 member, 4-10 member, 3-7 member, 4-7 member, and 5-6 member heterocycloalkyl groups. The heterocycloalkyl group further comprises a spiro ring and a crosslinking ring (for example, a 5-10 membered crosslinking ring biheterocycloalkyl group in which one or more of the ring-forming carbon atoms are substituted with heteroatoms independently selected from N, O, S, Si, P, and B). The heterocycloalkyl group can be linked via ring-forming carbon atoms or ring-forming heteroatoms. In some embodiments, the heterocycloalkyl group contains 0-3 double bonds. In some embodiments, the heterocycloalkyl group contains 0-2 double bonds.

[0338] The above heterocycloalkyl group further includes a group having one or more aromatic rings fused to the above non-aromatic heterocycle (i.e., having a common bond with the heterocycloalkyl group), such as piperidine, morpholine, or benzo or thieno derivatives of azepane. The heterocycloalkyl group containing the fused aromatic ring can be linked via any ring-forming atoms, including the ring-forming atoms of the fused aromatic ring. In some embodiments, the above heterocycloalkyl group contains 3 to 10 ring-forming atoms, 4 to 10 ring-forming atoms, 3 to 7 ring-forming atoms, or 5 to 6 ring-forming atoms. In some embodiments, the above heterocycloalkyl group has 1 to 4 heteroatoms, 1 to 3 heteroatoms, 1 to 2 heteroatoms, or 1 heteroatom. In some embodiments, the above heterocycloalkyl group is a monocyclic 4 to 6-membered heterocycloalkyl group having one or two heteroatoms independently selected from N, O, S, Si, and B, and simultaneously having one or more ring atoms substituted with oxo.

[0339] Exemplary heterocycloalkyl groups include pyrrolidine-2-one, 1,3-isoxazolidine-2-one, pyranyl group, tetrahydropyranyl group, oxetanyl group, azetidinyl group, morpholinyl group, thiomorpholinyl group, piperazinyl group, tetrahydrofuranyl group, tetrahydrothienyl group, piperidinyl group, pyrrolidinyl group, isoxazolidinyl group, isothiazolidinyl group, pyrazolidinyl group, oxazolidinyl group, thiazolidinyl group, and imidazolidinyl group. , azepanyl group, benzazapentenyl group, 1,2,3,4-tetrahydroisoquinolyl group, azabicyclo[3.1.0]hexyl group, diazabicyclo[3.1.0]hexyl group, oxabicyclo[2.1.1]hexyl group, azabicyclo[2.2.1]heptyl group, diazabicyclo[2.2.1]heptyl group, azabicyclo[3.1.1]heptyl group, diazabicyclo[3.2.1]heptyl group, azabicyclo[3. 2.1]octyl group, oxabicyclo[2.2.2]octyl group, azabicyclo[2.2.2]octyl group, diazabicyclo[2.2.2]octyl group, azaadamantyl group, diazadamantyl group, oxadamantyl group, azaspiro[3.3]heptyl group, azaspiro[3.3]heptyl group, oxa-azaspiro[3.3]heptyl group, azaspiro[3.4]octyl group, diazaspiro[3.4]octyl group, oxa-azaspiro[3.4]octyl group, o This includes, but is not limited to, xa-azaspiro[3,5]nonyl group, azaspiro[2,5]octyl group, diazaspiro[2,5]octyl group, azaspiro[4,4]nonyl group, diazaspiro[4,4]nonyl group, oxa-azaspiro[4,4]nonyl group, azaspiro[4,5]decyl group, diazaspiro[4,5]decyl group, diazaspiro[4,4]nonyl group, oxa-diazaspiro[4,4]nonyl group, octahydropyrrolo[3,4-c]pyrrolyl group, etc.

[0340] In some embodiments, a heterocycloalkyl group refers to any 3- to 10-membered monocyclic or bicyclic saturated ring structure containing at least one heteroatom selected from O, N, and S. The heterocycloalkyl group can be linked via any heteroatom or carbon atom, provided that it has a stable structure that can be produced. Exemplary heterocycloalkyl groups include, but are not limited to, azepanyl, azilidinyl, azetidinyl, pyrrolidinyl, dioxolanyl, imidazolidinyl, pyrazolidinyl, piperadinyl, piperidinyl, dioxanyl, morpholinyl, dithianyl, thiomorpholinyl, oxazepanyl, oxylanyl, oxetanyl, quinuclidinyl, tetrahydrofuranyl, tetrahydropyranyl, and piperadinyl groups.

[0341] In some embodiments, the term “spiroheterocycloalkyl group,” when used alone or as part of a substituent, refers to a non-aromatic ring comprising two rings, where at least one ring is selected from a heterocycloalkyl group and the two rings share one carbon atom.

[0342] As used herein, unless otherwise specified, “arylcycloalkyl” refers to a cycloalkyl group substituted with an aryl group.

[0343] As used herein, unless otherwise specified, “aryl heterocycloalkyl” refers to a heterocycloalkyl group substituted with an aryl group.

[0344] As used herein, unless otherwise specified, “aryl heteroaryl group” means a heteroaryl group substituted with an aryl group.

[0345] As used herein, unless otherwise specified, “biaryl group” refers to an aryl group substituted with an aryl group.

[0346] As used herein, unless otherwise specified, “heteroarylcycloalkyl” refers to a cycloalkyl group substituted with a heteroaryl group.

[0347] As used herein, unless otherwise specified, “heteroarylheterocycloalkyl” refers to a heterocycloalkyl group substituted with a heteroaryl group.

[0348] As used herein, unless otherwise specified, “heteroarylaryl group” refers to an aryl group substituted with a heteroaryl group.

[0349] As used herein, unless otherwise specified, “biheteroaryl group” refers to a heteroaryl group substituted with a heteroaryl group.

[0350] As used herein, "halogen" or "halogen" includes fluorine, chlorine, bromine, and iodine.

[0351] As used herein, unless otherwise specified, “alkoxy group” refers to an -O-alkyl group. Exemplary alkoxy groups include methoxy, ethoxy, propoxy (e.g., n-propoxy and isopropoxy), and t-butoxy groups.

[0352] As used herein, unless otherwise specified, “hydroxyalkyl group” refers to an alkyl group substituted with an OH group.

[0353] As used herein, unless otherwise specified, “cyanoalkyl group” refers to an alkyl group substituted with CN.

[0354] As used herein, unless otherwise specified, “alkoxyalkyl group” refers to an alkyl group substituted with an alkoxy group.

[0355] As used herein, unless otherwise specified, “alkoxyalkoxy group” refers to an alkoxy group substituted with an alkoxy group.

[0356] As used herein, unless otherwise specified, “haloalkoxy group” refers to an -O-(haloalkyl group).

[0357] As used herein, unless otherwise specified, “arylalkyl group” refers to an alkyl group substituted with an aryl group, and “cycloalkylalkyl group” refers to an alkyl group substituted with a cycloalkyl group. An exemplary arylalkyl group is the benzyl group.

[0358] As used herein, unless otherwise specified, “heteroarylalkyl” refers to an alkyl group substituted with a heteroaryl group, and “heterocycloalkylalkyl” refers to an alkyl group substituted with a heterocycloalkyl group.

[0359] As used herein, unless otherwise specified, “oxo” refers to an oxygen substituent (i.e., =O) linked via a double bond.

[0360] As used herein, unless otherwise specified, the term “optionally substituted” above means either non-substituted or substituted.

[0361] As used herein, unless otherwise specified, the term “substituted” means that one or more hydrogen atoms in the group are substituted with homologous or homologous substituents independently selected from the following: Exemplary substituents include D, halogen, oxo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, and C1-C6 alkyl-NR. c1 R d1 ,-(CH2CH2O) o C1-C6 alkyl groups (where o is selected from 1 to 10), C 2-6 Alkenil-NR c R d , C2-6 アルキニル-NR c R d 、OC 2-6 アルキル-NR c R d 、CN、NO2、N3、OR a 、SR a 、C(O)R b 、C(O)NR c R d 、-CH2C(O)NR c R d 、C(O)OR a 、OC(O)R b 、OC(O)NR c R d 、-NR c R d 、NR c C(O)R b 、NR c C(O)NR c R d 、NR c C(O)OR a 、C(=NR g )NR c R d 、NR c1 C(=NR g )NR c R d 、P(R f )2、P(OR e )2、P(O)R e R f 、P(O)OR e OR f 、S(O)R b 、-SO(=NR b )、S(O)NR c R d 、S(O)2R b 、NR c S(O)2R b 、S(O)2NR c R dThe aryl group, heteroaryl group, spirocycloalkyl group, spiroheterocycloalkyl group, cycloalkyl group, or heterocycloalkyl group is included, but is not limited to these, and among them, the aryl group, heteroaryl group, spirocycloalkyl group, spiroheterocycloalkyl group, cycloalkyl group, or heterocycloalkyl group may be optionally D, halogen, oxo, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl group, or C1-C6 alkyl-NR c1 R d1 , C 2-6 Alkenil-NR c1 R d1 , C 2-6 Alkinyl-NR c1 R d1 , OC 2-6 Alkyl-NR c1 R d1 , CN, NO2, N3, OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 -CH2C(O)NR c1 R d1 , C(O)OR a1 ,OC(O)R b1 , OC(O)NR c1 R d1 , -NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)NR c1 R d1 , NR c1 C(O)OR a1 , C(=NR g1 )NR c1 R d1 , NR c1 C(=NR g1 )NR c1 R d1 , P(R f1 )2, P(OR e1 )2, P(O)R e1 R f1 , P(O)OR e1 Ure f1 , S(O)R b1, S(O)NR c1 R d1 S(O)2R b1 , NR c1 S(O)2R b1 , S(O)2NR c1 R d1 It is substituted with a substituent selected from the following.

[0362] The compounds described in this invention may be asymmetric (for example, having one or more stereocenters). Unless otherwise specified, all stereoisomers, such as enantiomers and diastereomers, are included within the scope of this invention. Compounds containing asymmetrically substituted carbon atoms described in this invention may be optically active or racemic. Methods for producing optically active forms from optically active starting materials are known in the art, for example, by resolution of racemic mixtures or stereoselective synthesis. Many geometric isomers of olefins, such as C=N double bonds, may be present in the compounds described in this invention, and all stable isomers are also within the scope of this invention. Cis and trans geometric isomers of the compounds described in this invention are also within the scope of this invention and can be separated into mixtures of isomers or into individual isomers.

[0363] The compounds described in the present invention further include tautomers. Tautomers are formed by the exchange of a single bond with an adjacent double bond and the resulting transfer of a proton. Tautomers include proton transition tautomers having the same chemical formula and total charge. Exemplary proton transition tautomers include keto-enol tautomerism, amide-imido acid tautomerism, lactam-lactide tautomerism, amide-imido acid tautomerism, and enamine-imido tautomerism, in which the proton can tautomerize at two or more positions in the heterocyclic system in the cyclic structure, for example, 1H- and 3H-imidazoles, 1H-, 2H- and 4H-1,2,4-triazoles, 1H- and 2H-isoindole, and 1H- and 2H-pyrazoles. Tautomers may be in equilibrium or may form a single form by fixing the space through appropriate substitution.

[0364] In some cases, the compounds described in the present invention may exist in the form of rotational isomers. The descriptions of the compounds of the present invention are intended to include any single rotational isomer and any mixture of rotational isomers in any ratio, and do not represent any particular rotational isomer. A description of a particular rotational isomer refers to the rotational isomer described above and basically does not include any other rotational isomers.

[0365] The present invention further comprises isotope-labeled compounds of the compounds or intermediates described in the present invention. An isotope refers to an atom having the same number of atoms but a different molecular weight. For example, isotopes of hydrogen include protium and deuterium.

[0366] In some embodiments, the compounds or salts thereof described in the present invention are substantially separated. "Substantially separated" means that the compounds are at least partially or substantially separated from the environment in which they were formed or detected. Partial separation may include, for example, a composition rich in the compounds of the present invention. Substantially separated may include a composition containing at least about 50% by weight, at least about 60% by weight, at least about 70% by weight, at least about 80% by weight, at least about 90% by weight, at least about 95% by weight, at least about 97% by weight, or at least about 99% by weight of the compounds or salts thereof of the present invention. Methods for separating compounds and salts thereof are common in the art.

[0367] The present invention also includes pharmaceutically acceptable salts of the compounds described herein. As used herein, “pharmaceutically acceptable salt” refers to a derivative of the compounds described herein, where the parent compound is modified by converting an existing acidic or base moiety to its salt form. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic salts of basic residues (e.g., amines) and base or organic salts of acidic residues (e.g., carboxylic acids). The pharmaceutically acceptable salts of the present invention include, for example, non-toxic salts of parent compounds formed from non-toxic inorganic or organic acids. The pharmaceutically acceptable salts of the present invention can be synthesized from parent compounds containing basic or acidic moieties by conventional chemical methods. Typically, these salts can be produced by reacting the free acidic or base form of these compounds with stoichiometric amounts of a suitable base or acid in water or an organic solvent or a mixture thereof, generally preferred in non-aqueous media such as ether, ethyl acetate, ethanol, isopropanol, or acetonitrile. A list of suitable salts is given in Remington's Pharmaceutical Sciences, 17th edition, Mack Publishing Company, Easton, Pa., 1985, page 1418 and Journal of Pharmaceutical Science, 66, 2 (1977), each of which is incorporated herein by reference in its entirety.

[0368] The term "pharmaceutically acceptable" as used herein means a compound, substance, composition and / or dosage form that, within reasonable medical judgment, does not cause excessive toxicity, irritation, allergic reactions or other problems or complications, and has a reasonable benefit-to-hazard ratio for contact with human and animal tissues.

[0369] "Pharmacologically acceptable excipients" refer to substances that, when added to a pharmacological composition or used in other ways as a medium, carrier, or diluent, facilitate the administration of a drug, and are compatible with it, non-toxic, biologically resistant, and suitable for other biological administration to a subject, such as inert substances. Examples of excipients include calcium carbonate, calcium phosphate, various sugars and various types of starches, cellulose derivatives, gelatin, vegetable oils, and polyethylene glycol.

[0370] A "solvate" refers to a physical complex formed by a compound represented by formula I and one or more solvent molecules.

[0371] A "leaving group" refers to one atom or set of atoms that is substituted in a chemical reaction, and these are stable substances with bonding electrons, for example, generally forming anions. Preferably, the leaving group is selected from halogens, especially fluorine, chlorine, bromine or iodine, and groups including (methylsulfonyl)oxy, [(4-methylphenyl)sulfonyl]oxy, [(trifluoromethyl)sulfonyl]oxy, [(nonafluorobutyl)sulfonyl]oxy, [(4-bromophenyl)sulfonyl]oxy, [(4-nitrophenyl)sulfonyl]oxy, [(2-nitrophenyl)sulfonyl]oxy, [(4-isopropylphenyl)sulfonyl]oxy, [(2,4,6-triisopropylphenyl)sulfonyl]oxy, [(2,4,6-trimethylphenyl)sulfonyl]oxy, [(4-tert-butyl-tert-butylphenyl)sulfonyl]oxy, (phenylsulfonyl)oxy, and [(4-methoxyphenyl)sulfonyl]oxy.

[0372] "Subject" includes human beings. The terms "human," "patient," and "subject" may be used interchangeably herein.

[0373] In one embodiment, “treating or treating” any disease or condition means improving the disease or condition (i.e., preventing or reducing the progression of the disease or at least one of its clinical symptoms). In another embodiment, “treatment” means improving at least one physical parameter that may not be recognizable to the subject. In yet another embodiment, “treatment” means regulating the disease or condition at the physical level (e.g., stabilization of recognizable symptoms), the physiological level (e.g., stabilization of physical parameters), or both levels. In yet another embodiment, “treatment” means delaying the onset of the disease or condition.

[0374] The phrase "compounds of the present invention" and equivalent expressions are intended to cover the compounds represented by Formula I as described herein, and their respective subgenera, and, where permitted in the context, such expressions include stereoisomers (e.g., enantiomers, diastereomers) and structural isomers (e.g., tautomers) and pharmaceutically acceptable salts of the compounds represented by Formula I.

[0375] As used herein, the term “isotope variant” refers to a compound having an isotopic ratio greater than the natural abundance of one or more atoms among the atoms constituting the compound. For example, an “isotope variant” of a compound may be radiolabeled, i.e., containing one or more radioactive isotopes, or, for example, deuterium ( 2 H or D), carbon-13 ( 13 C), nitrogen-15( 15 Non-radioactive isotopes such as N) can be used. It should be understood that in compounds in which such isotopic substitution has been performed, the following atoms may change if present, for example, any hydrogen 2 It may also be H / D, and any carbon 13 It may be C, or any nitrogen 15 It may be N, and the presence and position of such an atom can be determined within the capabilities of a person skilled in the art.

[0376] It should also be understood that compounds having the same molecular formula but differing in the bonding properties or order of atoms or the spatial arrangement of atoms are called "isomers." Isomers with different spatial arrangements of atoms are called "stereoisomers," and examples include diastereomers, enantiomers, and rotational isomers. The compounds of the present invention may have one or more chiral centers, and therefore such compounds may be produced as individual (R)- or (S)-stereoisomers or mixtures thereof at each chiral center. Unless otherwise specified, the description or naming of a particular compound in the specification and claims is intended to include its racemic or all other stereoisomers and mixtures. If a structure has one chiral center but the specific stereochemistry of that center is not shown, the structure includes two enantiomers, either individually or as a mixture of enantiomers. If a structure has one or more chiral centers but the specific stereochemistry of those centers is not shown, the structure includes all enantiomers and diastereomers, either individually or as a mixture. Methods for measuring stereochemistry and separating stereoisomers are well known in the field.

[0377] Pharmaceutical composition The present invention further provides pharmaceutical compositions comprising a compound represented by formula (I), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated thereof, and a pharmaceutically acceptable carrier.

[0378] The pharmaceutical composition may be in a form suitable for oral administration (e.g., tablets, lozenges, hard or soft capsules, aqueous or oily suspensions, emulsions, dispersible powders or granules, syrups or elixirs), for injectable use (e.g., water or oily suspensions, or emulsions, sesame oil, corn oil, cottonseed oil or peanut oil, and elixirs, mannitol, glucose or sterile aqueous solutions, and similar drug carriers), for topical use (e.g., creams, ointments, gels, or aqueous or oily solutions or suspensions), for inhalation use (e.g., fine powders or liquid aerosols), for inhalation administration (e.g., fine powders), or for parenteral administration (e.g., sterile aqueous or oily solutions for intravenous, subcutaneous, intramuscular, intraperitoneal or intramuscular administration, or suppositories for rectal administration).

[0379] The composition can be obtained by conventional procedures using common medicinal excipients well known in the art. Accordingly, the composition for oral use may contain, for example, one or more colorants, sweeteners, flavorings and / or preservatives.

[0380] A therapeutically effective amount of the compound shown in formula (I) or a pharmaceutically acceptable salt thereof can effectively treat or inhibit, slow the progression of, and / or alleviate the symptoms associated with the proliferative conditions referred to herein.

[0381] The amount of active ingredient required to be combined with one or more excipients to produce a single dosage form varies depending on the individual being treated and the specific route of administration. For example, a formulation for oral administration to humans typically contains, for example, 0.1 mg to 1000 mg of the compound represented by formula (I) or a pharmaceutically acceptable salt thereof, and an appropriate and convenient amount of excipients, the amount of which can vary between about 5% and about 98% of the total weight of the composition.

[0382] The dose of the compound represented by formula (I) used for therapeutic or preventive purposes varies, based on well-known medical principles, depending on the nature and severity of the condition, the age and sex of the animal or patient, and the route of administration.

[0383] The following describes non-limiting examples of pharmaceutical compositions and methods for producing the same.

[0384] Method of administration The compounds shown in formula (I) above, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions containing these compounds may be administered to subjects by any convenient method of administration, whether systemic / circumferential or topical (i.e., to the desired site of action).

[0385] Methods of administration include, but are not limited to, oral (e.g., by ingestion), oral cavity, sublingual, transdermal (e.g., by patches, ointments, etc.), transmucosal (e.g., by patches, ointments, etc.), intranasal (e.g., by nasal spray), ocular (e.g., by eye drops), pulmonary (e.g., by inhalation or blowing therapy, e.g., by aerosol, e.g., by mouth or nose), rectal (e.g., by suppositories or enteral preparations), vaginal (e.g., by pessaries), parenteral (e.g., by injection, including subcutaneous, intradermal, intramuscular, intravenous, intraarterial, intracardiac, intrathecal, intravertebral, intrasacral, subcapsular, intraorbital, intraperitoneal, intratracheal, subepidermal, intraarticular, subarachnoid, and intrathoracic), and implantation in a depot or reservoir, including, but not limited to, subcutaneous or intramuscular.

[0386] How to use The above method typically involves administering a therapeutically effective dose of the compound of the present invention to a subject. The therapeutically effective dose of the combination of target compounds will vary depending on the expected application (in vitro or in vivo) and the subject and disease symptoms being treated, such as the subject's weight and age, the severity of the disease symptoms, and the method of administration, which can be readily determined by those skilled in the art. The term also applies to doses that induce a specific response in target cells, such as a decrease in the proliferation or downregulation of the activity of the target protein. The specific dose will vary depending on the specific compound selected, the administration plan followed, whether or not it is administered in combination with other compounds, the time of administration, the tissue to which it is administered, and the physical delivery system on which it is carried.

[0387] The above-described method of investigation is useful for the treatment of diseases associated with PARG. Any disease symptoms directly or indirectly caused by abnormal activity or expression levels of PARG may be expected disease symptoms.

[0388] The compounds of the present invention and pharmaceutical compositions containing them can be administered alone or in combination with medical therapies to treat any of the above-mentioned diseases. Medical therapies include, for example, surgery and radiotherapy (e.g., gamma radiation, neutron radiation therapy, electron beam radiation therapy, proton therapy, brachiotherapy, whole-body radioisotopes).

[0389] In other embodiments, the compounds and pharmaceutical compositions described in the present invention may be administered alone or in combination with one or more other agents to treat any of the above-mentioned diseases.

[0390] In other ways, the compounds and pharmaceutical compositions described in the present invention can be administered in combination with nuclear receptor agonists.

[0391] In other ways, the compounds and pharmaceutical compositions described in the present invention can be administered in combination with antagonists of nuclear receptor drugs.

[0392] In other ways, the compounds and pharmaceutical compositions described in the present invention can be administered in combination with antiproliferative agents.

[0393] synthesis The compounds described in the present invention, including their salts, can be produced using known organic synthesis techniques and can be synthesized according to any one of various possible synthetic routes, such as the scheme described below.

[0394] The above reaction for producing the compounds of the present invention can be carried out in a suitable solvent, which can be easily selected by an expert in the field of organic synthesis. The suitable solvent does not necessarily have to react with the starting materials (reactants), intermediates, or products at the above temperature in which the reaction is carried out; for example, the temperature range may be from the freezing temperature of the solvent to the boiling temperature of the solvent. The predetermined reaction may be carried out in one solvent or a mixture of one or more solvents. Based on the above specific reaction steps, a person skilled in the art can select a solvent suitable for the specific reaction step.

[0395] The preparation of the compounds of the present invention can involve the above-mentioned protection and deprotection of various chemical groups. The need for the above-mentioned protection and deprotection, and the selection of the appropriate protecting group, can be readily determined by those skilled in the art. Disclosed chemical protecting groups include, for example, in Kocienski, Protecting Groups, (Thieme, 2007); Robertson, Protecting Group Chemistry, (Oxford University Press, 2000); Smith et al., March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 8th Ed. (Wiley, 2019); Peturssion et al., “Protecting Groups in Carbohydrate Chemistry,” J Chem. Educ, 1997, 74(11), 1297; and Wuts et al., Protective Groups in Organic Synthesis, 5th Ed. (Wiley, 2014).

[0396] The reaction can be monitored based on any suitable method known in the field. For example, the formation of the product can be monitored by nuclear magnetic resonance spectroscopy (e.g., 1 H or 13C) It can be monitored by spectroscopic means such as infrared spectroscopy, spectrophotometric methods (e.g., ultraviolet-visible light), mass spectrometry, or chromatography such as high-performance liquid chromatography (HPLC) or thin-layer chromatography.

[0397] The terms "ambient temperature," "room temperature," and "rt" used in this invention generally refer to temperatures such as reaction temperatures in this field, and to the temperature of the space during the reaction operation, for example, a temperature of about 20°C to about 30°C.

[0398] The compounds of the present invention can be produced according to various production routes known in the literature. The following scheme provides general guidance on the production of the compounds described in the present invention. Those skilled in the art should understand that various compounds of the present invention can be produced by modifying or optimizing the production methods in the following scheme using general knowledge of organic chemistry. An exemplary synthesis method for producing the compounds of the present invention is shown in the following scheme.

[0399] The above concepts described in the present invention will be illustrated by providing the following examples. While the above examples are provided as examples, they should not be considered to limit the more general examples described herein.

[0400] [Table 1(1)] [Table 1(2)]

[0401] Synthesis scheme The amino derivatives represented by formulas 1-5 can be prepared by the method shown in scheme 1. Compounds 1-3 are compound 1-1 (of which, W 1It can be produced by reacting a halogen (e.g., Cl, Br, or I) or a pseudohalogen (e.g., OTf or OMs) with a suitable amine derivative 1-2 in the presence of a base such as Hug's base. Compounds 1-3 and difluoromethyl-1,3,4-thiadiazole derivatives 1-4 (where W is a halogen (e.g., Cl, Br, or I) or a pseudohalogen (e.g., OTf or OMs)) can be coupled under standard Buchwald coupling conditions (e.g., in the presence of a palladium catalyst such as BrettPhos Pd G3, t-BuXphos Pd G3, RuPhos Pd G3, or XantPhos Pd G3, and a base such as t-BuOK, t-BuONa, Cs2CO3, or K2CO3) or under Ullmann coupling conditions (e.g., in the presence of a catalyst such as CuI or CsF, and a ligand such as N1,N2-dimethylcyclohexane-1,2-diamine or N-methylimidazole) to obtain compound 1-5. Compounds 1-5 can also be obtained by nucleophilic aryl substitution reactions of compounds 1-3 and difluoromethyl-1,3,4-thiadiazole derivatives 1-4 in the presence of a base (e.g., Cs2CO3, K2CO3).

[0402] [ka] The series of tricyclic ether derivatives shown in formulas 2-5 can be prepared by the method shown in scheme 2. Compound 2-3 is compound 2-1 (of which, W 1It can be produced by reacting compound 2-1 with a halogen (e.g., Cl, Br, or I) or pseudohalogen (e.g., OTf or OMs) and a suitable alcohol derivative 2-2 in the presence of a base such as KOH, NaH, NaHMDS, KHMDS, or n-BuLi. Alternatively, compound 2-1 and a suitable alcohol derivative 2-2 can be reacted under Ullmann coupling conditions (e.g., in the presence of a catalyst such as CuI or K3PO4, and a ligand such as a proline derivative or BINAP) or under Buchwald-Hartwig coupling conditions (e.g., Pd2(dba)3, Bippyphos, RockPhos, FcP t Compound 2-3 can be obtained by coupling compound 2-3 with a palladium catalyst such as Bu2, a ligand, and a base such as t-BuOK, K3PO4, Cs2CO3, or K2CO3. Compound 2-5 can also be obtained by nucleophilic aryl substitution reaction of compound 2-3 and the difluoromethyl-1,3,4-thiadiazole derivative 2-4 in the presence of a base (e.g., Cs2CO3, K2CO3).

[0403] [ka] The tricyclic derivatives represented by formulas 3-7 and 3-8 can be prepared by the method shown in scheme 3. Compound 3-1 (of which, W 1Alkenyl compounds 3-4 can be obtained by reacting alkenylboronic acid or boronic acid ester 3-2 (of which n is 0, 1, 2, 3, 4, 5, or 6) with a halogen (e.g., Cl, Br, or I) or pseudohalogen (e.g., OTf or OMs) under standard Suzuki coupling conditions (e.g., in the presence of a palladium catalyst such as Pd(dppf)Cl2 and a base such as K2CO3), or by reacting olefin derivative 3-3 (of which n is 0, 1, 2, 3, 4, 5, or 6) under standard Heck coupling conditions (e.g., in the presence of a palladium catalyst such as Pd(OAc)2, a base such as TEA, and a ligand such as tris(2-methoxyphenyl)phosphine). Alkenyl compounds 3-4 can be obtained by hydrogenating alkenyl compounds 3-4 in the presence of a palladium catalyst such as Pd / C or Pd(OH)2 / C to obtain the corresponding compound 3-5. Compound 3-4 or compound 3-5 can be coupled with the difluoromethyl-1,3,4-thiadiazole derivative 3-6 according to a method similar to that in Scheme 1 to obtain the corresponding compound 3-7 or compound 3-8.

[0404] [ka] The series of tricyclic derivatives shown in formulas 4-5 can be prepared by the method shown in scheme 4. Compound 4-3 is compound 4-1 (of which, W 1 Compound 4-3 can be obtained by reacting a halogen (e.g., Cl, Br, or I) or pseudohalogen (e.g., OTf or OMs) with a suitable terminal alkyne derivative 4-2 (of which n is 0, 1, 2, 3, 4, 5, or 6) under Sonogashira coupling conditions (e.g., in the presence of a catalyst such as Pd(PPh3)2Cl2, CuI, and a base such as TEA and DIPEA). Compound 4-5 can be obtained by coupling compound 4-3 with the difluoromethyl-1,3,4-thiadiazole derivative 4-4 according to a method similar to Scheme 1.

[0405] [ka] The series of tricyclic thioether derivatives shown in Formula 5-5 can be prepared by the method shown in Scheme 5. Compound 5-3 is compound 5-1 (of which, W 1 Compound 5-3 can be obtained by reacting a suitable thiol 5-2 with a halogen (e.g., Cl, Br, or I) or pseudohalogen (e.g., OTf or OMs) in the presence of a base such as KOH or NaH. Compound 5-5 can be obtained by coupling compound 5-3 with the difluoromethyl-1,3,4-thiadiazole derivative 5-4 according to a method similar to that in Scheme 1.

[0406] [ka] The tricyclic derivatives represented by formulas 6-4, 6-6, 6-8, and 6-11 can be prepared by the method shown in Scheme 6. The tricyclic thioether derivative 6-1 is reacted with a suitable halogenating agent such as SO2Cl2, or oxidized with a suitable oxidizing agent such as m-CPBA, NaClO, NaIO4, UHP (hydrogen peroxide-urea complex), or potassium persulfate complex salt to obtain an important intermediate tricyclic derivative 6-2 (of which W 1 is a halogen (e.g., Cl) or pseudo-halogen (e.g., SO2R) A or SOR A It can be converted to a tricyclic derivative 6-2 (of which, W 1A tricyclic derivative shown in formula 6-4 can be obtained by reacting a suitable amine derivative 6-3 with a suitable alcohol derivative 6-3 in the presence of a base such as Hugnog's base, or under standard Buchwald coupling conditions (e.g., in the presence of a palladium catalyst such as BrettPhos Pd G3, t-BuXphos Pd G3, RuPhos Pd G3 or XantPhos Pd G3, and a base such as t-BuOK, t-BuONa, Cs2CO3, or K2CO3), or under Ullmann coupling conditions (e.g., CuI, CsF, and a ligand such as N1,N2-dimethylcyclohexane-1,2-diamine or N-methylimidazole), or by reacting a suitable alcohol derivative 6-5 with a base such as KOH, NaH, NaHMDS, KHMDS, or n-BuLi, to obtain a tricyclic derivative shown in formula 6-6.

[0407] Tricyclic chloride derivative 6-2 (of which, W 1 By reacting compound 6-2 (where n is Cl) with appropriate terminal alkyne derivatives 6-7 (of which n is 0, 1, 2, 3, 4, 5, or 6) under Sonogashira coupling conditions (for example, in the presence of a catalyst such as Pd(PPh3)2Cl2 or CuI, and a base such as TEA or DIPEA), a tricyclic derivative shown in formula 6-8 can be obtained. Similarly, by Heck coupling compound 6-2 with olefin derivative 6-10 (of which n is 0, 1, 2, 3, 4, 5, or 6) under standard Heck conditions (for example, in the presence of a palladium catalyst such as Pd(OAc)2, a base such as TEA, and a ligand such as tris(2-methoxyphenyl)phosphine), a tricyclic alkenyl compound 6-11 can be obtained. Alternatively, the tricyclic alkenyl compound 6-11 can be obtained by reacting the above tricyclic chloride derivative 6-2 with an alkenylboronic acid or boronic acid ester 6-9 (of which n is 0, 1, 2, 3, 4, 5, or 6) under standard Suzuki coupling conditions (for example, in the presence of a palladium catalyst such as Pd(dppf)Cl2 and a base such as K2CO3).

[0408] [ka] The tricyclic intermediates shown in the series of formulas 7-7 can be prepared by the method shown in Scheme 6. Sulfonamide 7-3 can be prepared by reacting sulfonyl chloride 7-1 and amine 7-2 in the presence of a base such as Hug's base. Sulfonamide 7-3 and 2-cyanoacetamide can be coupled in the presence of a base such as NaH, t-BuONa, or t-BuOK to obtain compound 7-4, which can be further converted to indole derivative 7-5 by reacting the nitro group with a suitable reducing agent such as Zn / FeCl3 in an acidic medium or Fe / NH4Cl, followed by cyclization under the corresponding reaction conditions. Indole derivative 7-5 and alkyl orthoformate ester 7-6 can be reacted in the presence of an acid such as p-TsOH or HCl to produce the target product indole-pyrimidone 7-7, which can be reacted with a halogenating agent such as SOCl2, POCl3, or POBr3 and a catalytic amount of DMF (of which W 1 The reaction is carried out in the presence or absence of (where is Cl or Br), or TfCl or MsCl (of which W 1 By reacting with (where W1 is OTf or OMs) in the presence of a base such as Hugngs' base, it can be further converted to intermediates 7-8 (of which W1 is a halogen (e.g., Cl, or Br) or pseudohalogens (e.g., OTf or OMs)).

[0409] [ka] The series of tricyclic intermediates shown in formula 8-8 can be prepared by the method shown in scheme 8. Compound 8-1 (of which, W 2 is a halogen (e.g., Cl, Br, or I) or a pseudohalogen (e.g., OTf or OMs), and W 3Compound 8-2 is coupled to a halogen (e.g., Br, or I) or pseudohalogen (e.g., OTf) under Buchwald coupling conditions (e.g., BrettPhosPd G3, t-BuXphosPd G3, RuPhosPd G3, or XantPhosPd The compounds can be coupled (in the presence of a palladium catalyst such as G3 and a base such as t-BuOK, t-BuONa, Cs2CO3, or K2CO3), and then subjected to an intramolecular Heck cyclization reaction under standard Heck reaction conditions (for example, in the presence of a palladium catalyst such as bis(triphenylphosphine)palladium dichloride, palladium acetate, or tetrakis(triphenylphosphine)palladium and a base such as Na2CO3, K2CO3, or NaOAc) to obtain the tricyclic compound 8-3, which can then be reacted with an oxidizing agent such as N-chlorosuccinimide or sodium hypochlorite, or a suitable reagent such as 1,3-dichloro-5,5-dimethylimidazolidin-2,4-dione to further convert it to the corresponding sulfonyl chloride 8-4. Sulfonyl chloride 8-4 and amine 8-5 can be reacted in the presence of a base such as Hug's base to obtain sulfonamide 8-6, which can then be reacted with an oxidizing agent such as hydrogen peroxide, potassium peroxymonosulfonate, and m-chloroperbenzoic acid to convert it to compound 8-7. Compound 8-7 can be reacted with a halogenating agent such as SOCl2, POCl3, or POBr3, or with TfCl or MsCl, in the presence of a base such as Hug's base to obtain intermediate 8-8 (of which W 1 It can be converted to a halogen (e.g., Cl, or Br) or a pseudohalogen (e.g., OTf or OMs).

[0410] [ka] Alternatively, the tricyclic intermediates shown in the series of formulas 9-10 can be prepared by the method shown in scheme 9. Tricyclic compound 9-3 can be prepared by a method similar to that in scheme 5, by reacting compound 9-1 with a suitable aniline 9-2. The benzyl group of compound 9-3 is removed and hydrogenated in the presence of a catalyst such as Pd / C or Pd(OH)2 / C to obtain the corresponding OH compound 9-4. Compound 9-4 is reacted with trifluoromethanesulfonic anhydride to obtain compound 9-5, which is further converted to 9-6 by reacting with phenylmethanethiol or sodium phenylmethanethiolate in the presence of a base such as Hug's base, Cs2CO3, t-BuOK, or t-BuONa. Compound 9-6 can be oxidized with an oxidizing reagent such as N-chlorosuccinimide or sodium hypochlorite to obtain the sulfonyl chloride 9-7, which can then be reacted with a suitable amine 9-8 in the presence of a base such as Hug's base, Na2CO3, or K2CO3. Subsequently, the protecting group Tf of compound 9-9 can be removed under basic conditions such as NaOH or KOH, further converting it to the target intermediate 9-10.

[0411] [ka] Alternatively, the tricyclic intermediates represented by the series of formulas 10-3 and 10-5 can be prepared by the method shown in scheme 10. Compound 10-1 (of which, W 2 Compounds 10-2 and 10-4 can be obtained by Buchwald coupling of compounds 10-2 and 10-4 with a halogen (e.g., Cl, Br, or I) or pseudohalogen (e.g., OTf or OMs) under corresponding standard conditions (e.g., in the presence of a palladium catalyst such as BrettPhosPd G3, t-BuXphosPd G3, RuPhosPd G3, or XantPhosPd G3, and a base such as t-BuOK, t-BuONa, Cs2CO3, or K2CO3), followed by intramolecular cyclization in the presence of a Lewis acid such as AlCl3, ZnCl2, or other acidic medium such as polyphosphate or POCl3 to produce compounds 10-3 and 10-5.

[0412] [ka] Similarly, the tricyclic intermediates represented by the series of formulas 11-3 and 11-5 can be prepared by the method shown in scheme 11. Compound 11-1 (of which, W 3 Compounds 11-2 and 11-5 can be obtained by Buchwald coupling of compounds 11-2 and 11-5 with a halogen (e.g., Cl, Br, or I) or pseudohalogen (e.g., OTf or OMs) under corresponding standard conditions (e.g., in the presence of a palladium catalyst such as BrettPhos Pd G3, t-BuXphos Pd G3, RuPhos Pd G3, or XantPhos Pd G3, and a base such as t-BuOK, t-BuONa, Cs2CO3, or K2CO3), followed by an intramolecular Heck cyclization reaction in a standard reaction (e.g., in the presence of a palladium catalyst such as bis(triphenylphosphine)palladium dichloride, palladium acetate, or tetrakis(triphenylphosphine)palladium, and a base such as Na2CO3, K2CO3, or NaOAc).

[0413] [ka] A series of tricyclic intermediates represented by formula 12-7 (where A is O or S) can be prepared by the method shown in scheme 12. Compound 12-3 is compound 12-1 (where W 2Compound 12-4 can be obtained by nucleophilic alkylation reaction of 2-cyanoalkyl acetate 12-2 (where R is an alkyl group (e.g., Me, Et, or t-Bu)) with a halogen (e.g., F, Cl, Br, or I) or pseudohalogen (e.g., OTf or OMs)) in the presence of a strong base such as t-BuOK, t-BuONa, or NaH. Compound 12-4 can be obtained by reducing nitro compound 12-3 with a reducing agent such as Zn powder or Fe powder under acidic conditions (e.g., acetic acid or HCl), followed by an intramolecular cyclization reaction. Compound 12-4 can be obtained by heating compound 12-4 with acetal 12-5 containing alpha-H in the presence of a base such as NaOMe or NaOEt. Compound 12-6 can be obtained by reacting halogenating reagents such as SOCl2, POCl3, or POBr3, or 12-7 (where W 1 The halogenation reaction is carried out with OTf or OMs) or TfCl or MsCl in the presence of a base such as Hugnig's base, and intermediates 12-7 (of which, W 1 (where Cl or Br can be obtained.)

[0414] [ka] Example 1. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-(2-morpholinoethoxy)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] Step 1. N-(1-cyanocyclopropyl)-4-(2-morpholinoethoxy)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] At 0°C, 2-morpholinoethyl-1-ol (567 mg, 4.3 mmol) was dissolved in THF (15 mL) and NaH (346 mg, 8.6 mmol, 60% suspended in mineral oil) was added. The reaction mixture was heated under reflux for 2 hours. After cooling to rt, 4-chloro-N-(1-cyanocyclopropyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (1.0 g, 2.9 mmol, Int A) was added to the reaction mixture. The resulting mixture was stirred at 60°C for 30 minutes, then cooled to rt, quenched with saturated NH4Cl aqueous solution (1 mL), and then concentrated under reduced pressure. The residue was purified by flash chromatography on a C18 column and eluted with MeCN / H2O (5%~29%) to obtain the target compound (400 mg), which was a yellow solid. LCMS calculated value C 20 H 23 N6O4S [M+H] + :m / z=443.1, measured value 443.2.

[0415] Step 2. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-(2-morpholinoethoxy)-9H-pyrimido[4,5-b]indole-7-sulfonamide Method A. N-(1-cyanocyclopropyl)-4-(2-morpholinoethoxy)-9H-pyrimide[4,5-b]indole-7-sulfonamide (400 mg, 0.9 mmol), 2-bromo-5-(difluoromethyl)-1,3,4-thiadiazole (484.1 mg, 2.3 mmol), CuI (138 mg, 0.7 mmol), (1R,2R)-N 1 ,N 2A mixture of dimethylcyclohexane-1,2-diamine (205.5 mg, 1.45 mmol) and CsF (550 mg, 3.62 mmol) in 1,4-dioxane (4 mL) was degassed, packed with N2, and substituted three times. The mixture was stirred at 110°C for 5 hours. After cooling to rt, the reaction mixture was diluted with H2O (10 mL) and extracted with EA (10 mL × 3). The combined organic phase was washed with saturated brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column flash chromatography and eluted with MeOH / DCM (0-5%) to obtain the crude product (210 mg). The crude product was purified by prep-HPLC on a C18 column and eluted with MeCN / H2O (50-60%, containing 0.5% TFA) to obtain the target compound (158.2 mg), a white solid. LCMS calculated value C 23 H 23 F2N8O4S2[M+H] + :m / z=577.1, measured value 577.1.

[0416] Method B. Cs2CO3 (196 mg, 0.6 mmol) was added to a mixture of N-(1-cyanocyclopropyl)-4-(2-morpholinoethoxy)-9H-pyrimido[4,5-b]indole-7-sulfonamide (89 mg, 0.2 mmol) and 2-bromo-5-(difluoromethyl)-1,3,4-thiadiazole (130 mg, 0.6 mmol) in DMF (3 mL). The mixture was stirred at rt for 16 hours and then concentrated under reduced pressure. The residue was purified by flash chromatography on a C18 column and eluted with MeCN / H2O (40-55%, containing 0.5% TFA) to obtain the target compound (43 mg) as a white solid. LCMS calculated value C 23 H 23 F2N8O4S2[M+H] + :m / z=577.1, measured value 577.1.

[0417] The compounds shown in Table 1 were prepared using Int A and a suitable Int X (alcohol derivative) or a commercially available raw material (CAM, alcohol derivative) according to a method similar to that of Example 1.

[0418] [Table 2(1)] [Table 2(2)]

[0419] Example 13. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-(methyl(2-morpholinoethyl)amino)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] Step 1. N-(1-cyanocyclopropyl)-4-(methyl(2-morpholinoethyl)amino)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] To a solution of 4-chloro-N-(1-cyanocyclopropyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (1.76 g, 5.0 mmol, Int A) in MeCN (20 mL), N-methyl-2-morpholinoethyl-1-amine (1.0 g, 6.6 mmol) and Et3N (1.54 g, 15.2 mmol) were added. The mixture was stirred at 80°C for 1 hour, then cooled to rt. The reaction mixture was filtered, the filter cake was washed with water, and dried under reduced pressure to obtain the target compound (1.5 g), which was a brown solid. LCMS calculation value C 21 H 26 N7O3S [M+H] + :m / z=456.2, measured value 456.2.

[0420] Step 2. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-(methyl(2-morpholinoethyl)amino)-9H-pyrimido[4,5-b]indole-7-sulfonamide Method C. N-(1-cyanocyclopropyl)-4-(methyl(2-morpholinoethyl)amino)-9H-pyrimido[4,5-b]indole-7-sulfonamide (1.5 g, 3.3 mmol), 2-bromo-5-(difluoromethyl)-1,3,4-thiadiazole (2.8 g, 13.2 mmol), CuI (0.5 g, 2.6 mmol), (1R,2R)-N 1 ,N 2 A 1,4-dioxane (15 mL) solution of -dimethylcyclohexane-1,2-diamine (0.75 g, 5.3 mmol) and CsF (2.0 g, 13.2 mmol) was degassed, packed with N2, and substituted three times. The mixture was stirred overnight at 110°C. It was cooled to rt, and the reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column flash chromatography and eluted with MeOH / DCM (0-6%) to obtain the crude product (500 mg). The crude product was further purified by prep-HPLC on a C18 column and eluted with MeCN / H2O (50-60%) to obtain the target product (325 mg), which was a white solid. 1 1H NMR (400 MHz, DMSO-d 6 ) δ 9.49 (d,J = 1.6 Hz,1H),9.36 (s,1H),8.68 (s,1H),8.26 (d,J = 8.4 Hz,1H),8.00 (dd,J = 8.4,1.8 Hz,1H),7.7 (t,J F-H = 53.6 Hz,1H),3.95 (t,J = 6.4 Hz,2H),3.41 (s,3H),3.35 (t,J = 4.6 Hz,4H),2.65 (t,J = 6.4 Hz,2H),2.30 (t,J = 4.4 Hz,4H),1.46-1.39 (m,2H),1.34-1.25 (m,2H). LCMS calculated value C 24 H 26 F2N9O3S2[M+H] + :m / z=590.2, measured value 590.2.

[0421] Method D. A mixture of N-(1-cyanocyclopropyl)-4-(methyl(2-morpholinoethyl)amino)-9H-pyrimido[4,5-b]indole-7-sulfonamide (91 mg, 0.2 mmol) and 2-bromo-5-(difluoromethyl)-1,3,4-thiadiazole (173 mg, 0.8 mmol) in DMF (3 mL) was mixed with Cs2CO3 (196 mg, 0.6 mmol). The mixture was stirred at rt for 16 hours and then concentrated under reduced pressure. The residue was purified by flash chromatography on a C18 column and eluted with MeCN / H2O (50-55%, containing 0.5% TFA) to obtain the target compound (53 mg) as a white solid. LCMS calculated value C 24 H 26 F2N9O3S2[M+H] + :m / z=590.2, measured value 590.2.

[0422] The compounds shown in Table 2 were prepared using Int A (sulfonamide derivative) and a suitable Int X (amine derivative) or a commercially available raw material (CAM, amine derivative) according to a method similar to that of Example 13.

[0423] [Table 3(1)] [Table 3(2)]

[0424] Example 25. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-(methylthio)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] Step 1. N-(1-cyanocyclopropyl)-4-(methylthio)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] To a solution of 4-chloro-N-(1-cyanocyclopropyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (100 mg, 0.3 mmol, Int A) in DMF (2 mL), NaSMe (35 mg, 0.5 mmol) was added. The reaction mixture was stirred at 100°C for 2 hours. It was then cooled to rt, diluted with water (4 mL), and filtered. The filtered cake was dried under reduced pressure to obtain the target compound (90 mg), which was a yellow solid. LCMS calculated value C 15 H 14 N5O2S2[M+H] + :m / z=360.1, measured value 360.0.

[0425] Step 2. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-(methylthio)-9H-pyrimido[4,5-b]indole-7-sulfonamide A mixture of N-(1-cyanocyclopropyl)-4-(methylthio)-9H-pyrimido[4,5-b]indole-7-sulfonamide (36 mg, 0.1 mmol), 2-bromo-5-(difluoromethyl)-1,3,4-thiadiazole (43 mg, 0.2 mmol), and Cs2CO3 (65 mg, 0.2 mmol) in DMF (1 mL) was stirred overnight at rt. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by prep-HPLC on a C18 column and eluted with MeCN / H2O (30-75%, containing 0.5% TFA) to obtain the target product (27.5 mg), which was a white solid. 1 H NMR (400 MHz,DMSO-d6) δ 9.49 (s,2H),9.18 (s,1H),8.43 (d,J = 8.4 Hz,1H),8.21 (d,J = 8.4 Hz,1H),7.70 (t,J F-H = 53.4 Hz,1H),2.67 (s,3H),1.49-1.39 (m,2H),1.34-1.22 (m,2H). LCMS calculated value C 18 H 14 F2N7O2S3[M+H] + :m / z=494.0, measured value 494.0.

[0426] The compounds shown in Table 3 were prepared using Int A and a suitable Int X (thiol derivative) or a commercially available raw material (CAM, thiol derivative) according to a method similar to that of Example 25.

[0427] [Table 4]

[0428] Example 28. N-(1-cyanocyclopropyl)-4-(4-(diethylamino)piperidine-1-yl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] To a mixture of 4-chloro-N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (144 mg, 0.3 mmol, Int B) and DIEA (78 mg, 0.6 mmol) in MeCN (2 mL), N,N-diethylpiperidine-4-amine (40 mg, 0.33 mmol) was added. The reaction mixture was stirred at 60°C for 3 hours. The resulting mixture was concentrated under reduced pressure. The residue was purified by prep-HPLC on a C18 column and eluted with MeCN / H2O (30-40%, containing 0.5% TFA) to obtain the target compound (130 mg) as a white solid. LCMS calculated value C 26 H 30 F2N9O2S2[M+H] + :m / z=602.2, measured value 602.2.

[0429] The compounds shown in Table 4 were prepared using Int B and a suitable Int X (amine derivative) or a commercially available raw material (CAM, amine derivative) according to a method similar to that of Example 28.

[0430] [Table 5(1)] [Table 5(2)] [Table 5(3)] [Table 5(4)] [Table 5(5)] [Table 5(6)] [Table 5(7)] [Table 5(8)] [Table 5(9)]

[0431] Example 82. N-(7-(N-(1-cyanocyclopropyl)sulfamoyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-9H-pyrimido[4,5-b]indole-4-yl)-2-morpholinoacetamide [ka] Step 1. 2-Molfolinoacetamide [ka] Morpholine (2.0 g, 20 mmol) was added to a mixture of 2-chloroacetamide (2.8 g, 30 mmol) in EtOH (30 mL), NaI (6.0 g, 40 mmol), and K2CO3 (8.28 g, 60 mmol). The mixture was stirred at 85°C for 6 hours. The reaction mixture was diluted with H2O and extracted with EA (30 mL x 3). The combined organic phase was washed with saturated brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column flash chromatography and eluted with MeOH / DCM (2-10%) to obtain the target compound (1.1 g), which was a yellow solid. LCMS calculated value: C6H 13 N2O2[M+H] + m / z = 145.1, measured value 145.2.

[0432] Step 2. N-(7-(N-(1-cyanocyclopropyl)sulfamoyl)-9H-pyrimido[4,5-b]indole-4-yl)-2-morpholinoacetamide [ka] A mixture of 1,4-dioxane (5 mL) containing 4-chloro-N-(1-cyanocyclopropyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (250 mg, 0.72 mmol, Int A), Pd(OAc)2 (50 mg, 0.22 mmol), Cs2CO3 (705 mg, 2.16 mmol), xantphos (209 mg, 0.36 mmol), and 2-morpholinoacetamide (156 mg, 1.08 mmol) was degassed, packed with N2, and substituted three times. The mixture was stirred at 90°C for 16 hours. The reaction mixture was diluted with H2O (20 mL) and extracted with DCM (20 mL x 3). The combined organic phase was washed with saturated brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by prep-TLC using a silica gel column, and eluted with MeOH / DCM (0-10%) to obtain the target compound (60 mg), which was a yellow solid. LCMS calculated value C 20 H 22 N7O4S [M+H] +:m / z=456.1, measured value 456.1.

[0433] Step 3. N-(7-(N-(1-cyanocyclopropyl)sulfamoyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-9H-pyrimido[4,5-b]indole-4-yl)-2-morpholinoacetamide A mixture of N-(7-(N-(1-cyanocyclopropyl)sulfamoyl)-9H-pyrimido[4,5-b]indole-4-yl)-2-morpholinoacetamide (55 mg, 0.12 mmol), 2-bromo-5-(difluoromethyl)-1,3,4-thiadiazole (103 mg, 0.48 mmol), and Cs2CO3 (117 mg, 0.36 mmol) in DMF (2 mL) was stirred overnight at rt. The reaction mixture was filtered and then concentrated under reduced pressure. The residue was purified by prep-HPLC on a C18 column and eluted with MeCN / H2O (15-75%, containing 0.1% TFA) to obtain the target product (13.6 mg), a white solid. LCMS calculated value C 23 H 22 F2N9O4S2[M+H] + :m / z=590.1, measured value 590.1.

[0434] Example 83. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-((2-morpholinoethyl)thio)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] Step 1. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-mercapto-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] 4-Chloro-N-(1-cyanocyclopropyl)-9-[5-(difluoromethyl)-1,3,4-thiadiazole-2-yl]pyrimido[4,5-b]indole-7-sulfonamide (60 mg, 0.13 mmol, Int B) was dissolved in DMAc (6 mL) and NaHS (20.9 mg, 0.37 mmol) was added. The mixture was stirred at 100°C for 3 hours, then poured into water and extracted with EA (20 mL x 3). The organic phase was washed with saturated brine, dried over Na2SO4, and concentrated under reduced pressure to obtain a crude product compound (52 mg) which was a yellow solid. LCMS calculation value C 17 H 12 F2N7O2S3[M+H] + :m / z=480.0, measured value 479.8.

[0435] Step 2. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-((2-morpholinoethyl)thio)-9H-pyrimido[4,5-b]indole-7-sulfonamide A mixture of N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-mercapto-9H-pyrimido[4,5-b]indole-7-sulfonamide (50 mg, 0.1 mmol) and 4-(2-chloroethyl)morpholine (19.4 mg, 0.1 mmol) in MeCN (2 mL) was mixed with K2CO3 (43.2 mg, 0.31 mmol). The mixture was stirred at 60°C for 2 hours. The reaction mixture was quenched with water and then extracted with EA (20 mL × 3). The organic phase was washed with saturated brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by prep-HPLC on a C18 column and eluted with MeCN / H2O (25-75%, containing 0.1% TFA) to obtain the target compound (31.3 mg) as a white solid. LCMS calculated value C 23 H 23 F2N8O3S3[M+H] + :m / z=593.1, measured value 593.0.

[0436] Example 84. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-((2-methoxyethyl)thio)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] The compound was prepared according to a method similar to step 2 of Example 83, with 4-(2-chloroethyl)morpholine substituted with 2-methoxyethyl chloride. LCMS calculated value C 20 H 18 F2N7O3S3[M+H] + :m / z=538.1, measured value 538.0.

[0437] Example 85. (E)-N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-(3-morpholinoprop-1-en-1-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] Step 1. (E)-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)morpholine [ka] A mixture of (E)-2-(3-chloroprop-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (500 mg, 2.5 mmol), morpholine (323 mg, 3.7 mmol), and K2CO3 (683 mg, 5.0 mmol) in ACN (6 mL) was degassed, packed with N2, and substituted three times. The mixture was stirred at 25°C for 12 hours, diluted with H2O, and extracted with EA (20 mL × 3). The combined organic phase was washed with saturated brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by prep-HPLC on a C18 column and eluted with MeCN / H2O (25%~75%) to obtain the target compound (100 mg) as a white solid. LCMS calculated value C13 H 25 BNO3[M+H] + :m / z=254.2, measured value 254.1.

[0438] Step 2. (E)-N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-(3-morpholinoprop-1-en-1-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide A mixture of 1,4-dioxane (10 mL) containing 4-chloro-N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (80 mg, 0.17 mmol, Int B), (E)-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)morpholine (63 mg, 0.25 mmol), NaHCO3 (42 mg, 0.5 mmol), and Pd(dppf)Cl2 (12 mg, 0.017 mmol) was degassed, packed with N2, substituted three times, and then stirred at 70°C for 12 hours. The reaction mixture was diluted with H2O and extracted with EA (20 mL x 3). The combined organic phases were washed with saturated saline solution, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by prep-HPLC on a C18 column and eluted with MeCN / H2O (20-55%, containing 0.1% TFA) to obtain the target compound (5.2 mg) as a white solid. LCMS calculated value C 24 H 23 F2N8O3S2[M+H] + :m / z=573.1, measured value 573.0.

[0439] Example 86. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-(3-morpholinoprop-1-in-1-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] To a solution of 4-chloro-N-(1-cyanocyclopropyl)-9-(5-(methyldifluoromethyl)-1,3,4-thiadiazole-2-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (60.0 mg, 0.12 mmol, Int B) in DMF (6 mL), TEA (38 mg, 0.38 mmol) was added, and the mixture was stirred at 25°C for 45 min. To the above mixture, Pd(PPh3)2Cl2 (9 mg, 0.013 mmol), CuI (12 mg, 0.06 mmol), and 4-(prop-2-in-1-yl)morpholine (46.7 mg, 0.374 mmol) were added. The reaction mixture was stirred at 45°C for 4 hours, then diluted with H2O and extracted with EA (20 mL x 3). The combined organic phase was washed with saturated brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by prep-TLC using a silica gel column, and eluted with MeOH / DCM (5%) to obtain the target compound (12.4 mg) as a yellow solid. LCMS calculated value C 24 H 21 F2N8O3S2[M+H] + :m / z=571.1, measured value 571.0.

[0440] Example 87. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-(3-morpholinopropyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] To a mixture of N-(1-cyanocyclopropyl)-9-[5-(methyldifluoromethyl)-1,3,4-thiadiazole-2-yl]-4-[3-(morpholin-4-yl)prop-1-in-1-yl]pyrimido[4,5-b]indole-7-sulfonamide (25 mg, 0.044 mmol, Example 86) in siRNA (10 mL), Pd / C (10 mg, palladium loading 10%) and Pd(OH)2 / C (10 mg, palladium loading 10%) were added, the mixture was degassed, H2 was packed, and the mixture was substituted three times. The mixture was stirred overnight under rt, the reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by prep-TLC on a silica gel column and eluted with MeOH / DCM (10%) to obtain the target compound (15.4 mg) as a white solid. LCMS calculated value C 24 H 25 F2N8O3S2[M+H] + :m / z=575.1, measured value 575.1.

[0441] Example 88. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-(3-hydroxy-3-methylbuto-1-in-1-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] The compound was prepared according to a method similar to that of Example 86, using 2-methyl-3-buty-2-ol and Int B as starting materials. LCMS calculated value C 22 H 18 F2N7O3S2[M+H] + :m / z=530.1, measured value 530.0.

[0442] Example 89. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-(3-hydroxy-3-methylbutyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] The compound was prepared according to a method similar to that of Example 87, using N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-(3-hydroxy-3-methylbuto-1-in-1-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (Example 88) as a starting material. LCMS calculated value C 22 H 22 F2N7O3S2[M+H] + :m / z=534.1, measured value 534.1.

[0443] Example 90. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-((4-methylmorpholine-3-yl)methoxy)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] At 0°C, a mixture of 4-chloro-N-(1-cyanocyclopropyl)-9-[5-(difluoromethyl)-1,3,4-thiadiazole-2-yl]pyrimido[4,5-b]indole-7-sulfonamide (50 mg, 0.1 mmol, Int B) and (4-methylmorpholine-3-yl)methanol (20 mg, 0.16 mmol) in THF (2 mL) was mixed with sodium tert-butoxide (20 mg, 0.21 mmol), and the mixture was stirred at 25°C for 2 hours. The reaction mixture was quenched with saturated NH4Cl aqueous solution (10 mL) and extracted with EA (10 mL × 3). The organic phase was washed with saturated brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by prep-TLC using a silica gel column and eluted with MeOH / DCM (5%) to obtain the target compound (19.2 mg) as a white solid. LCMS calculated value C 23 H 23 F2N8O4S2[M+H] + :m / z=577.1, measured value 577.1.

[0444] Example 91. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-(2-(1,1-dioxoisothiazolidine-2-yl)ethoxy)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] Step 1. ((3-chloropropyl)sulfonyl)glycine methyl ester [ka] At 0°C, 3-chloropropane-1-sulfonyl chloride (2.18 g, 12.3 mmol) was added to a mixture of methyl 2-aminoacetate (1 g, 11.2 mmol) and DIEA (5.79 g, 44.8 mmol) in THF (20 mL) and then stirred at rt for 2 hours. The reaction mixture was diluted with water and extracted with EA (20 mL x 3). The combined organic phase was washed with saturated brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column flash chromatography and eluted with SiO2SO4 (30-40%) to obtain the target compound (1.2 g), a yellow oily substance. LCMS calculated value: C6H 13 ClNO4S [M+H] + :m / z=230.0, measured value 230.0.

[0445] Step 2. 2-(1,1-Dioxoisothiazolidine-2-yl)methyl acetate [ka] At 0°C, 500 mg (2.2 mmol) of methyl 2-[(3-chloropropyl)sulfonamide]acetate was added to a 10 mL (DMF) solution of NaH (105 mg, 2.6 mmol, 60% suspended in mineral oil), and the mixture was stirred at 0°C for 3 hours. The resulting mixture was quenched with water and extracted with EA (30 mL x 3). The combined organic phases were washed with saturated brine, dried over Na₂SO₄, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by prep-TLC using a silica gel column and eluted with EA / PE (0-50%) to obtain the target compound (200 mg), a yellow oily substance. LCMS calculated value: C6H 12 NO4S [M+H] + :m / z=194.0, measured value 194.0.

[0446] Step 3. 2-(2-hydroxyethyl)isothiazolidine 1,1-dioxide [ka] At 0°C, 200 mg, 1.05 mmol of methyl 2-[(3-chloropropyl)sulfonamide]acetate was dissolved in 10 mL of THF, to which LiBH4 (114 mg, 5.2 mmol) was added. The mixture was stirred overnight under rt. The reaction mixture was quenched with saturated aqueous solution NH4Cl (10 mL) and extracted with EA (20 mL x 3). The combined organic phases were washed with saturated brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by prep-TLC using a silica gel column and eluted with MeOH / DCM (0-5%) to obtain the target compound (50 mg), a yellow oily substance. LCMS calculated value: C5H 12 NO3S [M+H] + :m / z=166.0, measured value 166.0.

[0447] Step 4. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-(2-(1,1-dioxoisothiazolidine-2-yl)ethoxy)-9H-pyrimido[4,5-b]indole-7-sulfonamide The compound was prepared according to a method similar to that of Example 90, using 2-(2-hydroxyethyl)isothiazolidine 1,1-dioxide and Int B as starting materials. LCMS calculated value C 22 H 21 F2N8O5S3[M+H] + :m / z=611.1, measured value 611.0.

[0448] [Table 6(1)] [Table 6(2)] [Table 6(3)] [Table 6(4)] [Table 6(5)] [Table 6(6)] [Table 6(7)] [Table 6(8)]

[0449] Example 92. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-(morpholine-3-ylmethoxy)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] Step 1. 3-(((7-(N-(1-cyanocyclopropyl)sulfamoyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-9H-pyrimido[4,5-b]indole-4-yl)oxy)methyl)morpholine-4-carboxylate tert-butyl [ka] At 0°C, t-BuONa (24 mg, 0.24 mmol) was added to a solution of 4-chloro-N-(1-cyanocyclopropyl)-9-[5-(difluoromethyl)-1,3,4-thiadiazole-2-yl]pyrimido[4,5-b]indole-7-sulfonamide (60 mg, 0.12 mmol, Int B) and 3-(hydroxymethyl)morpholine-4-carboxylate tert-butyl (41 mg, 0.18 mmol) in THF (4 mL). The mixture was stirred at 25°C for 2 hours, quenched with saturated NH4Cl aqueous solution (10 mL), and extracted with DCM (10 mL × 3). The combined organic phase was washed with saturated brine, dried over Na2SO4, and then concentrated under reduced pressure. The residue was purified by prep-TLC on a silica gel column and eluted with siRNA / PE (50%) to obtain the target compound (63 mg), which was a white solid. LCMS calculated value C27H27F2N8O6S2 [MH] - :m / z=661.2, measured value 661.1.

[0450] Step 2. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-(morpholine-3-ylmethoxy)-9H-pyrimido[4,5-b]indole-7-sulfonamide A solution of 3-(((7-(N-(1-cyanocyclopropyl)sulfamoyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-9H-pyrimido[4,5-b]indole-4-yl)oxy)methyl)morpholine-4-carboxylate tert-butyl (60 mg, 0.1 mmol) in DCM (4 mL) and TFA (2 mL) was stirred at rt for 1 hour. The mixture was concentrated under reduced pressure. The residue was purified by prep-HPLC on a C18 column and eluted with MeCN / H2O (35-65%) to obtain the target compound (26.2 mg), which was a white solid. 1 1H NMR: (400 MHz, DMSO-d 6 ) 1 1H NMR: (400 MHz, DMSO-d 6 ) δ 9.55-9.43 (m,2H),9.34-9.22 (m,1H),9.07 (s,1 H),8.57 (d,J = 8.0 Hz,1H),8.10 (d,J = 8.0 Hz,1H),7.71 (t,J F-H = 53.2 Hz,1H),4.99-4.82 (m,2H),4.24-4.16 (m,1H),4.04-3.93 (m,2H),3.84-3.70 (m,2H),3.43-3.38 (m,1H),3.27-3.19 (m,1H),1.48-1.39 (m,2H),1.34-1.26 (m,2H). LCMS calculated value C22H21F2N8O4S2 [M+H] + :m / z=563.1, measured value 563.0.

[0451] Example 93. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-((3S,4R)-4-(ethylamino)-3-fluoropiperidine-1-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] Step 1. (3S,4R)-4-acetamido-3-fluoropiperidine-1-carboxylate tert-butyl [ka] At 0-5°C, DIEA (2.7 g, 20.6 mmol) was added to a solution of (3S,4R)-4-amino-3-fluoropiperidine-1-carboxylate tert-butyl (3.0 g, 13.7 mmol) in THF (30 mL), followed by the addition of acetyl chloride (1.1 g, 13.7 mmol) dropwise. The reaction mixture was stirred at 0-5°C for 1 hour, then stirred at rt for 20 minutes. The reaction mixture was quenched with water (15 mL) and extracted with dichloromethane (30 mL x 2). The combined organic phases were washed with saturated brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to obtain the target compound (4.0 g, crude product), which was a white solid. LCMS calculated value C 12 H 21 FN2O3Na [M+Na] + :m / z=283.1, measured value 283.1.

[0452] Step 2. (3S,4R)-4-(ethylamino)-3-fluoropiperidine-1-carboxylate tert-butyl [ka] At rt, a solution of (3S,4R)-4-acetamido-3-fluoropiperidine-1-carboxylate tert-butyl (4.0 g, 15.4 mmol) in THF (15 mL) was mixed with BH3 / THF (40 mL, 160 mmol, 4 M). The reaction mixture was stirred overnight at 60°C, quenched with methanol (50 mL), and then concentrated under reduced pressure to obtain the target compound (4.0 g, crude product), a white solid, which was used directly in the next step without further purification. LCMS calculated value C 12 H 24 FN2O2[M+H] + :m / z=247.2, measured value 247.1.

[0453] Step 3. (3S,4R)-N-ethyl-3-fluoropiperidine-4-amine dihydrochloride [ka] To a solution of (3S,4R)-4-(ethylamino)-3-fluoropiperidine-1-carboxylate tert-butyl (4.0 g, 16.2 mmol) in methanol (8 mL), HCl / dioxane (20 mL, 80 mmol, 4 M) was added and the mixture was stirred at rt for 1 hour. The reaction mixture was concentrated under reduced pressure to obtain the target compound (3.2 g, crude product), a white solid HCl salt, which was used directly in the next step without further purification. LCMS calculation value: C7H 16 FN2[M+H] + :m / z=147.1, measured value 147.1.

[0454] Step 4. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-((3S,4R)-4-(ethylamino)-3-fluoropiperidine-1-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide 4-chloro-N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (5.4 g, 11.2 mmol, Int B) and (3S,4R)-N-ethyl-3-fluoropiperidine-4-amine dihydrochloride (3.2 g, 14.6 mmol) were mixed in acetonitrile (100 mL) and DIEA (5.8 g, 44.9 mmol). The reaction mixture was stirred at 25°C for 3 hours and then concentrated under reduced pressure. Acetonitrile (15 mL) was added to the residue, followed by water (80 mL) and aqueous Na2CO3 solution (25 mL). The mixture was filtered, the solid was collected, and dried under vacuum at 40°C to obtain the target compound (4.1 g, yield 62%), which was a yellow solid. LCMS calculation value C 24 H 25 F3N9O2S2[M+H] + :m / z=592.2, measured value 592.1.

[0455] Example 94. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-((3S,5S)-3,5-dimethylpiperazine-1-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] Step 1. (2S,6S)-4-(7-(N-(1-cyanocyclopropyl)sulfamoyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-9H-pyrimido[4,5-b]indole-4-yl)-2,6-dimethylpiperazine-1-carboxylate tert-butyl [ka] 4-Chloro-N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (428 mg, 0.89 mmol, Int B) and (2S,6S)-2,6-dimethylpiperazine-1-carboxylate tert-butyl (200 mg, 0.93 mmol) were mixed in acetonitrile (9 mL) to which DIEA (172 mg, 1.33 mmol) was added. The reaction mixture was stirred at 25°C for 3 hours and then concentrated under reduced pressure. Acetonitrile (1.5 mL) was added to the residue, followed by water (6.5 mL) and aqueous Na2CO3 solution (0.2 mL). The mixture was filtered, the solid was collected, and dried under vacuum at 40°C to obtain the target compound (480 mg, yield 82%) as a yellow solid. LCMS calculation value C 28 H 32 F2N9O4S2[M+H] + m / z = 660.2, measured value 660.1.

[0456] Step 2. N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-((3S,5S)-3,5-dimethylpiperazine-1-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (2S,6S)-4-(7-(N-(1-cyanocyclopropyl)sulfamoyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-9H-pyrimido[4,5-b]indole-4-yl)-2,6-dimethylpiperazine-1-carboxylate tert-butyl (100 mg, 0.15 mmol) was added to a mixture of dichloromethane (1 mL) with TFA (69 mg, 0.61 mmol). The reaction mixture was stirred at 25°C for 3 hours and then concentrated under reduced pressure. The residue was purified by pre-HPLC on a C18 column and eluted with MeCN / H2O (2%~70%, containing 0.1% NH4HCO3) to obtain the target compound (40 mg, yield 47.7%) as a white solid. LCMS calculated value C 23 H 24 F2N9O2S2[M+H] + :m / z=560.1, measured value 560.1.

[0457] Int A. 4-Chloro-N-(1-cyanocyclopropyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] Step 1. 4-Chloro-N-(1-cyanocyclopropyl)-3-nitrobenzenesulfonamide [ka] At 0-5°C, 1-aminocyclopropyl-1-carbonitride hydrochloride (55.6 g, 469 mmol), pyridine (500 mL), and DMAP (19.1 g, 156 mmol) were mixed in MeCN (500 mL) and 4-chloro-3-nitrobenzenesulfonyl chloride (100 g, 391 mmol). The resulting mixture was then stirred at rt for 2 hours. The reaction mixture was poured into ice water (500 mL) and the pH was adjusted to ~3 with aqueous HCl (1 N) at 0-5°C. The aqueous phase was extracted with  (300 mL × 3). The combined organic phases were washed with saturated brine (500 mL), dried over anhydrous Na₂SO₄, filtered, and the filtrate was concentrated under reduced pressure. The residue was slurryed with MTBE (100 mL) at 20°C for 2 hours. The formed solid was collected by filtration and then dried under vacuum to obtain the target compound (75 g, yield 63.6%) as a yellow solid. 1 H NMR: (400 MHz,DMSO-d6) δ 9.54 (s,1H),8.51 (s,1H),8.09-8.14 (m,2H),1.47-1.51 (m,2H),1.31-1.35 (m,2H). LCMS calculated value C 10 H7ClN3O4S [MH] - :m / z=300.0. Measured value: 300.0.

[0458] Step 2. 2-amino-6-(N-(1-cyanocyclopropyl)sulfamoyl)-1H-indole-3-carboxamide [ka] At 0°C, 2-cyanoacetamide (41.8 g, 497 mmol) was added to a solution of DMF (750 mL) with NaH (39.8 g, 994 mmol, 60% suspended in mineral oil). The mixture was stirred at 0°C for 30 min, then 4-chloro-N-(1-cyanocyclopropyl)-3-nitrobenzenesulfonamide (75.0 g, 249 mmol) was added at 0°C. The mixture was stirred at 20°C for 1 hour. The reaction solution was poured into ice water (500 mL) in several batches, and the pH was adjusted to ~3 with concentrated HCl solution (12 N) at 0-5°C. DMF (750 mL) was added to the above solution, then FeCl3 (120 g, 744 mmol) was added at 20°C. The mixture was heated to 60°C, then Zn (162 g, 2.48 mol) was added in several batches. The mixture was heated to 100°C and stirred for 2 hours. The completion of the reaction was monitored by LC-MS. After cooling, the reaction mixture was filtered through diatomaceous earth. The filtrate was extracted with DCM (500 mL x 6). The combined organic phase was dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated under vacuum. The residue was purified by silica gel column flash chromatography and eluted with siRNA / PE (0-100%) to obtain the target product (30.0 g, yield 18.9%), which was a yellow foamy substance. LC-MS calculated value C 13 H 12 N5O3S [MH] - :m / z=318.1, measured value 318.0.

[0459] Step 3. N-(1-cyanocyclopropyl)-4-oxo-4,9-dihydro-3H-pyrimido[4,5-b]indole-7-sulfonamide [ka] At 20°C, concentrated HCl solution (12 N, 161 mL) was added to a mixture of 2-amino-6-(N-(1-cyanocyclopropyl)sulfamoyl)-1H-indole-3-carboxamide (28.0 g, 87.7 mmol) in trimethoxymethane (560 mL). The mixture was stirred at 60°C for 1 hour. The consumption of the starting material was monitored by LC-MS. The reaction mixture was filtered. The filtered cake was dried under vacuum to obtain the target product (20.0 g, 69.3% yield), which was a yellow solid. 1 H NMR: (400 MHz,DMSO-d6) δ 12.7 (s,1H),12.5 (s,1H),9.07 (s,1H),8.24 (s,1H),8.17 (d,J = 8.0 Hz,1H),7.96 (s,1H),7.71 (d,J = 10.0 Hz,1H),1.37-1.42 (m,2H),1.22-1.27 (m,2H). LCMS calculated value C 14 H 10 N5O3S [MH] - :m / z=328.1, measured value 328.1.

[0460] Step 4. 4-Chloro-N-(1-cyanocyclopropyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] A mixture of N-(1-cyanocyclopropyl)-4-oxo-4,9-dihydro-3H-pyrimido[4,5-b]indole-7-sulfonamide (18.0 g, 54.7 mmol) in POCl3 (720 mL) was stirred at 100°C for 16 hours. The consumption of the starting material was monitored by LC-MS. The mixture was concentrated under reduced pressure. The residue was purified by silica gel column flash chromatography and eluted with siRNA / PE (0-100%) to obtain the target product (10 g, yield 47.3%) as a pale yellow solid. LC-MS calculated value C 14 H9ClN5O2S [MH] - :m / z=346.0, measured value 345.9.

[0461] Int B. 4-Chloro-N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] At 0-5°C, sulfonyl chloride (10.7 g, 101 mmol) was added to a solution of N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazole-2-yl)-4-(methylthio)-9H-pyrimido[4,5-b]indole-7-sulfonamide (10.0 g, 20.3 mmol, Example 25) in MeCN (100 mL). The resulting mixture was stirred at rt for 5 hours. The mixture was filtered, the precipitate was collected, washed with MeCN (10 mL x 3), and then dried under reduced pressure to obtain the target compound (8.2 g), which was a yellow solid. LCMS calculation value C 17 H 11 ClF2N7O2S2[M+H] + m / z = 482.0. Measured value: 482.1.

[0462] Int 1. 1-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylprop-1-one [ka] Step 1. 1-(2-((tert-butyldimethylsilyl)oxy)ethyl)piperazine [ka] TBSCl (7.5 g, 50 mmol) was added to a mixture of 2-(piperazin-1-yl)ethyl-1-ol (5.2 g, 40 mmol) and imidazole (5.5 g, 60 mmol) in DCM (100 mL). The reaction mixture was stirred overnight in rt. The mixture was then concentrated under reduced pressure, the residue was diluted with SiO (100 mL), and then washed with water and saturated brine. The organic phase was dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to obtain the target compound (9.8 g), a yellow oily substance. LCMS calculated value C 12 H 29 N2OSi [M+H] + :m / z=245.2, measured value 245.2.

[0463] Step 2. 1-(4-(2-((tert-butyldimethylsilyl)oxy)ethyl)piperazin-1-yl)-2-methylprop-1-one [ka] Isobutyryl chloride (1.28 g, 12 mmol) was added to a 20 mL DCM mixture of 1-(2-((tert-butyldimethylsilyl)oxy)ethyl)piperazine (2.45 g, 10 mmol) and TEA (1.56 g, 15 mmol). The reaction mixture was stirred in rt for 3 hours and then concentrated under reduced pressure. The residue was diluted with SiO2 (100 mL) and washed with water and saturated brine. The organic phase was dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column flash chromatography and eluted with SiO2 / PE (20-55%) to obtain the target compound (1.0 g) as a colorless oil. LCMS calculated value C 16 H 35 N2O2Si [M+H] + :m / z=315.2, measured value 315.2.

[0464] Step 3. 1-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylprop-1-one A solution of 1-(4-(2-((tert-butyldimethylsilyl)oxy)ethyl)piperazin-1-yl)-2-methylprop-1-one (1.0 g, 3.3 mmol) in HCl (10 mL, 4.0 M 1,4-dioxane solution) was stirred overnight under rt. The reaction mixture was concentrated under reduced pressure. The resulting solid was washed with PE to obtain the target compound (0.45 g), which is a white solid HCl salt. LCMS calculation value C 10 H 20 N2O2[M+H] + :m / z=201.2, measured value 201.1.

[0465] Int 2. 4-(2-hydroxyethyl)-N,N-dimethylpiperazine-1-carboxamide [ka] Step 1. 4-(2-((tert-butyldimethylsilyl)oxy)ethyl)-N,N-dimethylpiperazine-1-carboxamide [ka] Dimethylcarbamoyl chloride (1.28 g, 12 mmol) was added to a 20 mL DCM mixture of 1-(2-((tert-butyldimethylsilyl)oxy)ethyl)piperazine (2.45 g, 10 mmol, Int 1, Step 1) and TEA (1.56 g, 15 mmol). The reaction mixture was stirred in rt for 3 hours and then concentrated under reduced pressure. The residue was diluted with SiO2 (100 mL) and then washed with water and saturated brine. The combined organic phase was dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column flash chromatography and eluted with SiO2 / PE (60-80%) to obtain the target compound (1.5 g) as a colorless oil. LCMS calculated value C 15 H 34 N3O2Si [M+H] + :m / z=316.2, measured value 316.2.

[0466] Step 2. 4-(2-hydroxyethyl)-N,N-dimethylpiperazine-1-carboxamide A solution of 4-(2-((tert-butyldimethylsilyl)oxy)ethyl)-N,N-dimethylpiperazine-1-carboxamide (1.5 g, 3.9 mmol) in HCl (15 mL, 4.0 M 1,4-dioxane solution) was stirred overnight under rt. The reaction mixture was concentrated under reduced pressure. The resulting solid was washed with PE to obtain the target compound (0.9 g), a white solid HCl salt. LCMS calculation value: C9H 20 N3O2[M+H] + :m / z=202.2, measured value 202.2.

[0467] Int3.(3S,4S)-N,N-diethyl-3-fluoropiperidine-4-amine [ka] Step 1. (3S,4S)-4-(diethylamino)-3-fluoropiperidine-1-carboxylate tert-butyl [ka] Iodoethane (1.4 g, 9 mmol) was added to a mixture of (3S,4S)-4-amino-3-fluoropiperidine-1-carboxylate tert-butyl (650 mg, 3 mmol) and Cs2CO3 (3.91 g, 12 mmol) in MeCN (20 mL). The mixture was stirred overnight at 50°C. The reaction mixture was concentrated under reduced pressure, diluted with toluene (60 mL), and then washed with water and saturated brine. The organic phase was dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column flash chromatography and eluted with toluene / PE (60-80%) to obtain the target compound (530 mg) as a colorless oil. LCMS calculated value C 14 H 28 FN2O2[M+H] + :m / z=275.2, measured value 275.2.

[0468] Step 2. (3S,4S)-N,N-diethyl-3-fluoropiperidine-4-amine A solution of (3S,4S)-4-(diethylamino)-3-fluoropiperidine-1-carboxylate tert-butyl (530 mg, 1.93 mmol) in HCl (5 mL, 4.0 M 1,4-dioxane solution) was stirred at rt for 4 hours. The reaction mixture was concentrated under reduced pressure. The resulting solid was washed with PE to obtain the target compound (330 mg), a white solid HCl salt. LCMS calculation value: C9H 20 FN2[M+H] + :m / z=175.2, measured value 175.2.

[0469] The intermediates shown in Table 6 (Int#, where # is an integer) were prepared using suitable commercially available amines and iodoethane as raw materials, following a method similar to that used for Int3.

[0470] [Table 7]

[0471] Int 7.(3'S)-3',4,4-trifluoro-1,4'-bipiperidine [ka] Step 1. (S)-3-fluoro-4-oxopiperidine-1-carboxylate tert-butyl [ka] Dess-Martin oxidizing agent (1.16 g, 5.5 mmol) was added to a solution of (3S,4R)-3-fluoro-4-hydroxypiperidine-1-carboxylate tert-butyl (1.0 g, 4.6 mmol) in DCM (10 mL). The reaction mixture was stirred under low pressure for 8 hours. The mixture was then concentrated under reduced pressure, and the residue was purified by silica gel column flash chromatography. Elution was performed in DCM / EA (30-50%) to obtain the target compound (500 mg) as a white solid. LCMS calculated value C 10 H 17 FNO3[M+H]+ :m / z=218.1, measured value 218.1.

[0472] Step 2. (3'S)-3',4,4-trifluoro-[1,4'-bipiperidine]-1'-carboxylate tert-butyl [ka] To a solution of (S)-3-fluoro-4-oxopiperidine-1-carboxylate tert-butyl (500 mg, 2.30 mmol) in DCM (10 mL), 4,4-difluoropiperidine (560 mg, 4.6 mmol) was added. The reaction mixture was stirred at rt for 30 min, and then NaBH(OAc)3 (976 mg, 4.60 mmol) was added. The mixture was stirred at rt for 2 h, quenched with water, and then extracted with ethyl acetate (10 mL × 3). The combined organic phase was washed with saturated saline, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to obtain the target compound (240 mg), a yellow oily substance. LCMS calculated value C 15 H 26 F3N2O2[M+H] + :m / z=323.2, measured value 323.2.

[0473] Step 3. (3'S)-3',4,4-trifluoro-1,4'-bipiperidine (3'S)-3',4,4-trifluoro-[1,4'-bipiperidine]-1'-carboxylate tert-butyl (240 mg, 0.77 mmol) was added to a 1 mL DCM solution with HCl solution (1 mL, 4 M 1,4-dioxane solution). The reaction mixture was stirred at rt for 3 hours and concentrated under reduced pressure to obtain the target compound (140 mg), a yellow solid HCl salt. LCMS calculation value C 10 H 18 FN2[M+H] + :m / z=223.1, measured value 223.1.

[0474] Int 9.(1R,4R)-N,N-diethyl-2-azabicyclo[2.2.1]heptan-5-amine [ka] Step 1. (1R,4R)-5-(diethylamino)-2-azabicyclo[2.2.1]heptane-2-carboxylate tert-butyl [ka] To a solution of (1R,4R)-5-oxo-2-azabicyclo[2.2.1]heptane-2-carboxylate tert-butyl (420 mg, 2.0 mmol) in DCM (10 mL), diethylamine solution (366 mg, 5.0 mmol, 2.0 M THF solution) was added. The reaction mixture was stirred at rt for 30 min, and then NaBH(OAc)3 (850 mg, 4.0 mmol) was added. The mixture was stirred at rt for a further 2 h, quenched with water, and then extracted with ethyl acetate (10 mL × 3). The combined organic phase was washed with saturated brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to obtain the target compound (440 mg), a yellow oily substance. LCMS calculated value C 15 H 29 N2O2[M+H] + :m / z=269.2, measured value 269.2.

[0475] Step 2. (1R,4R)-N,N-diethyl-2-azabicyclo[2.2.1]heptan-5-amine To a solution of (1R,4R)-5-(diethylamino)-2-azabicyclo[2.2.1]heptane-2-carboxylate tert-butyl (270 mg, 1.0 mmol) in DCM (2 mL), an HCl solution (2 mL, 4 M 1,4-dioxane solution) was added. The reaction mixture was stirred at rt for 5 hours and concentrated under reduced pressure to obtain the target compound (170 mg), a yellow solid HCl salt. LCMS calculation value C 10 H 21 N2[M+H] + :m / z=169.2, measured value 169.2.

[0476] Int 10.(1R,4R)-N,N-diethyl-2-azabicyclo[2.2.1]heptan-5-amine [ka] Step 1. (1R,4R)-5,5-difluoro-2-azabicyclo[2.2.1]heptane-2-carboxylate tert-butyl [ka] To a solution of (1R,4R)-5-oxo-2-azabicyclo[2.2.1]heptane-2-carboxylate tert-butyl (420 mg, 2.0 mmol) in DCM (40 mL), DAST (1.3 g, 8.0 mmol) was added. The mixture was stirred overnight under rt, quenched with NaHCO3 solution, and then extracted with DCM (10 mL × 3). The combined organic phase was washed with saturated brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column flash chromatography and eluted with siRNA / PE (20-40%) to obtain the target compound (120 mg), a yellow oily substance. LCMS calculated value C 11 H 18 F2NO2[M+H] + :m / z=234.2, measured value 234.1.

[0477] Step 2. (1R,4R)-N,N-diethyl-2-azabicyclo[2.2.1]heptane-5-amine (1R,4R)-5,5-difluoro-2-azabicyclo[2.2.1]heptane-2-carboxylate tert-butyl (120 mg, 1.0 mmol) was added to a solution of DCM (4 mL) with TFA (1 mL). The reaction mixture was stirred under rt for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain the target compound (70 mg), a yellow solid HCl salt. LCMS calculation value: C6H 10 F2N [M+H] + :m / z=134.1, measured value 134.1.

[0478] Int 11.(R)-(1-methylpiperazin-2-yl)methanol [ka] Step 1. (R)-3-(hydroxymethyl)-4-methylpiperazine-1-carboxylate tert-butyl [ka] To a solution of (R)-3-(hydroxymethyl)piperazine-1-carboxylate tert-butyl (500 mg, 2.3 mmol) in MeOH (12 mL), sodium acetate (303 mg, 3.7 mmol), paraformaldehyde (375 mg, 4.2 mmol), and sodium cyanoborohydride (218 mg, 3.5 mmol) were added. The mixture was stirred at rt for 1 hour, quenched with saturated NaHCO3 solution (20 mL), and then extracted with DCM (50 mL). The organic phase was dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column flash chromatography and eluted with MeOH / DCM (0-5%) to obtain the target product (421 mg), a yellow oily substance. LCMS calculated value C 11 H 23 N2O3[M+H] + :m / z=231.2, measured value 231.0.

[0479] Step 2. (R)-(1-methylpiperazin-2-yl)methanol To a solution of (R)-3-(hydroxymethyl)-4-methylpiperazine-1-carboxylate tert-butyl (421 mg, 1.8 mmol) in DCM (3 mL), an HCl solution (3 mL, 4 M 1,4-dioxane solution) was added. The reaction mixture was stirred under pressure for 5 hours. The reaction mixture was concentrated under reduced pressure to obtain the target compound (230 mg), which is the HCl salt of a yellow oily substance. LCMS calculation value: C6H 14 N2O [M+H] + :m / z=131.1, measured value 131.1.

[0480] Int 15. (S)-N-methyl-1-(tetrahydrofuran-3-yl)methylamine [ka] Step 1. Methanesulfonic acid (R)-(tetrahydrofuran-3-yl)methyl [ka] At 0°C, methanesulfonyl chloride (570 mg, 5.0 mmol) was added to a 4 mL solution of (S)-(tetrahydrofuran-3-yl)methanol (406 mg, 4.0 mmol) and triethylamine (610 mg, 6.0 mmol) in dimethylcellulose (DCM). The mixture was stirred at rt for 2 hours, diluted with H2O, and then extracted with 3 x 10 mL DCM solutions. The combined organic phase was washed with saturated brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to obtain the target compound (710 mg), a yellow oily substance. LCMS calculation value: C6H 13 O4S [M+H] + :m / z=181.1, measured value 181.1.

[0481] Step 2. (S)-N-methyl-1-(tetrahydrofuran-3-yl)methylamine A mixture of methanesulfonic acid (R)-(tetrahydrofuran-3-yl)methyl (710 mg, 4.0 mmol) and MeNH2 solution (30% EtOH solution, 20 mL) was stirred in a sealed tube at 70°C for 16 hours. The reaction mixture was cooled and then concentrated under reduced pressure. The residue was purified by prep-TLC using a silica gel column and eluted with MeOH / DCM (10%) to obtain the target compound (120 mg) as a colorless oil. LCMS calculation value: C6H 13 NO [M+H] + :m / z=116.1, measured value 116.1.

[0482] Int 16.(R)-N-methyl-1-(tetrahydrofuran-3-yl)methylamine [ka] The compound was prepared according to a method similar to steps 1-2 of Int 15, using (R)-(tetrahydrofuran-3-yl)methanol as a starting material. LCMS calculated value: C6H 13 NO [M+H]+ :m / z=116.1, measured value 116.1.

[0483] Int 17. 2-(1H-imidazole-1-yl)-N-methylethyl-1-amine [ka] Step 1. (2-(1H-imidazole-1-yl)ethyl)(methyl)carbamate tert-butyl [ka] A mixture of tert-butyl (2-chloroethyl)(methyl)carbamate (400 mg, 2.05 mmol), 1H-imidazole (836 mg, 12.3 mmol), and K2CO3 (849 mg, 6.15 mmol) in DMF (5 mL) was stirred at 80°C for 3 hours. The reaction mixture was diluted with H2O and extracted with EA (20 mL x 3). The combined organic phase was washed with saturated saline, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by prep-TLC using a silica gel column and eluted with MeOH / DCM (10%) to obtain the target compound (280 mg), a yellow oily substance. LCMS calculated value C 11 H 20 N3O2[M+H] + :m / z=226.2, measured value 226.1.

[0484] Step 2. 2-(1H-imidazole-1-yl)-N-methylethyl-1-amine To a solution of (2-(1H-imidazole-1-yl)ethyl)(methyl)carbamate tert-butyl (280 mg, 1.8 mmol) in DCM (2 mL), an HCl solution (2 mL, 8 mmol, 4 M 1,4-dioxane solution) was added. The reaction mixture was stirred at rt for 2 hours and concentrated under reduced pressure to obtain the target compound (130 mg), which is the HCl salt of a yellow oily substance. LCMS calculation value: C6H 12 N3[M+H] + :m / z=126.1, measured value 126.1.

[0485] Int 18. 1-Methyl-3-(2-(methylamino)ethyl)imidazolin-2-one [ka] Step 1. Methyl(2-(3-methyl-2-oxoimidazolin-1-yl)ethyl)carbamate tert-butyl [ka] Cs2CO3 (1.0 g, 3.1 mmol) was added to a mixture of (2-chloroethyl)(methyl)carbamate tert-butyl (200 mg, 1 mmol) and 1-methylimidazolin-2-one (618 mg, 6.2 mmol) in DMF (5 mL). The mixture was stirred at 80°C for 3 hours, diluted with H2O, and extracted with EA (20 mL × 3). The combined organic phase was washed with saturated brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by prep-TLC using a silica gel column and eluted with EA / PE (20%) to obtain the target compound (50 mg), which was a yellow solid. LCMS calculated value C 12 H 24 N3O3, [M+H] + :m / z=258.2, measured value 258.3. Step 2. 1-Methyl-3-(2-(methylamino)ethyl)imidazoline-2-one To a solution of (2-(1H-imidazole-1-yl)ethyl)(methyl)carbamate tert-butyl (50 mg, 0.2 mmol) in DCM (1 mL), an HCl solution (1 mL, 4 M 1,4-dioxane solution) was added. The reaction mixture was stirred under RT for 2 hours, and then concentrated under reduced pressure to obtain the target compound (40 mg), which is the HCl salt of a yellow oily substance. LCMS calculation value: C7H 16 N3O [M+H] + :m / z=158.1, measured value 158.3. Int 19. 1-(2-(methylamino)ethyl)pyrrolidine-2-one [ka] Step 1. (2-(4-chlorobutanamide)ethyl)(methyl)carbamate tert-butyl [ka] At 0°C, 4-chlorobutyryl chloride (1.20 g, 8.6 mmol) was added to a 20 mL DCM mixture of (2-aminoethyl)(methyl)carbamate tert-butyl (1.0 g, 5.7 mmol) and TEA (1.74 g, 17.2 mmol). The mixture was stirred at 0°C for 1 hour, diluted with H2O, and then extracted with DCM (10 mL × 3). The combined organic phase was washed with saturated brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by prep-TLC using a silica gel column and eluted with EA / PE (10%) to obtain the target compound (500 mg), which was a yellow solid. LCMS calculated value C 12 H 24 ClN2O3,[M+H] + :m / z=279.1, measured value 279.1. Step 2. Methyl(2-(2-oxopyrrolidine-1-yl)ethyl)carbamate tert-butyl [ka] At 0°C, 500 mg (1.8 mmol) of tert-butyl (2-(4-chlorobutanamide)ethyl)(methyl)carbamate was added to a 10 mL solution of DMF, to which NaH (215 mg, 5.4 mmol, 60% suspended in mineral oil) was added. The mixture was stirred at 0°C for 1 hour. The reaction mixture was diluted with H2O and extracted with ethyl acetate (20 mL x 3). The combined organic phases were washed with saturated brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by prep-TLC using a silica gel column and eluted with EA / PE (20%) to obtain the target compound (300 mg), which was a yellow solid. LCMS calculated value C 12 H 23 N2O3,[M+H] + :m / z=243.1, measured value 243.2. Step 3. 1-(2-(methylamino)ethyl)pyrrolidine-2-one To a solution of 250 mg, 1.0 mmol of methyl (2-(2-oxopyrrolidine-1-yl)ethyl)carbamate tert-butyl in DCM (2 mL), an HCl solution (2 mL, 4 M 1,4-dioxane solution) was added. The reaction mixture was stirred under pressure for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain the target compound (200 mg), a yellow solid HCl salt. LCMS calculation value: C7H 15 N2O [M+H] + :m / z=143.1, measured value 143.2. Int 20. Methyl[(4-methylmorpholine-3-yl)methyl]amine [ka] Step 1. Methyl(4-methylmorpholine-3-yl)methyl methanesulfonic acid [ka] At 0°C, methanesulfonyl chloride (420 mg, 3.7 mmol) was added to a 10 mL DCM mixture of (4-methylmorpholine-3-yl)methanol (400 mg, 3.1 mmol) and triethylamine (617 mg, 6.1 mmol). The mixture was stirred at 25°C for 2 hours. The reaction mixture was diluted with H2O and extracted with 3 x 10 mL DCMs. The combined organic phase was washed with saturated brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to obtain the target compound (600 mg), a yellow oily substance. LCMS calculation value: C7H 16 NO4S [M+H] + :m / z=210.1, measured value 210.1. Step 2. Methyl[(4-methylmorpholine-3-yl)methyl]amine A 30% solution of 4-methylmorpholine-3-formaldehyde (600 mg, 4.65 mmol) in EtOH (30 mL) of MeNH2 was stirred in a sealed tube at 70°C for 16 hours. The reaction mixture was cooled and then concentrated under reduced pressure. The residue was purified by prep-TLC using a silica gel column and eluted with MeOH / DCM (10%) to obtain the target compound (80 mg), which was a colorless oil. 1 1H NMR: (400 MHz, DMSO-d 6 ) δ 3.89-3.64 (m,3H),3.48-3.36 (m,3H),3.07-2.94 (m,2H),2.74-2.68 (m,1H),2.51 (s,3H),2.27 (s,3H). LCMS calculated value C7H 17 N2O [M+H] + m / z = 145.1, measured value 145.2. Int 21.(R)-N-methyl-1-(4-methylmorpholin-3-yl)methylamine [ka] The compound was prepared according to a method similar to steps 1-2 of Int 20, using (R)-(4-methylmorpholine-3-yl)methanol as a starting material. LCMS calculated value: C7H 17 N2O [M+H] + m / z = 145.1, measured value 145.2. Int 22.(S)-N-methyl-1-(4-methylmorpholin-3-yl)methylamine [ka] The compound was prepared according to a method similar to steps 1-2 of Int 20, using (S)-(4-methylmorpholine-3-yl)methanol as a starting material. LCMS calculated value: C7H 17 N2O [M+H] + m / z = 145.1, measured value 145.2. Int 23.2-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-N-methylethyl-1-amine [ka] Step 1. (2-(3,5-dimethyl-1H-1,2,4-triazole-1-yl)ethyl)(methyl)carbamate tert-butyl [ka] A mixture of tert-butyl (2-chloroethyl)(methyl)carbamate (100 mg, 0.5 mmol) and 3,5-dimethyl-1H-1,2,4-triazole (297 mg, 3.1 mmol) in DMF (5 mL) was mixed with K2CO3 (211 mg, 1.5 mmol). The mixture was stirred at 80°C for 3 hours, diluted with H2O, and extracted with EA (15 mL × 3). The combined organic phase was washed with saturated brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by prep-TLC using a silica gel column, eluted with PE / EA = 5:1, and the target compound (100 mg) was obtained as a yellow solid. LCMS calculated value C 12 H 23 N4O2, [M+H] + :m / z=255.2, measured value 255.2. Step 2. 2-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-N-methylethyl-1-amine (2-(3,5-dimethyl-1H-1,2,4-triazole-1-yl)ethyl)(methyl)carbamate tert-butyl (80 mg, 0.31 mmol) was added to a 1 mL DCM solution with HCl solution (1 mL, 4 M 1,4-dioxane solution). The reaction mixture was stirred under pressure for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain the target compound (60 mg), a yellow solid HCl salt. LCMS calculation value: C7H 15 N4[M+H] + :m / z=155.1, measured value 155.2. Int 24. 2-(2-(methylamino)ethyl)isothiazolidine 1,1-dioxide [ka] Step 1. (2-((3-chloropropyl)sulfonamide)ethyl)(methyl)carbamate tert-butyl [ka] At 0°C, 3-chloropropane-1-sulfonyl chloride (1.11 g, 6.2 mmol) was added to a mixture of (2-aminoethyl)(methyl)carbamate tert-butyl (1.0 g, 5.7 mmol) and DIEA (1.0 g, 7.4 mmol) in THF (60 mL). The reaction mixture was stirred in rt for 2 hours, concentrated under reduced pressure, diluted with H2O, and extracted with DCM (30 mL x 3). The combined organic phase was washed with saturated brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column flash chromatography and eluted with EA / PE (0-33%) to obtain the target compound (1.1 g), which was a yellow solid. TLC: Rf = 0.5 (PE / EA = 1:1).

[0486] 1 1H NMR: (400 MHz, DMSO-d 6 ) δ 7.27 (s,1H),3.79-3.69 (m,2H),3.26-3.19 (m,2H),3.16-2.99 (m,4H),2.85-2.74 (m,3H),2.14-2.03 (m,2H),1.43-1.33 (m,9H). Step 2. (2-(1,1-dioxoiisothiazolidine-2-yl)ethyl)(methyl)carbamate tert-butyl [ka] At 0°C, 500 mg (1.6 mmol) of tert-butyl (2-((3-chloropropyl)sulfonamide)ethyl (methyl)carbamate was added to a 20 mL solution of DMF, to which NaH (190 mg, 4.7 mmol, 60% suspended in mineral oil) was added. The mixture was stirred at 0°C for 2 hours, quenched with water, and extracted with EA (30 mL x 3). The organic phase was washed with saturated brine, dried over Na₂SO₄, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by prep-TLC on a silica gel column and eluted with EA / PE (0-50%) to obtain the target compound (320 mg) as a yellow solid. TLC: Rf = 0.6 (PE / EA = 1:1).

[0487] 1 1H NMR: (400 MHz, DMSO-d 6 ) δ. 3.33-3.28 (m,2H),3.26-3.11 (m,4H),3.05-2.95 (m,2H),2.84-2.74 (m,3H),2.20 (s,2H),1.43-1.33 (m,9H). Step 3. 2-(2-(methylamino)ethyl)isothiazolidine 1,1-dioxide To a solution of (2-(1,1-dioxoiisothiazolidined-2-yl)ethyl)(methyl)carbamate tert-butyl (300 mg, 1.1 mmol) in DCM (2 mL), an HCl solution (2 mL, 4 M 1,4-dioxane solution) was added. The reaction mixture was stirred under pressure for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain the target compound (60 mg), which is a yellow solid HCl salt. 1 1H NMR: (400 MHz, DMSO-d 6 ) δ 3.29-3.18 (m,6H),3.12-3.03 (m,2H),2.63-2.52 (m,4H),2.30-2.19 (m,2H). LCMS calculated value C6H15N2O2S [M+H] + :m / z=179.1, measured value 179.1. Int 25. cis-4-((methylamino)methyl)cyclohexane-1-ol [ka] Step 1. cis-4-((tert-butyldimethylsilyl)oxy)cyclohexane-1-carboxylic acid [ka] TBSCl (2.1 g, 13.9 mmol) was added to a mixture of cis-4-hydroxycyclohexane-1-carboxylic acid (1 g, 6.9 mmol) and imidazole (1.88 g, 27.8 mmol) in DMF (20 mL). The reaction mixture was stirred overnight at 25°C. The reaction mixture was diluted with H2O (40 mL) and extracted with SiO (30 mL × 3). The combined organic phase was washed with saturated brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography and eluted with SiO / PE (5-20%) to obtain the target compound (0.85 g) as a colorless oil. LCMS calculated value C 13 H 27 O3Si [M+H] + :m / z=259.2, measured value 259.2. Step 2. cis-4-((tert-butyldimethylsilyl)oxy)-N-methylcyclohexane-1-carboxamide [ka] At 0°C, HATU (4.88 g, 12.8 mmol) and DIEA (4.14 g, 32.1 mmol) were added to a mixture of cis-4-((tert-butyldimethylsilyl)oxy)cyclohexane-1-carboxylic acid (0.83 g, 3.2 mmol) and methylamine hydrochloride (0.43 g, 6.4 mmol) in DMF (40 mL) at 0°C. The reaction mixture was stirred overnight in rt. The reaction mixture was diluted with H2O (80 mL) and extracted with SiO2 (50 mL x 3). The combined organic phase was washed with saturated brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography using a silica gel column and eluted with SiO2 / PE (10-35%) to obtain the target compound (0.6 g) as a colorless oil. LCMS calculated value C 14H 29 NO2SiNa [M+Na] + :m / z=294.2, measured value 294.2. Step 3. cis-1-(-4-((tert-butyldimethylsilyl)oxy)cyclohexyl)-N-methylmethylamine [ka] At 0°C, a solution of cis-4-((tert-butyldimethylsilyl)oxy)-N-methylcyclohexane-1-carboxamide (0.5 g, 1.84 mmol) in THF (10 mL) was mixed with a BH3-THF complex solution (10 mL, 1 M THF solution). The reaction mixture was stirred overnight in rt. The reaction mixture was gradually quenched with MeOH (2 mL), diluted with water (30 mL), and extracted with RINKAN (30 mL × 3). The combined organic phases were washed with saturated brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by prep-TLC on a silica gel column and eluted with MeOH / DCM (20%) to obtain the target compound (0.4 g), a colorless oil. LCMS calculated value C 14 H 32 ONSi [M+H] + :m / z=258.2, measured value 258.2. Step 4. cis-4-((methylamino)methyl)cyclohexane-1-ol A solution of cis-1-((-4-((tert-butyldimethylsilyl)oxy)cyclohexyl)-N-methylmethylamine (0.3 g, 1.16 mmol) in HCl (5 mL, 4 M 1,4-dioxane solution) was stirred at 25°C for 2 hours. The reaction mixture was concentrated to obtain the target compound (0.2 g), which was a yellow solid. LC-MS calculation value: C8H 18 NO [M+H] + :m / z=144.1, measured value 144.2. Int 26. 2-(4,4-difluoropiperidine-1-yl)-N-methylethyl-1-amine [ka] Step 1. (2-(4,4-difluoropiperidine-1-yl)ethyl)(methyl)carbamate tert-butyl [ka] At 0°C, a mixture of tert-butyl methyl(2-oxoethyl)carbamate (200 mg, 1.2 mmol) and 4,4-difluoropiperidine (167 mg, 1.4 mmol) in THF (10 mL) was mixed with NaBH3CN (220 mg, 3.5 mmol). The mixture was stirred at 25°C for 16 hours, diluted with H2O, and extracted with EA (20 mL × 3). The combined organic phase was washed with saturated brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by prep-TLC using a silica gel column and eluted with EA / PE (20%) to obtain the target compound (150 mg), which was a yellow solid. LCMS calculated value C 13 H 25 F2N2O2,[M+H] + :m / z=279.2, measured value 279.2. Step 2.2-(4,4-difluoropiperidine-1-yl)-N-methylethyl-1-amine To a solution of (2-(4,4-difluoropiperidine-1-yl)ethyl)(methyl)carbamate tert-butyl (100 mg, 0.36 mmol) in DCM (1 mL), an HCl solution (1 mL, 4 M 1,4-dioxane solution) was added. The reaction mixture was stirred under rot for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain the target compound (100 mg), a yellow solid HCl salt. LCMS calculation value: C8H 17 F2N2[M+H] + m / z = 179.1, measured value 179.3. Int 27. 4-(2-(methylamino)ethyl)thiomorpholine 1,1-dioxide [ka] The compound was prepared according to a method similar to steps 1-2 of Int 26, using thiomorpholine 1,1-dioxide as a starting material. LCMS calculated value: C7H 17N2O2S [M+H] + :m / z=193.1, measured value 193.1. Int 28. N-methyl-1-(1-methylpyrrolidine-2-yl)methylamine [ka] Step 1. Methyl(1-methylpyrrolidine-2-yl)methyl methanesulfonic acid [ka] At 0°C, methanesulfonyl chloride (148 mg, 1.3 mmol) was added dropwise to a mixture of (1-methylpyrrolidine-2-yl)methanol (100 mg, 0.86 mmol) and TEA (263 mg, 2.6 mmol) in DCM (4 mL). The reaction mixture was stirred at rt for 2 hours. The reaction mixture was diluted with H2O (20 mL) and extracted with DCM (20 mL x 3). The combined organic phase was washed with saturated saline, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to obtain the target compound (130 mg). TLC Rf = 0.2 (PE / siRNA = 1:1, I2). Step 2. N-methyl-1-(1-methylpyrrolidine-2-yl)methylamine A methylamine solution (30 mL, 2.0 M EtOH solution) of (1-methylpyrrolidine-2-yl)methyl methanesulfonic acid (130 mg, 0.67 mmol) was stirred at 70°C for 16 hours. The reaction mixture was diluted with H2O (30 mL) and extracted with DCM (20 mL x 3). The organic phase was washed with saturated brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by prep-TLC using a silica gel column and eluted with MeOH / DCM (20%) to obtain the target compound (60 mg) as a yellow solid. LCMS calculated value: C7H 17 N2,[M+H] + m / z = 129.1, measured value 129.3. Example A. Biological experiment PARG enzyme activity experiment The HTRF test was used to in vitro evaluate the inhibitory ability of compounds on PARG activity. C-terminal His6-tag PARG was expressed in E. coli and isolated and stored at -80°C. Tests were performed with 1× buffer, which contained 50 mM Tris pH 7.4, 0.1 mg / mL BSA, 3 mM EDTA, 0.4 mM EGTA, 1 mM DTT, 50 mM KCl, and 0.01% Tween20. Using a liquid workstation (Labcyte, Echo665), compounds dissolved in DMSO were separated into a 384-well plate (PerkinElmer, Catalog#6008280), and 10 concentration points obtained by 4-fold gradient dilution were measured. 5 μL of enzyme mixture [hPARG (C-terminal His6-tag, 4.2 μM), 65 pM final] was added to the test well. The test plate was sealed with a sealing film and pre-incubated at room temperature. Then, 5 μL of the substrate mixture [biotinylated-NAD ribosylated PARP1 (6.1 μM), 8 nM final] was added to the reaction. After incubation at room temperature for 10 minutes, 2.5 μL of Streptavidin-Eu cryptate (Cisbio, Catalog #610SAKLA) and 2.5 μL of Mab anti 6HIS-XL665 (Cisbio, Catalog #61HISXLA) were added to the test plate, and it was incubated at room temperature for a further 60 minutes. Data was read using a multifunctional microplate reader (PerkinElmer, Envision 2015) in time-resolved fluorescence (TRF) mode, with excitation wavelengths of 337 nm and emission wavelengths of 620 nm and 665 nm. The mean HTRF signal value (1% DMSO well) of the high control group was calculated and used as the blank control (VC). The mean HTRF signal value of the low control group (without enzyme) was calculated and used as the positive control. %Inhibition=(Signal cmpd -Signal Ave_VC ) / (Signal Ave_PC -Signal Ave_VC ) × 100. I C 50The values ​​were determined by fitting the data to four standard parameters using the Hill gradient in GraphPad Prism software. From the above test results, it was found that the compound of the present invention is a ligand for PARG. 50 The data is shown in Table 7. "+" indicates IC 50 The value is >1 μM, and "++" indicates IC 50 The value is 0.1 μM <IC 50 This indicates that the minimum impedance is ≤1 μM, and "+++" represents IC. 50 The value was shown to be ≤0.1 μM. Cell activity test Cell activity studies were conducted using the Kuramochi cell line. The cells were maintained in RPMI (Hyclone, catalog number SH3080901B) containing 10% v / v FBS (AusGeneX, catalog number FBS500-S) and 1% v / v penicillin / streptomycin (Gibco, catalog number 15140122). Cells were inoculated at a density of 400 cells / well into 96-well plates (PerkinElmer, catalog number 6005680). Using a multichannel pipette, the DMSO solution containing the compounds was added to the cell culture plates and tested at nine different concentrations after a 3-fold dilution. Cells were incubated at 37°C in a 5% CO2 incubator for 7 days. Cell activity was measured using the Cell Titer-Glo reagent (Promega, catalog number G7573) according to the operating steps in the reagent's instruction manual. Luminescence signals were measured using a multimode microplate reader (Perkin Elmer, Envision 2105, BMG, or ClarioStar Plus). The average value of DMSO-treated wells was used as the high control (HC). The average value of culture medium only was used as the low control (LC).

[0488] %inhibition=(Signal Ave_HC -Signal cmpd ) / (Signal Ave_HC -Signal Ave_LC ) × 100. I C 50The values ​​were determined by fitting the data to the standard four parameters using the Hill gradient in GraphPad Prism software. 50 The values ​​were as follows. "+" indicates IC 50 The value is >1 μM, and "++" indicates IC 50 The value is 0.1 μM <IC 50 The value is ≤1 μM, and "+++" indicates IC 50 The value was shown to be ≤0.1 μM. [Table 8]

[0489] Although the present invention has been fully explained by examples, it should be noted that various changes and modifications will be obvious to those skilled in the art. These changes and modifications should be included within the scope of the claims appended to the present invention.

Claims

1. A compound represented by formula (I), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof, 【Chemistry 1】 【Chemistry 2】 It is either a single bond or a double bond. X is O or NR ４ And, X １ is C or N, X ２ is N or C, X ３ is N or C, X ４ is C or N, X ５ is C or N, 【Transformation 3】 teeth, 【Chemistry 4】 And, 【Transformation 5】 teeth, 【Transformation 6】 And, Y １ and Y ３ are each independently selected from N or CR ５ and Y ２ is N or CR ６ And, Y ４ is S, O or NR ７ And, Y ５ , Y ７ and Y ８ N or CR ８ Selected from, Y ６ is S, O or NR ９ And, Z １ It is a 5-10 member heteroaryl group, and R is optionally selected. １０ Substituted with 1, 2, 3, 4, or 5 substituents independently selected from, Z ２ H, D, halogen, CN, NO ２ SF ５ , C １ -C ８ alkyl group, C ２ -C ８ Alkenyl group, C ２ -C ８ Alkynyl group, C ６ -C １０ Aryl group, C ３ -C １０ Cycloalkyl groups, 5-10 membered heteroaryl groups, 4-14 membered heterocycloalkyl groups, NR Ｃ R Ｄ , OR Ａ , SR Ａ , NHOR Ａ , C(O)R Ｂ , C(O)OR Ａ , C(O)NR Ｃ R Ｄ , OC(O)NR Ｃ R Ｄ , NR Ｃ C(O)R Ｂ , NR Ｃ C(O)NR Ｃ R Ｄ , NR Ｃ C(O)OR Ａ , NR Ｃ S(O) ２ R Ｂ S(O)R Ｂ S(O)NR Ｃ R Ｄ , S(O) ２ R Ｂ , S(O) ２ NR Ｃ R Ｄ , or NR Ｃ S(O) ２ NR Ｃ R Ｄ And of which, C １ -C ８ alkyl group, C ２ -C ８ Alkenyl group, C ２ -C ８ Alkynyl group, C ６ -C １０ Aryl group, C ３ -C １０ Cycloalkyl groups, 5-10 membered heteroaryl groups, or 4-14 membered heterocycloalkyl groups are optionally selected for R １１ Substituted with 1, 2, 3, 4, or 5 substituents independently selected from, R １ 、 R ２ and R ３ are each independently H, D, CN, C １ -C ３ alkyl group, C ２ -C ３ alkenyl group, C ２ -C ３ alkynyl group, C ３ -C ７ cycloalkyl group, or a 4- to 7-membered heterocycloalkyl group, and among them, the C １ -C ３ alkyl group, C ２ -C ３ alkenyl group, C ２ -C ３ alkynyl group, C ３ -C ７ cycloalkyl group, or a 4- to 7-membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from D, halogen, CN, OH, C １ -C ６ alkyl group, C １ -C ６ haloalkyl group, -O-C １ -C ６ alkyl group, -OC １ -C ６ haloalkyl group Or, R ２ and R ３ C ３ -C ７ A cycloalkyl group or a 4- to 7-membered heterocycloalkyl group is formed, and of which, the C ３ -C ７ Cycloalkyl groups and 4- to 7-membered heterocycloalkyl groups can be optionally composed of D, halogens, CN, or NO. ２ , oxo, OH, C １ -C ６ alkyl group, C １ -C ６ Haloalkyl group, -O-C １ -C ６ Alkyl alkyl group, -OC １ -C ６ Substituted with one, two, three, or four substituents independently selected from the haloalkyl group, R ４ is H, D, CN, OR Ｂ , or C １ -C ４ It is an alkyl group, and optionally has at least one R ４Ａ It is replaced by, and of those, each R ４Ａ These are independently D, F, Cl, CN, NH ２ OH, -O-C １ -C ６ Alkyl alkyl group, -OC １ -C ６ Haloalkyl groups, selectively substituted C ３ -C ７ Selected from cycloalkyl groups or selectively substituted 4- to 7-membered heterocycloalkyl groups, where the selectively substituted substituents are D, halogen, CN, OH, and C. １ -C ４ alkyl group, C １ -C ４ Haloalkyl group, -O-C １ -C ４ Alkyl alkyl group, -OC １ -C ４ It is a haloalkyl group, Or, R １ and R ４ These, together with the atoms linked to them, form a 5-7 member partially unsaturated cycloalkyl group, optionally consisting of D, halogen, CN, and CF. ３ NO ２ , oxo, OH, C １ -C ６ alkyl group, C １ -C ６ Haloalkyl group, -O-C １ -C ６ Alkyl alkyl group, -OC １ -C ６ Substituted with one, two, three, or four substituents independently selected from the haloalkyl group, R ５ H, D, CN, halogen, SF ５ OH, NH ２ ,CHO,COOH,C １ -C ３ alkyl group, C ２ -C ３ Alkenyl group, C ２ -C ３ Alkynyl group, C １ -C ３ Haloalkyl group, C １ -C ３ Cyanoalkyl groups, OR Ａ , NR Ｃ R Ｄ or C(O)R Ｂ And, R ６ H, D, CN, halogen, OH, NH ２ SF ５ , C １ -C ３ alkyl group, C １ -C ３ Haloalkyl group, -O-C １ -C ３ Alkyl alkyl group, -OC １ -C ３ Haloalkyl group, C １ -C ３ It is a cyanoalkyl group, R ７ and R ９ These are H, D, and C, respectively, independently. １ -C ６ alkyl group, C １ -C ６ Haloalkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C １ -C ６ Alkyl-OR Ａ , C １ -C ６ Alkyl-CN, C １ -C ６ Alkyl-NR Ｃ R Ｄ , C(O)R Ｂ , C(O)NR Ｃ R Ｄ Selected from, Each R ８ These are H, D, halogen, CN, and NO, respectively, independently. ２ , C １ -C ６ alkyl group, C １ -C ６ Haloalkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, OR Ａ , SR Ａ SF ５ , NHOR Ａ , C(O)OR Ａ , C(O)R Ｂ , C(O)NR Ｃ R Ｄ , OC(O)NR Ｃ R Ｄ , NR Ｃ R Ｄ , NR Ｃ C(O)R Ｂ , NR Ｃ C(O)NR Ｃ R Ｄ , NR Ｃ C(O)OR Ａ , NR Ｃ S(O) ２ R Ｂ , B (OR Ｃ ) ( OR Ｄ ), C (=NR Ｃ ) NR Ｃ R Ｄ , NR Ｄ C (=NR Ｃ ) NR Ｃ R Ｄ , NR Ｄ C (=NR Ｃ ) R Ｂ P(O)R Ｅ R Ｆ , P(O)OR Ｅ OR Ｆ , OP(O)OR Ｅ OR Ｆ , S(O)(=NR Ｂ ) R Ｂ S(O)R Ｂ S(O)NR Ｃ R Ｄ , S(O) ２ R Ｂ , S(O) ２ NR Ｃ R Ｄ , NR Ｃ S(O) ２ NR Ｃ R Ｄ , or NR Ｃ S(O)(=NR Ｂ ) R Ｂ Selected from among, of which C １ -C ６ alkyl group, C ２ -C ６ Alkenyl group, or C ２ -C ６ The alkynyl group can be optionally R １２ Substituted with one, two, or three substituents independently selected from, Each R １０ These are H, D, halogen, and C, respectively, independently. １ -C ６ alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C １ -C ６ Haloalkyl groups, OC １ -C ６ Alkyl alkyl groups, OC １ -C ６ Haloalkyl groups, OC ３ -C ７ Cycloalkyl groups, C ３ -C ７ Cycloalkyl groups, CN, NO ２ , N ３ , or SF ５ Selected from among, of which C １ -C ６ alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group or C ３ -C ７ Cycloalkyl groups are optionally R １２ Substituted with one, two, or three substituents independently selected from, Two R's １０ These, along with the atoms linked to them, are oxo, C ３－ C １０ A cycloalkyl group or a 4- to 10-membered heterocycloalkyl group is formed, and of which, the C ３－ C １０ Cycloalkyl groups or 4- to 10-membered heterocycloalkyl groups are optionally D, halogens, and C. １ -C ６ alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C １ -C ６ Haloalkyl group, C １ -C ６ - Cyanoalkyl groups, CN, NO ２ , oxo, OR ａ , SR ａ SF ５ , NHOR ａ , C(O)R ｂ , C(O)NR ｃ R ｄ , C(O)OR ａ OC(O)R ｂ , OC(O)NR ｃ R ｄ , NR ｃ R ｄ , NR ｃ C(O)R ｂ , NR ｃ C(O)NR ｃ R ｄ , NR ｃ C(O)OR ａ , B (OR ｃ ) ( OR ｄ ), C (=NR ｃ ) NR ｃ R ｄ , NR ｄ C (=NR ｃ ) NR ｃ R ｄ , NR ｄ C (=NR ｃ ) R ｂ , OP(O)OR ｅ OR ｆ , P(O)OR ｅ OR ｆ , S(O)(=NR ｂ ) R ｂ S(O)R ｂ S(O)NR ｃ R ｄ , S(O) ２ R ｂ , NR ｃ S(O) ２ R ｂ , S(O) ２ NR ｃ R ｄ , NR ｃ S(O) ２ NR ｃ R ｄ , NR ｃ S(O)(=NR ｂ ) R ｂ Cy ４ Substituted with one, two, or three substituents independently selected from, of which Cy ４ is C ６ -C １０ Aryl group, C ３ -C １０ The group consists of a cycloalkyl group, a 5-10 membered heteroaryl group, and a 4-10 membered heterocycloalkyl group, among which Cy ４ The following can be selected arbitrarily: D, halogen, CN, NO ２ OH, oxo, NH ２ NHC １ -C ４ alkyl group, N(C) １ -C ４ Alkyl) ２ , C １ -C ３ alkyl group, C １ -C ３ Haloalkyl groups, OC １ -C ３ Alkyl alkyl groups, OC １ -C ３ Haloalkyl groups, OC ２ -C ３ Alkyl OH, OC ２ -C ３ Alkyl-O-C １ -C ６ Alkyl alkyl group, or SF ５ Substituted with one, two, three, or four substituents independently selected from, Each R １１ These are H, D, halogen, CN, and NO, respectively, independently. ２ , N ３ , oxo, C １ -C ６ alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, OR Ａ , SR Ａ SF ５ , NR Ｃ OR Ａ , C(O)R Ｂ , C(=S)R Ｂ , C(O)NR Ｃ R Ｄ , C(O)N(R Ｃ ) OR Ａ , C(O)OR Ａ OC(O)R Ｂ , OC(O)NR Ｃ R Ｄ , NR Ｃ R Ｄ , NR Ｃ C(O)R Ｄ , NR Ｃ C(O)NR Ｃ R Ｄ , NR Ｃ C(O)OR Ａ , B (OR Ｃ ) ( OR Ｄ ), C (=NR Ｃ ) NR Ｃ R Ｄ , NR Ｄ C (=NR Ｃ ) NR Ｃ R Ｄ , NR Ｄ C (=NR Ｃ ) R Ｂ , SiR Ｇ R Ｈ R Ｉ P(O)R Ｅ R Ｆ , P(O)OR Ｅ OR Ｆ , OP(O)OR Ｅ OR Ｆ , S(O)(=NR Ｂ ) R Ｂ S(O)R Ｂ S(O)NR Ｃ R Ｄ , S(O) ２ R Ｂ , NR Ｃ S(O) ２ R Ｂ , S(O) ２ NR Ｃ R Ｄ , NR Ｃ S(O) ２ NR Ｃ R Ｄ , NR Ｃ S(O)(=NR Ｂ ) R Ｂ Cy ３ , C １ -C ６ Alkyl-Cy ３ , OCy ３ , or O-C １ -C ６ Alkyl-Cy ３ Selected from among, of which C １ -C ６ alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ The alkynyl group can be optionally R １２ Substituted with 1, 2, 3, 4, or 5 substituents independently selected from, Each R １２ These are H, D, halogen, CN, and NO, respectively, independently. ２ , N ３ , C １ -C ６ alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C １ -C ６ Haloalkyl groups, OC １ -C ６ Alkyl OH, OC １ -C ６ Alkyl-O-C １ -C ６ Alkyl alkyl group, OR ａ１ , SR ａ１ SF ５ , NHOR ａ１ , C(O)R ｂ１ , C(O)NR ｃ１ R ｄ１ , C(O)OR ａ１ , OC(O)OR ａ１ OC(O)R ｂ１ , OC(O)NR ｃ１ R ｄ１ , NR ｃ１ R ｄ１ , NR ｃ１ C(O)R ｂ１ , NR ｃ１ C(O)NR ｃ１ R ｄ１ , NR ｃ１ C(O)OR ａ１ , B (OR ｃ１ ) ( OR ｄ１ ), C (=NR ｃ１ ) NR ｃ１ R ｄ１ , NR ｄ１ C (=NR ｃ１ ) NR ｃ１ R ｄ１ , NR ｄ１ C (=NR ｃ１ ) R ｂ１ , P(O)OR ｅ１ OR ｆ１ , OP(O)OR ｅ１ OR ｆ１ , S(O)(=NR ｂ１ ) R ｂ１ S(O)R ｂ１ S(O)NR ｃ１ R ｄ１ , S(O) ２ R ｂ１ , NR ｃ１ S(O) ２ R ｂ１ , S(O) ２ NR ｃ１ R ｄ１ , NR ｃ１ S(O) ２ NR ｃ１ R ｄ１ , NR ｃ１ S(O)(=NR ｂ１ ) R ｂ１ , C ６ -C １０ Aryl group, C ３ -C １０ Selected from cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups, of which the C ６ -C １０ Aryl group, C ３ -C １０ Cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups can be optionally D, halogens, CN, or NO. ２ NH ２ NHC １ -C ４ alkyl group, N(C) １ -C ４ Alkyl) ２ , C １ -C ３ alkyl group, C １ -C ３ Haloalkyl groups, OC １ -C ３ Alkyl alkyl groups, OC １ -C ３ Haloalkyl groups, OC ２ -C ３ Alkyl OH, OC ２ -C ３ Alkyl-O-C １ -C ６ Alkyl alkyl group, or SF ５ Substituted with 1, 2, 3, 4, or 5 substituents independently selected from, Cy ３ C is independent ６ -C １０ Aryl group, C ３ -C １０ Selected from cycloalkyl groups, 5-10 membered heteroaryl groups, or 4-10 membered heterocycloalkyl groups, among which Cy ３ R is chosen at will. １３ Substituted with 1, 2, 3, 4, or 5 substituents independently selected from, Each R １３ These are D, halogen, and C, respectively, independently. １ -C ６ alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C １ -C ６ Haloalkyl group, C １ -C ６ Alkyl OH, C １ -C ６ Alkyl-O-C １ -C ６ Alkyl alkyl groups, CN, NO ２ , N ３ , OR ａ１ , SR ａ１ SF ５ , NHOR ａ１ , C(O)R ｂ１ , C(O)NR ｃ１ R ｄ１ , C(O)OR ａ１ OC(O)R ｂ１ , OC(O)NR ｃ１ R ｄ１ , NR ｃ１ R ｄ１ , NR ｃ１ C(O)R ｂ１ , NR ｃ１ C(O)NR ｃ１ R ｄ１ , NR ｃ１ C(O)OR ａ１ , B (OR ｃ１ ) ( OR ｄ１ ), C (=NR ｃ１ ) NR ｃ１ R ｄ１ , NR ｄ１ C (=NR ｃ１ ) NR ｃ１ R ｄ１ , NR ｄ１ C (=NR ｃ１ ) R ｂ１ P(O)R ｅ１ R ｆ１ , P(O)OR ｅ１ OR ｆ１ , OP(O)OR ｅ１ OR ｆ１ , S(O)(=NR ｂ１ ) R ｂ１ S(O)R ｂ１ S(O)NR ｃ１ R ｄ１ , S(O) ２ R ｂ１ , NR ｃ１ S(O) ２ R ｂ１ , S(O) ２ NR ｃ１ R ｄ１ , NR ｃ１ S(O) ２ NR ｃ１ R ｄ１ , NR ｃ１ S(O)(=NR ｂ１ ) R ｂ１ , C ６ -C １０ Aryl group, C ３ -C １０ Selected from cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups, of which the C ６ -C １０ Aryl group, C ３ -C １０ Cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups can be optionally D, halogens, CN, or NO. ２ NH ２ NHC １ -C ４ alkyl group, N(C) １ -C ４ Alkyl) ２ , C １ -C ３ alkyl group, C １ -C ３ Haloalkyl groups, OC １ -C ３ Alkyl alkyl groups, OC １ -C ３ Haloalkyl groups, OC ２ -C ３ Alkyl OH, OC ２ -C ３ Alkyl-O-C １ -C ６ Alkyl alkyl group, or SF ５ Substituted with 1, 2, 3, 4, or 5 substituents independently selected from, Each R １４ These are H, D, and NO, respectively, independently. ２ CN, halogen, oxo, SF ５ , C １ -C ８ alkyl group, C ２ -C ８ Alkenyl group, C ２ -C ８ Alkynyl group, C ６ -C １４ Aryl group, C ３ -C １４ Cycloalkyl groups, 5-14 membered heteroaryl groups, or 4-14 membered heterocycloalkyl groups, OR ａ , SR ａ SF ５ , NHOR ａ , C(O)R ｂ , C(O)NR ｃ R ｄ , C(O)OR ａ OC(O)R ｂ , OC(O)NR ｃ R ｄ , NR ｃ R ｄ , NR ｃ C(O)R ｂ , NR ｃ C(O)NR ｃ R ｄ , NR ｃ C(O)OR ａ , B (OR ｃ ) ( OR ｄ ), C (=NR ｃ ) NR ｃ R ｄ , NR ｄ C (=NR ｃ ) NR ｃ R ｄ , NR ｄ C (=NR ｃ ) R ｂ P(O)R ｅ R ｆ , P(O)OR ｅ OR ｆ , OP(O)OR ｅ OR ｆ S(O)R ｂ S(O)NR ｃ R ｄ , S(O) ２ R ｂ , NR ｃ S(O) ２ R ｂ , S(O) ２ NR ｃ R ｄ , NR ｃ S(O) ２ NR ｃ R ｄ , or NR ｃ S(O)(=NR ｂ ) R ｂ Selected from among, of which C １ -C ８ alkyl group, C ２ -C ８ Alkenyl group, C ２ -C ８ Alkynyl group, C ６ -C １４ Aryl group, C ３ -C １４ Cycloalkyl groups, 5-14 membered heteroaryl groups, or 4-14 membered heterocycloalkyl groups are optionally D, NO ２ CN, halogen, oxo, SF ５ , C １ -C ６ alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C １ -C ６ Haloalkyl group, C １ -C ６ Alkyl OH, C １ -C ６ Alkyl-O-C １ -C ６ Alkyl alkyl groups, CN, NO ２ , N ３ , OR ａ１ , SR ａ１ SF ５ , NHOR ａ１ , C(O)R ｂ１ , C(O)NR ｃ１ R ｄ１ , C(O)OR ａ１ OC(O)R ｂ１ , OC(O)NR ｃ１ R ｄ１ , NR ｃ１ R ｄ１ , NR ｃ１ C(O)R ｂ１ , NR ｃ１ C(O)NR ｃ１ R ｄ１ , NR ｃ１ C(O)OR ａ１ , B (OR ｃ１ ) ( OR ｄ１ ), C (=NR ｃ１ ) NR ｃ１ R ｄ１ , NR ｄ１ C (=NR ｃ１ ) NR ｃ１ R ｄ１ , NR ｄ１ C (=NR ｃ１ ) R ｂ１ P(O)R ｅ１ R ｆ１ , P(O)OR ｅ１ OR ｆ１ , OP(O)OR ｅ１ OR ｆ１ , S(O)(=NR ｂ１ ) R ｂ１ S(O)R ｂ１ S(O)NR ｃ１ R ｄ１ , S(O) ２ R ｂ１ , NR ｃ１ S(O) ２ R ｂ１ , S(O) ２ NR ｃ１ R ｄ１ , NR ｃ１ S(O) ２ NR ｃ１ R ｄ１ , NR ｃ１ S(O)(=NR ｂ１ ) R ｂ１ , C ６ -C １０ Aryl group, C ３ -C １０ Substituted with 1, 2, 3, 4, or 5 substituents independently selected from cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups, Each R Ａ is independently H, D, C １ -C ６ alkyl group, C ２ -C ６ alkenyl group, C ２ -C ６ alkynyl group, C ３ -C １０ cycloalkyl group, 4- to 10-membered heterocycloalkyl group, C ６ -C １０ aryl group, 5- to 10-membered heteroaryl group, C ６ -C １０ aryl-C １ -C ６ alkyl group, 5- to 10-membered heteroaryl-C １ -C ６ alkyl group, C ３ -C １０ cycloalkyl-C １ -C ６ alkyl group, or 4- to 10-membered heterocycloalkyl-C １ -C ６ alkyl group, and among them, the C １ -C ６ alkyl group, C ２ -C ６ alkenyl group, C ２ -C ６ alkynyl group, C ３ -C １０ cycloalkyl group, 4- to 10-membered heterocycloalkyl group, C ６ -C １０ aryl group, 5- to 10-membered heteroaryl group, C ６ -C １０ aryl-C １ -C ６ alkyl group, 5- to 10-membered heteroaryl-C １ -C ６ alkyl group, C ３ -C １０ cycloalkyl-C １ -C ６ alkyl group, or 4- to 10-membered heterocycloalkyl-C １ -C ６ alkyl group is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from R １４ and Each R Ｂ These are H, D, and C, respectively, independently. １ -C ６ alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C １０ Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C ６ -C １０ Aryl group, 5-10 membered heteroaryl group, C ６ -C １０ Aryl-C １ -C ６ Alkyl, 5-10 member heteroaryl-C １ -C ６ alkyl group, C ３ -C １０ Cycloalkyl-C １ -C ６ Alkyl alkyl groups, or 4-10 member heterocycloalkyl-C １ -C ６ Selected from alkyl groups, of which the C １ -C ６ alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C １０ Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C ６ -C １０ Aryl group, 5-10 membered heteroaryl group, C ６ -C １０ Aryl-C １ -C ６ Alkyl, 5-10 member heteroaryl-C １ -C ６ alkyl group, C ３ -C １０ Cycloalkyl-C １ -C ６ Alkyl alkyl groups, or 4-10 member heterocycloalkyl-C １ -C ６ Alkyl alkyl groups are optionally R １４ Substituted with 1, 2, 3, 4, or 5 substituents independently selected from, R Ｃ and R Ｄ are each independently H, D, C １ -C ６ alkyl group, C ２ -C ６ alkenyl group, C ２ -C ６ alkynyl group, C ３ -C １０ cycloalkyl group, 4- to 10-membered heterocycloalkyl group, C ６ -C １０ aryl group, 5- to 10-membered heteroaryl group, C ６ -C １０ aryl-C １ -C ６ alkyl group, 5- to 10-membered heteroaryl-C １ -C ６ alkyl group, C ３ -C １０ cycloalkyl-C １ -C ６ alkyl group, or 4- to 10-membered heterocycloalkyl-C １ -C ６ alkyl group, wherein the C １ -C ６ alkyl group, C ２ -C ６ alkenyl group, C ２ -C ６ alkynyl group, C ３ -C １０ cycloalkyl group, 4- to 10-membered heterocycloalkyl group, C ６ -C １０ aryl group, 5- to 10-membered heteroaryl group, C ６ -C １０ aryl-C １ -C ６ alkyl group, 5- to 10-membered heteroaryl-C １ -C ６ alkyl group, C ３ -C １０ cycloalkyl-C １ -C ６ alkyl group, or 4- to 10-membered heterocycloalkyl-C １ -C ６ alkyl group is optionally R １４ Substituted with 1, 2, 3, 4, or 5 substituents independently selected from, Or, R Ｃ and R Ｄ These, together with the N atoms linked to them, form 4- to 7-membered heterocycloalkyl groups, and can optionally consist of D, halogen, oxo, CN, and C. １ -C ４ alkyl group, C １ -C ４ Haloalkyl group, C １ -C ４ Alkyl-CN, OR ａ , SR ａ , C(O)R ｂ , NR ｃ R ｄ Substituted with 1, 2, 3, 4, or 5 substituents independently selected from, R ａ and R ａ１ These are H, D, and C, respectively, independently. １ -C ４ alkyl group, C ２ -C ４ Alkenyl group, C ２ -C ４ Alkynyl group, phenyl group, C ３ -C ７ Selected from cycloalkyl groups, 5-6 membered heteroaryl groups, or 4-7 membered heterocycloalkyl groups, of which the C １ -C ４ alkyl group, C ２ -C ４ Alkenyl group, C ２ -C ４ Alkynyl group, phenyl group, C ３ -C ７ Cycloalkyl groups, 5-6 membered heteroaryl groups, or 4-7 membered heterocycloalkyl groups are optionally D, OH, CN, -NH ２ ,-NH(C １ -C ４ Alkyl), -N(C １ -C ４ Alkyl) ２ , halogen, C １ -C ４ alkyl group, C １ -C ４ Alkoxy group, C １ -C ４ Haloalkyl groups, or C １ -C ４ Substituted with one, two, or three substituents independently selected from the haloalkoxy group, R ｂ and R ｂ１ These are H, D, and C, respectively, independently. １ -C ４ alkyl group, C ２ -C ４ Alkenyl group, C ２ -C ４ Alkynyl group, C ６－ C １０ Aryl group, 5-10 membered heteroaryl group, C ３－ C １０ Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C ６－ C １０ Aryl-C １ -C ４ Alkyl, 5-10 member heteroaryl-C １ -C ４ alkyl group, C ３ -C １０ Cycloalkyl-C １ -C ４ Alkyl alkyl groups, or 4-10 member heterocycloalkyl-C １ -C ４ Selected from alkyl groups, of which the C １ -C ４ alkyl group, C ２ -C ４ Alkenyl group, C ２ -C ４ Alkynyl group, C ６－ C １０ Aryl group, 5-10 membered heteroaryl group, C ３－ C １０ Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C ６－ C １０ Aryl-C １ -C ４ Alkyl, 5-10 member heteroaryl-C １ -C ４ alkyl group, C ３ -C １０ Cycloalkyl-C １ -C ４ Alkyl alkyl groups, or 4-10 member heterocycloalkyl-C １ -C ４ Alkyl alkyl groups can be optionally D, OH, halogen, CN, or -NH. ２ ,-NH(C １ -C ４ Alkyl), -N(C １ -C ４ Alkyl) ２ , C １ -C ４ alkyl group, C １ -C ４ Haloalkyl group, -OC １ -C ４ Alkyl alkyl group or -OC １ -C ４ Haloalkyl group, C ６－ C １０ Aryl group, C ３ -C １０ Substituted with 1, 2, 3, 4, or 5 substituents independently selected from cycloalkyl groups, 5-10 membered heteroaryl groups, or 4-10 membered heterocycloalkyl groups, R ｃ , R ｄ , R ｃ１ and R ｄ１ These are H, D, and C, respectively, independently. １ -C ４ alkyl group, C ２ -C ４ Alkenyl group, C ２ -C ４ Alkynyl group, C ６－ C １０ Aryl group, 5-10 membered heteroaryl group, C ３－ C １０ Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C ６－ C １０ Aryl-C １ -C ４ Alkyl, 5-10 member heteroaryl-C １ -C ４ alkyl group, C ３－ C １０ Cycloalkyl-C １ -C ４ Alkyl, 4-10 member heterocycloalkyl-C １ -C ４ alkyl group, C ６－ C １０ Aryl-C ３－ C １０ Cycloalkyl groups, C ６－ C １０ Aryl-4 to 10-membered heterocycloalkyl groups, C ６－ C １０ Aryl-5 to 10-membered heteroaryl group, bis(C) ６ -C １０ aryl), 5-10 member heteroaryl-C ３－ C １０ Cycloalkyl groups, 5-10 member heteroaryl groups - 4-10 member heterocycloalkyl groups, 5-10 member heteroaryl groups - C ６－ C １０ Selected from aryl groups or bis (5-10 membered heteroaryls), of which the C １－４ alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ６－ C １０ Aryl group, 5-10 membered heteroaryl group, C ３－ C １０ Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C ６－ C １０ Aryl-C １ -C ４ Alkyl, 5-10 member heteroaryl-C １ -C ４ alkyl group, C ３－ C １０ Cycloalkyl-C １ -C ４ Alkyl, 4-10 member heterocycloalkyl-C １ -C ４ alkyl group, C ６－ C １０ Aryl-C ３－ C １０ Cycloalkyl groups, C ６－ C １０ Aryl-4 to 10-membered heterocycloalkyl groups, C ６－ C １０ Aryl-5 to 10-membered heteroaryl group, bis(C) ６－ C １０ aryl), 5-10 member heteroaryl-C ３－ C １０ Cycloalkyl groups, 5-10 member heteroaryl groups - 4-10 member heterocycloalkyl groups, 5-10 member heteroaryl groups - C ６－ C １０ The aryl group, or bis(5-10 membered heteroaryl), can be optionally D, halogen, OH, CN, or -NH ２ ,-NH(C １ -C ４ Alkyl), -N(C １ -C ４ Alkyl) ２ , C １ -C ４ Alkyl alkyl group, O-C １ -C ４ alkyl group, C １ -C ４ Haloalkyl group, O-C １ -C ４ Haloalkyl group, C １ -C ４ Alkyl-OH, C １ -C ４ Alkyl-CN, C ６ -C １０ Aryl group, 5-10 membered heteroaryl group, C(O)OR ａ１ , C(O)R ｂ１ , S(O) ２ R ｂ１ , C １ -C ４ Alkyl-O-C １ -C ４ Alkyl groups, and C １ -C ４ Alkyl-O-C １ -C ４ Substituted with 1, 2, 3, 4, or 5 substituents independently selected from the alkyl-O-, Or, R ｃ and R ｄ These, together with the N atoms linked to them, form 4- to 7-membered heterocycloalkyl groups, and optionally D, OH, CN, -NH ２ ,-NH(C １ -C ４ Alkyl), -N(C １ -C ４ Alkyl) ２ , halogen, C １ -C ４ alkyl group, C １ -C ４ Alkoxy group, C １ -C ４ Haloalkyl group, C １ -C ４ Haloalkoxy group, C １ -C ４ Hydroxyalkyl group, C １ -C ４ Cyanoalkyl group, C ６ -C １０ Aryl group, 5-10 membered heteroaryl group, C(O)OR ａ１ , C(O)R ｂ１ , S(O) ２ R ｂ１ , C １ -C ４ Alkoxy-C １ -C ４ Alkyl groups, and C １ -C ４ Alkoxy-C １ -C ４ Substituted with one, two, or three substituents independently selected from the alkoxy group, Or, R ｃ１ and R ｄ１ These, together with the N atoms linked to them, form 4- to 7-membered heterocycloalkyl groups, and optionally D, OH, CN, -NH ２ ,-NH(C １ -C ４ Alkyl), -N(C １ -C ４ Alkyl) ２ , halogen, C １ -C ４ alkyl group, C １ -C ４ Alkoxy group, C １ -C ４ Haloalkyl group, C １ -C ４ Haloalkoxy group, C １ -C ４ Hydroxyalkyl group, C １ -C ４ Cyanoalkyl group, C ６ -C １０ Aryl group, 5-10 membered heteroaryl group, C(O)OR ａ１ , C(O)R ｂ１ , S(O) ２ R ｂ１ , C １ -C ４ Alkoxy-C １ -C ４ Alkyl groups, and C １ -C ４ Alkoxy-C １ -C ４ Substituted with one, two, or three substituents independently selected from the alkoxy group, R Ｅ , R ｅ and R ｅ１ These are H, D, and C, respectively, independently. １ -C ４ alkyl group, C １ -C ４ Haloalkyl group, C ２ -C ４ Alkenyl group, (C １ -C ４ Alkoxy)-C １ -C ４ alkyl group, C ２ -C ４ Alkynyl group, C ６ -C １０ Aryl group, 5-10 membered heteroaryl group, C ３ -C １０ Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C ６ -C １０ Aryl-C １ -C ４ alkyl group, C ３ -C １０ Cycloalkyl-C １ -C ４ Alkyl, 5-10 member heteroaryl-C １ -C ４ Alkyl alkyl groups, or 4-10 member heterocycloalkyl-C １ -C ４ Selected from alkyl groups, R Ｆ , R ｆ and R ｆ１ These are H, D, and C, respectively, independently. １ -C ４ alkyl group, C ２ -C ４ Alkenyl group, C ２ -C ４ Alkynyl group, C ６ -C １０ Aryl group, 5-10 membered heteroaryl group, C ３ -C １０ Selected from cycloalkyl groups or 4- to 10-membered heterocycloalkyl groups, R Ｇ , R Ｈ and R Ｉ Each of them is independently C １ -C ４ Characterized by being selected from alkyl groups or phenyl groups, The compound represented by formula (I), or its pharmaceutically acceptable salts, stereoisomers, solvates, N-oxides, tautomers, isotopic variants, prodrugs, or deuterated compounds.

2. The compound is represented by formula (Ie), 【Transformation 7】 or a pharmaceutically acceptable salt thereof, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound, Eventually, R １ , R ２ , R ３ , X, Y １ , Y ２ , Y ３ , Y ５ , Y ７ , Y ８ Z １ , and Z ２ The definition is as follows (I), The compound according to claim 1.

3. Z １ This is a 5-6 membered heteroaryl group having 1, 2, or 3 heteroatoms independently selected from N, O, and S, and R is optionally selected. １０ It is substituted with 1, 2, 3, or 4 substituents independently selected from Z, preferably Z １ This is a five-membered heteroaryl group having one, two, or three heteroatoms independently selected from N, O, and S, and R is optionally selected. １０ It is characterized by being substituted with one, two, or three substituents independently selected from the above. The compound according to claim 1 or 2.

4. Z １ teeth 【Transformation 8】 Characterized by, The compound according to claim 3.

5. Z １ teeth 【Chemistry 9】 Characterized by, The compound according to claim 4.

6. Z １ teeth 【Chemistry 10】 Characterized by, The compound according to claim 5.

7. Z １ teeth 【Chemistry 11】 Characterized by, The compound according to claim 6.

8. The compound is represented by formula (III), 【Chemistry 12】 or pharmaceutically acceptable salts, stereoisomers, solvates, N-oxides, tautomers, isotopic variants, prodrugs, or deuterated compounds, among which R １ , R ２ , R ３ , R １０ , X, Y １ , Y ２ , Y ３ , Y ５ , Y ７ , Y ８ , and Z ２ The definition is characterized by being as shown in formula (I), The compound according to any one of claims 1 to 7.

9. R １ H, D, CN, C １ -C ３ Alkyl alkyl groups, optionally D, halogen, CN, OH, Me, CF ３ , OMe, OCF ３ , characterized by being substituted with 1, 2, 3, 4, or 5 substituents independently selected from OEt, The compound according to any one of claims 1 to 8.

10. R １ are H, D, CN, CH ３ CD ３ ,CH ２ CH ３ CF ３ CHF ２ ,CH ２ F, CH ２ CH ２ F, CH ２ OH, CH ２ OCH ３ or CH ２ Characterized by being CN, The compound according to claim 9.

11. R ２ and R ３ These atoms, together with the carbon atoms linked to them, form a cyclopropyl group, a cyclobutyl group, an oxetanyl group, or a siletanyl group, and each substituent can optionally be D, halogen, CN, or NO. ２ , oxo, OH, C １ -C ６ alkyl group, C １ -C ６ Haloalkyl group, -O-C １ -C ６ Alkyl alkyl group, -OC １ -C ６ It is characterized by being substituted with one, two, three, or four substituents independently selected from the haloalkyl group. The compound according to any one of claims 1 to 10.

12. The aforementioned 【Chemistry 13】 Characterized by having a structure The compound according to any one of claims 1 to 11.

13. The aforementioned compound is represented by formula (IV), 【Chemistry 14】 or pharmaceutically acceptable salts, stereoisomers, solvates, N-oxides, tautomers, isotopic variants, prodrugs, or deuterated compounds, among which, Ring C is C ３ -C ７ The C is a cycloalkyl group or a 4- to 7-membered heterocycloalkyl group. ３ -C ７ Cycloalkyl groups and 4- to 7-membered heterocycloalkyl groups can be optionally composed of D, halogens, CN, or NO. ２ , oxo, OH, C １ -C ６ alkyl group, C １ -C ６ Haloalkyl group, -O-C １ -C ６ Alkyl alkyl group, -OC １ -C ６ Substituted with one, two, three, or four substituents independently selected from the haloalkyl group, Each R １ , R １０ , X, Y １ , Y ２ , Y ３ , Y ５ , Y ７ , Y ８ , and Z ２ The definition is characterized by being as shown in formula (I), The compound according to any one of claims 1 to 10.

14. Ring C is a cyclopropyl group, a cyclobutyl group, an oxetanyl group, or a siletanyl group, and each substituent can be optionally D, halogen, CN, or NO. ２ , oxo, OH, C １ -C ６ alkyl group, C １ -C ６ Haloalkyl group, -O-C １ -C ６ Alkyl alkyl group, -OC １ -C ６ Substituted with one, two, three, or four substituents independently selected from the haloalkyl group, The compound according to claim 13.

15. The aforementioned compound is represented by formula (IVa), 【Chemistry 15】 Alternatively, a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound, of which each R １ , R １０ , X, Y １ , Y ２ , Y ３ , Y ５ , Y ７ , Y ８ , and Z ２ The definition is characterized by being as shown in formula (I), The compound according to any one of claims 1 to 14.

16. X is characterized by being O, The compound according to any one of claims 1 to 15.

17. X is NR ４ And R ４ is H, D, CN, OR Ｂ , C １ -C ４ It is an alkyl group, and optionally has at least one R ４Ａ Characterized by being replaced by, The compound according to any one of claims 1 to 15.

18. Y １ is N, Y ２ are N and Y ３ CR ５ Y １ is N, Y ２ are N and Y ３ is N, Y １ is N, Y ２ CR ６ , and Y ３ CR ５ Y １ is N, Y ２ CR ６ , and Y ３ is N, Y １ CR ５ , Y ２ are N and Y ３ CR ５ Y １ CR ５ , Y ２ are N and Y ３ is N, or Y １ CR ５ , Y ２ CR ６ , and Y ３ CR ５ Characterized by, The compound according to any one of claims 1 to 17.

19. Y １ CH, Y ２ CH and Y ３ is CH, or Y １ CH, Y ２ CF and Y ３ It is characterized by being CH, The compound according to claim 18.

20. Each R ５ These are independently H, D, F, Cl, or CH ３ Characterized by being selected from, The compound according to any one of claims 1 to 18.

21. Each R ６ are H, D, F, Cl, OH, NH ２ or characterized by being CN, The compound according to any one of claims 1 to 18.

22. Y ５ CR ８ , Y ７ CR ８ , and Y ８ CR ８ Y ５ CR ８ , Y ７ CR ８ , and Y ８ is N, Y ５ CR ８ , Y ７ are N and Y ８ CR ８ Y ５ CR ８ , Y ７ are N and Y ８ is N, Y ５ is N, Y ７ CR ８ , and Y ８ CR ８ Y ５ is N, Y ７ CR ８ , and Y ８ is N, Y ５ is N, Y ７ are N and Y ８ CR ８ is, or Y ５ is N, Y ７ are N and Y ８ It is characterized by being N, The compound according to any one of claims 1 to 21.

23. Y ５ is N, Y ７ CH and Y ８ CH is Y ５ is N, Y ７ is CCH ３ , and Y ８ CH is Y ５ is N, Y ７ CH and Y ８ is N, or Y ５ is N, Y ７ is CCH ３ , and Y ８ It is characterized by being N, The compound according to claim 22.

24. R ８ H, D, C １ -C ６ Characterized by being an alkyl group, The compound according to any one of claims 1 to 22.

25. R ８ H, D, CH ３ Characterized by, The compound according to claim 24.

26. R １０ H, D, halogen, C １ -C ６ Alkyl alkyl group, or C １ -C ６ Characterized by being a haloalkyl group, The compound according to any one of claims 1 to 25.

27. R １０ H, D, halogen, methyl group, ethyl group, isopropyl group, tert-butyl group, CF ３ CHF ２ ,CH ２ F, or CDF ２ Characterized by, The compound according to claim 26.

28. R １０ CHF ２ Characterized by, The compound according to claim 27.

29. Z ２ NR Ｃ R Ｄ , OR Ａ , SR Ａ , NR Ｃ C(O)R Ｂ , C １ -C ８ alkyl group, C ２ -C ８ Alkenyl group, C ２ -C ８ It is an alkynyl group, and of which, the C １ -C ８ alkyl group, C ２ -C ８ Alkenyl group, C ２ -C ８ The alkynyl group can be optionally R １１ It is characterized by being substituted with one, two, three, four, or five substituents independently selected from The compound according to any one of claims 1 to 28.

30. Z ２ NR Ｃ R Ｄ Characterized by, A compound according to any one of claims 1 to 29.

31. R Ｃ H, D, C １ -C ６ alkyl group, C ６ -C １０ Aryl-C １ -C ６ Alkyl, 5-10 member heteroaryl-C １ -C ６ alkyl group, C ３ -C １０ Cycloalkyl-C １ -C ６ Alkyl alkyl groups, or 4-10 member heterocycloalkyl-C １ -C ６ It is an alkyl group, and among them, the C １ -C ６ alkyl group, C ６ -C １０ Aryl-C １ -C ６ Alkyl, 5-10 member heteroaryl-C １ -C ６ alkyl group, C ３ -C １０ Cycloalkyl-C １ -C ６ Alkyl alkyl groups, or 4-10 member heterocycloalkyl-C １ -C ６ Alkyl alkyl groups are optionally R １４ It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from, preferably R Ｃ H, D, C １ -C ６ Characterized by being an alkyl group, A compound according to any one of claims 1 to 30.

32. R Ｃ H, D, CH ３ CD ３ ,CH ２ CH ３ Characterized by, The compound according to claim 31.

33. R Ｄ H, D, C １ -C ６ alkyl group, C ３ -C １０ Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C ６ -C １０ Aryl group, 5-10 membered heteroaryl group, C ６ -C １０ Aryl-C １ -C ６ Alkyl, 5-10 member heteroaryl-C １ -C ６ alkyl group, C ３ -C １０ Cycloalkyl-C １ -C ６ Alkyl alkyl groups, or 4-10 member heterocycloalkyl-C １ -C ６ It is an alkyl group, and among them, the C １ -C ６ alkyl group, C ３ -C １０ Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C ６ -C １０ Aryl group, 5-10 membered heteroaryl group, C ６ -C １０ Aryl-C １ -C ６ Alkyl, 5-10 member heteroaryl-C １ -C ６ alkyl group, C ３ -C １０ Cycloalkyl-C １ -C ６ Alkyl alkyl groups, or 4-10 member heterocycloalkyl-C １ -C ６ Alkyl alkyl groups are optionally R １４ It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from, preferably R Ｄ H, D, -CH ３ , -CD ３ ien-CH ２ CH ３ , 【Chemistry 16】 Characterized by, The compound according to any one of claims 1 to 32.

34. Z ２ is OR Ａ Characterized by, A compound according to any one of claims 1 to 29.

35. Z ２ SR Ａ Characterized by, A compound according to any one of claims 1 to 29.

36. R Ａ H, D, C １ -C ６ alkyl group, C ３ -C １０ Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C ３ -C １０ Cycloalkyl-C １ -C ６ Alkyl alkyl groups, or 4-10 member heterocycloalkyl-C １ -C ６ It is an alkyl group, and among them, the C １ -C ６ alkyl group, C ３ -C １０ Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C ３ -C １０ Cycloalkyl-C １ -C ６ Alkyl alkyl groups, or 4-10 member heterocycloalkyl-C １ -C ６ Alkyl alkyl groups are optionally R １４ Substituting with 1, 2, 3, 4, or 5 substituents independently selected from R, preferably each R Ａ These are independently H, D, and -CH ３ , -CD ３ ien-CH ２ CH ３ , -CF ３ ien-CH ２ CH ２ OH, -CH ２ CH ２ OCH ３ tetrahydrofuranyl group, 【Chemistry 17】 Characterized by being selected from, A compound according to any one of claims 1 to 29 or 34 to 35.

37. R Ｂ C １ -C ６ alkyl group, C ３ -C １０ Cycloalkyl-C １ -C ６ Alkyl alkyl groups, or 4-10 member heterocycloalkyl-C １ -C ６ Selected from alkyl groups, of which the C １ -C ６ alkyl group, C ３ -C １０ Cycloalkyl-C １ -C ６ Alkyl alkyl groups, or 4-10 member heterocycloalkyl-C １ -C ６ Alkyl alkyl groups are optionally R １４ It is substituted with 1, 2, 3, 4, or 5 substituents independently selected from, preferably R Ｂ teeth [Chemistry 18] Characterized by, A compound according to any one of claims 1 to 29.

38. Each R １４ These are independently H, D, CN, halogen, oxo, and SF ５ , C １ -C ８ alkyl group, C ６ -C １４ Aryl group, C ３ -C １４ Cycloalkyl groups, 5-14 membered heteroaryl groups, or 4-14 membered heterocycloalkyl groups, OR ａ , SR ａ SF ５ , NHOR ａ , C(O)R ｂ , C(O)NR ｃ R ｄ , C(O)OR ａ , NR ｃ R ｄ , or NR ｃ C(O)R ｂ Selected from among, of which C １ -C ８ alkyl group, C ６ -C １４ Aryl group, C ３ -C １４ Cycloalkyl groups, 5-14 membered heteroaryl groups, or 4-14 membered heterocycloalkyl groups are optionally D, NO ２ CN, halogen, oxo, SF ５ , C １ -C ６ alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C １ -C ６ Haloalkyl group, C １ -C ６ Alkyl OH, C １ -C ６ Alkyl-O-C １ -C ６ Alkyl alkyl groups, CN, NO ２ , N ３ , OR ａ１ , SR ａ１ SF ５ , NHOR ａ１ , C(O)R ｂ１ , C(O)NR ｃ１ R ｄ１ , C(O)OR ａ１ OC(O)R ｂ１ , OC(O)NR ｃ１ R ｄ１ , NR ｃ１ R ｄ１ , NR ｃ１ C(O)R ｂ１ Substituting with 1, 2, 3, 4, or 5 substituents independently selected from R, preferably each R １４ These are independently H, D, CN, halogen, oxo, and SF ５ ien-CH ３ , -CD ３ ien-CH ２ CH ３ -OH, -OCH ３ , -OCH ２ CH ３ , -NH ２ , -N(CH ３ ) ２ , -N(CH ２ CH ３ ) ２ , -C(O)CH(CH ３ ) ２ , -COOH, -C(O)N(CH ３ ) ２ , or 【Chemistry 19】 Characterized by being selected from, A compound according to any one of claims 1 to 37.

39. Z ２ C １ -C ８ alkyl group, C ２ -C ８ Alkenyl group, C ２ -C ８ It is an alkynyl group, and each substituent is optionally R １１ It is characterized by being substituted with one, two, three, four, or five substituents independently selected from A compound according to any one of claims 1 to 29.

40. Each R １１ These are independently H, D, halogen, CN, and N ３ , oxo, OR Ａ , SR Ａ SF ５ , C(O)R Ｂ , C(O)NR Ｃ R Ｄ , C(O)OR Ａ OC(O)R Ｂ , OC(O)NR Ｃ R Ｄ , NR Ｃ R Ｄ , NR Ｃ C(O)R Ｄ Cy ３ Selected from, preferably each R １１ These are independently H, D, halogen, CN, -OH, and -OCH. ３ , -OCH ２ CH ３ , -NH ２ , - NHCH ３ , -N(CH ３ ) ２ , -N(CH ２ CH ３ ) ２ Characterized by being selected from a morpholinyl group or a pyrazolyl group, A compound according to any one of claims 1 to 29 or 39.

41. Said Z ２ SH, OCF ２ CF ３ , 【Chemistry 20】 【Chemistry 21】 Characterized by having a structure A compound according to any one of claims 1 to 40.

42. Z ２ It is a 4-14 member heterocycloalkyl group, and R is optionally selected. １１ It is characterized by being substituted with one, two, three, four, or five substituents independently selected from the above. A compound according to any one of claims 1 to 29.

43. Z ２ These are piperidinyl group, piperazinyl group, morpholinyl group, octahydropyrrolo[3,4-c]pyrrolyl group, octahydro-1H-pyrrolo[3,2-c]pyridinyl group, 2-azabicyclo[2.2.1]heptyl group, 2,5-diazabicyclo[2.2.1]heptyl group, 5,6,7,8-tetrahydroimidazo[1,5-a]pyradinyl group, 5,6,7,8-te The substituents are trahydroimidazo[1,2-a]pyrazinyl group, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl group, 5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazinyl group, 4,7-diazaspiro[2.5]octyl group, and 1,8-diazaspiro[4.5]decyl group, and each substituent is optionally R １１ It is characterized by being substituted with one, two, three, four, or five substituents independently selected from the above. The compound according to claim 42.

44. Each R １１ These are independently H, D, halogen, CN, and N ３ , oxo, C １ -C ６ Alkyl alkyl group, OR Ａ , SR Ａ SF ５ , NR Ｃ OR Ａ , C(O)R Ｂ , NR Ｃ R Ｄ Cy ３ Selected from among, of which C １ -C ６ Alkyl alkyl groups are optionally R １２ Substituting with 1, 2, 3, 4, or 5 substituents independently selected from R, preferably each R １１ These are independently H, D, halogen, CN, and N ３ , oxo, -CH ３ , -CD ３ ,CH ２ F, CHF ２ CF ３ ien-CH ２ CH ３ , -CH(CH ３ ) ２ ien-CH ２ OH, -CH ２ OCH ３ ien-CH ２ NH ２ ien-CH ２ NHCH ３ ien-CH ２ N(CH ３ ) ２ -OH, -OCH ３ , -OCH ２ CH ３ , -NH ２ , - NHCH ３ , -N(CH ３ ) ２ , - NHCH ２ CH ３ , -N(CH ２ CH ３ ) ２ It is characterized by being selected from a morpholinyl group, a pyrazolyl group, or a 4,4-difluoro-1-piperidinyl group. A compound according to any one of claims 1 to 29 or 42 to 43.

45. Said Z ２ teeth, 【Chemistry 22】 Characterized by having a structure A compound according to any one of claims 1 to 29 or 42 to 44.

46. The compound shown in formula (I) above is 【Chemistry 23】 【Chemistry 24】 【Chemistry 25】 【Chemistry 26】 【Chemistry 27】 【Chemistry 28】 【Chemistry 29】 or characterized by being selected from pharmaceutically acceptable salts thereof, A compound according to any one of claims 1 to 45.

47. The compound shown in formula (I) above is 【Transformation 30】 【Chemistry 31】 【Chemistry 32】 【Transformation 33】 or characterized by being selected from pharmaceutically acceptable salts thereof, The compound according to claim 46.

48. The compound shown in formula (I) above is 【Transformation 34】 【Chemistry 35】 【Transformation 36】 【Chemistry 37】 or characterized by being selected from pharmaceutically acceptable salts thereof, The compound according to claim 46.

49. A pharmaceutical composition comprising a compound according to any one of claims 1 to 48, or a pharmaceutically acceptable salt, stereoisomer, prodrug, chelate, or non-covalent complex thereof, and at least one pharmaceutically acceptable carrier or excipient. Pharmaceutical composition.

50. Application of a compound according to any one of claims 1 to 48, or a pharmaceutically acceptable salt or stereoisomer, prodrug, chelate, or non-covalent complex, or the pharmaceutical composition according to claim 49, in the manufacture of a therapeutic agent.

51. The aforementioned drug is characterized by being used as a PARG inhibitor. The application described in claim 50.

52. The drug is characterized by being used to treat cancer. The application according to claim 50 or 51.

53. The cancer is characterized by being selected from breast cancer, ovarian cancer, stomach cancer, prostate cancer, pancreatic cancer, uterine cancer, cervical cancer, endometrial cancer, lung cancer, brain cancer, bile duct cancer, and hematological cancer. The application described in claim 52.

54. A method for inhibiting PARG, comprising administering to the patient a compound according to any one of claims 1 to 48, or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide or prodrug thereof, or a pharmaceutical composition according to claim 49. method.

55. A method for treating a disease associated with PARG inhibition, comprising administering to a patient a therapeutically effective amount of a compound according to any one of claims 1 to 48, or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, or prodrug thereof, or a pharmaceutical composition according to claim 49. method.

56. The aforementioned disease is characterized by being cancer. The method according to claim 55.

57. The cancer is characterized by being selected from breast cancer, ovarian cancer, stomach cancer, prostate cancer, pancreatic cancer, uterine cancer, cervical cancer, endometrial cancer, lung cancer, brain cancer, bile duct cancer, and hematological cancer. The method according to claim 56.

58. Application of a compound according to any one of claims 1 to 48 in combination with surgery, chemotherapy, radiotherapy, targeted therapy, other DDR modifiers, immunotherapy, and gene and cell therapies in the manufacture of a cancer treatment.

59. The targeted therapy is characterized by being selected from kinase inhibitors, growth factor inhibitors, and cyclin-dependent kinase inhibitors. The application described in claim 58.

60. The DDR regulator is characterized by being selected from DNA-PK inhibitors, ATM inhibitors, ATR inhibitors, CHK1 inhibitors, WEE1 inhibitors, CDK1 inhibitors, LIG4 inhibitors, HIF-1 inhibitors, HDAC inhibitors, RAD51 inhibitors, Polθ inhibitors, WRN inhibitors, PRMT5 inhibitors, MAT2A inhibitors, and PKMYT1 inhibitors. The application described in claim 58.

61. A compound represented by formula (A), 【Transformation 38】 W １ is a leaving group, preferably W １ is halogen, C １ -C ３ Alkyl-SO ２ -, phenyl-SO ２ -, -SC １ -C ４ Alkyl group, -S-phenyl group, -OC １ -C ４ Alkyl alkyl group, -OC １ -C ４ It is a haloalkyl group, of which C １ -C ４ Alkyl groups and phenyl groups can be optionally replaced with halogens, CN, or NOs. ２ SF ５ OH, C １ -C ４ alkyl group, C １ -C ４ Haloalkyl group, -O-C １ -C ４ Alkyl alkyl group, -OC １ -C ４ Substituted with a haloalkyl group, more preferably, W １ F, Cl, Br, I, OTf, OTs, OMs, -SCH ３ , -SCH ２ CH ３ -S-phenyl group, -OCF ２ CF ３ And, Eventually, R １ , R ２ , R ３ , X, Y １ , Y ２ , Y ３ , Y ５ , Y ７ , Y ８ , and Z １ The definition is characterized by being as shown in formula (I), compound.

62. The compound is shown in (Aa), 【Chemistry 39】 Eventually, W １ , R １ , R ２ , R ３ , R １０ , X, Y １ , Y ２ , Y ３ , Y ５ , Y ７ , and Y ８ The definition is characterized by being as shown in formula (A), The compound according to claim 61.

63. The compound is shown in (Ab), 【Chemistry 40】 Eventually, W １ The definition is as shown in formula (A), and the ring C, R １ , R １０ , X, Y １ , Y ２ , Y ３ , Y ５ , Y ７ , and Y ８ The definition is characterized by being as shown in formula (IV), The compound according to claim 62.

64. The aforementioned compound, 【Chemistry 41】 or characterized by being selected from the salt thereof The compound according to claim 63.

65. A compound represented by formula (B), 【Chemistry 42】 W ２ is a leaving group, preferably W ２ is, -SC １ -C ４ Alkyl group, -S-phenyl group, -OC １ -C ４ Alkyl alkyl group, or -OC １ -C ４ It is a haloalkyl group, of which C １ -C ４ Alkyl groups and phenyl groups can be optionally replaced with halogens, CN, or NOs. ２ SF ５ OH, C １ -C ４ alkyl group, C １ -C ４ Haloalkyl group, -O-C １ -C ４ Alkyl alkyl group, -OC １ -C ４ Substituted with a haloalkyl group, more preferably, W ２ Ha-SCH ３ , -SCH ２ CH ３ -S-phenyl group, or -OCF ２ CF ３ And, Eventually, R １ , R ２ , R ３ , X, Y １ , Y ２ , Y ３ , Y ５ , Y ７ , and Y ８ The definition is characterized by being as shown in formula (I), compound.

66. The aforementioned compound is shown in (Ba), 【Chemistry 43】 Eventually, W ２ The definition is as shown in equation (B), and ring C, R １ , X, Y １ , Y ２ , Y ３ , Y ５ , Y ７ , and Y ８ The definition is characterized by being as shown in formula (IV), The compound according to claim 65.

67. The aforementioned compound, 【Chemistry 44】 or characterized by being selected from the salt thereof The compound according to claim 66.

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