Tricyclic heterocyclic derivatives, compositions thereof and uses thereof

Abstract

The present disclosure relates to tricyclic heterocyclic derivatives represented by the following formula (I), their pharmaceutical compositions, preparation methods, and therapeutic uses. JPEG2025515506000440.jpg3160

Description

[Technical Field]

[0001] The present disclosure relates to tricyclic heterocyclic derivatives that function as PARG inhibitors, methods for preparing the tricyclic heterocyclic derivatives, pharmaceutical compositions, and their use in treating diseases associated with PARG activity, such as cancer and other diseases. [Background technology]

[0002] DNA damage repair (DDR) is a series of processes by which cells recognize and correct damage to DNA molecules that encode the genome. However, once cancer develops, DNA repair pathways can be a double-edged sword, as they can also promote the repair and survival of cancer cells in response to chemotherapy and radiation therapy. Therefore, cancers with impaired DNA repair are more susceptible to DNA damage and rely on complementary repair pathways, which may be developed and harnessed for therapeutic use.

[0003] Because abnormal DDR can usually lead to cancer cells being more susceptible to specific DNA damage, defective DDR can be exploited for molecular targeting of cancer therapies. Targeting DNA repair defects has been validated as an effective strategy in cancer treatment. For example, poly(ADP-ribose) polymerase (PARP) inhibitors have been successfully used to treat BRCA-deficient breast, ovarian, prostate, and pancreatic cancers (Audeh MW et al., 2010).

[0004] Poly(ADP-ribosylation) (PARylation) is a unique post-translational modification that maintains genome stability through distinct molecular pathways, particularly DNA repair pathways (Kraus WL et al., 2015). Binding of PARP to broken DNA and the rapid synthesis of PARP itself as poly(ADP-ribose) are among the first events in the single-strand DNA repair process. Currently, PARP inhibitors primarily inhibit the catalytic activity of PARP1 and PARP2, thereby inhibiting PARP1 / 2-dependent DNA repair. Recently, clinical resistance to PARP inhibitors has been reported (Drost and Jonkers, 2014) (Barber LJ et al., 2013) (Tobalina L et al., 2021), prompting a need for alternative inhibitors of DNA damage repair mechanisms.

[0005] Poly(ADP-ribosylation) (PARylation) is a transient post-translational modification that can be rapidly degraded by PAR glycohydrolase (PARG) (Barkauskaite E et al., 2015). When PARP binds to PAR, its catalytic activity is reduced, and activation of PARG helps restore PARP to its catalytically active state (Curtin and Szabo, 2013). Similar to PARP, PARG can also promote the repair of DNA double-strand breaks (DSBs) and single-strand breaks (SSBs) (Mortusewicz O et al., 2011). In addition to its key 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; Guastaferro T et al., 2013; Caiafa P et al., 2009). Evidence suggests that PARG deficiency reduces the viability of BRCA2-deficient cells by inhibiting DSB repair (Fathers C et al., 2012). However, other tumor mutations may cause defects in the DSB repair mechanism (so-called "BRCA-ness"), potentially increasing the sensitivity of tumor cells to PARG inhibition.

[0006] However, PARG deficiency does not result in sensitivity to all therapeutic agents (e.g., gemcitabine, camptothecin), suggesting that PARG function is specific to certain 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 deficiency can result in lung, cervical, and pancreatic cancer cells becoming 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).

[0007] Several studies have shown that PARG inhibition may offer a therapeutic advantage to PARP inhibitor-resistant cells (Fisher AE et al., 2007). It has also been reported that gene expression patterns resulting from PARG deficiency in breast cancer cells are significantly different from those resulting from PARP deficiency (Frizzell KM et al., 2009). Due to replication fork stalling and replication collapse, ovarian cancer cells respond differently to PARP and PARG inhibitors, and are more sensitive to the latter (Pillay N et al., 2019) (Coulson-Filmer C et al., 2021).

[0008] Recent studies have also revealed that PARG and PARP inhibition have different mechanisms. Unlike PARP deficiency, PARG gene deficiency leads to decreased NAD levels, resulting in energy depletion and resulting in lung cancer cell death (Erdelyi K et al., 2009). PARG inhibition can also sequester NAD to enhance the metabolic lethality of alkylating agents in IDH-mutant tumor cells (Nagashima H et al., 2020).

[0009] Existing cell-permeable PARG inhibitors are limited to compounds such as tannic acid, gallotannin, and PDD 00017273. These compounds have 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).

[0010] An object of the present disclosure is to provide a cell membrane-permeable PARG inhibitor. Summary of the Invention

[0011] In particular, the present disclosure relates to compounds represented by formula (I) below, or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof, wherein the variables are defined herein: [ka]

[0012] In another aspect, the present disclosure provides a pharmaceutical composition comprising a compound of Formula (I), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof, and at least one pharmaceutically acceptable carrier.

[0013] In another aspect, the present disclosure provides a method for inhibiting PARG, comprising contacting PARG with a compound of formula (I), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof.

[0014] In another aspect, the present disclosure provides a method for treating cancer and other diseases, comprising administering to a patient an effective amount of a compound of Formula (I), a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof.

[0015] One or more embodiments are described in detail below, and other features, objects, and advantages will become apparent from the description and claims.

[0016] Detailed Description The present disclosure will be more fully understood by reference to the following description, including the following definitions and examples. Certain features of the compositions and methods described in separate aspects herein may be provided in combined form in a single aspect. Alternatively, for convenience of description, various features of the compositions and methods described in a single aspect may be provided alone or in any subcombination.

[0017] Before the present disclosure is further described, it is to be understood that this disclosure is not limited to particular embodiments described herein, and the terminology used herein is used for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present disclosure.

[0018] In particular, the present disclosure relates to a compound represented by the following formula (I): or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof: [ka] [In the formula, X is O or NR 5 and X 1 is C, X 2 is N or C, X 3 is N or C, X 4 is C, [ka] Y is N or CR 15 and Y 1 is N or CR 6 and Y 2 is N or CR 7 and Y 3 is N or CR 8 and Y 4 is N or CR 4 and Y 5 is N or CR 4 and Y 6 are S, O and NR 14 selected from the group consisting of Y 7 are S, O and NR 16 selected from the group consisting of Cy 1 is R 9 is a 5- to 10-membered heteroaryl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Cy 2 is C6~C 10 Aryl groups, C3-C 10 a cycloalkyl group, a 5- to 10-membered heteroaryl group, and a 4- to 14-membered heterocycloalkyl group (wherein the C6 to C 10 Aryl groups, C3-C 10 The cycloalkyl group, 5- to 10-membered heteroaryl group, or 4- to 14-membered heterocycloalkyl group is independently R 10 optionally substituted with 1, 2, 3, 4 or 5 substituents selected from R 1 , R 2 and R 3are each independently selected from the group consisting of H, D, CN, a C1-C3 alkyl group, a C2-C3 alkenyl group, a C2-C3 alkynyl group, a C3-C7 cycloalkyl group, and a 4- to 7-membered heterocycloalkyl group (wherein the C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C3-C7 cycloalkyl group, or 4- to 7-membered heterocycloalkyl group is optionally substituted with 1 to 5 substituents independently selected from D, halogen, CN, OH, a C1-C6 alkyl group, a C1-C6 haloalkyl group, —O—C1-C6 alkyl group, and —O—C1-C6 haloalkyl group); Or, R 2 and R 3 together with the carbon atoms linked thereto form a C3-C7 cycloalkyl group or a 4- to 7-membered heterocycloalkyl group, wherein the C3-C7 cycloalkyl group or the 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, a C1-C6 alkyl group, a C1-C6 haloalkyl group, —O—C1-C6 alkyl group, and —O—C1-C6 haloalkyl group, R 4 is H, D, halogen, OH, CN, NO2, SF5, C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, -O-C1-C3 alkyl group, and NR C R D wherein said C1-C3 alkyl group, C2-C3 alkenyl group, and C2-C3 alkynyl group are optionally substituted with halogen or CN; R 5 H, D, CN, OR B and a C1 to C4 alkyl group, wherein the C1 to C4 alkyl group is selected from the group consisting of R 5A and optionally substituted with at least one of: 5Aare each independently selected from the group consisting of D, F, Cl, CN, NH2, OH, -O-C1 to C6 alkyl group, -O-C1 to C6 haloalkyl group, optionally substituted C3 to C7 cycloalkyl group, and optionally substituted 4 to 7 membered heterocycloalkyl group, and further wherein said optionally substituted means substituted with any substituent selected from the group consisting of D, halogen, CN, OH, C1 to C4 alkyl group, C1 to C4 haloalkyl group, -O-C1 to C4 alkyl group, and -O-C1 to C4 haloalkyl group), Or, R 1 and R 5 together with the atoms connected thereto form a 5- to 7-membered partially saturated heterocycloalkyl group, wherein said 5- to 7-membered partially saturated heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, CF, NO, oxo, OH, C-C alkyl, C-C haloalkyl, -O-C-C alkyl, and -O-C-C haloalkyl; R 6 , R 7 and R 15 are each independently H, D, halogen, CN, NO2, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, OR A , S.R. A , SF5, NHOR A , C(O)OR A , C(O)R B , C(O)NR C R D , OC(O)NR C R D , N.R. C R D , N.R. C C(O)R B , N.R. C C(O)NR C R D , N.R. C C(O)OR A , N.R. C S(O)2R B , B(OR C )(OR D ), C(=NRC )NR C R D , N.R. D C(=NR C )NR C R D , N.R. 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)2R B , S(O)NR C R D , N.R. C S(O)NR C R D , and N.R. C S(O)(=NR B )R B wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, or the C2-C6 alkynyl group is independently selected from the group consisting of R 11 optionally substituted with 1, 2 or 3 substituents selected from R 8 is selected from the group consisting of H, D, CN, halogen, OH, NH2, a C1-C3 alkyl group, a C1-C3 haloalkyl group, -O-C1-C3 alkyl group, -O-C1-C3 haloalkyl group, a C1-C3 cyanoalkyl group, and SF5; Each R 9 are independently selected from the group consisting of 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, and SF5 (wherein said C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, or C3-C7 cycloalkyl group is independently selected from the group consisting of R 11optionally substituted with 1, 2 or 3 substituents selected from Each R 10 are independently H, D, halogen, CN, NO2, N3, oxo group, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, OR A , S.R. A , SF5, 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 , N.R. C R D , N.R. C C(O)R D , N.R. C C(O)NR C R D , N.R. C C(O)OR A , B(OR C )(OR D ), C(=NR C )NR C R D , N.R. D C(=NR C )NR C R D , N.R. 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 , N.R. CS(O)2R B , S(O)NR C R D , N.R. C S(O)NR C R D , N.R. C S(O)(=NR B )R B , Cy 3 , C1-C6 alkyl-Cy 3 , O.C.y. 3 , and O-C1-C6 alkyl-Cy 3 wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, and the C2-C6 alkynyl group are independently selected from the group consisting of R 11 optionally substituted with 1, 2, 3, 4 or 5 substituents selected from The Two R's 10 are oxo groups together with the atoms connected to them, C3-C 10 A cycloalkyl group or a 4- to 10-membered heterocycloalkyl group is formed (wherein the C3 to C 10 The cycloalkyl group or the 4-10 membered heterocycloalkyl group is independently selected from D, halogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C1-C6 haloalkyl group, a C1-C6 cyanoalkyl group, CN, NO2, an oxo group, OR a , S.R. 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 , N.R. c R d , N.R. c C(O)R b , N.R. c C(O)NR c R d , N.R. c C(O)OR a , B(OR c )(OR d ), C(=NR c )NR c Rd , N.R. d C(=NR c )NR c R d , N.R. 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)2R b , N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , N.R. c S(O)(=NR b )R b , Cy 4 and wherein Cy is optionally substituted with 1, 2, or 3 substituents selected from 4 is C6~C 10 Aryl groups, C3-C 10 cycloalkyl groups, 5- to 10-membered heteroaryl groups, and 4- to 10-membered heterocycloalkyl groups, and further wherein said C6 to C 10 Aryl groups, C3-C 10 The cycloalkyl group, the 5- to 10-membered heteroaryl group, and the 4- to 10-membered heterocycloalkyl group are optionally substituted by 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, NO, OH, oxo, NH, NHC-C alkyl group, N(C-C alkyl group), C-C alkyl group, C-C haloalkyl group, OC-C alkyl group, OC-C haloalkyl group, OC-C alkyl-OH, OC-C alkyl-O—C-C alkyl group, and SF; Cy 3 are independent, C6~C 10 Aryl groups, C3-C 10a cycloalkyl group, a 5- to 10-membered heteroaryl group, and a 4- to 10-membered heterocycloalkyl group (wherein the C6 to C 10 Aryl groups, C3-C 10 The cycloalkyl group, the 5- to 10-membered heteroaryl group, and the 4- to 10-membered heterocycloalkyl group are independently unsubstituted or R 12 optionally substituted with 1, 2, 3, 4 or 5 substituents selected from Each R 11 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 alkyl-OH, OC1-C6 alkyl-O-C1-C6 alkyl group, OR a1 , S.R. 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 , N.R. c1 R d1 , N.R. c1 C(O)R b1 , N.R. c1 C(O)NR c1 R d1 , N.R. c1 C(O)OR a1 , B(OR c1 )(OR d1 ), C(=NR c1 )NR c1 R d1 , N.R. d1 C(=NR c1 )NR c1 R d1 , N.R. d1 C(=NR c1 )R b1 , P(O)OR e1 OR f1 , OP(O)OR e1 OR f1 , S(O)(=NR b1 )Rb1 , S(O)R b1 , S(O)NR c1 R d1 , S(O)2R b1 , N.R. c1 S(O)2R b1 , S(O)NR c1 R d1 , N.R. c1 S(O)NR c1 R d1 , N.R. c1 S(O)(=NR b1 )R b1 , C6~C 10 Aryl groups, C3-C 10 a cycloalkyl group, a 5- to 10-membered heteroaryl group, and a 4- to 10-membered heterocycloalkyl group (wherein the C6 to C 10 Aryl groups, C3-C 10 the cycloalkyl group, the 5- to 10-membered heteroaryl group, and the 4- to 10-membered heterocycloalkyl group are independently unsubstituted or optionally substituted with 1, 2, 3, 4, or 5 substituents selected from D, halogen, CN, NO, NH, NHC alkyl group, N(C alkyl group), C alkyl group, C haloalkyl group, OC alkyl group, OC haloalkyl group, OC alkyl-OH, OC alkyl-O—C alkyl group, and SF; Each R 12 are independently D, halogen, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl group, C1-C6 alkyl-OH, C1-C6 alkyl-O-C1-C6 alkyl group, CN, NO2, N3, OR a1 , S.R. 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 , N.R. c1 R d1 , N.R. c1 C(O)Rb1 , N.R. c1 C(O)NR c1 R d1 , N.R. c1 C(O)OR a1 , B(OR c1 )(OR d1 ), C(=NR c1 )NR c1 R d1 , N.R. d1 C(=NR c1 )NR c1 R d1 , N.R. 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)2R b1 , N.R. c1 S(O)2R b1 , S(O)NR c1 R d1 , N.R. c1 S(O)NR c1 R d1 , N.R. c1 S(O)(=NR b1 )R b1 , C6~C 10 Aryl groups, C3-C 10 a cycloalkyl group, a 5- to 10-membered heteroaryl group, and a 4- to 10-membered heterocycloalkyl group (wherein the C6 to C 10 Aryl groups, C3-C 10the cycloalkyl group, the 5- to 10-membered heteroaryl group, and the 4- to 10-membered heterocycloalkyl group are independently unsubstituted or optionally substituted with 1, 2, 3, 4, or 5 substituents selected from D, halogen, CN, NO, NH, NHC alkyl group, N(C alkyl group), C alkyl group, C haloalkyl group, OC alkyl group, OC haloalkyl group, OC alkyl-OH, OC alkyl-O—C alkyl group, and SF; Each R 13 are independently H, D, OH, CN, halogen, oxo group, C1-C4 alkyl group, C1-C4 haloalkyl group, C1-C4 cyanoalkyl group, OC1-C4 alkyl group, OC1-C4 haloalkyl group, OC1-C4 alkyl-OH, OC1-C4 alkyl-O-C1-C4 alkyl group, OC1-C4 alkyl-O-C1-C4 haloalkyl group, C1-C4 alkyl-O-C1-C4 alkyl group, C1-C4 alkyl-O-C1-C4 haloalkyl group, optionally substituted C3-C7 cycloalkyl group, optionally substituted 4-7 membered heterocycloalkyl group, SF5, OR a , S.R. a , C(O)R b , OC(O)NR c R d , N.R. c R d , N.R. c C(O)R b , N.R. c C(O)NR c R d , N.R. c C(O)OR a , S(O)R b , S(O)NR c R d , S(O)2R b , N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , and B(OR c )(OR d) (wherein the optionally substituted means substituted with a substituent selected from the group consisting of D, halogen, CN, OH, C1-C4 alkyl group, C1-C4 haloalkyl group, —O—C1-C4 alkyl group, and —O—C1-C4 haloalkyl group), R 14 and R 16 are each selected from the group consisting of H, D, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C1-C6 alkyl-OH, a C1-C6 alkyl-CN, and a C1-C6 alkyl-O—C1-C6 alkyl group; R A are independently H, D, a C1-C6 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10 is selected from the group consisting of an aryl group, a 5- to 10-membered heteroaryl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, and a heterocycloalkylalkyl group (wherein the C1-C6 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10 The aryl group, 5- to 10-membered heteroaryl group, arylalkyl group, heteroarylalkyl group, cycloalkylalkyl group, or heterocycloalkylalkyl group may independently be D, OH, CN, halogen, C1-C4 alkyl group, NO2, oxo group, OR a , S.R. 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 , N.R. c R d , N.R. c C(O)R b , N.R. c C(O)NR c Rd , N.R. c C(O)OR a , B(OR c )(OR d ), C(=NR c )NR c R d , N.R. d C(=NR c )NR c R d , N.R. 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)2R b , N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , and N.R. c S(O)(=NR b )R b optionally substituted with 1, 2, 3, 4 or 5 substituents selected from R B are independently H, D, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10 is selected from the group consisting of an aryl group, a 5- to 10-membered heteroaryl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, and a heterocycloalkylalkyl group (wherein the C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10The aryl group, 5- to 10-membered heteroaryl group, arylalkyl group, heteroarylalkyl group, cycloalkylalkyl group, or heterocycloalkylalkyl group is independently R 13 optionally substituted with 1, 2, 3, 4 or 5 substituents selected from R C and R D are each independently selected from the group consisting of H, D, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C7 cycloalkyl group, a 4- to 7-membered heterocycloalkyl group, a phenyl group, a 5- to 6-membered heteroaryl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, and a heterocycloalkylalkyl group (wherein the C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C7 cycloalkyl group, a 4- to 7-membered heterocycloalkyl group, a phenyl group, a 5- to 6-membered heteroaryl group, an arylarylalkyl group, a cycloalkylalkyl group, and a heterocycloalkylalkyl group). The alkyl group, heteroarylalkyl group, cycloalkylalkyl group, or heterocycloalkylalkyl group is independently D, OH, CN, halogen, oxo group, C1-C4 alkyl group, C1-C4 haloalkyl group, C1-C4 cyanoalkyl group, OC1-C4 alkyl group, OC1-C4 haloalkyl group, OC2-C4 alkyl-OH, OC2-C4 alkyl-O-C1-C4 alkyl group, OC2-C4 alkyl-O-C1-C4 haloalkyl group, C1-C4 alkyl-O-C1-C4 alkyl group, C1-C4 alkyl-O-C1-C4 haloalkyl group, SF5, OC(O)NR c R d , N.R. c R d , N.R. c C(O)R b , S(O)NR c R d , S(O)2R b , N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , and B(OR c )(OR d), optionally substituted with 1, 2, 3, 4 or 5 substituents selected from Or, R C and R D form a 4- to 7-membered heterocycloalkyl group together with the N atom linked thereto, wherein the 4- to 7-membered heterocycloalkyl group is optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from D, OH, oxo, CN, —NH, —NH(C1-C4 alkyl group), —N(C1-C4 alkyl group), halogen, C1-C4 alkyl group, C1-C4 haloalkyl group, C1-C4 cyanoalkyl group, OC1-C4 alkyl group, and OC1-C4 haloalkyl group, OC2-C4 alkyl-OH, OC2-C4 alkyl-O—C1-C4 alkyl group, and OC2-C4 alkyl-O—C1-C4 haloalkyl group; R a and R a1 are each independently selected from the group consisting of H, D, 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- to 6-membered heteroaryl group, and a 4- to 7-membered heterocycloalkyl group (wherein the C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, phenyl group, C3-C7 cycloalkyl group, 5- to 6-membered heteroaryl group, or 4- to 7-membered heterocycloalkyl group is optionally substituted by 1, 2, or 3 substituents independently selected from D, OH, CN, —NH2, —NH(C1-C4 alkyl group), —N(C1-C4 alkyl group)2, halogen, a C1-C4 alkyl group, a C1-C4 alkoxy group, a C1-C4 haloalkyl group, and a C1-C4 haloalkoxy group); R b and R b1are each independently selected from the group consisting of H, D, 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- to 6-membered heteroaryl group, or a 4- to 7-membered heterocycloalkyl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, and a heterocycloalkylalkyl group; wherein the C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, phenyl group, C3-C7 cycloalkyl group, a 5- to 6-membered heteroaryl group, a 4- to 7-membered heterocycloalkyl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, or a heterocycloalkylalkyl group is independently selected from the group consisting of D, OH, CN, -NH2, -NH(C1-C4 alkyl group), -N(C1-C4 alkyl group)2, halogen, a C1-C4 alkyl group, a C1-C4 alkoxy group, a C1-C4 haloalkyl group, a C1-C4 haloalkoxy group, a C6-C 10 Aryl groups, C3-C 10 optionally substituted with 1, 2, or 3 substituents selected from a cycloalkyl group, a 5- to 10-membered heteroaryl group, and a 4- to 10-membered heterocycloalkyl group; R c and R d are each independently H, D, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 a cycloalkyl group, a 4- to 10-membered heterocycloalkyl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, a heterocycloalkylalkyl group, an arylcycloalkyl group, an arylheterocycloalkyl group, an arylheteroaryl group, a diaryl group, a heteroarylcycloalkyl group, a heteroarylheterocycloalkyl group, a heteroarylaryl group, and a diheteroaryl group (wherein the C 1~4 Alkyl group, C 2~4 Alkenyl group, C 2~4 Alkynyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C10 The cycloalkyl group, 4-10 membered heterocycloalkyl group, arylalkyl group, heteroarylalkyl group, cycloalkylalkyl group, heterocycloalkylalkyl group, arylcycloalkyl group, arylheterocycloalkyl group, arylheteroaryl group, diaryl group, heteroarylcycloalkyl group, heteroarylheterocycloalkyl group, heteroarylaryl group, or diheteroaryl group is independently D, OH, CN, -NH2, -NH(C1-C4 alkyl group), -N(C1-C4 alkyl group)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 groups, 5- to 10-membered heteroaryl groups, C(O)OR a1 , C(O)R b1 , S(O)2R b1 , C1-C4 alkyl-O—C1-C4 alkyl group, and C1-C4 alkyl-O—C1-C4 alkyl-O—; Or, R c and R d form a 4- to 7-membered heterocycloalkyl group together with the N atom linked thereto (wherein the 4- to 7-membered heterocycloalkyl group is independently selected from D, OH, CN, -NH2, -NH(C1-C4 alkyl group), -N(C1-C4 alkyl group)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 groups, 5- to 10-membered heteroaryl groups, C(O)OR a1 , C(O)R b1 , S(O)2R b1 , a C1-C4 alkoxy-C1-C4 alkyl group, and a C1-C4 alkoxy-C1-C4 alkoxy group), R c1 and R d1are each independently H, D, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 a cycloalkyl group, a 4- to 10-membered heterocycloalkyl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, and a heterocycloalkylalkyl group (wherein the C1-C4 alkyl group, C1-C4 haloalkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 the cycloalkyl group, 4-10 membered heterocycloalkyl group, arylalkyl group, heteroarylalkyl group, cycloalkylalkyl group, or heterocycloalkylalkyl group is optionally substituted with 1, 2, or 3 substituents independently selected from D, OH, CN, —NH, —NH(C1-C4 alkyl group), —N(C1-C4 alkyl group), halogen, a C1-C4 alkyl group, a C1-C4 alkoxy group, a C1-C4 haloalkyl group, and a C1-C4 haloalkoxy group; Or, R c1 and R d1 form a 4- to 7-membered heterocycloalkyl group together with the N atom linked thereto (wherein the 4- to 7-membered heterocycloalkyl group is selected from the group consisting of D, OH, CN, -NH2, -NH(C1-C4 alkyl group), -N(C1-C4 alkyl group)2, halogen, C1-C4 alkyl group, C1-C4 alkoxy group, C1-C4 haloalkyl group, and C 1-4 optionally substituted with 1, 2, or 3 substituents independently selected from haloalkoxy groups; R E , R e and R e1 are each independently H, D, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C2-C4 alkenyl group, a (C1-C4 alkoxy)-C1-C4 alkyl group, a C2-C4 alkynyl group, a C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C6-C 10 Aryl-C1-C4 alkyl group, C3-C 10 selected from the group consisting of cycloalkyl-C1-C4 alkyl groups, 5- to 10-membered heteroaryl-C1-C4 alkyl groups, and 4- to 10-membered heterocycloalkyl-C1-C4 alkyl groups; R F , R f and R f1 are each independently H, D, a C1-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 selected from the group consisting of cycloalkyl groups and 4- to 10-membered heterocycloalkyl groups, R G , R H and R I are each independently selected from the group consisting of a C1-C4 alkyl group and a phenyl group.

[0019] In some embodiments, there is provided a compound represented by formula (I), which is represented by formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), or (Iq): or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof. [ka] (In the formula, R 1 , R 2 , R 3 , X, X 1 , X 2 , X 3 , X 4 , Y, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , Y 7, Cy 1 , and Cy 2 The definitions of are the same as in formula (I).

[0020] In some embodiments, there is provided a compound represented by the formula (I), which is represented by the following formula (Ia), (Id), (Ie), (If), (Ig), or (Ih), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof. [ka] (In the formula, R 1 , R 2 , R 3 , X, X 3 , X 4 , Y, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , Cy 1 , and Cy 2 The definitions of are the same as in formula (I).

[0021] In some embodiments, there is provided a compound represented by the formula (I), which is represented by the following formula (Ib), (Ii), (Ij), (Ik), (Il), or (Im), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof. [ka] (In the formula, R 1 , R 2 , R 3 , X, X 3 , X 4 , Y, Y 1 , Y 2 , Y 5 , Y 6 , Y 7 , Cy 1 , and Cy 2The definitions of are the same as in formula (I).

[0022] In some embodiments, there is provided a compound represented by the formula (I), which is represented by the following formula (Ic), (In), (Io), (Ip), or (Iq), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof: [ka] (In the formula, R 1 , R 2 , R 3 , X, X 3 , X 4 , Y, Y 1 , Y 2 , Y 3 , Y 5 , Y 6 , Cy 1 , and Cy 2 The definitions of are the same as in formula (I).

[0023] In some embodiments, Y 3 is N, Y 4 is CR 4 , Y 5 is CR 4 is.

[0024] In some embodiments, Y 3 is N, Y 4 is N, Y 5 is CR 4 is.

[0025] In some embodiments, Y 3 is N, Y 4 is N, Y 5 is N.

[0026] In some embodiments, Y 3 is N, Y 4 is CR 4 , Y 5 is N.

[0027] In some embodiments, Y 3 is CR 4 , Y 4 is CR 4 , Y 5 is CR 4 is.

[0028] In some embodiments, Y 3 is CR 4 , Y 4 is N, Y 5 is CR 4 is.

[0029] In some embodiments, Y 3 is CR 4 , Y 4 is N, Y 5 is N.

[0030] In some embodiments, Y 3 is CR 4 , Y 4 is CR 4 , Y 5 is N.

[0031] In some embodiments, Y 5 is N, Y 7 is S.

[0032] In some embodiments, Y 5 is N, Y 7 is O.

[0033] In some embodiments, Y 5 is N, Y 7 is NR 16 is.

[0034] In some embodiments, Y 5 is CR 4 , Y 7 is S.

[0035] In some embodiments, Y 5 is CR 4 , Y 7is O.

[0036] In some embodiments, Y 5 is CR 4 , Y 7 is NR 16 is.

[0037] In some embodiments, Y 3 is N, Y 5 is N.

[0038] In some embodiments, Y 3 is N, Y 5 is CR 4 is.

[0039] In some embodiments, Y 3 is CR 8 , Y 5 is N.

[0040] In some embodiments, Y 3 is CR 8 , Y 5 is CR 4 is.

[0041] In some embodiments, Y 1 is N, Y 6 is S.

[0042] In some embodiments, Y 1 is N, Y 6 is O.

[0043] In some embodiments, Y 1 is N, Y 6 is NR 14 is.

[0044] In some embodiments, Y 1 is CR 6 , Y 6 is S.

[0045] In some embodiments, Y 1 is CR6 , Y 6 is O.

[0046] In some embodiments, Y 1 is CR 6 , Y 6 is NR 14 is.

[0047] In some embodiments, Y 1 is N, Y 2 is N.

[0048] In some embodiments, Y 1 is N, Y 2 is CR 7 is.

[0049] In some embodiments, Y 1 is CR 6 , Y 2 is N.

[0050] In some embodiments, Y 1 is CR 6 , Y 2 is CR 7 is.

[0051] In some embodiments, Y is N, Y 1 is CR 6 , Y 2 is CR 7 is.

[0052] In some embodiments, Y is N, Y 1 is CR 6 , Y 2 is N.

[0053] In some embodiments, Y is N, Y 1 is N, Y 2 is CR 7 is.

[0054] In some embodiments, Y is N, Y 1 is N, Y 2 is N.

[0055] In some embodiments, Y is CR 15 , Y 1 is CR 6 , Y 2 is CR 7 is.

[0056] In some embodiments, Y is CR 15 , Y 1 is CR 6 , Y 2 is N.

[0057] In some embodiments, Y is CR 15 , Y 1 is N, Y 2 is CR 7 is.

[0058] In some embodiments, Y is CR 15 , Y 1 is N, Y 2 is N.

[0059] In some embodiments, Y is N, Y 1 is N or CR 6 , Y 2 is N or CR 7 and Y 1 or Y 2 At most one of them is N.

[0060] In some embodiments, there is provided a compound represented by the formula (I), which is a compound represented by the following formula (II): [ka] [In the formula, X is O or NR 5 and Y 1 is N or CR 6 and Y 2 is N or CR 7 and Y 1 and Y 2 at most one of is N, Y 3 is N or CR 8 and n is 0, 1, or 2; Cy 1 is R 9 is a 5- to 10-membered heteroaryl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Cy 2 is C6~C 10 Aryl groups, C3-C 10 a cycloalkyl group, a 5- to 10-membered heteroaryl group, and a 4- to 14-membered heterocycloalkyl group (wherein the C6 to C 10 Aryl groups, C3-C 10 The cycloalkyl group, 5- to 10-membered heteroaryl group, or 4- to 14-membered heterocycloalkyl group is independently R 10 optionally substituted with 1, 2, 3, 4 or 5 substituents selected from R 1 , R 2 and R 3 are each independently selected from the group consisting of H, D, CN, a C1-C3 alkyl group, a C2-C3 alkenyl group, a C2-C3 alkynyl group, a C3-C7 cycloalkyl group, and a 4- to 7-membered heterocycloalkyl group (wherein the C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C3-C7 cycloalkyl group, or 4- to 7-membered heterocycloalkyl group is optionally substituted with 1 to 5 substituents independently selected from D, halogen, CN, OH, a C1-C6 alkyl group, a C1-C6 haloalkyl group, —O—C1-C6 alkyl group, and —O—C1-C6 haloalkyl group); Or, R 2 and R 3together with the carbon atoms linked thereto form a C3-C7 cycloalkyl group or a 4- to 7-membered heterocycloalkyl group, wherein the C3-C7 cycloalkyl group or the 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, a C1-C6 alkyl group, a C1-C6 haloalkyl group, —O—C1-C6 alkyl group, and —O—C1-C6 haloalkyl group, R 4 is H, D, halogen, OH, CN, NO2, SF5, C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, -O-C1-C3 alkyl group, and NR C R D wherein said C1-C3 alkyl group, C2-C3 alkenyl group, and C2-C3 alkynyl group are optionally substituted with halogen or CN; R 5 H, D, CN, OR B and a C1 to C4 alkyl group, wherein the C1 to C4 alkyl group is selected from the group consisting of R 5A and optionally substituted with at least one of: 5A are each independently selected from the group consisting of D, F, Cl, CN, NH2, OH, -O-C1 to C6 alkyl group, -O-C1 to C6 haloalkyl group, optionally substituted C3 to C7 cycloalkyl group, and optionally substituted 4 to 7 membered heterocycloalkyl group, and further wherein said optionally substituted means substituted with any substituent selected from the group consisting of D, halogen, CN, OH, C1 to C4 alkyl group, C1 to C4 haloalkyl group, -O-C1 to C4 alkyl group, and -O-C1 to C4 haloalkyl group), Or, R 1 and R 5together with the atoms connected thereto form a 5- to 7-membered partially saturated heterocycloalkyl group, wherein said 5- to 7-membered partially saturated heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, CF, NO, oxo, OH, C-C alkyl group, C-C haloalkyl group, -O-C-C alkyl group, and -O-C-C haloalkyl group; R 6 and R 7 are each independently H, D, halogen, CN, NO2, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, OR A , S.R. A , SF5, NHOR A , C(O)OR A , C(O)R B , C(O)NR C R D , OC(O)NR C R D , N.R. C R D , N.R. C C(O)R B , N.R. C C(O)NR C R D , N.R. C C(O)OR A , N.R. C S(O)2R B , B(OR C )(OR D ), C(=NR C )NR C R D , N.R. D C(=NR C )NR C R D , N.R. 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)RB , S(O)NR C R D , S(O)2R B , S(O)NR C R D , N.R. C S(O)NR C R D , and N.R. C S(O)(=NR B )R B wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, or the C2-C6 alkynyl group is independently selected from the group consisting of R 11 optionally substituted with 1, 2 or 3 substituents selected from R 8 is selected from the group consisting of H, D, CN, halogen, OH, NH2, a C1-C3 alkyl group, a C1-C3 haloalkyl group, -O-C1-C3 alkyl group, -O-C1-C3 haloalkyl group, a C1-C3 cyanoalkyl group, and SF5; Each R 9 are independently selected from the group consisting of H, D, halogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C1-C6 haloalkyl group, an OC1-C6 alkyl group, an OC1-C6 haloalkyl group, an OC3-C7 cycloalkyl group, a C3-C7 cycloalkyl group, CN, NO2, N3, and SF5 (wherein said C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, or C3-C7 cycloalkyl group is independently selected from the group consisting of R 11 optionally substituted with 1, 2 or 3 substituents selected from Each R 10 are independently H, D, halogen, CN, NO2, N3, oxo group, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, OR A , S.R. A , SF5, 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 , N.R. C R D , N.R. C C(O)R D , N.R. C C(O)NR C R D , N.R. C C(O)OR A , B(OR C )(OR D ), C(=NR C )NR C R D , N.R. D C(=NR C )NR C R D , N.R. 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 , N.R. C S(O)2R B , S(O)NR C R D , N.R. C S(O)NR C R D , N.R. C S(O)(=NR B )R B , Cy 3 , C1-C6 alkyl-Cy 3 , O.C.y. 3 , and O-C1-C6 alkyl-Cy 3 wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, and the C2-C6 alkynyl group are independently selected from the group consisting of R11 optionally substituted with 1, 2, 3, 4 or 5 substituents selected from Or, two R's 10 are oxo groups together with the atoms connected to them, C3-C 10 A cycloalkyl group or a 4- to 10-membered heterocycloalkyl group is formed (wherein the C3 to C 10 The cycloalkyl group or the 4-10 membered heterocycloalkyl group is independently selected from D, halogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C1-C6 haloalkyl group, a C1-C6 cyanoalkyl group, CN, NO2, an oxo group, OR a , S.R. 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 , N.R. c R d , N.R. c C(O)R b , N.R. c C(O)NR c R d , N.R. c C(O)OR a , B(OR c )(OR d ), C(=NR c )NR c R d , N.R. d C(=NR c )NR c R d , N.R. 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)2R b, N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , N.R. c S(O)(=NR b )R b , Cy 4 and wherein Cy is optionally substituted with 1, 2, or 3 substituents selected from 4 is C6~C 10 Aryl groups, C3-C 10 cycloalkyl groups, 5- to 10-membered heteroaryl groups, and 4- to 10-membered heterocycloalkyl groups, and further wherein said C6 to C 10 Aryl groups, C3-C 10 The cycloalkyl group, the 5- to 10-membered heteroaryl group, and the 4- to 10-membered heterocycloalkyl group are optionally substituted by 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, NO, OH, oxo, NH, NHC-C alkyl group, N(C-C alkyl group), C-C alkyl group, C-C haloalkyl group, OC-C alkyl group, OC-C haloalkyl group, OC-C alkyl-OH, OC-C alkyl-O—C-C alkyl group, and SF; Cy 3 are independent, C6~C 10 Aryl groups, C3-C 10 a cycloalkyl group, a 5- to 10-membered heteroaryl group, and a 4- to 10-membered heterocycloalkyl group (wherein the C6 to C 10 Aryl groups, C3-C 10 The cycloalkyl group, the 5- to 10-membered heteroaryl group, and the 4- to 10-membered heterocycloalkyl group are independently unsubstituted or R 12 optionally substituted with 1, 2, 3, 4 or 5 substituents selected from Each R 11are 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 alkyl-OH, OC1-C6 alkyl-O-C1-C6 alkyl group, OR a1 , S.R. 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 , N.R. c1 R d1 , N.R. c1 C(O)R b1 , N.R. c1 C(O)NR c1 R d1 , N.R. c1 C(O)OR a1 , B(OR c1 )(OR d1 ), C(=NR c1 )NR c1 R d1 , N.R. d1 C(=NR c1 )NR c1 R d1 , N.R. 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)2R b1 , N.R. c1 S(O)2R b1 , S(O)NR c1 R d1 , N.R. c1 S(O)NR c1 R d1 , N.R. c1 S(O)(=NR b1 )Rb1 , C6~C 10 Aryl groups, C3-C 10 a cycloalkyl group, a 5- to 10-membered heteroaryl group, and a 4- to 10-membered heterocycloalkyl group (wherein the C6 to C 10 Aryl groups, C3-C 10 the cycloalkyl group, the 5- to 10-membered heteroaryl group, and the 4- to 10-membered heterocycloalkyl group are independently unsubstituted or optionally substituted with 1, 2, 3, 4, or 5 substituents selected from D, halogen, CN, NO, NH, NHC alkyl group, N(C alkyl group), C alkyl group, C haloalkyl group, OC alkyl group, OC haloalkyl group, OC alkyl-OH, OC alkyl-O—C alkyl group, and SF; Each R 12 are independently D, halogen, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl group, C1-C6 alkyl-OH, C1-C6 alkyl-O-C1-C6 alkyl group, CN, NO2, N3, OR a1 , S.R. 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 , N.R. c1 R d1 , N.R. c1 C(O)R b1 , N.R. c1 C(O)NR c1 R d1 , N.R. c1 C(O)OR a1 , B(OR c1 )(OR d1 ), C(=NR c1 )NR c1 R d1 , N.R. d1 C(=NR c1 )NR c1 R d1, N.R. 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)2R b1 , N.R. c1 S(O)2R b1 , S(O)NR c1 R d1 , N.R. c1 S(O)NR c1 R d1 , N.R. c1 S(O)(=NR b1 )R b1 , C6~C 10 Aryl groups, C3-C 10 a cycloalkyl group, a 5- to 10-membered heteroaryl group, and a 4- to 10-membered heterocycloalkyl group (wherein the C6 to C 10 Aryl groups, C3-C 10 the cycloalkyl group, the 5- to 10-membered heteroaryl group, and the 4- to 10-membered heterocycloalkyl group are independently unsubstituted or optionally substituted with 1, 2, 3, 4, or 5 substituents selected from D, halogen, CN, NO, NH, NHC alkyl group, N(C alkyl group), C alkyl group, C haloalkyl group, OC alkyl group, OC haloalkyl group, OC alkyl-OH, OC alkyl-O—C alkyl group, and SF; R A are independently H, D, a C1-C6 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10is selected from the group consisting of an aryl group, a 5- to 10-membered heteroaryl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, and a heterocycloalkylalkyl group (wherein the C1-C6 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10 The aryl group, 5- to 10-membered heteroaryl group, arylalkyl group, heteroarylalkyl group, cycloalkylalkyl group, or heterocycloalkylalkyl group may independently be D, OH, CN, halogen, C1-C4 alkyl group, NO2, oxo group, OR a , S.R. 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 , N.R. c R d , N.R. c C(O)R b , N.R. c C(O)NR c R d , N.R. c C(O)OR a , B(OR c )(OR d ), C(=NR c )NR c R d , N.R. d C(=NR c )NR c R d , N.R. 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)2Rb , N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , and N.R. c S(O)(=NR b )R b optionally substituted with 1, 2, 3, 4 or 5 substituents selected from R B are independently H, D, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10 is selected from the group consisting of an aryl group, a 5- to 10-membered heteroaryl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, and a heterocycloalkylalkyl group (wherein the C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10 The aryl group, 5- to 10-membered heteroaryl group, arylalkyl group, heteroarylalkyl group, cycloalkylalkyl group, or heterocycloalkylalkyl group is independently R 13 optionally substituted with 1, 2, 3, 4 or 5 substituents selected from Each R 13 are independently H, D, OH, CN, halogen, oxo group, C1-C4 alkyl group, C1-C4 haloalkyl group, C1-C4 cyanoalkyl group, OC1-C4 alkyl group, OC1-C4 haloalkyl group, OC1-C4 alkyl-OH, OC1-C4 alkyl-O-C1-C4 alkyl group, OC1-C4 alkyl-O-C1-C4 haloalkyl group, C1-C4 alkyl-O-C1-C4 alkyl group, C1-C4 alkyl-O-C1-C4 haloalkyl group, optionally substituted C3-C7 cycloalkyl group, optionally substituted 4-7 membered heterocycloalkyl group, SF5, OR a , S.R. a , C(O)Rb , OC(O)NR c R d , N.R. c R d , N.R. c C(O)R b , N.R. c C(O)NR c R d , N.R. c C(O)OR a , S(O)R b , S(O)NR c R d , S(O)2R b , N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , and B(OR c )(OR d ) (wherein the optionally substituted means substituted with a substituent selected from the group consisting of D, halogen, CN, OH, C1-C4 alkyl group, C1-C4 haloalkyl group, —O—C1-C4 alkyl group, and —O—C1-C4 haloalkyl group), R C and R Dare each independently selected from the group consisting of H, D, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C7 cycloalkyl group, a 4- to 7-membered heterocycloalkyl group, a phenyl group, a 5- to 6-membered heteroaryl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, and a heterocycloalkylalkyl group (wherein the C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C7 cycloalkyl group, a 4- to 7-membered heterocycloalkyl group, a phenyl group, a 5- to 6-membered heteroaryl group, an arylarylalkyl group, a cycloalkylalkyl group, and a heterocycloalkylalkyl group). The alkyl group, heteroarylalkyl group, cycloalkylalkyl group, or heterocycloalkylalkyl group is independently D, OH, CN, halogen, oxo group, C1-C4 alkyl group, C1-C4 haloalkyl group, C1-C4 cyanoalkyl group, OC1-C4 alkyl group, OC1-C4 haloalkyl group, OC2-C4 alkyl-OH, OC2-C4 alkyl-O-C1-C4 alkyl group, OC2-C4 alkyl-O-C1-C4 haloalkyl group, C1-C4 alkyl-O-C1-C4 alkyl group, C1-C4 alkyl-O-C1-C4 haloalkyl group, SF5, OC(O)NR c R d , N.R. c R d , N.R. c C(O)R b , S(O)NR c R d , S(O)2R b , N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , and B(OR c )(OR d ), optionally substituted with 1, 2, 3, 4 or 5 substituents selected from Or, R C and R Dform a 4- to 7-membered heterocycloalkyl group together with the N atom linked thereto, wherein the 4- to 7-membered heterocycloalkyl group is optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from D, OH, oxo, CN, —NH, —NH(C1-C4 alkyl group), —N(C1-C4 alkyl group), halogen, or a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C1-C4 cyanoalkyl group, an O-C1-C4 alkyl group, or an O-C1-C4 haloalkyl group, an O-C2-C4 alkyl-OH, an O-C2-C4 alkyl-O—C1-C4 alkyl group, or an O-C2-C4 alkyl-O—C1-C4 haloalkyl group; R a and R a1 are each independently selected from the group consisting of H, D, 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- to 6-membered heteroaryl group, and a 4- to 7-membered heterocycloalkyl group (wherein the C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, phenyl group, C3-C7 cycloalkyl group, 5- to 6-membered heteroaryl group, or 4- to 7-membered heterocycloalkyl group is optionally substituted by 1, 2, or 3 substituents independently selected from D, OH, CN, —NH2, —NH(C1-C4 alkyl group), —N(C1-C4 alkyl group)2, halogen, a C1-C4 alkyl group, a C1-C4 alkoxy group, a C1-C4 haloalkyl group, and a C1-C4 haloalkoxy group); R b and R b1are each independently selected from the group consisting of H, D, 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- to 6-membered heteroaryl group, a 4- to 7-membered heterocycloalkyl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, and a heterocycloalkylalkyl group; wherein the C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, phenyl group, C3-C7 cycloalkyl group, a 5- to 6-membered heteroaryl group, a 4- to 7-membered heterocycloalkyl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, or a heterocycloalkylalkyl group is independently selected from the group consisting of D, OH, CN, -NH2, -NH(C1-C4 alkyl group), -N(C1-C4 alkyl group)2, halogen, a C1-C4 alkyl group, a C1-C4 alkoxy group, a C1-C4 haloalkyl group, a C1-C4 haloalkoxy group, a C6-C 10 Aryl groups, C3-C 10 optionally substituted with 1, 2, or 3 substituents selected from a cycloalkyl group, a 5- to 10-membered heteroaryl group, and a 4- to 10-membered heterocycloalkyl group; R c and R d are each independently H, D, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 a cycloalkyl group, a 4- to 10-membered heterocycloalkyl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, a heterocycloalkylalkyl group, an arylcycloalkyl group, an arylheterocycloalkyl group, an arylheteroaryl group, a diaryl group, a heteroarylcycloalkyl group, a heteroarylheterocycloalkyl group, a heteroarylaryl group, and a diheteroaryl group (wherein the C 1~4 Alkyl group, C 2~4 Alkenyl group, C 2~4 Alkynyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C10 The cycloalkyl group, 4-10 membered heterocycloalkyl group, arylalkyl group, heteroarylalkyl group, cycloalkylalkyl group, heterocycloalkylalkyl group, arylcycloalkyl group, arylheterocycloalkyl group, arylheteroaryl group, diaryl group, heteroarylcycloalkyl group, heteroarylheterocycloalkyl group, heteroarylaryl group, or diheteroaryl group is independently D, OH, CN, -NH2, -NH(C1-C4 alkyl group), -N(C1-C4 alkyl group)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 groups, 5- to 10-membered heteroaryl groups, C(O)OR a1 , C(O)R b1 , S(O)2R b1 , C1-C4 alkyl-O—C1-C4 alkyl group, and C1-C4 alkyl-O—C1-C4 alkyl-O—; Or, R c and R d form a 4- to 7-membered heterocycloalkyl group together with the N atom linked thereto (wherein the 4- to 7-membered heterocycloalkyl group is independently selected from D, OH, CN, -NH2, -NH(C1-C4 alkyl group), -N(C1-C4 alkyl group)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 groups, 5- to 10-membered heteroaryl groups, C(O)OR a1 , C(O)R b1 , S(O)2R b1 , a C1-C4 alkoxy-C1-C4 alkyl group, and a C1-C4 alkoxy-C1-C4 alkoxy group), R c1 and R d1are each independently H, D, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 a cycloalkyl group, a 4- to 10-membered heterocycloalkyl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, and a heterocycloalkylalkyl group (wherein the C1-C4 alkyl group, C1-C4 haloalkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 the cycloalkyl group, 4-10 membered heterocycloalkyl group, arylalkyl group, heteroarylalkyl group, cycloalkylalkyl group, or heterocycloalkyl group is optionally substituted with 1, 2, or 3 substituents independently selected from D, OH, CN, —NH, —NH(C1-C4 alkyl group), —N(C1-C4 alkyl group), halogen, a C1-C4 alkyl group, a C1-C4 alkoxy group, a C1-C4 haloalkyl group, and a C1-C4 haloalkoxy group; Or, R c1 and R d1 together with the N atom linked thereto form a 4- to 7-membered heterocycloalkyl group, wherein the 4- to 7-membered heterocycloalkyl group is independently selected from D, OH, CN, -NH, -NH(C1-C4 alkyl group), -N(C1-C4 alkyl group), halogen, C1-C4 alkyl group, C1-C4 alkoxy group, C1-C4 haloalkyl group, and C 1-4 optionally substituted with 1, 2 or 3 substituents selected from haloalkoxy groups, R E , R e and R e1 are each independently H, D, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C2-C4 alkenyl group, a (C1-C4 alkoxy)-C1-C4 alkyl group, a C2-C4 alkynyl group, a C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C6-C 10 Aryl-C1-C4 alkyl group, C3-C 10 selected from the group consisting of cycloalkyl-C1-C4 alkyl groups, 5- to 10-membered heteroaryl-C1-C4 alkyl groups, and 4- to 10-membered heterocycloalkyl-C1-C4 alkyl groups; R F , R f and R f1 are each independently H, D, a C1-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 selected from the group consisting of cycloalkyl groups and 4- to 10-membered heterocycloalkyl groups, R G , R H and R I are each independently selected from the group consisting of a C1 to C4 alkyl group and a phenyl group.

[0061] In some embodiments, X is O or NR 5 In some embodiments, X is O. In other embodiments, X is NR 5 is.

[0062] In the compound represented by (I), R 5 H, D, CN, OR B and a C1-C4 alkyl group, wherein the C1-C4 alkyl group is selected from the group consisting of R 5A and optionally substituted with at least one of: 5Aare each independently selected from the group consisting of D, F, Cl, CN, NH2, OH, -O-C1-C6 alkyl group, -O-C1-C6 haloalkyl group, optionally substituted C3-C7 cycloalkyl group, and optionally substituted 4-7 membered heterocycloalkyl group, and further wherein said optionally substituted means substituted with any substituent selected from the group consisting of D, halogen, CN, OH, C1-C4 alkyl group, C1-C4 haloalkyl group, -O-C1-C4 alkyl group, and -O-C1-C4 haloalkyl group).

[0063] In some embodiments, R 5 is H. In some embodiments, R 5 is D. In some embodiments, R 5 is CN. In some embodiments, R 5 is OR B is.

[0064] In some embodiments, R 5 is selected from the group consisting of C1 to C4 alkyl groups (wherein the C1 to C4 alkyl groups are R 5A and optionally substituted with at least one of: 5A are each independently selected from the group consisting of D, F, Cl, CN, NH2, OH, -O-C1-C6 alkyl group, -O-C1-C6 haloalkyl group, optionally substituted C3-C7 cycloalkyl group, and optionally substituted 4-7 membered heterocycloalkyl group, and further wherein said optionally substituted means substituted with any substituent selected from the group consisting of D, halogen, CN, OH, C1-C4 alkyl group, C1-C4 haloalkyl group, -O-C1-C4 alkyl group, and -O-C1-C4 haloalkyl group).

[0065] In some embodiments, Y is N or CR 15 is.

[0066] In some embodiments, Y 1 is N or CR6 In some embodiments, Y 1 is N. In some other embodiments, Y 1 is CR 6 is.

[0067] In some embodiments, Y 2 is N or CR 7 In some embodiments, Y 2 is N. In some other embodiments, Y 2 is CR 7 is.

[0068] In some embodiments, Y 1 and Y 2 At most one of Y is N. In some embodiments, 1 is N, Y 2 is CR 7 In some other embodiments, Y 1 is CR 6 , Y 2 is N. In some other embodiments, Y 1 is CR 6 , Y 2 is CR 7 is.

[0069] In the compound represented by (I), R 6 and R 7 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 , S.R. A , SF5, NHOR A , C(O)OR A , C(O)R B , C(O)NR C R D , OC(O)NR C R D , N.R. C R D , N.R. C C(O)R B , N.R. C C(O)NR CR D , N.R. C C(O)OR A , N.R. C S(O)2R B , B(OR C )(OR D ), C(=NR C )NR C R D , N.R. D C(=NR C )NR C R D , N.R. 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)2R B , S(O)NR C R D , N.R. C S(O)NR C R D , and N.R. C S(O)(=NR B )R B wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, or the C2-C6 alkynyl group is independently selected from the group consisting of R 11 Optionally substituted with 1, 2 or 3 substituents selected from:

[0070] In some embodiments, R 6 are each independently H, D, halogen, CN, NO2, OR A , S.R. A , SF5, a C1-C6 alkyl group, and a C1-C6 haloalkyl group. 6 is H. In some embodiments, R 6 is D. In some embodiments, R6 is halogen. In some embodiments, R 6 is F. In some embodiments, R 6 is Cl. In some embodiments, R 6 is Br. In some embodiments, R 6 is I. In some embodiments, R 6 is CN. In some embodiments, R 6 is NO. In some embodiments, R 6 is SF5. In some embodiments, R 6 is OR A and examples include, but are not limited to, -OH, -OMe, and -OCF. In some embodiments, R 6 is SR A and examples include, but are not limited to, -SMe.

[0071] In some embodiments, R 6 is R 11 and C1-C6 alkyl groups (e.g., C1-C5 alkyl groups, C1-C4 alkyl groups, C1-C3 alkyl groups, C1-C2 alkyl groups) optionally substituted with 1, 2, or 3 substituents independently selected from, for example, but not limited to, -CH3 and -CH2CH3. In some embodiments, R 6 is a C1 to C6 haloalkyl group, for example, -CF3, -CHF2, -CH2F.

[0072] In some embodiments, R 6 is R 11 In some embodiments, R is a C2-C6 alkenyl group optionally substituted with 1, 2, or 3 substituents independently selected from 6 is R 11 is a C2-C6 alkynyl group optionally substituted with 1, 2, or 3 substituents independently selected from:

[0073] In some embodiments, R 6is B(OR C )(OR D ), for example, B(OH). In some embodiments, R 6 NHOR A In some embodiments, R 6 is NR C R D Examples include -NH2, -NCH3, and -N(CH3)2.

[0074] In some embodiments, R 7 are each independently H, D, halogen, or OR A , CN, NO2, and SF5. In some embodiments, R 7 are each independently selected from the group consisting of H, D, F, Cl, OH, CN, NO, and SF. 7 is H. In some embodiments, R 7 is D. In some embodiments, R 7 is halogen. In some embodiments, R 7 is F. In some embodiments, R 7 is Cl. In some embodiments, R 7 is Br. In some embodiments, R 7 is I. In some embodiments, R 7 is OR A In some embodiments, R 7 is CN. In some embodiments, R 7 is NO. In some embodiments, R 7 is SF5.

[0075] In some embodiments, R 7 is SR A In some embodiments, R 7 is B(OR C )(OR D), for example B(OH). In some embodiments, R 7 NHOR A In some embodiments, R 7 is NR C R D is.

[0076] In some embodiments, R 7 is R 11 and R is a C1-C6 alkyl group (e.g., a C1-C5 alkyl group, a C1-C4 alkyl group, a C1-C3 alkyl group, a C1-C2 alkyl group) optionally substituted with 1, 2, or 3 substituents independently selected from, for example, but not limited to, —CH3. In some embodiments, R 7 is a C1-C6 haloalkyl group, such as, but not limited to, -CF3.

[0077] In some embodiments, R 7 is R 11 In some embodiments, R is a C2-C6 alkenyl group optionally substituted with 1, 2, or 3 substituents independently selected from 7 is R 11 is a C2-C6 alkynyl group optionally substituted with 1, 2, or 3 substituents independently selected from:

[0078] In some embodiments, each R 15 are independently H, D, halogen, CN, NO2, OR A , S.R. A , SF5, a C1-C6 alkyl group, and a C1-C6 haloalkyl group. 15 is H. In some embodiments, R 15 is D. In some embodiments, R 15 is halogen. In some embodiments, R 15 is F. In some embodiments, R 15 is Cl. In some embodiments, R 15is Br. In some embodiments, R 15 is I. In some embodiments, R 15 is CN. In some embodiments, R 15 is NO. In some embodiments, R 15 is SF5. In some embodiments, R 15 is OR A and examples include, but are not limited to, -OH, -OMe, and -OCF. In some embodiments, R 15 is SR A and examples include, but are not limited to, -SMe.

[0079] In some embodiments, R 15 is R 11 and C1-C6 alkyl groups (e.g., C1-C5 alkyl groups, C1-C4 alkyl groups, C1-C3 alkyl groups, C1-C2 alkyl groups) optionally substituted with 1, 2, or 3 substituents independently selected from, for example, but not limited to, -CH3 and -CH2CH3. In some embodiments, R 15 is a C1 to C6 haloalkyl group, for example, -CF3, -CHF2, -CH2F.

[0080] In some embodiments, R 15 is R 11 In some embodiments, R is a C2-C6 alkenyl group optionally substituted with 1, 2, or 3 substituents independently selected from 15 is R 11 is a C2-C6 alkynyl group optionally substituted with 1, 2, or 3 substituents independently selected from:

[0081] In some embodiments, R 15 is B(OR C )(OR D ), for example, B(OH). In some embodiments, R 15 NHOR AIn some embodiments, R 15 is NR C R D Examples include -NH2, -NCH3, and -N(CH3)2.

[0082] In some embodiments, Y 3 is N or CR 8 In some embodiments, Y 3 is N. In some other embodiments, Y 3 is CR 8 is.

[0083] In the compound represented by (I), R 8 are each selected from the group consisting of H, D, CN, halogen, OH, NH, C1-C3 alkyl groups (for example, but not limited to, CH3, CH2CH3, CH2CH2CH3, CH(CH3)2), C1-C3 haloalkyl groups (C1 haloalkyl groups, C2 haloalkyl groups, C3 haloalkyl groups, for example, but not limited to, CF3, CHF2, CH2F), -O-C1-C3 alkyl groups (for example, but not limited to, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2), -O-C1-C3 haloalkyl groups (for example, -O-C1-C3 haloalkyl groups, -O-C1-C2 haloalkyl groups), C1-C3 cyanoalkyl groups (for example, C1-C3 cyanoalkyl groups, C1-C2 cyanoalkyl groups), and SF5.

[0084] In some other embodiments, R 8 is selected from the group consisting of H, D, F, Cl, OH, NH2, CN, CH3, CF3, OMe, OCF3, and SF5.

[0085] In some embodiments, R 8 is H. In some embodiments, R 8 is D. In some embodiments, R 8 is F. In some embodiments, R 8is Cl. In some embodiments, R 8 is OH. In some embodiments, R 8 is CN.

[0086] In some embodiments, R 8 is a C1-C3 alkyl group, such as, but not limited to, CH3. In some embodiments, R 8 is a C1-C3 haloalkyl group, such as, but not limited to, CF3. In some embodiments, R 8 is an —O—C1-C3 alkyl group, such as, but not limited to, OMe. In some embodiments, R 8 is an -OC1-C3 haloalkyl group, such as, but not limited to, OCF3. In some embodiments, R 8 is SF5.

[0087] In the compound represented by (I) above, n is 0, 1, or 2. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2.

[0088] In some embodiments, R 1 , R 2 and R 3 are each independently selected from the group consisting of H, D, CN, a C1-C3 alkyl group, a C2-C3 alkenyl group, a C2-C3 alkynyl group, a C3-C7 cycloalkyl group, and a 4- to 7-membered heterocycloalkyl group (wherein the C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C3-C7 cycloalkyl group, and 4- to 7-membered heterocycloalkyl group are independently substituted with 1 to 5 (e.g., 1, 2, 3, 4, or 5) substituents selected from D, halogen, CN, OH, a C1-C6 alkyl group, a C1-C6 haloalkyl group, —O—C1-C6 alkyl group, and —O—C1-C6 haloalkyl group).

[0089] In some embodiments, R 1 is selected from the group consisting of H, D, CN, a C1-C3 alkyl group, a C2-C3 alkenyl group, a C2-C3 alkynyl group, a C3-C7 cycloalkyl group, and a 4- to 7-membered heterocycloalkyl group (wherein said C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C3-C7 cycloalkyl group, and 4- to 7-membered heterocycloalkyl group are independently optionally substituted with 1 to 5 (e.g., 1, 2, 3, 4, or 5) substituents selected from D, halogen, CN, OH, a C1-C6 alkyl group, a C1-C6 haloalkyl group, —O—C1-C6 alkyl group, and —O—C1-C6 haloalkyl group).

[0090] In some embodiments, R 1 are independently selected from the group consisting of H, D, CN, a C1-C3 alkyl group, a C2-C3 alkenyl group, a C2-C3 alkynyl group, a C3-C7 cycloalkyl group, and a 4- to 7-membered heterocycloalkyl group (wherein said C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C3-C7 cycloalkyl group, or 4- to 7-membered heterocycloalkyl group is optionally substituted with 1 to 5 (e.g., 1, 2, 3, 4, or 5) substituents independently selected from D, halogen (e.g., F, Cl, Br, or I), CN, OH, Me, CF3, OMe, OCF3, and OEt).

[0091] In some embodiments, R 1 is independently selected from the group consisting of H, D, CN, CH3, CD3, CH2CH3, CF3, CHF2, CH2F, CH2CH2F, CH2OH, CH2OCH3, and CH2CN, and the like.

[0092] In some embodiments, R 1 is independently selected from the group consisting of CN, CH, CHCH, CF, CHF, CHF, and CHCHF. 1 is CF3. In some embodiments, R 1is CHF2. In some embodiments, R 1 is CHF. In some embodiments, R 1 is CH3. In some embodiments, R 1 is CN.

[0093] In some embodiments, R 1 and R 5 together with the atoms connected thereto form a 5- to 7-membered partially saturated heterocycloalkyl group (e.g., a 5-membered partially saturated heterocycloalkyl group, a 6-membered partially saturated heterocycloalkyl group, a 7-membered partially saturated heterocycloalkyl group), wherein the 5- to 7-membered partially saturated heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, CF, NO, oxo, OH, a C-C alkyl group, a C-C haloalkyl group, —O—C-C alkyl group, and —O—C-C haloalkyl group.

[0094] In some embodiments, R 1 and R 5 together with the atoms connected thereto form a 5- to 7-membered partially saturated heterocycloalkyl group, wherein said 5- to 7-membered partially saturated heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, CF, NO, oxo, OH, Me, CF, OMe, OCF, OEt.

[0095] In some embodiments, R 2is selected from the group consisting of H, D, CN, a C1-C3 alkyl group, a C2-C3 alkenyl group, a C2-C3 alkynyl group, a C3-C7 cycloalkyl group, and a 4- to 7-membered heterocycloalkyl group (wherein said C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C3-C7 cycloalkyl group, and 4- to 7-membered heterocycloalkyl group are independently optionally substituted with 1 to 5 (e.g., 1, 2, 3, 4, or 5) substituents selected from D, halogen, CN, OH, a C1-C6 alkyl group, a C1-C6 haloalkyl group, —O—C1-C6 alkyl group, and —O—C1-C6 haloalkyl group).

[0096] In some embodiments, R 2 are independently selected from the group consisting of H, D, CN, a C1-C3 alkyl group, a C2-C3 alkenyl group, a C2-C3 alkynyl group, a C3-C7 cycloalkyl group, and a 4- to 7-membered heterocycloalkyl group (wherein said C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C3-C7 cycloalkyl group, or 4- to 7-membered heterocycloalkyl group is optionally substituted with 1 to 5 (e.g., 1, 2, 3, 4, or 5) substituents independently selected from D, halogen, CN, OH, Me, CF3, OMe, OCF3, and OEt).

[0097] In some embodiments, R 2 is selected from the group consisting of a C1-C3 alkyl group, a C2-C3 alkenyl group, a C2-C3 alkynyl group, a C3-C7 cycloalkyl group, and a 4- to 7-membered heterocycloalkyl group (wherein the C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C3-C7 cycloalkyl group, and 4- to 7-membered heterocycloalkyl group are independently optionally substituted with 1 to 5 (e.g., 1, 2, 3, 4, or 5) substituents selected from D, halogen, CN, OH, a C1-C6 alkyl group, a C1-C6 haloalkyl group, —O—C1-C6 alkyl group, and —O—C1-C6 haloalkyl group).

[0098] In some embodiments, R 3is selected from the group consisting of H, D, CN, a C1-C3 alkyl group, a C2-C3 alkenyl group, a C2-C3 alkynyl group, a C3-C7 cycloalkyl group, and a 4- to 7-membered heterocycloalkyl group (wherein said C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C3-C7 cycloalkyl group, and 4- to 7-membered heterocycloalkyl group are independently optionally substituted with 1 to 5 (e.g., 1, 2, 3, 4, or 5) substituents selected from D, halogen, CN, OH, a C1-C6 alkyl group, a C1-C6 haloalkyl group, —O—C1-C6 alkyl group, and —O—C1-C6 haloalkyl group).

[0099] In some embodiments, R 3 are independently selected from the group consisting of H, D, CN, a C1-C3 alkyl group, a C2-C3 alkenyl group, a C2-C3 alkynyl group, a C3-C7 cycloalkyl group, and a 4- to 7-membered heterocycloalkyl group (wherein said C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C3-C7 cycloalkyl group, or 4- to 7-membered heterocycloalkyl group is optionally substituted with 1 to 5 (e.g., 1, 2, 3, 4, or 5) substituents independently selected from D, halogen, CN, OH, Me, CF3, OMe, OCF3, and OEt).

[0100] In some embodiments, R 3 are independently selected from the group consisting of a C1-C3 alkyl group, a C2-C3 alkenyl group, a C2-C3 alkynyl group, a C3-C7 cycloalkyl group, and a 4- to 7-membered heterocycloalkyl group (wherein said C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C3-C7 cycloalkyl group, and 4- to 7-membered heterocycloalkyl group are optionally substituted with 1 to 5 substituents independently selected from D, halogen, CN, OH, a C1-C6 alkyl group, a C1-C6 haloalkyl group, —O—C1-C6 alkyl group, and —O—C1-C6 haloalkyl group).

[0101] In some embodiments, R 2 and R3 together with the carbon atoms linked thereto form a C3-C7 cycloalkyl group or a 4- to 7-membered heterocycloalkyl group (wherein the C3-C7 cycloalkyl group or the 4- to 7-membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, NO2, oxo group, OH, a C1-C6 alkyl group, a C1-C6 haloalkyl group, —O—C1-C6 alkyl group, and —O—C1-C6 haloalkyl group).

[0102] In some embodiments, R 2 and R 3 together with the carbon atoms connected thereto form a 4- to 7-membered heterocycloalkyl group (e.g., a 4-membered heterocycloalkyl group, a 5-membered heterocycloalkyl group, a 6-membered heterocycloalkyl group, a 7-membered heterocycloalkyl group), wherein the 4- to 7-membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, NO, oxo, OH, a C1-C6 alkyl group, a C1-C6 haloalkyl group, —O—C1-C6 alkyl group, and —O—C1-C6 haloalkyl group.

[0103] In some embodiments, R 2 and R 3 together with the carbon atoms connected thereto form a C3-C7 cycloalkyl group (e.g., a C3 cycloalkyl group, a C4 cycloalkyl group, a C5 cycloalkyl group, a C6 cycloalkyl group, a C7 cycloalkyl group), wherein the C3-C7 cycloalkyl group is optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, NO2, oxo group, OH, a C1-C6 alkyl group, a C1-C6 haloalkyl group, —O—C1-C6 alkyl group, and —O—C1-C6 haloalkyl group).

[0104] In some embodiments, R 2 and R 3together with the carbon atom attached thereto form a cyclobutyl group, wherein said cyclobutyl group is optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, NO, oxo, OH, C1-C6 alkyl, C1-C6 haloalkyl, —O—C1-C6 alkyl, and —O—C1-C6 haloalkyl. In some embodiments, R 2 and R 3 together with the carbon atom attached thereto form a cyclopropyl group, wherein said cyclopropyl group is optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, NO, oxo, OH, a C1-C6 alkyl group, a C1-C6 haloalkyl group, —O—C1-C6 alkyl group, and —O—C1-C6 haloalkyl group.

[0105] In some embodiments, R 2 and R 3 together with the carbon atom to which they are attached form a cyclobutyl group. 2 and R 3 together with the carbon atom to which they are attached form a cyclopropyl group.

[0106] In the compound represented by (I), each R 4 are independently H, D, halogen, OH, CN, NO2, SF5, C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, -OC1-C3 alkyl group, and NR C R D wherein said C1-C3 alkyl group, C2-C3 alkenyl group, and C2-C3 alkynyl group are optionally substituted with halogen or CN.

[0107] In some embodiments, each R 4 are independently selected from the group consisting of H, D, OH, CN, NO, SF, halogen, and a C-C alkyl group, wherein said C-C alkyl group is optionally substituted with halogen or CN.

[0108] In some embodiments, each R 4 is independently selected from the group consisting of H, D, halogen (eg, F, Cl, Br, or I), and a C1-C3 alkyl group.

[0109] In some embodiments, each R 4 is independently selected from the group consisting of H, D, F, Cl, and CH3.

[0110] In some embodiments, Cy 1 is a 5- to 10-membered heteroaryl group (e.g., a 5-membered heteroaryl group, a 6-membered heteroaryl group, a 7-membered heteroaryl group, an 8-membered heteroaryl group, a 9-membered heteroaryl group, or a 10-membered heteroaryl group) (wherein the 5- to 10-membered heteroaryl group is R 9 and optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0111] In some embodiments, Cy 1 is a 6-membered heteroaryl group, wherein the 6-membered heteroaryl group is R 9 and optionally substituted with 1, 2, 3, or 4 substituents independently selected from:

[0112] In some embodiments, Cy 1 is a 5-membered heteroaryl group, wherein the 5-membered heteroaryl group is R 9 and optionally substituted with 1, 2, or 3 substituents independently selected from:

[0113] [ka]

[0114] [ka]

[0115] [ka]

[0116] In some embodiments, in Formula (I), each R 9 are independently selected from the group consisting of H, D, halogen, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl group, OC1-C6 alkyl group, C1-C6 haloalkyl group, OC3-C7 cycloalkyl group, C3-C7 cycloalkyl group, CN, NO2, N3, and SF5 (wherein said C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, or C3-C7 cycloalkyl group is independently selected from the group consisting of R 11 Optionally substituted with 1, 2 or 3 substituents selected from:

[0117] In some embodiments, each R 9 is H. In some embodiments, each R 9 is D. In some embodiments, each R 9 In some embodiments, each R is a halogen. 9 is independently selected from the group consisting of F, Cl, Br, and I. In some embodiments, each R 9 is CN. In some embodiments, each R 9 is NO. In some embodiments, each R 9 is N3. In some embodiments, each R 9 is SF5.

[0118] In some other embodiments, each R 9 are independently selected from the group consisting of a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, and a C1-C6 haloalkyl group (wherein the C1-C6 alkyl group, C2-C6 alkenyl group, or C2-C6 alkynyl group is independently selected from the group consisting of R 11 Optionally substituted with 1, 2 or 3 substituents selected from:

[0119] In some other embodiments, each R 9 are independently selected from the group consisting of a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, and a C1-C6 haloalkyl group. 9 is a C1-C6 alkyl group. In some embodiments, each R 9 is a methyl group. In some embodiments, each R 9 is an ethyl group. In some embodiments, each R 9 is an isopropyl group. In some embodiments, each R 9 is a tert-butyl group.

[0120] In some other embodiments, each R 9 is a C2-C6 alkenyl group. 9 is a C2-C6 alkynyl group. 9 is a C1-C6 haloalkyl group. In some embodiments, each R 9 is CF. In some embodiments, each R 9 is CHF. In some embodiments, each R 9 is CHF. In some embodiments, each R 9 is CDF2.

[0121] In some other embodiments, each R 9 are independent, R 11 In some further embodiments, each R 9 is independently selected from a C3 to C7 cycloalkyl group. 9 is a cyclobutyl group. In some other embodiments, each R 9 is a cyclopropyl group.

[0122] In some other embodiments, each R 9are independently selected from the group consisting of an OC1-C6 alkyl group, an OC1-C6 haloalkyl group, and an OC3-C7 cycloalkyl group (wherein the C1-C6 alkyl group or the C3-C7 cycloalkyl group is R 11 In some embodiments, each R 9 are independently selected from optionally substituted O—C alkyl groups. In some embodiments, each R 9 are independently selected from optionally substituted O—C haloalkyl groups. In some embodiments, each R 9 is independently selected from optionally substituted O—C 3 -C 7 cycloalkyl groups.

[0123] In some embodiments, Cy 2 are independent, C6~C 10 Aryl groups, C3-C 10 is selected from the group consisting of a cycloalkyl group, a 5- to 10-membered heteroaryl group, and a 4- to 14-membered heterocycloalkyl group (wherein the C6 to C 10 Aryl groups, C3-C 10 The cycloalkyl group, 5- to 10-membered heteroaryl group, or 4- to 14-membered heterocycloalkyl group is independently R 10 and optionally substituted with 1, 2, 3, 4 or 5 substituents selected from:

[0124] In some embodiments, Cy 2 are independent, C6~C 10 Aryl groups, C3-C 10 is selected from the group consisting of a cycloalkyl group, a 5- to 10-membered heteroaryl group, and a 4- to 10-membered heterocycloalkyl group (wherein the C6 to C 10 Aryl groups, C3-C 10 The cycloalkyl group, 5- to 10-membered heteroaryl group, or 4- to 10-membered heterocycloalkyl group is independently R 10 and optionally substituted with 1, 2, 3, 4 or 5 substituents selected from:

[0125] In some embodiments, Cy 2 is R 10 C6-C optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 10 In some embodiments, Cy is an aryl group. 2 is R 10 is a phenyl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0126] In some embodiments, Cy 2 is R 10 In some embodiments, the heteroaryl group is a 5- to 10-membered heteroaryl group (e.g., a 5-membered heteroaryl group, a 6-membered heteroaryl group, a 7-membered heteroaryl group, an 8-membered heteroaryl group, a 9-membered heteroaryl group, or a 10-membered heteroaryl group) optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from: 2 teeth [ka] but is not limited to (where [R 10 ] 0-5 means that each ring is unsubstituted or contains 1, 2, 3, 4, or 5 R 10 (meaning it has been replaced by ).

[0127] In some embodiments, e.g., Cy 2 is selected from the group consisting of, but not limited to, pyrrolyl, furanyl, thiophenyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, triazolyl, thiadiazolyl, oxadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, indolinyl, indazolyl, benzo[d]imidazolyl, quinolyl, quinoxalyl, pyrrolo[3,2-b]pyridinyl, and indolizine groups, wherein each ring is 10 and optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0128] In some embodiments, Cy 2 teeth, [ka] but is not limited to (where [R 10 ] 0-3 means that each ring is unsubstituted or contains 1, 2 or 3 R 10 means that it is replaced by [R 10 ] 0-4 means that each ring is unsubstituted or contains 1, 2, 3 or 4 R 10 means that it is replaced by [R 10 ] 0-5 means that each ring is unsubstituted or contains 1, 2, 3, 4, or 5 R 10 (meaning it has been replaced by ).

[0129] In some embodiments, Cy 2 is R 10 C3-C optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 10 Cycloalkyl groups (e.g., C3 cycloalkyl groups, C4 cycloalkyl groups, C5 cycloalkyl groups, C6 cycloalkyl groups, C7 cycloalkyl groups, C8 cycloalkyl groups, C9 cycloalkyl groups, C 10 cycloalkyl group).

[0130] In some embodiments, Cy 2 is R 10 saturated C3-C optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 10 It is a cycloalkyl group.

[0131] In some embodiments, Cy 2 is R 10 saturated C optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from 3- C 10In some embodiments, Cy is a monocyclic cycloalkyl group. 2 is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl groups, where each ring is 10 In some embodiments, Cy is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 2 For example, [ka] but is not limited to (where [R 10 ] 0-5 means that each ring is unsubstituted or contains 1, 2, 3, 4, or 5 R 10 (meaning it has been replaced by ).

[0132] In some embodiments, Cy 2 is R 10 saturated C4-C optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 10 In some embodiments, Cy is a bicyclic cycloalkyl group. 2 is R 10 saturated C optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from 6- C 10 It is a bicyclic cycloalkyl group.

[0133] In some embodiments, Cy 2 is R 10 saturated C5-C optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 10 It is a spirocycloalkyl group.

[0134] In some embodiments, Cy 2 is R 10 C4-C optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 10In some embodiments, Cy is a bridged cycloalkyl group. 2 is R 10 C5-C optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 10 It is a bridged cycloalkyl group.

[0135] In some embodiments, Cy 2 is R 10 C7-C optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 10 In some embodiments, Cy is a fused cycloalkyl group. 2 is R 10 saturated C8-C optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 10 It is a fused cycloalkyl group.

[0136] In some embodiments, Cy 2 is R 10 Partially unsaturated C3-C optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 10 It is a cycloalkyl group.

[0137] In some embodiments, Cy 2 is R 10 Partially unsaturated C optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from 3- C 10 In some embodiments, Cy is a monocyclic cycloalkyl group. 2 is selected from the group consisting of cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadienyl, and cyclohexenyl groups, where each ring is 10 In some embodiments, e.g., Cy 2 teeth, [ka] but is not limited to (where [R 10 ] 0-5 means that each ring is unsubstituted or contains 1, 2, 3, 4, or 5 R 10 (meaning it has been replaced by ).

[0138] In some embodiments, Cy 2 is R 10 Partially unsaturated C4-C optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 10 In some embodiments, Cy is a bicyclic cycloalkyl group. 2 is R 10 Partially unsaturated C optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from 6- C 10 It is a bicyclic cycloalkyl group.

[0139] In some embodiments, Cy 2 is R 10 Partially unsaturated C optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from 5- C 10 In some embodiments, Cy is a spirocycloalkyl group. 2 is R 10 Partially unsaturated C7-C optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 10 It is a spirocycloalkyl group.

[0140] In some embodiments, Cy 2 is R 10 Partially unsaturated C4-C optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 10 In some embodiments, Cy is a bridged cycloalkyl group. 2 is R 10 Partially unsaturated C7-C optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 10 It is a bridged cycloalkyl group.

[0141] In some embodiments, Cy 2 is R 10 Partially unsaturated C7-C optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 10 In some embodiments, Cy is a fused cycloalkyl group. 2 is R 10 Partially unsaturated C8-C optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 10 It is a fused cycloalkyl group.

[0142] In some embodiments, Cy 2 is R 10 In some embodiments, Cy is a saturated 4- to 14-membered heterocycloalkyl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from: 2 is a saturated 4-14 membered heterocycloalkyl group having 1, 2, 3, or 4 heteroatoms independently selected from N, O, S, P, and Si, which heteroatoms are optionally substituted with one or more oxo or sulfido groups (e.g., S(O), S(O), or P(O)), wherein the 4-14 membered heterocycloalkyl group is 10 and optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0143] In some embodiments, Cy 2 is R 10 In some embodiments, Cy is a saturated 4-10 membered heterocycloalkyl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from: 2 is a saturated 4-10 membered heterocycloalkyl group having 1, 2, 3, or 4 heteroatoms independently selected from N, O, S, P, and Si, which heteroatoms are optionally substituted with one or more oxo or sulfido groups (e.g., S(O), S(O), or P(O)), wherein the 4-14 membered heterocycloalkyl group is10 and optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0144] In some embodiments, Cy 2 is R 10 and a saturated 4- to 14-membered monocyclic heterocycloalkyl group (e.g., a saturated 4-membered monocyclic heterocycloalkyl group, a saturated 5-membered monocyclic heterocycloalkyl group, a saturated 6-membered monocyclic heterocycloalkyl group, a saturated 7-membered monocyclic heterocycloalkyl group, a saturated 8-membered monocyclic heterocycloalkyl group, a saturated 9-membered monocyclic heterocycloalkyl group, a saturated 10-membered monocyclic heterocycloalkyl group, a saturated 11-membered monocyclic heterocycloalkyl group, a saturated 12-membered monocyclic heterocycloalkyl group, a saturated 13-membered monocyclic heterocycloalkyl group, or a saturated 14-membered monocyclic heterocycloalkyl group) optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from

[0145] In some embodiments, e.g., Cy 2 is selected from the group consisting of azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, dioxanyl, tetrahydropyranyl, tetrahydrothiopyranyl, piperazinyl, morpholinyl, azepanyl, diazocanyl, diazepanyl, oxazepanyl, azepanyl, thiomorpholine 1,1-dioxidyl, piperazinonyl, and tetrahydroxy-2H-thiopyran 1,1-dioxidyl, wherein each ring is selected from the group consisting of R 10 and optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0146] In some embodiments, e.g., Cy 2 teeth, [ka] but is not limited to (where [R 10 ] 0-5means that each ring is unsubstituted or contains 1, 2, 3, 4, or 5 R 10 (meaning it has been replaced by ).

[0147] In some embodiments, Cy 2 is R 10 and a saturated 4- to 14-membered bicyclic heterocycloalkyl group (e.g., a saturated 4-membered bicyclic heterocycloalkyl group, a saturated 5-membered bicyclic heterocycloalkyl group, a saturated 6-membered bicyclic heterocycloalkyl group, a saturated 7-membered bicyclic heterocycloalkyl group, a saturated 8-membered bicyclic heterocycloalkyl group, a saturated 9-membered bicyclic heterocycloalkyl group, a saturated 10-membered bicyclic heterocycloalkyl group, a saturated 11-membered bicyclic heterocycloalkyl group, a saturated 12-membered bicyclic heterocycloalkyl group, a saturated 13-membered bicyclic heterocycloalkyl group, or a saturated 14-membered bicyclic heterocycloalkyl group), optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from:

[0148] In some embodiments, e.g., Cy 2is an octahydropyrrolo[3,4-c]pyrrolyl group, a hexahydrofuro[3,4-c]pyrrolyl group, a hexahydrothieno[3,4-c]pyrrolyl group, an octahydrocyclopenta[b]pyrrolyl group, an octahydropyrrolo[3,2-b]pyrrolyl group, a hexahydrofuro[3,2-b]pyrrolyl group, an octahydropyrano[3,2-b]pyrrolyl group, an octahydropyrrolo[3,2-b]pyridinyl group, a hexahydropyrrolo[1,2-a]imidinyl group, and a hexahydropyrrolo[1,2-a]imidinyl group. dazolyl group, octahydropyrrolo[2,3-c]pyridinyl group, octahydropyrrolo[3,2-c]pyridinyl group, octahydroimidazo[1,2-a]pyridinyl group, octahydropyrrolo[3,4-c]pyridinyl group, decahydroquinolyl group, octahydrochromenyl group, decahydroquinoxalyl group, octahydropyrido[1,2-a]pyrazinyl group, octahydroxypyrazino[2,1-c][1,4]oxazinyl group, octa Hydropyrido[2,1-c][1,4]oxazinyl group, octahydropyrano[3,2-c]pyridinyl group, decahydro-2,6-naphthyridinyl group, octahydropyrano[3,4-c]pyridinyl group, octahydropyrrolo[1,2-a]pyrazinyl group, hexahydrooxazolo[3,4-a]pyrazinyl group, hexahydro-5H-cyclopenta[b][1,4]dioxinyl group, hexahydroimidazo[1,5-a]pyrazine-3 and hexahydropyrazino[2,1-c][1,4]oxazin-3(4H)-ketone, and hexahydropyrazino[2,1-c][1,4]oxazin-4(3H)-one, wherein each ring is selected from the group consisting of R 10 and optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0149] In some embodiments, e.g., Cy 2 teeth, [ka] but is not limited to (where [R 10 ] 0-5 means that each ring is unsubstituted or substituted with 1, 2, 3, 4 or 5 R10).

[0150] In some embodiments, Cy 2 is R 10 and a saturated 5- to 14-membered spiroheterocycloalkyl group (e.g., a saturated 5-membered spiroheterocycloalkyl group, a saturated 6-membered spiroheterocycloalkyl group, a saturated 7-membered spiroheterocycloalkyl group, a saturated 8-membered spiroheterocycloalkyl group, a saturated 9-membered spiroheterocycloalkyl group, a saturated 10-membered spiroheterocycloalkyl group, a saturated 11-membered spiroheterocycloalkyl group, a saturated 12-membered spiroheterocycloalkyl group, a saturated 13-membered spiroheterocycloalkyl group, or a saturated 14-membered spiroheterocycloalkyl group), optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from

[0151] In some embodiments, e.g., Cy 2are 2,6-diazaspiro[3.3]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, 2,6-diazaspiro[3.4]octanyl, 2,7-diazaspiro[3.5]nonanyl, 2,7-diazaspiro[4.4]nonanyl, 3,9-diazaspiro[5.5]undecanyl, 2-oxa-7-azaspiro[3.5]nonanyl, 2-oxa-6-azaspiro[3.4]octanyl, 7-oxa-2-azaspiro[3.5]nonanyl, 6-oxa-2-azaspiro[3.4]octanyl, 1-oxa-8-azaspiro[3.5]undecanyl, spiro[4.5]decanyl, 2-oxa-8-azaspiro[4.5]decanyl, 2-oxaspiro[3.5]nanyl, 4,7-diazaspiro[2.5]octanyl, 1-oxa-7-azaspiro[3.5]nonanyl, 5,8-diazaspiro[3.5]nonanyl, 7-oxa-4-azaspiro[2.5]octanyl, 4-oxa-7-azaspiro[2.5]octanyl, 8-oxa-5-azaspiro[3.5]nonanyl, and 5-oxa-8-azaspiro[3.5]nonanyl, wherein each ring is selected from the group consisting of R 10 and optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0152] In some embodiments, for example, Cy 2 teeth, [ka] but is not limited to (where [R 10 ] 0-5 means that each ring is unsubstituted or contains 1, 2, 3, 4, or 5 R 10 (meaning it has been replaced by ).

[0153] In some embodiments, Cy 2 is R 10and saturated 4- to 14-membered bridged cyclic heterocycloalkyl groups (e.g., saturated 4-membered bridged cyclic heterocycloalkyl groups, saturated 5-membered bridged cyclic heterocycloalkyl groups, saturated 6-membered bridged cyclic heterocycloalkyl groups, saturated 7-membered bridged cyclic heterocycloalkyl groups, saturated 8-membered bridged cyclic heterocycloalkyl groups, saturated 9-membered bridged cyclic heterocycloalkyl groups, saturated 10-membered bridged cyclic heterocycloalkyl groups, saturated 11-membered bridged cyclic heterocycloalkyl groups, saturated 12-membered bridged cyclic heterocycloalkyl groups, saturated 13-membered bridged cyclic heterocycloalkyl groups, saturated 14-membered bridged cyclic heterocycloalkyl groups), optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0154] In some embodiments, for example, Cy 2 are 2-azabicyclo[1.1.1]pentanyl, 5-azabicyclo[2.1.1]hexanal, 2-azabicyclo[2.2.1]heptanyl, 2-azabicyclo[2.2.2]octanyl, 6-azabicyclo[3.1.1]heptanyl, 3-azabicyclo[3.2.1]octanyl, 3-azabicyclo[3.3.1]nonanyl, 3-azabicyclo[3.3.2]decanyl, 3-azabicyclo[3.3.3]undecanyl, 3,6-diazabicyclo[3.1.1]heptanyl, 3,8-diazabicyclo[3.2.1]octanyl, 2,5-diazabicyclo[2.2.2]octanyl azabicyclo[3.1.1]octanyl, 3,6-diazabicyclo[3.1.1]heptanyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 3-oxa-6-azabicyclo[3.1.1]heptanyl, 2,5-diazabicyclo[2.2.1]heptanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-5-azabicyclo[2.2.2]octanyl, 3,8-diazabicyclo[3.2.1]octanyl, 8-oxa-3-azabicyclo[3.2.1]octanyl, and 3-oxa-8-azabicyclo[3.2.1]octanyl, wherein each ring is selected from the group consisting of R 10 and optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0155] [ka] but is not limited to (where [R 10 ] 0-5 means that each ring is unsubstituted or contains 1, 2, 3, 4, or 5 R 10 (meaning it has been replaced by ).

[0156] In some embodiments, Cy 2 is R 10 and 7- to 14-membered fused heterocycloalkyl groups (e.g., 7-membered fused heterocycloalkyl groups, 8-membered fused heterocycloalkyl groups, 9-membered fused heterocycloalkyl groups, 10-membered fused heterocycloalkyl groups, 11-membered fused heterocycloalkyl groups, 12-membered fused heterocycloalkyl groups, 13-membered fused heterocycloalkyl groups, 14-membered fused heterocycloalkyl groups), optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0157] In some embodiments, for example, Cy 2 are 5,6,7,8-tetrahydroimidazo[1,5-a]pyrazinyl group, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazinyl group, 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazinyl group, 4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridinyl group, 6,7,8,8a-tetrahydro-5H-[1,2,4]oxadiazolo[4,5-a]pyrazinyl group, 4,5,6,7-tetrahydroisoxa and 5,6,7,8-tetrahydropyrazolo[5,4-c]pyridinyl, 5,6,7,8-tetrahydro-1,7-naphthyridinyl, 5,6,7,8-tetrahydro-1,6-naphthyridinyl, 1,2,3,4-tetrahydro-2,7-naphthyridinyl, 1,2,3,4-tetrahydroisoquinolyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl, and 5,6,7,8-tetrahydropyrilo[3,4-d]pyrimidinyl, wherein each ring is selected from the group consisting of R 10and optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0158] In some embodiments, for example, Cy 2 teeth, [ka] but is not limited to (where [R 10 ] 0-5 means that each ring is unsubstituted or contains 1, 2, 3, 4, or 5 R 10 (meaning it has been replaced by ).

[0159] In some embodiments, Cy 2 is 1, 2, 3, 4 or 5 R 10 and a partially unsaturated 4- to 14-membered heterocycloalkyl group (e.g., a partially unsaturated 4-membered heterocycloalkyl group, a partially unsaturated 5-membered heterocycloalkyl group, a partially unsaturated 6-membered heterocycloalkyl group, a partially unsaturated 7-membered heterocycloalkyl group, a partially unsaturated 8-membered heterocycloalkyl group, a partially unsaturated 9-membered heterocycloalkyl group, a partially unsaturated 10-membered heterocycloalkyl group, a partially unsaturated 11-membered heterocycloalkyl group, a partially unsaturated 12-membered heterocycloalkyl group, a partially unsaturated 13-membered heterocycloalkyl group, or a partially unsaturated 14-membered heterocycloalkyl group).

[0160] In some embodiments, Cy 2 is 1, 2, 3, 4 or 5 R 10 is a partially unsaturated 4- to 14-membered monocyclic heterocycloalkyl group optionally substituted with

[0161] In some embodiments, for example, Cy 2is selected from the group consisting of 1,2,3,6-tetrahydropyridinyl, 3,6-dihydro-2H-pyranyl, 1,2,3,4-tetrahydropyridinyl, 3,4-dihydro-2H-pyranyl, 2,3-dihydro-1H-pyrrolyl, 2,5-dihydro-1H-pyrrolyl, 2,3-dihydrofuranyl, and 2,5-dihydrofuranyl groups, wherein each ring is selected from the group consisting of 1, 2, 3, 4, or 5 R 10 (optionally replaced by ).

[0162] In some embodiments, for example, Cy 2 teeth, [ka] but is not limited to (where [R 10 ] 0-5 means that each ring is unsubstituted or contains 1, 2, 3, 4, or 5 R 10 (meaning it has been replaced by ).

[0163] In some embodiments, Cy 2 is 1, 2, 3, 4 or 5 R 10 and a partially unsaturated 4-14 membered bicyclic heterocycloalkyl group (e.g., a partially unsaturated 6-membered bicyclic heterocycloalkyl group, a partially unsaturated 7-membered bicyclic heterocycloalkyl group, a partially unsaturated 8-membered bicyclic heterocycloalkyl group, a partially unsaturated 9-membered bicyclic heterocycloalkyl group, a partially unsaturated 10-membered bicyclic heterocycloalkyl group, a partially unsaturated 11-membered bicyclic heterocycloalkyl group, a partially unsaturated 12-membered bicyclic heterocycloalkyl group, a partially unsaturated 13-membered bicyclic heterocycloalkyl group, or a partially unsaturated 14-membered bicyclic heterocycloalkyl group).

[0164] In some embodiments, Cy 2 is 1, 2, 3, 4 or 5 R 10and a partially unsaturated 4- to 14-membered spiroheterocycloalkyl group (e.g., a partially unsaturated 7-membered spiroheterocycloalkyl group, a partially unsaturated 8-membered spiroheterocycloalkyl group, a partially unsaturated 9-membered spiroheterocycloalkyl group, a partially unsaturated 10-membered spiroheterocycloalkyl group, a partially unsaturated 11-membered spiroheterocycloalkyl group, a partially unsaturated 12-membered spiroheterocycloalkyl group, a partially unsaturated 13-membered spiroheterocycloalkyl group, or a partially unsaturated 14-membered spiroheterocycloalkyl group).

[0165] In some embodiments, Cy 2 is 1, 2, 3, 4 or 5 R 10 and a partially unsaturated 4- to 14-membered bridged cyclic heterocycloalkyl group optionally substituted with (e.g., a partially unsaturated 7-membered bridged cyclic heterocycloalkyl group, a partially unsaturated 8-membered bridged cyclic heterocycloalkyl group, a partially unsaturated 9-membered bridged cyclic heterocycloalkyl group, a partially unsaturated 10-membered bridged cyclic heterocycloalkyl group, a partially unsaturated 11-membered bridged cyclic heterocycloalkyl group, a partially unsaturated 12-membered bridged cyclic heterocycloalkyl group, a partially unsaturated 13-membered bridged cyclic heterocycloalkyl group, or a partially unsaturated 14-membered bridged cyclic heterocycloalkyl group).

[0166] In some embodiments, Cy 2 is 1, 2, 3, 4 or 5 R 10 and a partially unsaturated 4- to 14-membered fused heterocycloalkyl group (e.g., a partially unsaturated 8-membered fused heterocycloalkyl group, a partially unsaturated 9-membered fused heterocycloalkyl group, a partially unsaturated 10-membered fused heterocycloalkyl group, a partially unsaturated 11-membered fused heterocycloalkyl group, a partially unsaturated 12-membered fused heterocycloalkyl group, a partially unsaturated 13-membered fused heterocycloalkyl group, or a partially unsaturated 14-membered fused heterocycloalkyl group).

[0167] In some embodiments, in Formula (I), each R 10are independently H, D, halogen, CN, NO2, N3, oxo group, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, OR A , S.R. A , SF5, NR C OR A , C(O)R B , C(=S)R B , C(O)NR C R D , C(O)NR C OR A , C(O)OR A , C(=NR C )NR C R D ,OC(O)R B , OC(O)NR C R D , N.R. C R D , N.R. C C(O)R D , N.R. C C(O)NR C R D , N.R. C C(O)OR A , B(OR C )(OR D ), NR D C(=NR C )NR C R D , N.R. 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 , N.R. C S(O)2R B , S(O)NR C R D , N.R.C S(O)NR C R D , N.R. C S(O)(=NR B )R B , Cy 3 , C1-C6 alkyl-Cy 3 , O.C.y. 3 , O-C1-C6 alkyl-Cy 3 wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, and the C2-C6 alkynyl group are selected from the group consisting of 1, 2, 3, 4, or 5 R 11 (optionally replaced by ).

[0168] In some embodiments, each R 10 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 cyanoalkyl group, OR A , S.R. 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 , N.R. C R D , N.R. C C(O)R D , N.R. C C(O)NR C R D , N.R. C C(O)OR A , B(OR C )(OR D ), C(=NR C )NR C R D , N.R. D C(=NR C )NR C R D , N.R. 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)2R B , N.R. C S(O)2R B , S(O)NR C R D , N.R. C S(O)NR C R D , N.R. C S(O)(=NR B )R B , Cy 3 , C1-C6 alkyl-Cy 3 , O.C.y. 3 , and O-C1-C6 alkyl-Cy 3 is selected from the group consisting of:

[0169] In some embodiments, each R 10 is independently selected from the group consisting of H, D, halogen, CN, NO, N, oxo, and SF. 10 is H. In some embodiments, each R 10 is D. In some embodiments, each R 10 is halogen (e.g., F, Cl, Br, I). In some embodiments, each R 10 is CN. In some embodiments, each R 10 is NO. In some embodiments, each R 10 is N3. In some embodiments, each R 10 are independently selected from oxo groups, e.g., carbon atoms and heteroatoms may be substituted with one or more oxo or sulfide groups (e.g., C(O), S(O), C(S), or S(O), or P(O), etc.). In some embodiments, each R 10 is SF5.

[0170] In some embodiments, each R 10 are independently OR A In some embodiments, for example, each R 10 are independently selected from the group consisting of OH, OCH3, OCH2CH3, OCF3, and OCH2CF3.

[0171] In some embodiments, each R 10 is an independent SR A In some embodiments, each R 10 is independently NHOR A is selected from, for example, NHOH.

[0172] In some embodiments, each R 10 are independently C(O)R B Selected from.

[0173] In some embodiments, each R 10 are independent of each other, C(O)R B (where R B is H, D). In some embodiments, each R 10 is CHO.

[0174] In some embodiments, each R 10 are independently C(O)R B (where R B is a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10 are selected from the group consisting of aryl groups, 5- to 10-membered heteroaryl groups, arylalkyl groups, heteroarylalkyl groups, cycloalkylalkyl groups, and heterocycloalkylalkyl groups. 13 and substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0175] In some embodiments, each R 10are independent of each other, C(O)R B (where R B is a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 membered heteroaryl-C1-C6 alkyl group, C3-C 10 cycloalkyl-C1-C6 alkyl groups, and 4- to 10-membered heterocycloalkyl-C1-C6 alkyl groups, each of which is selected from the group consisting of R 13 and substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0176] In some embodiments, for example, each R 10 are independently C(O)CH3, C(O)CH2CH3, C(O)CH2CH2CH3, C(O)CH(CH3)2, C(O)CH2CH(CH3)2, C(O)C(CH3)3, C(O)CF3, C(O)CH2CF3, C(O)CH2OH, C(O)CH2OCH3, [ka] is selected from, but not limited to, (wherein [R 13 ] 0-3 means that each ring is unsubstituted or contains 1, 2 or 3 R 13 means that it is replaced by [R 13 ] 0-4 means that each ring is unsubstituted or contains 1, 2, 3 or 4 R 13 means that it is replaced by [R 13 ] 0-5 means that each ring is unsubstituted or contains 1, 2, 3, 4, or 5 R 13 (meaning it has been replaced by ).

[0177] In some embodiments, each R 10are independent, C(=S)R B In some embodiments, each R 10 is independently selected from the group consisting of C(=S)CH3, C(=S)CH2CH3, C(=S)CH2CH2CH3, C(=S)CH(CH3)2, and C(=S)C(CH3)3.

[0178] In some embodiments, each R 10 are independently C(O)NR C R D In some embodiments, each R 10 are independently selected from the group consisting of C(O)NH2, C(O)NHCH3, C(O)N(CH3)2, C(O)N(CH3)CH2CH3, C(O)N(CH3)CH2CF3, C(O)N(CH3)CH2CH2OH, C(O)N(CH3)CH2CH2OCH3, C(O)N(CH3)OCH3, C(O)N(CH3)CH2CH(CH3)OH.

[0179] In some embodiments, each R 10 is C(O)NR C OR A Selected from, for example, [ka] is.

[0180] In some embodiments, each R 10 are independent and C(O)OR A In some embodiments, each R 10 are independently selected from the group consisting of C(O)OH, C(O)OCH3, C(O)OCH2CH3, C(O)OCH2CH2CH3, C(O)OCH(CH3)2, and C(O)OC(CH3)3.

[0181] In some embodiments, each R 10 are independent, C(=NR C )NR C R DIn some further embodiments, each R 10 are independent and OC(O)R B In some further embodiments, each R 10 are independently OC(O)NR C R D Selected from.

[0182] In some other embodiments, each R 10 is independent, NR C R D In some further embodiments, each R 10 are independently selected from the group consisting of NH2, NHCH3, N(CH3)2, N(CH3)CH2CH3, and N(CH3)CH2CF3.

[0183] In some other embodiments, each R 10 is independent, NR C C(O)R D In some further embodiments, each R 10 is independent, NR C C(O)NR C R D In some further embodiments, each R 10 is independent, NR C C(O)OR A In some further embodiments, each R 10 is independent, NR D C(=NR C )NR C R D In some further embodiments, each R 10 is independent, NR D C(=NR C )R B Selected from.

[0184] In some other embodiments, each R 10 are independent of B(OR C )(OR D In some further embodiments, each R 10 are independentlyG R H R I For example, each R 10 is independently selected from Si(CH). In some other embodiments, each R 10 are independent, P(O)R E R F For example, each R 10 is independently selected from P(O)(CH). In some other embodiments, each R 10 are independent, P(O)OR E OR F In some further embodiments, each R 10 are independent and OP(O)OR E OR F In some further embodiments, each R 10 are independently determined as S(O)(=NR B )R B Selected from.

[0185] In some other embodiments, each R 10 are independent of each other, S(O)R B For example, each R 10 are independently selected from the group consisting of S(O)CH3, S(O)CH2CH3, S(O)CH(CH3)2, and S(O)C(CH3)3.

[0186] In some other embodiments, each R 10 are independently S(O)NR C R D Selected from.

[0187] In some other embodiments, each R 10 are independently S(O)2R B For example, each R 10 is independently selected from the group consisting of S(O)2CH3, S(O)2CH2CH3, S(O)2CH(CH3)2, and S(O)2C(CH3)3.

[0188] In some other embodiments, each R 10 is independent, NRC S(O)2R B In some further embodiments, each R 10 are independently S(O)2NR C R D In some further embodiments, each R 10 is independent, NR C S(O)NR C R D In some further embodiments, each R 10 is independent, NR C S(O)(=NR B )R B Selected from.

[0189] In some other embodiments, each R 10 is independent, Cy 3 For example, each R 10are independently a phenyl group, a naphthyl group, a pyrrolyl group, a furanyl group, a thiophenyl group, an imidazolyl group, an oxazolyl group, a thiazolyl group, a tetrazolyl group, a pyrazolyl group, a triazolyl group, a thiadiazolyl group, an oxadiazolyl group, a pyridinyl group, a pyrimidinyl group, a pyrazinyl group, a pyridazinyl group, an indolinyl group, an isoindolinyl group, an indolizine group, a benzofuranyl group, an isobenzofuranyl group, a benzo[b]thiophenyl group, a benzo[c]thiophenyl group, an indazolyl group, a benzo[b]thiophenyl group, a benzo[c]thiophenyl ...b 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, furo[3,2-b]pyridinyl group, furo[3,2-c]pyridinyl group, furo[2,3-c]pyridinyl group, furo[2,3-b]pyridinyl group, benzo[c]isooxazolyl group thiazolyl group, furo[3,4-b]pyridinyl group, furo[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]pyrimidinyl group, pyrrolo[2,3-b]pyrazinyl group, pyrrolo[2,3-d]pyridazinyl group, pyrrolo[2,3-d]pyrimidinyl group, pyrrolo[2,3-c]pyridazinyl group, pyrrolo[3,4-c]pyridazinyl group, pyrrolo[3,4-d]pyrimidinyl group, pyrrolo[3,4-b]pyrazinyl group, 6H-pyrrolo[3,4-c]pyridazinyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, dioxanyl, tetrahydropyranyl, tetrahydrothiopyranyl, piperazinyl, morpholinyl, azepanyl, diazocanyl, diazepanyl, azepanyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl groups, wherein each ring is selected from the group consisting of, but not limited to, 1, 2, 3, 4, or 5 R, 12 (optionally replaced by ).

[0190] In some other embodiments, for example, each R 10 teeth, [ka] but is not limited to (where [R 12 ] 0-2 means that each ring is unsubstituted or contains one or two R 12 means that it is replaced by [R 12 ] 0-3 means that each ring is unsubstituted or contains 1, 2 or 3 R 12 means that it is replaced by [R 12 ] 0-4 means that each ring is unsubstituted or contains 1, 2, 3 or 4 R 12 means that it is replaced by [R 12 ] 0-5 means that each ring is unsubstituted or contains 1, 2, 3, 4, or 5 R 12 (meaning it has been replaced by ).

[0191] In some other embodiments, each R 10 are independently C1-C6 alkyl-Cy 3 In some further embodiments, each R 10 are independently C1 alkyl-Cy 3 For example, each R 10is independent, [ka] In some further embodiments, each R 10 are independently C2 alkyl-Cy 3 In some further embodiments, each R 10 are independently C3 alkyl-Cy 3 In some further embodiments, each R 10 are independently C4 alkyl-Cy 3 In some further embodiments, each R 10 are independently C5 alkyl-Cy 3 In some further embodiments, each R 10 are independently C6 alkyl-Cy 3 Selected from.

[0192] In some other embodiments, each R 10 independently, OCy 3 In some further embodiments, each R 10 are independent, OC6~C 10 In some other embodiments, each R 10 are independent, OC3~C 10 In some further embodiments, each R 10 is independently selected from O-5 to 10 membered heteroaryl groups. 10 is independently selected from O-4 to 10-membered heterocycloalkyl groups.

[0193] In some other embodiments, each R 10 are independently O-C1-C6 alkyl-Cy 3 In some further embodiments, each R 10 are independently O-C1 alkyl-Cy 3 In some further embodiments, each R10 are independently O-C2 alkyl-Cy 3 In some further embodiments, each R 10 are independently O-C3 alkyl-Cy 3 In some further embodiments, each R 10 are independently O-C4 alkyl-Cy 3 In some further embodiments, each R 10 are independently O-C5 alkyl-Cy 3 In some further embodiments, each R 10 are independently O-C6 alkyl-Cy 3 Selected from.

[0194] In some embodiments, each R 10 are independently selected from C1 to C6 alkyl groups, wherein the C1 to C6 alkyl groups are selected from 1, 2, 3, 4, or 5 R 11 In some embodiments, each R 10 are independently 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, a pentyl group, a hexyl group, CH2F, CHF2, CF3, CH2CH2F, CH2CHF2, CH2CF3, CH2OH, CH2OCH3, CH2CH2OCH3, CH2SCH3, CH2CH2NCH3, CH2CN, [ka] It is selected from the group consisting of:

[0195] In some embodiments, each R 10 are independently selected from a C2-C6 alkenyl group (wherein the C2-C6 alkenyl group is selected from 1, 2, 3, 4, or 5 R 11 (optionally replaced by ).

[0196] In some embodiments, each R 10are independently selected from a C2-C6 alkynyl group (wherein the C2-C6 alkynyl group is selected from 1, 2, 3, 4, or 5 R 11 (optionally replaced by ).

[0197] In some embodiments, two R 10 together with the atom to which they are attached form an oxo group.

[0198] In some embodiments, two adjacent R 10 are C3 to C together with the atoms connected to them 10 (wherein the C3 to C 10 The 4- to 10-membered cycloalkyl group or the 4- to 10-membered heterocycloalkyl group is independently selected from D, halogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C1-C6 haloalkyl group, a C1-C6 cyanoalkyl group, CN, NO2, an oxo group, OR a , S.R. 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 , N.R. c R d , N.R. c C(O)R b , N.R. c C(O)NR c R d , N.R. c C(O)OR a , B(OR c )(OR d ), C(=NR c )NR c R d , N.R. d C(=NR c )NR c R d , N.R. d C(=NR c )R b , OP(O)ORe 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)2R b , N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , N.R. c S(O)(=NR b )R b , C6~C 10 Aryl groups, C3-C 10 and optionally substituted with 1, 2, or 3 substituents selected from a cycloalkyl group, a 5- to 10-membered heteroaryl group, and a 4- to 10-membered heterocycloalkyl group, wherein 10 Aryl groups, C3-C 10 The cycloalkyl group, the 5- to 10-membered heteroaryl group, and the 4- to 10-membered heterocycloalkyl group are optionally substituted with 1, 2, or 3 substituents independently selected from D, halogen, CN, NO, NH, NHC alkyl group, N(C alkyl group), C alkyl group, C haloalkyl group, OC alkyl group, OC haloalkyl group, OC alkyl-OH, OC alkyl-O—C alkyl group, and SF.

[0199] In some embodiments, two adjacent R 10 are C3 to C together with the atoms connected to them 10 (wherein the C3 to C 10 The membered cycloalkyl group is independently selected from D, halogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C1-C6 haloalkyl group, a C1-C6 cyanoalkyl group, CN, NO2, an oxo group, OR a , S.R.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 , N.R. c R d , N.R. c C(O)R b , N.R. c C(O)NR c R d , N.R. c C(O)OR a , B(OR c )(OR d ), C(=NR c )NR c R d , N.R. d C(=NR c )NR c R d , N.R. 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)2R b , N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , N.R. c S(O)(=NR b )R b , Cy 4 and wherein Cy is optionally substituted with 1, 2, or 3 substituents selected from 4 is C6~C 10 Aryl groups, C3-C 10cycloalkyl groups, 5- to 10-membered heteroaryl groups, and 4- to 10-membered heterocycloalkyl groups, and further wherein said C6 to C 10 Aryl groups, C3-C 10 The cycloalkyl group, the 5- to 10-membered heteroaryl group, and the 4- to 10-membered heterocycloalkyl group are independently optionally substituted with 1, 2, or 3 substituents selected from D, halogen, CN, NO, OH, oxo, NH, NHC alkyl group, N(C alkyl), C haloalkyl group, OC alkyl group, OC haloalkyl group, OC alkylOH, OC alkyl-O—C alkyl group, and SF.

[0200] In some embodiments, two adjacent R 10 form a 4- to 10-membered heterocycloalkyl group together with the atoms connected thereto (wherein the 4- to 10-membered heterocycloalkyl group is selected from the group consisting of D, halogen, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl group, C1-C6 cyanoalkyl group, CN, NO2, oxo group, OR a , S.R. 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 , N.R. c R d , N.R. c C(O)R b , N.R. c C(O)NR c R d , N.R. c C(O)OR a , B(OR c )(OR d ), C(=NR c )NR c R d , N.R. d C(=NR c)NR c R d , N.R. 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)2R b , N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , N.R. c S(O)(=NR b )R b , Cy 4 and wherein Cy is optionally substituted with 1, 2, or 3 substituents independently selected from 4 is C6~C 10 Aryl groups, C3-C 10 cycloalkyl groups, 5- to 10-membered heteroaryl groups, and 4- to 10-membered heterocycloalkyl groups, and further wherein said C6 to C 10 Aryl groups, C3-C 10 The cycloalkyl group, the 5- to 10-membered heteroaryl group, and the 4- to 10-membered heterocycloalkyl group are independently optionally substituted with 1, 2, or 3 substituents selected from D, halogen, CN, NO, OH, oxo, NH, NHC alkyl group, N(C alkyl), C haloalkyl group, OC alkyl group, OC haloalkyl group, OC alkylOH, OC alkyl-O—C alkyl group, and SF.

[0201] In some embodiments, Cy 3 each independently represents an optionally substituted C to C 10 Aryl groups, C3-C10 cycloalkyl groups, 5- to 10-membered heteroaryl groups, and 4- to 10-membered heterocycloalkyl groups, where each ring is independently unsubstituted or 12 and optionally substituted with 1, 2, 3, 4 or 5 substituents selected from:

[0202] In some embodiments, Cy 3 is R 12 C6-C optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 10 In some embodiments, Cy is an aryl group. 3 is R 12 In some embodiments, Cy is a phenyl group, a naphthyl group, optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 3 is R 12 is a phenyl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0203] In some embodiments, Cy 3 is R 12 is a 5- to 10-membered heteroaryl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0204] In some embodiments, Cy 3is a pyrrolyl group, a furanyl group, a thiophenyl group, an imidazolyl group, an oxazolyl group, a thiazolyl group, a tetrazolyl group, a pyrazolyl group, a triazolyl group, a thiadiazolyl group, an oxadiazolyl group, a pyridinyl group, a pyrimidinyl group, a pyrazinyl group, a pyridazinyl group, an indolinyl group, an isoindolinyl group, an indolizine group, a benzofuranyl group, an isobenzofuranyl group, a benzo[b]thiophenyl group, a benzo[c]thiophenyl group, an indazolyl group, a benzo[d]imidazolyl group, a 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, furo[3,2-b]pyridinyl group, furo[3,2-c]pyridinyl group, furo[2,3-c]pyridinyl group, furo[2,3-b]pyridinyl group, benzo[c]isoxazolyl group, furo[3,4-b]pyridinyl group, furo[3,4-b]pyridinyl group, furo[3,4-c]pyridinyl group, furo[3,2-b]pyridinyl group, furo[3,2-c]pyridinyl group, furo[2,3-b]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 a pyridinyl group, an imidazo[4,5-b]pyridinyl group, a pyrrolo[3,2-c]pyridazinyl group, a pyrrolo[3,2-d]pyrimidinyl group, a pyrrolo[2,3-b]pyrazinyl group, a pyrrolo[2,3-d]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]pyrazinyl group, and a 6H-pyrrolo[3,4-c]pyridazinyl group, wherein each ring is selected from the group consisting of R 12 and optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0205] In some embodiments, Cy3 is R 12 In some embodiments, Cy is a pyrimidinyl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 3 is R 12 In some embodiments, Cy is a pyridazinyl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 3 is R 12 In some other embodiments, Cy is a pyrazinyl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 3 is R 12 and a pyrazolyl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0206] In some other embodiments, Cy 3 is R 12 C3-C optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 10 It is a cycloalkyl group.

[0207] In some other embodiments, Cy 3 is R 12 In some other embodiments, Cy is a cycloheptyl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 3 is R 12 In some other embodiments, Cy is a cyclohexyl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 3 is R 12 In some other embodiments, Cy is a cyclopentyl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 3 is R 12 In some other embodiments, Cy is a cyclobutyl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 3 is R 12is a cyclopropyl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0208] In some other embodiments, Cy 3 is R 12 is a 4- to 10-membered heterocycloalkyl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0209] In some embodiments, Cy 3 is selected from the group consisting of azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, dioxanyl, tetrahydropyranyl, tetrahydrothiopyranyl, piperazinyl, morpholinyl, azepanyl, diazocanyl, diazepanyl, and azepanyl groups, wherein each ring is selected from the group consisting of 1, 2, 3, 4, or 5 R 12 (optionally replaced by ).

[0210] In some embodiments, Cy 3 is 4-methylpiperazin-1-yl.

[0211] In some other embodiments, each R 11 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 , S.R. 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 , N.R. c1 R d1 , N.R. c1 C(O)Rb1 , N.R. c1 C(O)NR c1 R d1 , N.R. c1 C(O)OR a1 , B(OR c1 )(OR d1 ), C(=NR c1 )NR c1 R d1 , N.R. d1 C(=NR c1 )NR c1 R d1 , N.R. 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)2R b1 , N.R. c1 S(O)2R b1 , S(O)NR c1 R d1 , N.R. c1 S(O)NR c1 R d1 , N.R. c1 S(O)(=NR b1 )R b1 , C6~C 10 Aryl groups, C3-C 10 It is selected from the group consisting of a cycloalkyl group, a 5- to 10-membered heteroaryl group, and a 4- to 10-membered heterocycloalkyl group.

[0212] In some embodiments, each R 11 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 , S.R. a1 , C(O)R b1 , C(O)NR c1 Rd1 , S(O)2R b1 , C6~C 10 Aryl groups, C3-C 10 is selected from the group consisting of a cycloalkyl group, a 5- to 10-membered heteroaryl group, and a 4- to 10-membered heterocycloalkyl group (wherein the C6 to C 10 Aryl groups, C3-C 10 The cycloalkyl group, the 5- to 10-membered heteroaryl group, and the 4- to 10-membered heterocycloalkyl group are independently unsubstituted or substituted with a substituent selected from D, halogen, CN, NO2, NH2, NHC1-C4 alkyl group, N(C1-C4 alkyl group)2, C1-C3 alkyl group, C1-C3 haloalkyl group, OC1-C3 alkyl group, OC1-C3 haloalkyl group, OC2-C3 alkylOH, OC2-C3 alkyl-O-C1-C6 alkyl group, and SF5.

[0213] In some embodiments, each R 11 is independently selected from the group consisting of H, D, halogen, CN, NO, N, and SF. 11 is H. In some embodiments, each R 11 is D. In some embodiments, each R 11 is halogen (e.g., F, Cl, Br, I). In some embodiments, each R 11 is CN. In some embodiments, each R 11 is NO. In some embodiments, each R 11 is N3. In some embodiments, each R 11 is SF5.

[0214] In some embodiments, each R 11 are independently selected from the group consisting of a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C1-C6 haloalkyl group, an O-C1-C6 alkyl-OH group, and an O-C1-C6 alkyl-O-C1-C6 alkyl group. In some embodiments, for example, each R 11are independently selected from the group consisting of CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, C(CH3)3, CH2F, CHF2, CF3, OCH2CH2OH, and OCH2CH2OCH3.

[0215] In some embodiments, each R 11 are independent, OR a1 In some embodiments, for example, each R 11 are independently selected from the group consisting of OH, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, OCH2F, OCHF2, and OCF3.

[0216] In some embodiments, each R 11 independently, SR a1 In some embodiments, each R 11 are independently selected from SCH3, etc.

[0217] In some embodiments, each R 11 independently, NHOR a1 In some embodiments, each R 11 are independent of each other, C(O)R b1 In some embodiments, each R 11 are independently C(O)NR c1 R d1 In some embodiments, each R 11 are independent and C(O)OR a1 In some embodiments, each R 11 are independent and OC(O)OR a1 In some embodiments, each R 11 are independent and OC(O)R b1 In some embodiments, each R 11 are independently OC(O)NR c1 R d1 Selected from.

[0218] In some embodiments, each R 11is independent, NR c1 R d1 In some embodiments, each R 11 is independent, NR c1 C(O)R b1 In some embodiments, each R 11 is independent, NR c1 C(O)NR c1 R d1 In some embodiments, each R 11 is independent, NR c1 C(O)OR a1 Selected from.

[0219] In some embodiments, each R 11 are independent of B(OR c1 )(OR d1 In some embodiments, each R 11 are independent, C(=NR c1 )NR c1 R d1 In some embodiments, each R 11 is independent, NR d1 C(=NR c1 )NR c1 R d1 In some embodiments, each R 11 is independent, NR d1 C(=NR c1 )R b1 Selected from.

[0220] In some embodiments, each R 11 are independent, P(O)OR e1 OR f1 In some embodiments, each R 11 are independent and OP(O)OR e1 OR f1 Selected from.

[0221] In some embodiments, each R 11 are independently determined as S(O)(=NR b1 )R b1In some embodiments, each R 11 are independent of each other, S(O)R b1 In some embodiments, each R 11 are independently S(O)NR c1 R d1 Selected from.

[0222] In some embodiments, each R 11 are independently S(O)2R b1 In some embodiments, each R 11 is independent, NR c1 S(O)2R b1 In some embodiments, each R 11 are independently S(O)2NR c1 R d1 In some embodiments, each R 11 is independent, NR c1 S(O)NR c1 R d1 In some embodiments, each R 11 is independent, NR c1 S(O)(=NR b1 )R b1 Selected from.

[0223] In some embodiments, each R 11 are independent, C6~C 10 Aryl groups, C3-C 10 is selected from the group consisting of a cycloalkyl group, a 5- to 10-membered heteroaryl group, and a 4- to 10-membered heterocycloalkyl group (wherein the C6 to C 10 Aryl groups, C3-C 10The cycloalkyl group, the 5- to 10-membered heteroaryl group, and the 4- to 10-membered heterocycloalkyl group are independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from D, halogen, CN, NO2, NH2, NHC1-C4 alkyl group, N(C1-C4 alkyl group)2, C1-C3 alkyl group, C1-C3 haloalkyl group, OC1-C3 alkyl group, OC1-C3 haloalkyl group, OC2-C3 alkylOH, OC2-C3 alkyl-O—C1-C6 alkyl group, and SF5.

[0224] In some embodiments, each R 12 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 , S.R. 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 , N.R. c1 R d1 , N.R. c1 C(O)R b1 , N.R. c1 C(O)NR c1 R d1 , N.R. c1 C(O)OR a1 , B(OR c1 )(OR d1 ), C(=NR c1 )NR c1 R d1 , N.R. d1 C(=NR c1 )NR c1 R d1 , N.R. 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)2R b1 , N.R. c1 S(O)2R b1 , S(O)NR c1 R d1 , N.R. c1 S(O)NR c1 R d1 , N.R. c1 S(O)(=NR b1 )R b1 , C6~C 10 Aryl groups, C3-C 10 is selected from the group consisting of a cycloalkyl group, a 5- to 10-membered heteroaryl group, and a 4- to 10-membered heterocycloalkyl group (wherein the C6 to C 10 Aryl groups, C3-C 10 The cycloalkyl group, the 5- to 10-membered heteroaryl group, and the 4- to 10-membered heterocycloalkyl group are independently unsubstituted or substituted with a substituent selected from D, halogen, CN, NO2, NH2, NHC1-C4 alkyl group, N(C1-C4 alkyl group)2, C1-C3 alkyl group, C1-C3 haloalkyl group, OC1-C3 alkyl group, OC1-C3 haloalkyl group, OC2-C3 alkylOH, OC2-C3 alkyl-O-C1-C6 alkyl group, and SF5.

[0225] In some embodiments, each R 12 are independently D, halogen, CN, NO2, N3, OR a1 , S.R. a1 , SF5, and NHOR a1 In some embodiments, each R 12 is D. In some embodiments, each R 12 is halogen (e.g., F, Cl, Br, I). In some embodiments, each R 12 is CN. In some embodiments, each R 12is NO. In some embodiments, each R 12 is N3. In some embodiments, each R 12 are independent, OR a1 (e.g., OH, OCH3, OCH2CH3, OCH2F, OCHF2, OCF3). In some embodiments, each R 12 is an independent SR a1 (e.g., SCH3). In some embodiments, each R 12 is independently selected from SF5. In some embodiments, each R 12 is independently NHOR a1 Selected from.

[0226] In some embodiments, each R 12 are independently C(O)R b1 In some embodiments, each R 12 are independently C(O)NR c1 R d1 In some embodiments, each R 12 are independently C(O)OR a1 Selected from.

[0227] In some embodiments, each R 12 is independently OC(O)R b1 In some embodiments, each R 12 are independently OC(O)NR c1 R d1 Selected from.

[0228] In some embodiments, each R 12 is independently NR c1 R d1 (e.g., NH, NHCH, N(CH)). In some embodiments, each R 12 is independently NR c1 C(O)R b1 In some embodiments, each R 12 is independently NR c1 C(O)NR c1 R d1In some embodiments, each R 12 is independently NR c1 C(O)OR a1 Selected from.

[0229] In some embodiments, each R 12 are independently B(OR c1 )(OR d1 In some embodiments, each R 12 are independently C(=NR c1 )NR c1 R d1 In some embodiments, each R 12 is independently NR d1 C(=NR c1 )NR c1 R d1 In some embodiments, each R 12 is independently NR d1 C(=NR c1 )R b1 Selected from.

[0230] In some embodiments, each R 12 are independently P(O)R e1 R f1 In some embodiments, each R 12 are independently P(O)OR e1 OR f1 In some embodiments, each R 12 is independently OP(O)OR e1 OR f1 Selected from.

[0231] In some embodiments, each R 12 are independently S(O)(=NR b1 )R b1 In some embodiments, each R 12 are independently S(O)R b1 In some embodiments, each R 12 are independently S(O)NR c1 R d1 Selected from.

[0232] In some embodiments, each R 12 are independently S(O)2R b1 In some embodiments, each R 12 is independently NR c1 S(O)2R b1 In some embodiments, each R 12 are independently S(O)NR c1 R d1 In some embodiments, each R 12 is independently NR c1 S(O)NR c1 R d1 In some embodiments, each R 12 is independently NR c1 S(O)(=NR b1 )R b1 Selected from.

[0233] In some other embodiments, each R 12 are independently selected from the group consisting of a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C1-C6 haloalkyl group, a C1-C6 alkylOH group, and a C1-C6 alkyl-O-C1-C6 alkyl group. 12 are independently selected from the group consisting of CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, C(CH3)3, CH2F, CHF2, CF3, CH2CF3, CH2OH, CH2CH2OH, CH(OH)CH3, and CH2OCH3.

[0234] In some other embodiments, each R 12 are independent, C6~C 10 Aryl groups, C3-C 10 is selected from the group consisting of a cycloalkyl group, a 5- to 10-membered heteroaryl group, and a 4- to 10-membered heterocycloalkyl group (wherein the C6 to C 10 Aryl groups, C3-C 10The cycloalkyl group, the 5- to 10-membered heteroaryl group, and the 4- to 10-membered heterocycloalkyl group are independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from D, halogen, CN, NO2, NH2, NHC1-C4 alkyl group, N(C1-C4 alkyl group)2, C1-C3 alkyl group, C1-C3 haloalkyl group, OC1-C3 alkyl group, OC1-C3 haloalkyl group, OC2-C3 alkylOH, OC2-C3 alkyl-O—C1-C6 alkyl group, and SF5.

[0235] In some other embodiments, each R 13 are independently H, D, OH, CN, halogen, oxo group, C1-C4 alkyl group, C1-C4 haloalkyl group, C1-C4 cyanoalkyl group, OC1-C4 alkyl group, OC1-C4 haloalkyl group, OC2-C4 alkylOH, OC2-C4 alkyl-O-C1-C4 alkyl group, OC2-C4 alkyl-O-C1-C4 haloalkyl group, C1-C4 alkyl-O-C1-C4 alkyl group, C1-C4 alkyl-O-C1-C4 haloalkyl group, optionally substituted C3-C7 cycloalkyl group, optionally substituted 4-7 membered heterocycloalkyl group, SF5, OR a , S.R. a , C(O)R b , OC(O)NR c R d , N.R. c R d , N.R. c C(O)R b , N.R. c C(O)NR c R d , N.R. c C(O)OR a , S(O)R b , S(O)NR c R d , S(O)2R b , N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , and B(ORc )(OR d ) (wherein the optionally substituted means substituted with a substituent selected from the group consisting of D, halogen, CN, OH, a C1-C4 alkyl group, a C1-C4 haloalkyl group, —O—C1-C4 alkyl group, and —O—C1-C4 haloalkyl group).

[0236] In some other embodiments, each R 13 is independently selected from the group consisting of H, D, OH, CN, halogen, oxo, and SF. 13 is H. In some embodiments, each R 13 is D. In some embodiments, each R 13 is OH. In some embodiments, each R 13 is CN. In some embodiments, each R 13 is halogen (e.g., F, Cl, Br). In some embodiments, each R 13 is an oxo group. In some embodiments, each R 13 is SF5.

[0237] In some other embodiments, each R 13 are independently selected from the group consisting of a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C1-C4 cyanoalkyl group, an O-C1-C4 alkyl group, an O-C1-C4 haloalkyl group, an O-C2-C4 alkyl-OH group, an O-C2-C4 alkyl-O-C1-C4 alkyl group, an O-C2-C4 alkyl-O-C1-C4 haloalkyl group, a C1-C4 alkyl-O-C1-C4 alkyl group, and a C1-C4 alkyl-O-C1-C4 haloalkyl group. In some embodiments, for example, each R 13 are independently selected from the group consisting of CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, C(CH3)3, CH2F, CHF2, CF3, CH2CF3, OCH3, OCH2CH3, OCF3, OCH2CH2OH, OCH2CH2OCH3, and OCH2CH2OCF3.

[0238] In some other embodiments, each R 13 are independently selected from the group consisting of optionally substituted C3-C7 cycloalkyl groups and optionally substituted 4- to 7-membered heterocycloalkyl groups (wherein the optionally substituted means substituted with a substituent selected from the group consisting of D, halogen, CN, OH, C1-C4 alkyl groups, C1-C4 haloalkyl groups, —O—C1-C4 alkyl groups, and —O—C1-C4 haloalkyl groups).

[0239] In some embodiments, each R 13 is independently selected from D, halogen, CN, OH, a C1-C4 alkyl group, a C1-C4 haloalkyl group, —O—C1-C4 alkyl group, a C3-C7 cycloalkyl group optionally substituted with —O—C1-C4 haloalkyl group.

[0240] In some embodiments, each R 13 is independently selected from D, halogen, CN, OH, a C1-C4 alkyl group, a C1-C4 haloalkyl group, —O—C1-C4 alkyl group, a 4-7 membered heterocycloalkyl group optionally substituted with —O—C1-C4 haloalkyl group.

[0241] In some other embodiments, each R 13 are independent, OR a , S.R. a , C(O)R b , OC(O)NR c R d , N.R. c R d , N.R. c C(O)R b , N.R. c C(O)NR c R d , N.R. c C(O)OR a , S(O)R b , S(O)NR c R d , S(O)2R b , N.R. c S(O)2R b , S(O)NR c Rd , N.R. c S(O)NR c R d , and B(OR c )(OR d ) is selected from the group consisting of

[0242] In some embodiments, each R 13 are independently OR a In some embodiments, each R 13 is an independent SR a Selected from.

[0243] In some embodiments, each R 13 are independently C(O)R b In some embodiments, each R 13 are independently OC(O)NR c R d Selected from.

[0244] In some embodiments, each R 13 is independently NR c R d In some embodiments, each R 13 is independently NR c C(O)R b In some embodiments, each R 13 is independently NR c C(O)NR c R d In some embodiments, each R 13 is independently NR c C(O)OR a Selected from.

[0245] In some embodiments, each R 13 are independently S(O)R b In some embodiments, each R 13 are independently S(O)NR c R d Selected from.

[0246] In some embodiments, each R 13 are independently S(O)2R b In some embodiments, each R 13 is independently NR c S(O)2R b In some embodiments, each R 13 are independently S(O)NR c R d Selected from.

[0247] In some embodiments, each R 13 is independently NR c S(O)NR c R d In some embodiments, each R 13 are independently B(OR c )(OR d ) are selected.

[0248] In some embodiments, R 14 and R 16 are each selected from the group consisting of H, D, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C1-C6 alkyl-OH, a C1-C6 alkyl-CN, and a C1-C6 alkyl-O—C1-C6 alkyl group.

[0249] In some embodiments, R 14 is H. In some embodiments, R 14 is D. In some embodiments, R 14 is a C1-C6 alkyl group. In some embodiments, R 14 is a C1-C6 haloalkyl group. In some embodiments, R 14 is a C2-C6 alkenyl group. In some embodiments, R 14 is a C2-C6 alkynyl group. In some embodiments, R 14 is C1-C6 alkyl-OH. In some embodiments, R 14is C1-C6 alkyl-CN. In some embodiments, R 14 is a C1-C6 alkyl-O-C1-C6 alkyl group.

[0250] In some embodiments, R 16 is H. In some embodiments, R 16 is D. In some embodiments, R 16 is a C1-C6 alkyl group. In some embodiments, R 16 is a C1-C6 haloalkyl group. In some embodiments, R 16 is a C2-C6 alkenyl group. In some embodiments, R 16 is a C2-C6 alkynyl group. In some embodiments, R 16 is C1-C6 alkyl-OH. In some embodiments, R 16 is C1-C6 alkyl-CN. In some embodiments, R 16 is a C1-C6 alkyl-O-C1-C6 alkyl group.

[0251] In the compound represented by formula (I), R A are independently H, D, a C1-C6 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10 is selected from the group consisting of an aryl group, a 5- to 10-membered heteroaryl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, and a heterocycloalkylalkyl group (wherein the C1-C6 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10 The aryl group, 5- to 10-membered heteroaryl group, arylalkyl group, heteroarylalkyl group, cycloalkylalkyl group, or heterocycloalkylalkyl group may independently be D, OH, CN, halogen, C1-C4 alkyl group, NO2, oxo group, OR a , S.R.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 , N.R. c R d , N.R. c C(O)R b , N.R. c C(O)NR c R d , N.R. c C(O)OR a , B(OR c )(OR d ), C(=NR c )NR c R d , N.R. d C(=NR c )NR c R d , N.R. 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)2R b , N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , N.R. c S(O)(=NR b )R b and optionally substituted with 1, 2, 3, 4 or 5 substituents selected from:

[0252] In some embodiments, R Aare independently selected from the group consisting of H, D, a C1-C6 alkyl group, a C2-C4 alkenyl group, and a C2-C4 alkynyl group (wherein the C1-C6 alkyl group, C2-C4 alkenyl group, or C2-C4 alkynyl group is independently selected from the group consisting of D, OH, CN, halogen, a C1-C4 alkyl group, NO2, an oxo group, OR a , S.R. 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 , N.R. c R d , N.R. c C(O)R b , N.R. c C(O)NR c R d , N.R. c C(O)OR a , B(OR c )(OR d ), C(=NR c )NR c R d , N.R. d C(=NR c )NR c R d , N.R. 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)2R b , N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , N.R. c S(O)(=NR b)R b and optionally substituted with 1, 2, 3, 4 or 5 substituents selected from:

[0253] In some other embodiments, R A are independent, C3~C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10 aryl groups, and 5- to 10-membered heteroaryl groups (wherein the C3 to C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10 The aryl group and the 5- to 10-membered heteroaryl group are independently selected from D, OH, CN, halogen, C1 to C4 alkyl group, NO2, oxo group, OR a , S.R. 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 , N.R. c R d , N.R. c C(O)R b , N.R. c C(O)NR c R d , N.R. c C(O)OR a , B(OR c )(OR d ), C(=NR c )NR c R d , N.R. d C(=NR c )NR c R d , N.R. 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)2R b , N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , N.R. c S(O)(=NR b )R b and optionally substituted with 1, 2, 3, 4 or 5 substituents selected from:

[0254] In some embodiments, R A are independently selected from the group consisting of an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, and a heterocycloalkylalkyl group (wherein the arylalkyl group, the heteroarylalkyl group, the cycloalkylalkyl group, or the heterocycloalkylalkyl group is independently selected from D, OH, CN, halogen, a C1-C4 alkyl group, NO2, an oxo group, OR a , S.R. 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 , N.R. c R d , N.R. c C(O)R b , N.R. c C(O)NR c R d , N.R. c C(O)OR a , B(OR c )(OR d ), C(=NR c )NR c R d , N.R. d C(=NR c )NR c R d , N.R. dC(=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)2R b , N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , N.R. c S(O)(=NR b )R b and optionally substituted with 1, 2, 3, 4 or 5 substituents selected from:

[0255] In some other embodiments, R A are independent, C6~C 10 Aryl-C1-C6 alkyl group, 5-10 membered heteroaryl-C1-C6 alkyl group, C3-C 10 is selected from the group consisting of cycloalkyl-C1-C6 alkyl groups and 4- to 10-membered heterocycloalkyl-C1-C6 alkyl groups (wherein the C6-C 10 Aryl-C1-C6 alkyl group, 5-10 membered heteroaryl-C1-C6 alkyl group, C3-C 10 The cycloalkyl-C1-C6 alkyl group or the 4- to 10-membered heterocycloalkyl-C1-C6 alkyl group is independently selected from D, OH, CN, halogen, a C1-C4 alkyl group, NO2, an oxo group, OR a , S.R. 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 , N.R. c Rd , N.R. c C(O)R b , N.R. c C(O)NR c R d , N.R. c C(O)OR a , B(OR c )(OR d ), C(=NR c )NR c R d , N.R. d C(=NR c )NR c R d , N.R. 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)2R b , N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , N.R. c S(O)(=NR b )R b and optionally substituted with 1, 2, 3, 4 or 5 substituents selected from:

[0256] In the compound represented by formula (I), R B are independently H, D, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10is selected from the group consisting of an aryl group, a 5- to 10-membered heteroaryl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, and a heterocycloalkylalkyl group (wherein the C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10 An aryl group, a 5- to 10-membered heteroaryl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, or a heterocycloalkylalkyl group is R 13 and optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0257] In some embodiments, R B are independently selected from the group consisting of H, D, a C1-C6 alkyl group, a C2-C6 alkenyl group, and a C2-C6 alkynyl group (wherein the C1-C6 alkyl group, C2-C6 alkenyl group, or C2-C6 alkynyl group, R 13 and optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0258] In some embodiments, R B is R 13 is a C2-C6 alkynyl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0259] In some embodiments, R B is R 13 is a C2-C6 alkenyl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0260] In some embodiments, R B is R 13 is a C1-C6 alkyl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0261] In some embodiments, R B is a C1-C6 alkyl group. In some embodiments, R B is a methyl group. In some embodiments, R B is an ethyl group. In some embodiments, R B is an n-propyl group. In some embodiments, R B is an isopropyl group. In some embodiments, R B is an isobutyl group. In some embodiments, R B is a tert-butyl group.

[0262] In some embodiments, R B is R 13 C3-C optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 10 In some embodiments, R B is R 13 In some embodiments, R is a cyclopropyl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from B is R 13 In some embodiments, R is a cyclobutyl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from B is R 13 In some embodiments, R is a cyclopentyl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from B is R 13 and a cyclohexyl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0263] In some other embodiments, R B is R 13 In some embodiments, R is a 4- to 10-membered heterocycloalkyl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Bis selected from the group consisting of azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, dioxanyl, tetrahydropyranyl, tetrahydrothiopyranyl, piperazinyl, morpholinyl, azepanyl, diazocanyl, diazepanyl, and azepanyl groups, wherein each ring is selected from the group consisting of R 13 and optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0264] In some other embodiments, R B is R 13 C6-C optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from 10 In some other embodiments, R B is a phenyl group, naphthyl group (wherein each ring is 13 and optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0265] In some other embodiments, R B is R 13 is a 5- to 10-membered heteroaryl group optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0266] In some other embodiments, R Bis a pyrrolyl group, a furanyl group, a thiophenyl group, an imidazolyl group, an oxazolyl group, a thiazolyl group, a tetrazolyl group, a pyrazolyl group, a triazolyl group, a thiadiazolyl group, an oxadiazolyl group, a pyridinyl group, a pyrimidinyl group, a pyrazinyl group, a pyridazinyl group, an indolinyl group, an isoindolinyl group, an indolizine group, a benzofuranyl group, an isobenzofuranyl group, a benzo[b]thiophenyl group, a benzo[c]thiophenyl group, an indazolyl group, a benzo[d]imidazolyl group, a 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, furo[3,2-b]pyridinyl group, furo[3,2-c]pyridinyl group, furo[2,3-c]pyridinyl group, furo[2,3-b]pyridinyl group, benzo[c]isoxazolyl group, furo[3,4-b]pyridinyl group, furo[3,4-b]pyridinyl group, furo[3,4-c]pyridinyl group, furo[3,2-b]pyridinyl group, furo[3,2-c]pyridinyl group, furo[2,3-b]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 a pyridinyl group, an imidazo[4,5-b]pyridinyl group, a pyrrolo[3,2-c]pyridazinyl group, a pyrrolo[3,2-d]pyrimidinyl group, a pyrrolo[2,3-b]pyrazinyl group, a pyrrolo[2,3-d]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]pyrazinyl group, and a 6H-pyrrolo[3,4-c]pyridazinyl group, wherein each ring is selected from the group consisting of R 13 and optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0267] In some other embodiments, RB is selected from the group consisting of an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, and a heterocycloalkylalkyl group, wherein the arylalkyl group, the heteroarylalkyl group, the cycloalkylalkyl group, or the heterocycloalkylalkyl group is selected from the group consisting of R 13 and optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0268] In some embodiments, R B is C6~C 10 Aryl-C1-C6 alkyl group, 5-10 membered heteroaryl-C1-C6 alkyl group, C3-C 10 is selected from the group consisting of cycloalkyl-C1-C6 alkyl groups and 4- to 10-membered heterocycloalkyl-C1-C6 alkyl groups (wherein the C6-C 10 Aryl-C1-C6 alkyl group, 5-10 membered heteroaryl-C1-C6 alkyl group, C3-C 10 The cycloalkyl-C1-C6 alkyl group or the 4- to 10-membered heterocycloalkyl-C1-C6 alkyl group is R 13 and optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0269] In some embodiments, R C and R D are each independently H, D, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C7 cycloalkyl group, a 4- to 7-membered heterocycloalkyl group, a phenyl group, a 5- to 6-membered heteroaryl group, a C6-C 10 Aryl-C1-C6 alkyl group, 5-10 membered heteroaryl-C1-C6 alkyl group, C3-C 10 and a 4- to 10-membered heterocycloalkyl-C1-C6 alkyl group, and a 4- to 10-membered heterocycloalkyl-C1-C6 alkyl group (wherein the C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C7 cycloalkyl group, 4- to 7-membered heterocycloalkyl group, phenyl group, 5- to 6-membered heteroaryl group, C6-C10 Aryl-C1-C6 alkyl group, 5-10 membered heteroaryl-C1-C6 alkyl group, C3-C 10 The cycloalkyl-C1-C6 alkyl group or the 4- to 10-membered heterocycloalkyl-C1-C6 alkyl group is independently D, OH, CN, halogen, oxo group, C1-C4 alkyl group, C1-C4 haloalkyl group, C1-C4 cyanoalkyl group, OC1-C4 alkyl group, OC1-C4 haloalkyl group, C1-C4 alkyl-O-C1-C4 alkyl group, C1-C4 alkyl-O-C1-C4 haloalkyl group, OC2-C4 alkylOH, OC2-C4 alkyl-O-C1-C4 alkyl group, OC2-C4 alkyl-O-C1-C4 haloalkyl group, SF5, OC(O)NR c R d , N.R. c R d , N.R. c C(O)R b , S(O)NR c R d , S(O)2R b , N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , or B(OR c )(OR d ) optionally substituted with 1, 2, 3, 4 or 5 substituents selected from:

[0270] In some embodiments, R C are independently H, D, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C7 cycloalkyl group, a 4- to 7-membered heterocycloalkyl group, a phenyl group, a 5- to 6-membered heteroaryl group, a C6-C 10 Aryl-C1-C6 alkyl group, 5-10 membered heteroaryl-C1-C6 alkyl group, C3-C 10and a 4- to 10-membered heterocycloalkyl-C1-C6 alkyl group, and a 4- to 10-membered heterocycloalkyl-C1-C6 alkyl group (wherein the C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C7 cycloalkyl group, 4- to 7-membered heterocycloalkyl group, phenyl group, 5- to 6-membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 membered heteroaryl-C1-C6 alkyl group, C3-C 10 The cycloalkyl-C1-C6 alkyl group or the 4- to 10-membered heterocycloalkyl-C1-C6 alkyl group is independently D, OH, CN, halogen, oxo group, C1-C4 alkyl group, C1-C4 haloalkyl group, C1-C4 cyanoalkyl group, OC1-C4 alkyl group, OC1-C4 haloalkyl group, C1-C4 alkyl-O-C1-C4 alkyl group, C1-C4 alkyl-O-C1-C4 haloalkyl group, OC2-C4 alkylOH, OC2-C4 alkyl-O-C1-C4 alkyl group, OC2-C4 alkyl-O-C1-C4 haloalkyl group, SF5, OC(O)NR c R d , N.R. c R d , N.R. c C(O)R b , S(O)NR c R d , S(O)2R b , N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , and B(OR c )(OR d ) optionally substituted with 1, 2, 3, 4 or 5 substituents selected from:

[0271] In some embodiments, R D are independently H, D, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C7 cycloalkyl group, a 4- to 7-membered heterocycloalkyl group, a phenyl group, a 5- to 6-membered heteroaryl group, a C6-C10 Aryl-C1-C6 alkyl group, 5-10 membered heteroaryl-C1-C6 alkyl group, C3-C 10 and a 4- to 10-membered heterocycloalkyl-C1-C6 alkyl group, and a 4- to 10-membered heterocycloalkyl-C1-C6 alkyl group (wherein the C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C7 cycloalkyl group, 4- to 7-membered heterocycloalkyl group, phenyl group, 5- to 6-membered heteroaryl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 membered heteroaryl-C1-C6 alkyl group, C3-C 10 The cycloalkyl-C1-C6 alkyl group or the 4- to 10-membered heterocycloalkyl-C1-C6 alkyl group is independently D, OH, CN, halogen, oxo group, C1-C4 alkyl group, C1-C4 haloalkyl group, C1-C4 cyanoalkyl group, OC1-C4 alkyl group, OC1-C4 haloalkyl group, C1-C4 alkyl-O-C1-C4 alkyl group, C1-C4 alkyl-O-C1-C4 haloalkyl group, OC2-C4 alkylOH, OC2-C4 alkyl-O-C1-C4 alkyl group, OC2-C4 alkyl-O-C1-C4 haloalkyl group, SF5, OC(O)NR c R d , N.R. c R d , N.R. c C(O)R b , S(O)NR c R d , S(O)2R b , N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , and B(OR c )(OR d Optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from:

[0272] In some other embodiments, R C and R Dtogether with the N atom linked thereto form a 4- to 7-membered heterocycloalkyl group, wherein the 4- to 7-membered heterocycloalkyl group is optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from D, OH, oxo, CN, —NH, —NH(C1-C4 alkyl group), —N(C1-C4 alkyl group), halogen, C1-C4 alkyl group, C1-C4 haloalkyl group, C1-C4 cyanoalkyl group, O-C1-C4 alkyl group, O-C4 haloalkyl group, O-C2-C4 alkylOH, O-C2-C4 alkyl-O—C1-C4 alkyl group, and O-C2-C4 alkyl-O—C1-C4 haloalkyl group.

[0273] In some embodiments, each R E are independently H, D, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C2-C4 alkenyl group, a (C1-C4 alkoxy group)-C1-C4 alkyl group, a C2-C4 alkynyl group, a C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10 Aryl-C1-C4 alkyl group, C3-C 10 It is selected from the group consisting of cycloalkyl-C1-C4 alkyl groups, 5- to 10-membered heteroaryl-C1-C4 alkyl groups, and 4- to 10-membered heterocycloalkyl-C1-C4 alkyl groups.

[0274] In some embodiments, each R F are independently H, D, a C1-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 It is selected from the group consisting of a cycloalkyl group and a 4- to 10-membered heterocycloalkyl group.

[0275] In some embodiments, each R a is H or D.

[0276] In some embodiments, each Ra are independently selected from the group consisting of a C1-C4 alkyl group, a C2-C4 alkenyl group, and a C2-C4 alkynyl group (wherein said C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, phenyl group, C3-C7 cycloalkyl group, 5- to 6-membered heteroaryl group, or 4- to 7-membered heterocycloalkyl group is optionally substituted by 1, 2, or 3 substituents independently selected from D, OH, CN, —NH2, —NH(C1-C4 alkyl group), —N(C1-C4 alkyl group)2, halogen, a C1-C4 alkyl group, a C1-C4 alkoxy group, a C1-C4 haloalkyl group, and a C1-C4 haloalkoxy group).

[0277] In some embodiments, each R a are independently selected from the group consisting of a phenyl group, a C3-C7 cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 4- to 7-membered heterocycloalkyl group (wherein said phenyl group, C3-C7 cycloalkyl group, 5- to 6-membered heteroaryl group, or 4- to 7-membered heterocycloalkyl group is optionally substituted with 1, 2, or 3 substituents independently selected from D, OH, CN, —NH2, —NH(C1-C4 alkyl group), —N(C1-C4 alkyl group)2, halogen, a C1-C4 alkyl group, a C1-C4 alkoxy group, a C1-C4 haloalkyl group, and a C1-C4 haloalkoxy group).

[0278] In some embodiments, each R b are independently H or D.

[0279] In some embodiments, each R b are independently selected from the group consisting of a C1-C4 alkyl group, a C2-C4 alkenyl group, and a C2-C4 alkynyl group (wherein the C1-C4 alkyl group, C2-C4 alkenyl group, and C2-C4 alkynyl group are independently selected from the group consisting of D, OH, CN, -NH2, -NH(C1-C4 alkyl group), -N(C1-C4 alkyl group)2, halogen, a C1-C4 alkyl group, a C1-C4 alkoxy group, a C1-C4 haloalkyl group, a C1-C4 haloalkoxy group, a C6-C10 Aryl groups, C3-C 10 Optionally substituted with 1, 2, or 3 substituents selected from a cycloalkyl group, a 5- to 10-membered heteroaryl group, and a 4- to 10-membered heterocycloalkyl group.

[0280] In some embodiments, each R b are independently a phenyl group, a C3-C7 cycloalkyl group, a 5- or 6-membered heteroaryl group, a 4- to 7-membered heterocycloalkyl group, a C6-C 10 Aryl-C1-C6 alkyl group, 5-10 membered heteroaryl-C1-C6 alkyl group, C3-C 10 and 4- to 10-membered heterocycloalkyl-C1-C6 alkyl groups, and 4- to 10-membered heterocycloalkyl-C1-C6 alkyl groups (wherein the phenyl group, C3-C7 cycloalkyl group, 5- to 6-membered heteroaryl group, 4- to 7-membered heterocycloalkyl group, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 membered heteroaryl-C1-C6 alkyl group, C3-C 10 The cycloalkyl-C1-C6 alkyl group or the 4- to 10-membered heterocycloalkyl-C1-C6 alkyl group is independently D, OH, CN, -NH2, -NH(C1-C4 alkyl group), -N(C1-C4 alkyl group)2, halogen, a C1-C4 alkyl group, a C1-C4 alkoxy group, a C1-C4 haloalkyl group, a C1-C4 haloalkoxy group, a C6-C 10 Aryl groups, C3-C 10 optionally substituted with 1, 2, or 3 substituents selected from a cycloalkyl group, a 5- to 10-membered heteroaryl group, or a 4- to 10-membered heterocycloalkyl group).

[0281] In some embodiments, R c and R d are each independently H, D, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C10 Aryl-C1-C6 alkyl group, 5-10 membered heteroaryl-C1-C6 alkyl group, C3-C 10 Cycloalkyl-C1-C6 alkyl group, 4-10 membered heterocycloalkyl-C1-C6 alkyl group, C6-C 10 Aryl-C3~C 10 Cycloalkyl groups, C6-C 10 Aryl group - 4-10 membered heterocycloalkyl group, C6-C 10 Aryl group - 5-10 membered heteroaryl group, bis(C6-C 10 aryl group), 5-10 membered heteroaryl-C3-C 10 Cycloalkyl group, 5-10 membered heteroaryl group, 4-10 membered heterocycloalkyl group, 5-10 membered heteroaryl-C6-C 10 aryl group, and bis(5- to 10-membered heteroaryl group) (wherein 1~4 Alkyl group, C 2~4 Alkenyl group, C 2~4 Alkynyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 membered heteroaryl-C1-C6 alkyl group, C3-C 10 Cycloalkyl-C1-C6 alkyl group, 4-10 membered heterocycloalkyl-C1-C6 alkyl group, C6-C 10 Aryl-C3~C 10 Cycloalkyl groups, C6-C 10 Aryl group - 4-10 membered heterocycloalkyl group, C6-C 10 Aryl group - 5-10 membered heteroaryl group, bis(C6-C 10 aryl group), 5-10 membered heteroaryl-C3-C 10 Cycloalkyl group, 5-10 membered heteroaryl group, 4-10 membered heterocycloalkyl group, 5-10 membered heteroaryl-C6-C 10The aryl group or bis(5- to 10-membered heteroaryl group) is independently D, OH, CN, -NH2, -NH(C1-C4 alkyl group), -N(C1-C4 alkyl group)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 groups, 5- to 10-membered heteroaryl groups, C(O)OR a1 , C(O)R b1 , S(O)2R b1 , C1-C4 alkyl-O—C1-C4 alkyl group, and C1-C4 alkyl-O—C1-C4 alkyl-O—).

[0282] In some embodiments, R c and R d and the N atom linked thereto form a 4- to 7-membered heterocycloalkyl group (e.g., a 4-membered heterocycloalkyl group, a 5-membered heterocycloalkyl group, a 6-membered heterocycloalkyl group, or a 7-membered heterocycloalkyl group). The 4- to 7-membered heterocycloalkyl group is selected from the group consisting of D, OH, CN, -NH, -NH(C1-C4 alkyl group), -N(C1-C4 alkyl group), 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 groups, 5- to 10-membered heteroaryl groups, C(O)OR a1 , C(O)R b1 , S(O)2R b1 , a C1-C4 alkoxy-C1-C4 alkyl group, and a C1-C4 alkoxy-C1-C4 alkoxy group).

[0283] In some embodiments, each R e is H. In some embodiments, each R e is D.

[0284] In some embodiments, each R e are independently selected from C1 to C4 alkyl groups. In some embodiments, each R e are independently selected from C1-C4 haloalkyl groups. In some embodiments, each R e are independently selected from C2 to C4 alkenyl groups.

[0285] In some embodiments, each R e is independently selected from (C1-C4 alkoxy)-C1-C4 alkyl. In some embodiments, each R e are independently selected from C2 to C4 alkynyl groups.

[0286] In some embodiments, each R e independently C6~C 10 In some embodiments, each R e are independently selected from 5- to 10-membered heteroaryl groups. In some embodiments, each R e are independently C3~C 10 In some embodiments, each R e are independently selected from 3 to 10-membered heterocycloalkyl groups.

[0287] In some embodiments, each R e independently C6~C 10 In some embodiments, each R e are independently C3~C 10 In some embodiments, each R e are independently selected from 5-10 membered heteroaryl-C1-C4 alkyl groups. In some embodiments, each R e are independently selected from 4 to 10-membered heterocycloalkyl-C1 to C4 alkyl groups.

[0288] In some embodiments, each R f is H or D.

[0289] In some embodiments, each R f are independently a C1 to C4 alkyl group, a C2 to C4 alkenyl group, a C2 to C4 alkynyl group, a C6 to C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 It is selected from the group consisting of a cycloalkyl group and a 4- to 10-membered heterocycloalkyl group.

[0290] In some embodiments, each R a1 is H or D.

[0291] In some embodiments, each R a1 are independently selected from the group consisting of 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- to 6-membered heteroaryl group, and a 4- to 7-membered heterocycloalkyl group (wherein said C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, phenyl group, C3-C7 cycloalkyl group, 5- to 6-membered heteroaryl group, or 4- to 7-membered heterocycloalkyl group is optionally substituted by 1, 2, or 3 substituents independently selected from D, OH, CN, —NH2, —NH(C1-C4 alkyl group), —N(C1-C4 alkyl group)2, halogen, a C1-C4 alkyl group, a C1-C4 alkoxy group, a C1-C4 haloalkyl group, and a C1-C4 haloalkoxy group).

[0292] In some embodiments, each R b1 are independently H, D, 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- to 6-membered heteroaryl group, a 4- to 7-membered heterocycloalkyl group, a C6-C 10 Aryl-C1-C6 alkyl group, 5-10 membered heteroaryl-C1-C6 alkyl group, C3-C 10and a 4- to 10-membered heterocycloalkyl-C1 to C6 alkyl group, and a 4- to 10-membered heterocycloalkyl-C1 to C6 alkyl group (wherein the C1 to C4 alkyl group, C2 to C4 alkenyl group, C2 to C4 alkynyl group, phenyl group, C3 to C7 cycloalkyl group, 5 to 6-membered heteroaryl group, 4 to 7-membered heterocycloalkyl group, C6 to C 10 Aryl-C1-C6 alkyl group, 5-10 membered heteroaryl-C1-C6 alkyl group, C3-C 10 The cycloalkyl-C1-C6 alkyl group or the 4- to 10-membered heterocycloalkyl-C1-C6 alkyl group is independently D, OH, CN, -NH2, -NH(C1-C4 alkyl group), -N(C1-C4 alkyl group)2, halogen, a C1-C4 alkyl group, a C1-C4 alkoxy group, a C1-C4 haloalkyl group, a C1-C4 haloalkoxy group, a C6-C 10 Aryl groups, C3-C 10 Optionally substituted with 1, 2, or 3 substituents selected from a cycloalkyl group, a 5- to 10-membered heteroaryl group, and a 4- to 10-membered heterocycloalkyl group.

[0293] In some embodiments, R c1 and R d1 are each independently H, D, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10 Aryl-C1-C6 alkyl group, 5-10 membered heteroaryl-C1-C6 alkyl group, C3-C 10 and 4- to 10-membered heterocycloalkyl-C1-C6 alkyl groups, and 4- to 10-membered heterocycloalkyl-C1-C6 alkyl groups (wherein the C1-C4 alkyl groups, C1-C4 haloalkyl groups, C2-C4 alkenyl groups, C2-C4 alkynyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C10 Aryl-C1-C6 alkyl group, 5-10 membered heteroaryl-C1-C6 alkyl group, C3-C 10 The cycloalkyl-C1-C6 alkyl group or the 4- to 10-membered heterocycloalkyl-C1-C6 alkyl group is optionally substituted with 1, 2, or 3 substituents independently selected from D, OH, CN, —NH2, —NH(C1-C4 alkyl group), —N(C1-C4 alkyl group)2, halogen, a C1-C4 alkyl group, a C1-C4 alkoxy group, a C1-C4 haloalkyl group, and a C1-C4 haloalkoxy group.

[0294] In some embodiments, R c1 and R d1 together with the N atom linked thereto form a 4- to 7-membered heterocycloalkyl group (e.g., a 4-membered heterocycloalkyl group, a 5-membered heterocycloalkyl group, a 6-membered heterocycloalkyl group, a 7-membered heterocycloalkyl group). (Here, the 4- to 7-membered heterocycloalkyl group is selected from D, OH, CN, -NH2, -NH(C1-C4 alkyl group), -N(C1-C4 alkyl group)2, halogen, a C1-C4 alkyl group, a C1-C4 alkoxy group, a C1-C4 haloalkyl group, and C 1-4 and optionally substituted with 1, 2, or 3 substituents independently selected from haloalkoxy groups.

[0295] In some embodiments, each R e1 are independently H or D.

[0296] In some embodiments, each R e1 are independently a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C2-C4 alkenyl group, a (C1-C4 alkoxy)-C1-C4 alkyl group, a C2-C4 alkynyl group, a C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C6-C 10 Aryl-C1-C4 alkyl group, C3-C 10It is selected from the group consisting of cycloalkyl-C1-C4 alkyl groups, 5- to 10-membered heteroaryl-C1-C4 alkyl groups, and 4- to 10-membered heterocycloalkyl-C1-C4 alkyl groups.

[0297] In some embodiments, each R f1 are independently H or D.

[0298] In some embodiments, each R f1 are independently a C1 to C4 alkyl group, a C2 to C4 alkenyl group, a C2 to C4 alkynyl group, a C6 to C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 It is selected from the group consisting of a cycloalkyl group and a 3- to 10-membered heterocycloalkyl group.

[0299] In some embodiments, R G , R H and R I are each a C1 to C4 alkyl group or a phenyl group.

[0300] In some embodiments, R G is a C1-C4 alkyl group or a phenyl group. G is selected from the group consisting of 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, and a phenyl group.

[0301] In some embodiments, R H is a C1-C4 alkyl group or a phenyl group. G is selected from the group consisting of 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, and a phenyl group.

[0302] In some embodiments, R I is a C1-C4 alkyl group or a phenyl group. Gis selected from the group consisting of 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, and a phenyl group.

[0303] In some embodiments, the compound represented by Formula (I) is a pharmaceutically acceptable salt thereof. 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 an N-oxide.

[0304] In some embodiments, there is provided a compound of formula (I), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof, wherein the compound is a compound of formula (IIA): [ka] (Wherein, each R 1 , R 2 , R 3 , R 4 , Cy 1 , Cy 2 , X, Y 1 , Y 2 , and Y 3 is defined as in formula (I).

[0305] In some embodiments, the compounds of formula (I) are compounds of formula (IIa) and (IIb), or pharmaceutically acceptable salts, stereoisomers, solvates, N-oxides, tautomers, isotopic variants, prodrugs, or deuterated compounds thereof. [ka] (Wherein, each R 1 , R 2 , R 3 , R 4 , R5 , Cy 1 , Cy 2 , Y 1 , Y 2 , and Y 3 is defined as in formula (I).

[0306] In some embodiments, the compound of formula (I) is a compound of formula (IIIa) and (IIIb), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof. [ka] (Wherein, each R 1 , R 2 , R 3 , R 5 , Cy 1 , Cy 2 , Y 1 , Y 2 , and Y 3 is defined as in formula (I).

[0307] In some embodiments, the compound of formula (I) is a compound of formula (IV), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof. [ka] (Wherein, each R 1 , R 2 , R 3 , R 8 , X, Cy 1 , Cy 2 , X, Y 1 , and Y 2 is defined as in formula (I).

[0308] In some embodiments, X in formula (IV) is NR 5In some embodiments, X in formula (IV) is O.

[0309] In the compound represented by formula (IV), each R 8 is selected from the group consisting of H, D, F, Cl, OH, CN, CF3, OMe, OCF3, and SF5. In some embodiments, R 8 is H. In some embodiments, R 8 is D. In some embodiments, R 8 is F. In some embodiments, R 8 is Cl. In some embodiments, R 8 is OH. In some embodiments, R 8 is CN. In some embodiments, R 8 is CF3. In some embodiments, R 8 is OMe. In some embodiments, R 8 is OCF3. In some embodiments, R 8 is SF5.

[0310] In some embodiments, the compound of formula (I) is a compound of formula (IVa) or (IVb), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof. [ka] (Wherein, each R 1 , R 2 , R 3 , R 5 , R 8 , Cy 1 , Cy 2 , Y 1 , and Y 2 is defined as in formula (I).

[0311] In some embodiments, Cy in Formula (IVa) 1is 1, 2, 3 or 4 R 9 In some embodiments, Cy is a 5- to 6-membered heteroaryl group optionally substituted with 1 is 1, 2, 3 or 4 R 9 In some embodiments, Cy is a 6-membered heteroaryl group optionally substituted with 1 is one, two or three R 9 is a 5-membered heteroaryl group optionally substituted with

[0312] In some embodiments, Cy in Formula (IVb) 1 is 1, 2, 3 or 4 R 9 In some embodiments, Cy is a 5- to 6-membered heteroaryl group optionally substituted with 1 is 1, 2, 3 or 4 R 9 In some embodiments, Cy is a 6-membered heteroaryl group optionally substituted with 1 is one, two or three R 9 is a 5-membered heteroaryl group optionally substituted with

[0313] In some embodiments, the compound of formula (I) is a compound of formula (Va), formula (Vb), or formula (Vc), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof. [ka] (Wherein, each R 1 , R 2 , R 3 , R 6 , R 7 , R 8 , Cy 1 , and Cy 2 is defined as in formula (I).

[0314] In some embodiments, in Formula (Va), Formula (Vb), or Formula (Vc), Cy1 is 1, 2, 3 or 4 R 9 In some embodiments, Cy is a 5- to 6-membered heteroaryl group optionally substituted with 1 is 1, 2, 3 or 4 R 9 In some embodiments, Cy is a 6-membered heteroaryl group optionally substituted with 1 is one, two or three R 9 A 5-membered heteroaryl group optionally substituted with

[0315] In some embodiments, Cy 1 teeth, [ka]

[0316] In some embodiments, Cy 1 teeth, [ka] In some embodiments, Cy 1 teeth [ka] is.

[0317] In some embodiments, there is provided a compound of formula (I), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof, wherein the compound is a compound of formula (VI): [ka] (Wherein, each R 1 , R 2 , R 3 , R 9 , Cy 2 , X, Y 1 , and Y 2is defined as in formula (I).

[0318] In some embodiments, there is provided a compound of formula (I), wherein the compound is represented by formula (VIa) or (VIb), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof. [ka] [In the formula, Cy 1 is a 5-membered heteroaryl group having 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, wherein said 5-membered heteroaryl group is selected from 1, 2, 3, or 4 R 9 (optionally substituted with each R 1 , R 2 , R 3 , R 5 , R 9 , Cy 2 , Y 1 , and Y 2 The definitions are the same as in formula (I)].

[0319] In some embodiments, the compound of formula (I) is a compound of formula (VII), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof. [ka] (Wherein, each R 1 , R 2 , R 3 , R 8 , R 9 , Cy 2 , X, Y 1 , and Y 2 is defined as in formula (I).

[0320] In some embodiments of formula (VII), X is NR5 In some embodiments of formula (VII) above, X is O.

[0321] In some embodiments, the compound of formula (I) is a compound of formula (VIIa) or formula (VIIb), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof. [ka] (Wherein, each R 1 , R 2 , R 3 , R 5 , R 8 , R 9 , Cy 2 , Y 1 , and Y 2 is defined as in formula (I).

[0322] In some embodiments, the compound of Formula (I) is a compound of Formula (VIIIa), Formula (VIIIb), or Formula (VIIIc), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof. [ka] (Wherein, each R 1 , R 2 , R 3 , R 6 , R 7 , R 8 , R 9 , and Cy 2 is defined as in formula (I).

[0323] In some embodiments, the compound of Formula (I) is a compound of Formula (IXa), Formula (IXb), or Formula (IXc), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof. [ka] (Wherein, each R 1 , R 2 , R 3 , R 6 , R 7 , R 8 , R 9 , and Cy 2 is defined as in formula (I).

[0324] In some embodiments, the compound represented by formula (I) is a compound represented by formula (Xa) or formula (Xb), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof. [ka] (Wherein, each R 1 , R 5 , R 6 , R 8 , R 9 , and Cy 2 is defined as in formula (I).

[0325] In some embodiments, R in the compounds represented by formula (Xa) and formula (Xb) 1 is independently selected from the group consisting of CN, CH, CD, CF, CHF, and CHF. In some embodiments, R 1 is CF. In some embodiments, R 1 is CHF2. In some embodiments, R 1 is CHF. In some embodiments, R1 is CH3. In some embodiments, R 1 is CD3. In some embodiments, R 1 is CN.

[0326] In some embodiments, in the compounds of formula (Xa) and formula (Xb), R 6 are H, D, OH, C1-C6 alkyl group, C1-C6 haloalkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, OR A , N.R. C R D In some embodiments, R 6 is H. In some embodiments, R 6 is D. In some embodiments, R 6 is a C1-C6 alkyl group, for example, —CH3. In some embodiments, R 6 is a C1-C6 haloalkyl group, for example, —CF3. In some embodiments, R 6 is a C2-C6 alkenyl group. In some embodiments, R 6 is a C2-C6 alkynyl group. In some embodiments, R 6 is OR A , for example, —OCH3, or —OCF3. In some embodiments, R 6 is NR C R D is.

[0327] In some other embodiments, R in the compounds represented by formula (Xa) and (Xb) 8 is selected from the group consisting of H, D, F, Cl, OH, CN, CH3, CF3, OMe, OCF3, and SF5. In some embodiments, R 8 is H. In some embodiments, R 8 is D. In some embodiments, R 8 is F. In some embodiments, R 8 is Cl. In some embodiments, R 8is OH. In some embodiments, R 8 is CN. In some embodiments, R 8 is CH3. In some embodiments, R 8 is CF. In some embodiments, R 8 is OMe. In some embodiments, R 8 is OCF3. In some embodiments, R 8 is SF5.

[0328] The present specification also contemplates, describes and encompasses stereoisomers of the compounds of formula (I), their pharmaceutically acceptable salts and solvates, and also describes methods of using the compounds of formula (I) and pharmaceutical compositions containing the compounds of formula (I).

[0329] In some embodiments, the compound represented by formula (I) is selected from the following compounds, or a pharmaceutically acceptable salt thereof: [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6] [Table 1-7] [Table 1-8] [Table 1-9] [Table 1-10] [Table 1-11] [Table 1-12]

[0330] As will be apparent, the compounds of formula (I) and all subgenera described herein may contain multiple chiral centers. Accordingly, multiple stereoisomers (enantiomers and diastereomers) exist for the compounds of formula (I) of the present disclosure (subgenera described herein). Any single stereoisomer of the compounds of formula (I) (subgenera described herein), as well as mixtures of such stereoisomers, are contemplated and encompassed by the present disclosure.

[0331] Pharmaceutically acceptable salts and solvates of the compounds of Formula (I) (including the subgenera described herein) are also included within the scope of this disclosure.

[0332] Isotopic variations of the compounds of formula (I) (including the subgenera described herein) are also included within the scope of the present disclosure.

[0333] The present disclosure further provides the use of a compound described herein or a pharmaceutically acceptable salt thereof in any of the methods described herein. The present disclosure further provides the application of a compound described herein or a pharmaceutically acceptable salt thereof in the preparation of a medicament for use in any of the methods described herein.

[0334] The present disclosure further provides a pharmaceutical composition comprising a compound according to the present disclosure, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier thereof.

[0335] The PARG inhibitors described in the present disclosure can be used to treat a variety of 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 blood cancer.

[0336] Routes of administration of the compounds described in this disclosure include, but are not limited to, oral administration, injection, topical administration, and inhalation administration.

[0337] The compounds described herein can be used as single agents in combination with other therapies, including one or more of the following cancer therapies: surgery, chemotherapy, radiation therapy, targeted therapy (e.g., kinase inhibitors, growth factor inhibitors, cyclin-dependent kinase inhibitors, etc.), other DDR modulating agents (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, PKMYT1 inhibitors, etc.), immunotherapy, gene therapy, or cell therapy.

[0338] It is an intermediate compound represented by the following formula (A). [ka] [In the formula, W 1 is a leaving group (e.g., a halogen such as Cl, Br, or I), a pseudohalogen (e.g., OTf, OTs, or OMs), etc.), X is O or NR 5 and Y 1 is N or CR 6 and Y 2 is N or CR 7 and Y1 and Y 2 at most one of is N, Y 3 is N or CR 8 and n is 0, 1, or 2; R 1 , R 2 and R 3 are each independently selected from the group consisting of H, D, CN, a C1-C3 alkyl group, a C2-C3 alkenyl group, a C2-C3 alkynyl group, a C3-C7 cycloalkyl group, and a 4- to 7-membered heterocycloalkyl group (wherein the C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, C3-C7 cycloalkyl group, or 4- to 7-membered heterocycloalkyl group is optionally substituted with 1 to 5 substituents independently selected from D, halogen, CN, OH, a C1-C6 alkyl group, a C1-C6 haloalkyl group, —O—C1-C6 alkyl group, and —O—C1-C6 haloalkyl group); Or, R 2 and R 3 together with the carbon atoms linked thereto form a C3-C7 cycloalkyl group or a 4- to 7-membered heterocycloalkyl group, wherein the C3-C7 cycloalkyl group or the 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, a C1-C6 alkyl group, a C1-C6 haloalkyl group, —O—C1-C6 alkyl group, and —O—C1-C6 haloalkyl group, R 4 is H, D, halogen, OH, CN, NO2, SF5, C1-C3 alkyl group, C2-C3 alkenyl group, C2-C3 alkynyl group, -O-C1-C3 alkyl group, and NR C R D wherein said C1-C3 alkyl group, C2-C3 alkenyl group, and C2-C3 alkynyl group are optionally substituted with halogen or CN; R 5 H, D, CN, OR Band C1-C4 alkyl groups, where the C1-C4 alkyl groups are selected from the group consisting of R 5A and optionally substituted with at least one of: 5A are each independently selected from the group consisting of D, F, Cl, CN, NH2, OH, -O-C1 to C6 alkyl group, -O-C1 to C6 haloalkyl group, optionally substituted C3 to C7 cycloalkyl group, and optionally substituted 4 to 7 membered heterocycloalkyl group, and further wherein said optionally substituted means substituted with any substituent selected from the group consisting of D, halogen, CN, OH, C1 to C4 alkyl group, C1 to C4 haloalkyl group, -O-C1 to C4 alkyl group, and -O-C1 to C4 haloalkyl group), Or, R 1 and R 5 together with the atoms connected thereto form a 5- to 7-membered partially saturated heterocycloalkyl group, wherein said 5- to 7-membered partially saturated heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 substituents independently selected from D, halogen, CN, CF, NO, oxo, OH, C-C alkyl group, C-C haloalkyl group, -O-C-C alkyl group, and -O-C-C haloalkyl group; R 6 and R 7 are each independently H, D, halogen, CN, NO2, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, OR A , S.R. A , SF5, NHOR A , C(O)OR A , C(O)R B , C(O)NR C R D , OC(O)NR C R D , N.R. C R D , N.R. C C(O)R B , N.R. C C(O)NR C R D , N.R. C C(O)ORA , N.R. C S(O)2R B , B(OR C )(OR D ), C(=NR C )NR C R D , N.R. D C(=NR C )NR C R D , N.R. 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)2R B , S(O)NR C R D , N.R. C S(O)NR C R D , and N.R. C S(O)(=NR B )R B wherein the C1-C6 alkyl group, the C2-C6 alkenyl group, or the C2-C6 alkynyl group is independently selected from the group consisting of R 11 optionally substituted with 1, 2 or 3 substituents selected from R 8 is selected from the group consisting of H, D, CN, halogen, OH, NH2, a C1-C3 alkyl group, a C1-C3 haloalkyl group, -O-C1-C3 alkyl group, -O-C1-C3 haloalkyl group, a C1-C3 cyanoalkyl group, and SF5; R A are independently H, D, a C1-C6 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10is selected from the group consisting of an aryl group, a 5- to 10-membered heteroaryl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, and a heterocycloalkylalkyl group (wherein the C1-C6 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10 The aryl group, 5- to 10-membered heteroaryl group, arylalkyl group, heteroarylalkyl group, cycloalkylalkyl group, or heterocycloalkylalkyl group may independently be D, OH, CN, halogen, C1-C4 alkyl group, NO2, oxo group, OR a , S.R. 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 , N.R. c R d , N.R. c C(O)R b , N.R. c C(O)NR c R d , N.R. c C(O)OR a , B(OR c )(OR d ), C(=NR c )NR c R d , N.R. d C(=NR c )NR c R d , N.R. 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)2Rb , N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , and N.R. c S(O)(=NR b )R b optionally substituted with 1, 2, 3, 4 or 5 substituents selected from R B are independently H, D, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10 is selected from the group consisting of an aryl group, a 5- to 10-membered heteroaryl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, and a heterocycloalkylalkyl group (wherein the C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C 10 Cycloalkyl groups, 4-10 membered heterocycloalkyl groups, C6-C 10 The aryl group, 5- to 10-membered heteroaryl group, arylalkyl group, heteroarylalkyl group, cycloalkylalkyl group, or heterocycloalkylalkyl group is independently R 13 optionally substituted with 1, 2, 3, 4 or 5 substituents selected from Each R 13 are independently H, D, OH, CN, halogen, oxo group, C1-C4 alkyl group, C1-C4 haloalkyl group, C1-C4 cyanoalkyl group, OC1-C4 alkyl group, OC1-C4 haloalkyl group, OC1-C4 alkyl-OH, OC1-C4 alkyl-O-C1-C4 alkyl group, OC1-C4 alkyl-O-C1-C4 haloalkyl group, C1-C4 alkyl-O-C1-C4 alkyl group, C1-C4 alkyl-O-C1-C4 haloalkyl group, optionally substituted C3-C7 cycloalkyl group, optionally substituted 4-7 membered heterocycloalkyl group, SF5, OR a , S.R. a , C(O)Rb , OC(O)NR c R d , N.R. c R d , N.R. c C(O)R b , N.R. c C(O)NR c R d , N.R. c C(O)OR a , S(O)R b , S(O)NR c R d , S(O)2R b , N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , and B(OR c )(OR d ) (wherein the optionally substituted means substituted with a substituent selected from the group consisting of D, halogen, CN, OH, C1-C4 alkyl group, C1-C4 haloalkyl group, —O—C1-C4 alkyl group, and —O—C1-C4 haloalkyl group), R C and R Dare each independently selected from the group consisting of H, D, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C7 cycloalkyl group, a 4- to 7-membered heterocycloalkyl group, a phenyl group, a 5- to 6-membered heteroaryl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, and a heterocycloalkylalkyl group (wherein the C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C7 cycloalkyl group, a 4- to 7-membered heterocycloalkyl group, a phenyl group, a 5- to 6-membered heteroaryl group, an arylarylalkyl group, a cycloalkylalkyl group, and a heterocycloalkylalkyl group). The alkyl group, heteroarylalkyl group, cycloalkylalkyl group, or heterocycloalkylalkyl group is independently D, OH, CN, halogen, oxo group, C1-C4 alkyl group, C1-C4 haloalkyl group, C1-C4 cyanoalkyl group, OC1-C4 alkyl group, OC1-C4 haloalkyl group, OC2-C4 alkyl-OH, OC2-C4 alkyl-O-C1-C4 alkyl group, OC2-C4 alkyl-O-C1-C4 haloalkyl group, C1-C4 alkyl-O-C1-C4 alkyl group, C1-C4 alkyl-O-C1-C4 haloalkyl group, SF5, OC(O)NR c R d , N.R. c R d , N.R. c C(O)R b , S(O)NR c R d , S(O)2R b , N.R. c S(O)2R b , S(O)NR c R d , N.R. c S(O)NR c R d , and B(OR c )(OR d ), optionally substituted with 1, 2, 3, 4 or 5 substituents selected from Or, R C and R Dtogether with the N atom linked thereto form a 4- to 7-membered heterocycloalkyl group, wherein the 4- to 7-membered heterocycloalkyl group is optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from D, OH, oxo, CN, —NH, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, halogen, or a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C1-C4 cyanoalkyl group, an OC1-C4 alkyl group, an OC1-C4 haloalkyl group, an OC2-C4 alkyl-OH, an OC2-C4 alkyl-O—C1-C4 alkyl group, or an OC2-C4 alkyl-O—C1-C4 haloalkyl group; R a and R a1 are each independently selected from the group consisting of H, D, 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- to 6-membered heteroaryl group, and a 4- to 7-membered heterocycloalkyl group (wherein the C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, phenyl group, C3-C7 cycloalkyl group, 5- to 6-membered heteroaryl group, or 4- to 7-membered heterocycloalkyl group is optionally substituted by 1, 2, or 3 substituents independently selected from D, OH, CN, —NH2, —NH(C1-C4 alkyl group), —N(C1-C4 alkyl group)2, halogen, a C1-C4 alkyl group, a C1-C4 alkoxy group, a C1-C4 haloalkyl group, and a C1-C4 haloalkoxy group); R b and R b1are each independently selected from the group consisting of H, D, 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- to 6-membered heteroaryl group, a 4- to 7-membered heterocycloalkyl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, and a heterocycloalkylalkyl group; wherein the C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, phenyl group, C3-C7 cycloalkyl group, a 5- to 6-membered heteroaryl group, a 4- to 7-membered heterocycloalkyl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, or a heterocycloalkylalkyl group is independently selected from the group consisting of D, OH, CN, -NH2, -NH(C1-C4 alkyl group), -N(C1-C4 alkyl group)2, halogen, a C1-C4 alkyl group, a C1-C4 alkoxy group, a C1-C4 haloalkyl group, a C1-C4 haloalkoxy group, a C6-C 10 Aryl groups, C3-C 10 optionally substituted with 1, 2, or 3 substituents selected from a cycloalkyl group, a 5- to 10-membered heteroaryl group, and a 4- to 10-membered heterocycloalkyl group; R c and R d are each independently H, D, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 a cycloalkyl group, a 4- to 10-membered heterocycloalkyl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, a heterocycloalkylalkyl group, an arylcycloalkyl group, an arylheterocycloalkyl group, an arylheteroaryl group, a diaryl group, a heteroarylcycloalkyl group, a heteroarylheterocycloalkyl group, a heteroarylaryl group, and a diheteroaryl group (wherein the C 1~4 Alkyl group, C 2~4 Alkenyl group, C 2~4 Alkynyl groups, C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C10 The cycloalkyl group, 4-10 membered heterocycloalkyl group, arylalkyl group, heteroarylalkyl group, cycloalkylalkyl group, heterocycloalkylalkyl group, arylcycloalkyl group, arylheterocycloalkyl group, arylheteroaryl group, diaryl group, heteroarylcycloalkyl group, heteroarylheterocycloalkyl group, heteroarylaryl group, or diheteroaryl group is independently D, OH, CN, -NH2, -NH(C1-C4 alkyl group), -N(C1-C4 alkyl group)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 groups, 5- to 10-membered heteroaryl groups, C(O)OR a1 , C(O)R b1 , S(O)2R b1 , C1-C4 alkyl-O—C1-C4 alkyl group, and C1-C4 alkyl-O—C1-C4 alkyl-O—; Or, R c and R d form a 4- to 7-membered heterocycloalkyl group together with the N atom linked thereto (wherein the 4- to 7-membered heterocycloalkyl group is selected from the group consisting of D, OH, CN, -NH2, -NH(C1-C4 alkyl group), -N(C1-C4 alkyl group), 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 groups, 5- to 10-membered heteroaryl groups, C(O)OR a1 , C(O)R b1 , S(O)2R b1 , a C1-C4 alkoxy-C1-C4 alkyl group, and a C1-C4 alkoxy-C1-C4 alkoxy group), R E and R eare each independently H, D, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C2-C4 alkenyl group, a (C1-C4 alkoxy)-C1-C4 alkyl group, a C2-C4 alkynyl group, a C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C6-C 10 Aryl-C1-C4 alkyl group, C3-C 10 selected from the group consisting of cycloalkyl-C1-C4 alkyl groups, 5- to 10-membered heteroaryl-C1-C4 alkyl groups, and 4- to 10-membered heterocycloalkyl-C1-C4 alkyl groups; R F and R f are each independently H, D, a C1-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C6-C 10 Aryl group, 5-10 membered heteroaryl group, C3-C 10 cycloalkyl groups, and 4- to 10-membered heterocycloalkyl groups.]

[0339] In some embodiments, the intermediate compound of formula (A) is represented by formula (Aa) or formula (Ab). [ka] (In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , Y 1 , Y 2 , and W 1 The definition of is the same as in formula (A).

[0340] In some embodiments, the intermediate compound is the compound shown below, or a salt thereof. [Table 2]

[0341] definition Unless otherwise stated, the following terms have the meanings set forth below. Other terms are defined elsewhere throughout the description.

[0342] As used herein, the singular forms "a / an" and "the" include plural referents unless the context clearly dictates otherwise. It should also be noted that the claims may be drafted to exclude any optional element. Accordingly, this statement serves as a prerequisite for using exclusive language such as "only" or "only" in connection with the description of claim elements, or for using restrictive language such as "not."

[0343] Throughout this specification, variables defining divalent linking groups are described. Specifically, each linking substituent includes both the forward and reverse forms of the linking substituent. For example, -NR(CR'R")- includes -NR(CR'R'')- and -(CR'R'')NR-, and is intended to disclose each form alone. When a structure requires a linking group, the Markush variable listed in that group is understood to be the linking group. For example, when a structure requires a linking group and an "alkyl group" or an "aryl group" is listed in the Markush group definition for that variable, it is understood that the "alkyl group" and "aryl group" refer to the linked alkyl and aryl groups, respectively.

[0344] The term "substituted" means that an atom or group of atoms replaces a hydrogen atom to form a "substituent" linked to another group. Unless otherwise specified, the term "substituted" refers to any number of substitutions, such as mono-, di-, tri-, tetra-, or penta-substitution, provided such substitution is permitted. Substituents are independently selected, and substitution can occur at any chemically accessible position. It should be understood that substitution at a particular atom is limited by valence. The term "optionally substituted" means unsubstituted or substituted. The term "substituted" means that a hydrogen atom has been removed and replaced with a substituent. A single divalent substituent, such as an oxo group, can replace two hydrogen atoms.

[0345] The term "Cn-Cm" refers to an inclusive range, 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, alkyl groups having 3 carbon atoms, alkyl groups having 4 carbon atoms, alkyl groups having 5 carbon atoms, and alkyl groups having 6 carbon atoms. A "C0 alkyl group" refers to a covalent bond.

[0346] The compounds of the present disclosure are stable compounds. As used herein, "stable" refers to a compound that is sufficiently stable during processing that it can be isolated from a reaction solution to a useful degree of purity, and preferably can be formulated as an effective therapeutic agent.

[0347] It is also to be understood that certain features of the present disclosure, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the present disclosure, which are, for brevity, described in the context of a single embodiment, may also be provided singly or in any suitable subcombination.

[0348] As used herein, unless otherwise stated, the term "alkyl group," by itself or as part of another substituent, refers to a straight-chain or branched-chain saturated hydrocarbon group. An alkyl group can contain 1 to about 20, 2 to about 20, 1 to about 10, 1 to about 8, 1 to 6, 1 to 4, or 1 to about 3 carbon atoms. Similarly, C 1~8 , C 1~8 An alkyl group is defined as a straight or branched chain alkyl group having 1, 2, 3, 4, 5, 6, 7, or 8 carbon atoms. Examples of 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, tert-butyl), pentyl (e.g., n-pentyl, isopentyl, neopentyl), and the like.

[0349] As used herein, unless otherwise specified, an "alkenyl group" refers to an alkyl group having one or more carbon-carbon double bonds. Examples of alkenyl groups include, but are not limited to, ethenyl groups, propenyl groups, and the like.

[0350] As used herein, unless otherwise specified, an "alkynyl group" refers to an alkyl group having one or more carbon-carbon triple bonds. Examples of alkynyl groups include, but are not limited to, ethynyl groups, propynyl groups, and the like.

[0351] As used herein, unless otherwise specified, "haloalkyl group" refers to an alkyl group having one or more halogen substituents. Examples of haloalkyl groups include, but are not limited to, CF3, C2F5, CHF2, CH2F, CCl3, CHCl2, C2Cl5, etc.

[0352] As used herein, unless otherwise specified, the term "aryl group" refers to an unsubstituted or substituted monocyclic or polycyclic (e.g., having 2, 3, or 4 fused rings) aromatic hydrocarbon. In some embodiments, an aryl group has 6 to about 20 carbon atoms. In some embodiments, an aryl group has 6 to about 14 carbon atoms. In some embodiments, an aryl group has 6 to about 10 carbon atoms. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, anthracene, phenanthryl, indanyl, and indenyl groups.

[0353] As used herein, unless otherwise specified, the term "cycloalkyl group" refers to an unsubstituted or substituted non-aromatic carbocycle (saturated or partially unsaturated ring), such as annulated alkyl, alkenyl, and alkynyl groups. Cycloalkyl groups include monocyclic and polycyclic (e.g., having 2, 3, or 4 fused rings) ring systems, such as fused rings, spirocyclic carbocycles, and bridged carbocycles (e.g., bridged bicycloalkyl groups). In some embodiments, a cycloalkyl group can have 3 to about 20 carbon atoms, 3 to about 14 carbon atoms, 3 to about 10 carbon atoms, or 3 to 7 carbon atoms. A cycloalkyl group can also have 0, 1, 2, or 3 double bonds and / or 0, 1, or 2 triple bonds. A cycloalkyl group can also be substituted with an oxo or sulfido group (e.g., —C(O)— or —C(S)—). The definition of cycloalkyl group also includes groups having one or more aromatic rings fused to the cycloalkyl ring (i.e., having a common bond with the cycloalkyl group), such as benzo derivatives such as pentane, pentene, and hexane groups. Cycloalkyl groups having one or more fused aromatic rings may be linked by an aromatic or non-aromatic ring. One or more ring-forming carbon atoms of a cycloalkyl group may be oxidized to form, for example, an oxo or sulfido substituent. In some embodiments, the cycloalkyl group is selected from C3 to C7 monocyclic cycloalkyl groups. In some embodiments, the cycloalkyl group is selected from C4 to C7 monocyclic cycloalkyl groups. 10The cycloalkyl group is selected from spirocyclic or bridged cycloalkyl groups. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptatrienyl, norbornenyl, norpinyl, norcarnyl, cubane, adamantane, bicyclo[1.1.1]pentyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptanyl, bicyclo[3.1.1]heptanyl, bicyclo[2.2.2]octanyl, spiro[3.3]heptanyl, and the like. In some embodiments, the cycloalkyl group is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups. In some embodiments, the cycloalkyl group is a group having 3 to 12 carbon atoms ("C3-C6"). 12 "), preferably a ring-containing non-aromatic hydrocarbon group having 3 to 6 carbon atoms ("C3-C6"). Examples of cycloalkyl groups include cyclopropyl groups (C 3; 3-membered), cyclobutyl group (C 4; 4-membered), cyclopropylmethyl group (C4), cyclopentyl group (C5), cyclohexyl group (C6), 1-methylcyclopropyl group (C4), 2-methylcyclopentyl group (C4), adamantyl group (C 10 ) etc.

[0354] The term "spirocycloalkyl group," when used alone or as part of a substituent group, refers to a non-aromatic hydrocarbon group containing two cycloalkyl groups, in which the two cycloalkyl groups typically share one carbon atom.

[0355] As used herein, unless otherwise specified, a "heteroaryl group" refers to an unsubstituted or substituted aromatic heterocycle having at least one heteroatom ring member, such as boron, sulfur, oxygen, or nitrogen. Heteroaryl groups include monocyclic and polycyclic (e.g., having 2, 3, or 4 fused rings) systems. Any N atom in a heteroaryl group can be oxidized to form an N-oxide. Examples of heteroaryl groups include, but are not limited to, pyridinyl, N-oxopyridinyl, pyrimidinyl, pyrazinyl, pyridazine, triazine, furanyl, quinolyl, isoquinolyl, thienyl, imidazolyl, thiazolyl, indolinyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 1,2,4-thiadiazolyl, isothiazolyl, benzothienyl, purinyl, carbazolyl, benzimidazolyl, and indolinyl groups. In some embodiments, the heteroaryl group has from 1 to about 20 carbon atoms, and in further embodiments, from about 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, hi some embodiments, the heteroaryl group has 1 to about 4, 1 to about 3, or 1 to 2 heteroatoms.

[0356] As used herein, unless otherwise specified, a "heterocycloalkyl group" refers to an unsubstituted or substituted monocyclic (saturated or partially unsaturated) or polycyclic heterocycle having at least one non-aromatic ring (saturated or partially unsaturated), in which one or more ring-forming carbon atoms of the heterocycloalkyl group are replaced with a heteroatom selected from N, O, S, Si, P, and B, and the ring-forming carbons and heteroatoms of the heterocycloalkyl group are optionally substituted with one or more oxo or sulfido groups (e.g., C(O), S(O), C(S), S(O), or P(O)). Heterocycloalkyl groups include monocyclic and polycyclic (e.g., having two fused rings) systems. Heterocycloalkyl groups include monocyclic and polycyclic 3- to 10-, 4- to 10-, 3- to 7-, 4- to 7-, and 5- to 6-membered heterocycloalkyl groups. Heterocycloalkyl groups also include spirocyclic and bridged rings (e.g., 5- to 10-membered biheterocycloalkyl bridged rings in which one or more ring-forming carbon atoms are replaced with a heteroatom independently selected from N, O, S, Si, P, and B). The heterocycloalkyl groups can be linked via a ring-forming carbon atom or a ring-forming heteroatom. In some embodiments, the heterocycloalkyl group contains 0 to 3 double bonds. In some embodiments, the heterocycloalkyl group contains 0 to 2 double bonds.

[0357] The heterocycloalkyl group also includes moieties having one or more aromatic rings fused (i.e., having a common bond) to a non-aromatic heterocycle, such as benzo or thiophene derivatives, such as piperidine, morpholine, and azepine. Heterocycloalkyl groups containing fused aromatic rings can be linked through any ring-forming atom, such as a ring-forming atom of the fused aromatic ring. In some embodiments, the heterocycloalkyl group has 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 heterocycloalkyl group has 1 to 4 heteroatoms, 1 to 3 heteroatoms, 1 to 2 heteroatoms, or 1 heteroatom. In some embodiments, the heterocycloalkyl group is a monocyclic 4- to 6-membered heterocycloalkyl group having 1 or 2 heteroatoms independently selected from N, O, S, and B and having one or more oxo (oxidized) ring members.

[0358] Examples of heterocycloalkyl groups include pyrrolidin-2-one, 1,3-isoxazolidin-2-one, pyranyl group, tetrahydropyran group, oxetanyl group, azetidinyl group, morpholino group, thiomorpholino group, piperazinyl group, tetrahydrofuranyl group, tetrahydrothiophenyl group, piperidinyl group, pyrrolidinyl group, isoxazolidinyl group, isothiazolidinyl group, pyrazolidinyl group, oxazolidinyl group, thiazolidinyl group, imidazolidinyl group, and azepanyl. group, benzazepine group, 1,2,3,4-tetrahydroisoquinoline group, azabicyclo[3.1.0]hexyl group, diazabicyclo[3.1.0]hexyl group, oxabicyclo[2.1.l]hexyl group, azabicyclo[2.2.l]heptanyl group, diazabicyclo[2.2.1]heptynyl group, diazabicyclo[3.1.l]heptanyl group, diazabicyclo[3.1.l]heptanyl group, azabicyclo[3.2.l]octanyl group, diazabicyclo[3.2.1]octanyl group, Oxabicyclo[2.2.2]octanyl, azabicyclo[2.2.2]octanyl, diazabicyclo[2.2.2]octanyl, azaadamantyl, diazaadamantyl, oxa-adamantyl, diazabicyclo[3.3]heptanyl, diazaspiro[3.3]heptanyl, oxa-azaspiro[3.3]heptanyl, azaspiro[3.4]octanyl, diazaspiro[3.4]octanyl, oxa-azaspiro[3.4]octanyl, oxa-aza Examples include, but are not limited to, spiro[3.5]nonanyl, azaspiro[2.5]octanyl, diazaspiro[2.5]octanyl, azaspiro[4.4]nonanyl, diazaspiro[4.4]nonanyl, oxa-azaspiro[4.4]nonanyl, azaspiro[4.5]decanyl, diazaspiro[4.5]decanyl, diazaspiro[4.4]nonanyl, oxa-diazaspiro[4.4]nonanyl, and octahydropyrrolo[3,4-c]pyrrolyl.

[0359] 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 may be attached to any heteroatom or carbon atom in the ring that results in a stable structure. Examples of heterocycloalkyl groups include, but are not limited to, azepanyl, aziridyl, azetidyl, pyrrolidyl, dioxolanyl, imidazolidyl, pyrazolidine, piperidyl, dioxanyl, morpholinyl, dithioanyl, thiomorpholinyl, oxazapanyl, oxiranyl, oxetanyl, quinuclidinyl, tetrahydrofuranyl, tetrahydropyranyl, and piperazinyl.

[0360] In some embodiments, the term "spiroheterocycloalkyl group," when used alone or as part of a substituent group, refers to a non-aromatic group that contains two rings, at least one of which is a heterocycloalkyl ring, and which share one carbon atom.

[0361] As used herein, unless otherwise specified, "arylcycloalkyl group" refers to a cycloalkyl group substituted with an aryl group.

[0362] As used herein, unless otherwise stated, "arylheterocycloalkyl group" refers to a heterocycloalkyl group substituted with an aryl group.

[0363] As used herein, unless otherwise specified, the term "arylheteroaryl group" refers to a heteroaryl group substituted with an aryl group.

[0364] As used herein, unless otherwise stated, the term "diaryl group" means an aryl group substituted with another aryl group.

[0365] As used herein, unless otherwise stated, "heteroarylcycloalkyl group" refers to a cycloalkyl group substituted with a heteroaryl group.

[0366] As used herein, unless otherwise stated, a "heteroarylheterocycloalkyl group" refers to a heterocycloalkyl group substituted with a heteroaryl group.

[0367] As used herein, unless otherwise stated, a "heteroarylaryl group" refers to an aryl group substituted with a heteroaryl group.

[0368] As used herein, unless otherwise stated, a "diheteroaryl group" refers to a heteroaryl group substituted with another heteroaryl group.

[0369] As used herein, "halo" or "halogen" includes fluorine, chlorine, bromine, and iodine.

[0370] As used herein, unless otherwise specified, "alkoxy" refers to an -O-alkyl group. Examples of alkoxy groups include methoxy, ethoxy, propoxy (e.g., n-propoxy and isopropoxy), tert-butoxy, and the like.

[0371] As used herein, unless otherwise stated, "hydroxyalkyl group" refers to an alkyl group substituted with OH.

[0372] As used herein, unless otherwise stated, a "cyanoalkyl group" refers to an alkyl group substituted with CN.

[0373] As used herein, unless otherwise specified, the term "alkoxyalkyl group" refers to an alkyl group substituted with an alkoxy group.

[0374] As used herein, unless otherwise specified, the term "alkoxyalkoxy group" refers to an alkoxy group substituted with an alkoxy group.

[0375] As used herein, unless otherwise stated, a "haloalkoxy group" refers to an --O-(haloalkyl) group.

[0376] As used herein, unless otherwise specified, an "arylalkyl group" refers to an alkyl group substituted with an aryl group, and a "cycloalkylalkyl group" refers to an alkyl group substituted with a cycloalkyl group. An example of an aralkyl group is a benzyl group.

[0377] As used herein, unless otherwise specified, a "heteroarylalkyl group" refers to an alkyl group substituted with a heteroaryl group, and a "heterocycloalkylalkyl group" refers to an alkyl group substituted with a heterocycloalkyl group.

[0378] As used herein, unless otherwise stated, an "oxo group" refers to an oxygen substituent connected through a double bond (ie, ═O).

[0379] As used herein, unless otherwise specified, the term "optionally substituted" means unsubstituted or substituted.

[0380] As used herein, unless otherwise specified, the term "substituted" refers to one or more hydrogen atoms in a group being independently replaced with the same or different substituents. Examples of 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 group (where o is 1-10), C 2~6 Alkenyl-NR c1 Rd1 、C 2~6 アルキニル-NR c1 R d1 、OC 2~6 アルキル-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 OR f1 、S(O)R b1 、-SO(=NR b1 )、S(O)NR c1 R d1 、S(O)2R b1 、NR c1 S(O)2R b1 、S(O)2NR c1 R d1, an aryl group, a heteroaryl group, a spirocycloalkyl group, a spiroheterocycloalkyl group, a cycloalkyl group, or a heterocycloalkyl group (wherein the aryl group, heteroaryl group, spirocycloalkyl group, spiroheterocycloalkyl group, or heterocycloalkyl group is independently selected from the group consisting of D, halogen, oxo group, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 haloalkyl group, C1-C6 alkyl-NR c1 R d1 , C 2~6 Alkenyl-NR c1 R d1 , C 2~6 Alkynyl-NR c1 R d1 , O.C. 2~6 Alkyl-NR c1 R d1 , CN, NO2, N3, OR a1 , S.R. 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 , N.R. c1 C(O)R b1 , N.R. c1 C(O)NR c1 R d1 , N.R. c1 C(O)OR a1 , C(=NR g1 )NR c1 R d1 , N.R. 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 OR f1 , S(O)R b1, S(O)NR c1 R d1 , S(O)2R b1 , N.R. c1 S(O)2R b1 , S(O)NR c1 R d1 and optionally substituted with a substituent selected from:

[0381] The compounds described herein may be asymmetric (e.g., possess one or more chiral centers). Unless otherwise specified, all stereoisomers, such as enantiomers and diastereomers, are included. Compounds containing asymmetric carbon atoms described herein can be isolated in optically active or racemic forms. Methods for preparing optically active forms from optically active starting materials, such as resolution of racemic mixtures or stereoselective synthesis, are known in the art. Many geometric isomers of olefins, C=N double bonds, and the like, can also be present in the compounds described herein, and all such stable isomers are encompassed within the scope of the present disclosure. Cis and trans geometric isomers of the compounds described herein are also described and can be isolated as a mixture of isomers or in separated isomeric forms.

[0382] The compounds of the present disclosure also include tautomeric forms. Tautomeric forms are caused by the migration of a proton, accompanied by the switching of a single bond and an adjacent double bond. Tautomeric forms include proton tautomers with the same chemical formula and isomeric protonation states and total charge. Examples of proton tautomers include ketone-enol pairs, amide-imidic acid pairs, lactam-lactim pairs, amide-imidic acid pairs, enamine-imine pairs, and ring structures in which protons occupy more than one position in a heterocyclic ring system, such as 1H- and 3H-imidazole, 1H-, 2H- and 4H-1,2,4-triazole, 1H- and 2H-isoindole, and 1H- and 2H-pyrazole. Some hydroxyl-substituted compounds are [ka] Tautomeric forms may exist in equilibrium or may be sterically locked into one form by appropriate substitution.

[0383] In some circumstances, the compounds described herein may exist as rotamers. A description of a compound of the present disclosure without a specific rotamer is intended to encompass any individual rotamer and any mixture of rotamers in any proportion. A description of a specific rotamer means that the described rotamer is substantially free of other rotamers.

[0384] The compounds of the present disclosure may further include all isotopes (also referred to as isotopes) of atoms present in intermediates or final compounds. "Isotopes" refer to atoms with the same atomic number but different molecular weights. For example, isotopes of hydrogen include tritium and deuterium. In some embodiments, the compounds of the present disclosure or their salts are substantially isolated. "Substantially isolated" means that the compound is at least partially or substantially isolated from the environment in which it is formed or detected. Partial isolation may include, for example, a composition enriched in the compounds of the present disclosure. Substantial isolation may include a composition containing at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% by weight of the compounds of the present disclosure or their salts. Methods for isolating compounds and their salts are common in the art.

[0385] The present disclosure also includes pharmaceutically acceptable salts of the compounds described herein. As used herein, "pharmaceutically acceptable salt" refers to a derivative of a compound described herein, which is formed by modifying the parent compound by converting an acidic or basic moiety present in the parent compound to its salt form. Examples of pharmaceutically acceptable salts include, but are not limited to, inorganic or organic acid salts of basic residues such as amines, and base or organic salts of acidic residues such as carboxylic acids. Pharmaceutically acceptable salts of the present disclosure include non-toxic salts of the parent compound, formed, for example, from non-toxic inorganic or organic acids. Pharmaceutically acceptable salts of the present disclosure can be synthesized from parent compounds containing a basic or acidic moiety by conventional chemical methods. Typically, the salts can be prepared by reacting the free acid or base form of these compounds with a stoichiometric amount of the appropriate base or acid in water, an organic solvent, or a mixture of both. Non-aqueous media such as ether, ethyl acetate, alcohols (ethanol, methanol, isopropanol, or butanol), or acetonitrile (ACN) are generally preferred. Lists of suitable salts are provided in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418, and Journal of Pharmaceutical Science, 66, 2 (1977), each of which is incorporated herein by reference.

[0386] The term "pharmaceutically acceptable" is used herein to refer to compounds, ingredients, compositions and / or dosage forms that are suitable, within the scope of sound medical judgment, for use in contact with human and animal tissues without excessive toxicity, irritation, allergic response, other problem or complication and that possess a reasonable benefit-risk ratio.

[0387] "Pharmaceutically acceptable excipient" means a substance that is non-toxic, biologically tolerable, or biologically suitable for administration to a subject, e.g., an inert substance, which is added to a pharmacological composition to facilitate administration of a drug or is used as a vehicle, carrier, or diluent and is compatible therewith. Examples of excipients include calcium carbonate, calcium phosphate, various sugars and starches, cellulose derivatives, gelatin, vegetable oils, and polyethylene glycols.

[0388] The term "solvate" refers to a compound of formula (I) that contains one or more solvent molecules.

[0389] The term "leaving group" refers to an atom or group of atoms that displaces bonding electrons in a chemical reaction, e.g., as a stable entity, usually forming an anion. Preferably, the leaving group is selected from the group consisting of halogen, especially chlorine, bromine, or iodine, (methylsulfonyl)oxy-, [(4-methylphenyl)sulfonyl]oxy-, [(trifluoromethyl)sulfonyl]oxy-, [(nonafluorobutyl)sulfonyl]oxy-, (4-bromophenyl)sulfonyl]oxy-, [(4-tert-butylphenyl)sulfonyl]oxy-, (phenylsulfonyl)oxy-, and [(4-methoxyphenyl)sulfonyl]oxy groups.

[0390] A "subject" includes a human. The terms "human," "patient," and "subject" are used interchangeably herein.

[0391] In one embodiment, "treating" or "treatment" of any disease or condition means ameliorating the disease or condition (i.e., preventing or reducing the progression of the disease or at least one clinical symptom). In another embodiment, "treatment" refers to the amelioration of at least one physical parameter, which may not be discernible to the subject. In another embodiment, "treatment" refers to modulating the disease or condition physically (e.g., stabilization of a discernible symptom), physiologically (e.g., stabilization of a physical parameter), or both. In another embodiment, "treatment" refers to delaying the onset of the disease or condition.

[0392] References to "compounds of the disclosure" and similar expressions are intended to encompass compounds of formula (I) herein and subgenera thereof, and, where the context permits, also include stereoisomers (e.g., enantiomers and diastereomers) and structural isomers (e.g., tautomers) of said compounds of formula (I), as well as pharmaceutically acceptable salts.

[0393] As used herein, the term "isotopic variant" refers to a compound that contains an isotope at one or more atoms that constitute the compound in a proportion greater than the natural abundance. For example, an "isotopic variant" of a compound may be radiolabeled, i.e., contain one or more radioactive isotopes, or may contain deuterium ( 2 H or D), carbon-13 ( 13 C), nitrogen-15( 15 In compounds where such isotopic substitutions have been made, the following atoms (if present) can be changed, for example, any hydrogen atom can be changed to 2 H / D, and any carbon 13 C, or any nitrogen 15 It is understood that the atoms may be N and that the presence and location of these atoms is within the ability of one skilled in the art to determine.

[0394] It should also be understood that compounds that have the same molecular formula but differ in the bonding characteristics or order of their atoms or the spatial arrangement of their atoms are referred to as "isomers." Isomers that differ in the spatial arrangement of their atoms are referred to as "stereoisomers," and include, for example, diastereomers, enantiomers, and rotamers. The compounds of the present disclosure may have one or more asymmetric centers. Thus, these compounds may be either (R)- or (S)-stereoisomers at each asymmetric center, or mixtures thereof. Unless otherwise indicated, the description or naming of a particular compound in the specification and claims is intended to encompass all stereoisomers and mixtures thereof, including racemates or other forms. If a structure contains one chiral center but no specific stereochemistry is indicated for that center, the structure contains both enantiomers, either singly or as mixtures of enantiomers. If a structure contains one or more chiral centers but no specific stereochemistry is indicated for those centers, the structure contains all enantiomers and diastereomers, either singly or as mixtures. Methods for the determination of stereochemistry and the separation of stereoisomers are well-known in the art.

[0395] Pharmaceutical Composition The disclosure also provides a pharmaceutical composition comprising a compound of Formula (I), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotopic variant, prodrug, or deuterated compound thereof, and a pharmaceutically acceptable carrier.

[0396] Pharmaceutical compositions may be administered via a form suitable for oral administration (e.g., tablets, pills, hard or soft capsules, aqueous or oily suspensions, emulsions, dispersible powders or particles, syrups or elixirs), a form suitable for injectable administration (e.g., aqueous or oily suspensions or emulsions containing sesame oil, corn oil, cottonseed oil or peanut oil, and elixirs, mannitol, glucose or sterile aqueous solutions, and similar pharmaceutical carriers), a form suitable for topical administration (e.g., creams, ointments, gels, or aqueous or oily solutions or suspensions, inhalation administration (e.g., fine powders or liquid sprays), insufflation administration (e.g., fine powders), or parenteral administration (e.g., sterile aqueous-oil solutions for intravenous, subcutaneous, intramuscular, peritoneal or intramuscular administration, or suppositories for rectal administration).

[0397] The compositions can be prepared according to conventional procedures using common pharmaceutical excipients well known in the art. Thus, compositions for oral administration can contain, for example, one or more coloring agents, sweeteners, flavoring agents and / or preservatives.

[0398] A therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, is an amount sufficient to treat or prevent, slow the progression of, and / or alleviate the symptoms associated with a proliferative disorder referred to herein.

[0399] The amount of active ingredient required to be combined with one or more excipients to produce a single dosage form will vary depending on the subject being treated and the particular route of administration. For example, a formulation for oral administration to humans will typically contain, for example, 0.1 mg to 1000 mg of a compound of formula (I) or a pharmaceutically acceptable salt thereof, and an appropriate amount of an excipient, comprising about 5% to about 98% by weight of the total composition.

[0400] In accordance with well-known medical principles, the dosage of the compounds of formula (I) administered for therapeutic or prophylactic purposes may vary depending on the nature and severity of the disease, the age and sex of the animal or patient, and the route of administration.

[0401] The following describes non-limiting examples of pharmaceutical compositions and methods for their preparation.

[0402] Administration method The compounds of formula (I) or pharmaceutically acceptable salts thereof, or pharmaceutical compositions containing these compounds, may be administered to a subject via any convenient route of administration, whether systemic / peripheral or local (i.e., to the desired site of action).

[0403] Routes of administration include, but are not limited to, oral (e.g., by ingestion), buccal, sublingual, transdermal (e.g., by patches, patches, etc.), transmucosal (e.g., by patches, patches, etc.), intranasal (e.g., by nose drops), intraocular (e.g., by eye drops), pulmonary (e.g., by inhalation or insufflation therapy, e.g., aerosols, e.g., oral or nasal therapy), rectal (e.g., by suppositories or enemas), vaginal (e.g., by pessaries), by injection, including, for example, subcutaneous, intradermal, intramuscular, intravenous, intraarterial, intracardiac, intrathecal, intravertebral, intracapsular, subcapsular, intraorbital, intraperitoneal, intratracheal, subcuticular, intraarticular, subarachnoid, and intrastemal, and by implantation of a depot or reservoir subcutaneously or intramuscularly.

[0404] How to use The methods typically involve administering to a subject an effective amount of a compound of the present disclosure. Effective amounts of the subject compounds in combination may vary depending on the intended use (in vitro or in vivo), or the subject and disease state being treated, such as the subject's weight and age, the severity of the disease state, the route of administration, etc., and can be readily determined by one of ordinary skill in the art. The term also applies to dosages for inducing a specific response in target cells, such as reducing proliferation or activity of a target protein. Specific dosages will vary depending on the particular compound selected, the administration scheme followed, whether or not it is co-administered with other compounds, the time of administration, the tissue of administration, and the physical delivery system by which it is delivered.

[0405] As used herein, "IC 50 The term "50% inhibitory concentration" refers to the half-maximal inhibitory concentration of an inhibitor for inhibiting a biological or biochemical function. This quantitative measurement indicates how much of a particular inhibitor is needed to inhibit a given biological process (or a component of the process, i.e., an enzyme, cell, cell receptor, or microorganism) by half. In other words, the half-maximal (50%) inhibitory concentration (IC) of a substance (also known as 50% IC or IC 50 , half maximal (50%) inhibitory concentration).

[0406] In some embodiments, the test method (measurement of PARG enzyme activity) includes measuring an IC50 value that is about equal to or less than a predetermined value in in vitro measurement. 50 In some embodiments, the IC value of PARG inhibition by the PARG inhibitor is used. 50Values ​​are about 1nM or less, 2nM or less, 5nM or less, 7nM or less, 10nM or less, 20nM or less, 30nM or less, 40nM or less, 50nM or less, 60nM or less, 70nM or less, 80nM or less, 90nM or less, 100nM or less, 120nM or less, 140nM or less, 150nM or less, 160nM or less, 170nM or less, 180nM or less, 190nM or less, 200nM or less, 225nM or less, 250nM or less, 275nM or less, 300nM or less, 325nM or less, 350nM or less, 375nM or less, 400nM or less, 425nM or less, 450nM or less, 475nM or less, 500nM or less, 550nM or less, 600nM or less, 650nM or less, 700nM or more, 750nM or less, 800nM or more, 850nM or more, 900nM or less, 950nM or less, 1μM or less, 1.1μM or less, 1.2μM or less, 1.3μM or less, 1.4μM or less, 1.5μM or less, 1.6μM or less, 1.7μM or less, 1.8μM or less, 1.9μM or less, 2μM or less, 5μM or less, 10μM or less, 15μM or less, 20μM or less, 25μM or less, 30μM or less, 40μM or less, 50μM, 60μM, 70μM, 80μM, 90μM, 100μM, 200μM, 300μM, 400μM, or 500μM or less (or a range defined by and including any two of the above numerical values).

[0407] The subject method is useful for treating diseases associated with PARG. Any disease caused directly or indirectly by abnormal activity or expression levels of PARG may be a suspected disease.

[0408] Different diseases related to PARG have been reported.Non-limiting examples of the diseases related to PARG include autoimmune disease, neurodegenerative disease (for example, Parkinson's disease), cardiovascular disease (for example, ischemic stroke and myocardial infarction), inflammatory disease (for example, septic shock), diabetes, and cancer such as breast cancer, ovarian cancer, gastric cancer, prostate cancer, pancreatic cancer, uterine cancer, cervical cancer, endometrial cancer, lung cancer, brain cancer, bile duct cancer and blood cancer.

[0409] Non-limiting examples of such diseases include breast cancer, invasive ductal carcinoma, invasive lobular carcinoma, Paget's disease of the breast, hereditary breast and ovarian cancer, medullary breast carcinoma, mucinous breast cancer, inflammatory breast cancer, ovarian cancer, ovarian epithelial cancer, ovarian germ cell tumor, ovarian low malignant potential tumor, gastric cancer, gastric malignant lymphoma, gastrointestinal cancer, gastrointestinal tract carcinoid tumor, gastrointestinal stromal tumor, gastrointestinal stromal tumor, prostate cancer, prostate acinar adenocarcinoma, prostate ductal adenocarcinoma, prostatic sarcoma, small cell prostate carcinoma, prostatic squamous cell carcinoma, pancreatic cancer, exocrine pancreatic cancer, neuroendocrine pancreatic cancer, uterine cancer, uterine sarcoma, endometrial sarcoma, cervical cancer, cervical squamous cell carcinoma, uterine adenocarcinoma, uterine adenosquamous carcinoma, small cell uterine Cervical cancer, cervical mucinous neoplasm, clear cell cervical cancer, cervical lymphoma, cervical sarcoma, endometrial cancer, endometrioid tumor, lung cancer, non-small cell lung cancer, small cell lung cancer, brain stem glioma, cerebral glioma, brain cancer, cerebellar astrocytic tumor, cerebral astrocytic tumor, head and neck cancer, glioblastoma multiforme, glioma, gliomatosis cerebri, ganglioglioma, ganglioneuroma, paraganglioma, primitive neuroectodermal tumor, pancreatic neuroendocrine tumor, optic pathway glioma, schwannoma, neuroblastoma, neuroblastoma, neurofibroma, neuroma, olfactory neuroblastoma, extrahepatic bile duct carcinoma, Bellini duct carcinoma, cholangiocarcinoma, acute eosinophilic leukemia, acute lymphocytic leukemia, acute megakaryocytic leukemia, Acute monocytic leukemia, non-matured acute myeloid leukemia, acute myeloid dendritic cell leukemia, acute myeloid leukemia, acute myeloid leukemia, acute early myeloid leukemia, adult T-cell leukemia, infiltrative NK cell leukemia, chronic lymphocytic leukemia, chronic monocytic leukemia, chronic myeloid leukemia, chronic neutrophilic leukemia, erythroid leukemia, hairy cell leukemia, leukemia, lymphocytic leukemia, lymphoma, macroglobulinemia, mast cell leukemia, monocytic leukemia, myeloid leukemia, T-cell acute lymphocytic leukemia, T-cell large granular lymphocytic leukemia, T-cell leukemia, T-cell prolymphocytic leukemia, AIDS-related lymphoma, vascular immunology These include, but are not limited to, blastic T-cell lymphoma, B-cell leukemia, B-cell lymphoma, cutaneous T-cell lymphoma, diffuse large granular B-cell lymphoma, enteropathy-associated T-cell lymphoma, follicular lymphoma, hepatosplenic T-cell lymphoma, Hodgkin's lymphoma, lymphangioma, lymphangiosarcoma, lymphoepithelioma, MALT lymphoma, mantle cell lymphoma, non-Hodgkin's lymphoma, non-Hodgkin's lymphoma, precursor T-lymphocytic lymphoma, primary central nervous system lymphoma, primary effusion lymphoma, small cell lymphoma, T-cell lymphoma, peripheral lymphoma, and the like.

[0410] In some embodiments, the method is used to treat a disease selected from the group consisting of tumor angiogenesis, autoimmune diseases, neurodegenerative conditions (e.g., Parkinson's disease), cardiovascular diseases (e.g., ischemic stroke and myocardial infarction), inflammatory diseases (e.g., septic shock), diabetes, and cancers such as breast cancer, ovarian cancer, gastric cancer, prostate cancer, pancreatic cancer, uterine cancer, cervical cancer, endometrial cancer, lung cancer, brain cancer, bile duct cancer, and blood cancer.

[0411] In another embodiment, the method is used to treat a disease selected from the group consisting of breast cancer, lung cancer, pancreatic cancer, prostate cancer, colon cancer, ovarian cancer, uterine cancer, and cervical cancer.

[0412] In another embodiment, the method is used to treat a disease selected from the group consisting of leukemias such as acute myeloid leukemia (AML), acute lymphocytic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, hairy cell leukemia, myelodysplastic syndromes, myeloproliferative disorders, chronic myelogenous leukemia (CML), mastocytosis, chronic lymphocytic leukemia (CLL), multiple myeloma (MM), myeloproliferative dysregulation syndromes (MDS), and epidermoid carcinoma.

[0413] The compounds of the present disclosure and pharmaceutical compositions containing them are used to treat any of the above diseases, either alone or in combination with medical therapies, including, for example, surgery and radiation therapy (e.g., gamma radiation, neutron therapy, electron beam therapy, proton therapy, brachytherapy, and total body radiation therapy).

[0414] In other aspects, the compounds of the present disclosure and pharmaceutical compositions containing them can be used alone or in combination with one or more other drugs to treat any of the above diseases.

[0415] In other methods, the compounds of the present disclosure and pharmaceutical compositions containing them can be administered in combination with agonists of nuclear receptor drugs.

[0416] In other methods, the compounds of the present disclosure and pharmaceutical compositions containing them can be administered in combination with antagonists of nuclear receptor drugs.

[0417] In other methods, the compounds of the present disclosure and pharmaceutical compositions comprising them can be administered in combination with an anti-proliferative agent.

[0418] Combination therapy The compounds of the present disclosure can be used as single agents or in combination with other therapies, including one or more cancer therapies selected from surgery, chemotherapy, radiation therapy, targeted therapy (e.g., growth factor inhibitors, kinase inhibitors, cyclin-dependent kinase inhibitors, etc.), other DDR modulating agents (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, PKMYT1 inhibitors, etc.), immunotherapy, gene therapy, and cell therapy.

[0419] To treat cancer and other proliferative diseases, the compounds of the present disclosure can be used in combination with medical therapies such as surgery, radiation therapy, or chemotherapy. Examples of radiation therapy include gamma radiation, neutron therapy, electron beam therapy, proton therapy, brachytherapy, and total body radiation therapy.Examples of suitable chemotherapeutic agents include other antiproliferative / antitumor drugs and combinations thereof used in medical oncology, such as alkylating agents (e.g., cisplatin, oxaliplatin, carboplatin, cyclophosphamide, nitrogen mustard, melphalan, chlorambucil, busulfan, temozolomide, nitrosoureas), antimetabolites (e.g., gemcitabine, and antifolates, such as 5-fluorouracil, tegafur, raltitrexed, methotrexate, cytarabine, and hydroxycarbamate). Fluoropyrimidine drugs such as benzodiazepines, etc.), antitumor antibiotics (e.g., anthracene ring antibiotics such as bleomycin, doxorubicin, daunorubicin, epirubicin, idarubicin, mitomycin C, actinomycin, and mithramycin), mitotic inhibitors (e.g., vinca alkaloids such as vincristine, vinblastine, vindesine, and vinorelbine, and antitumor drugs such as taxol and taxotere, and PLK inhibitors), topoisomerase inhibitors (e.g., etoposide, epipodophyllotoxins such as phenytoin and teniposide, amsacrine, topotecan, and camptothecin), cytostatics such as antiestrogens (e.g., tamoxifen, fulvestrant, toremifene, raloxifene, droloxifene, and iodoxifene), antiandrogens (e.g., bicalutamide, flutamide, nilutamide, and cyproterone acetate), LHRH antagonists or agonists (e.g., goserelin, leuprorelin, and buserelin), progestogens (e.g., methyl acetate, and one or more of the classes of anti-tumor agents selected from the group consisting of gestrol), aromatase inhibitors (e.g., anastrozole, letrozole, vorazole, and exemestane), and 5α-reductase inhibitors (e.g., finasteride), anti-invasive inhibitors, such as c-Src kinase family inhibitors (e.g., AZD0530, dasatinib, and bosutinib), and metalloprotease inhibitors (e.g., marimastat, inhibitors of urokinase-type plasminogen activator receptor function, antibodies to heparanase).

[0420] To treat cancer and other proliferative disorders, the compounds of the present disclosure can be used in combination with targeted therapies, such as those exemplified below. Examples of targeted therapies include inhibitors of growth factor function (e.g., the anti-erbB2 antibody trastuzumab, the anti-EGFR antibody panitumumab, the anti-erbB1 antibody cetuximab, and the antibodies described in Critical reviews in Stem et al.). oncology / haematology, 2005, Vol. 54, pp. 11-29); such other inhibitors: for example, tyrosine kinase inhibitors such as inhibitors of the epidermal growth factor family (e.g., EGFR family tyrosine kinase inhibitors such as gefitinib, erlotinib, CI1033, etc.); erbB2 tyrosine kinase inhibitors such as lapatinib; inhibitors of the hepatocyte growth factor family; inhibitors of the insulin growth factor family; inhibitors of the platelet-derived growth factor family such as imatinib and / or nilotinib; inhibitors of serine / threonine kinases (e.g., Ras / Raf inhibitors such as sorafenib, tipifarnib, and lonafarnib); inhibitors of cell signaling mediated by MEK and / or AKT kinase; c-kit inhibitors; abl kinase inhibitors; PI3 kinase inhibitors; Flt3 kinase inhibitors, CSF-1R kinase inhibitors; cyclin-dependent kinase inhibitors such as Aurora kinase inhibitors (e.g., AZD1152, PH739358, VX-680, MLN8054, R763, MP235, MP529, VX-528, and AX39459) and CDK2 and / or CDK4 inhibitors; antiangiogenic agents such as those that inhibit the action of vascular endothelial growth factor [e.g., bevacizumab, an anti-vascular endothelial growth factor antibody, e.g., For example, VEGF receptor tyrosine kinase inhibitors (e.g., vandetanib, vatalanib, sunitinib, axitinib, pazopanib, and AZD2171, compounds disclosed in WO 97 / 22596, WO 97 / 30035, WO 97 / 32856, and WO 98 / 13354, as well as compounds acting by other mechanisms (e.g., linomide, inhibitors of integrin αvβ3 function, and angiostatin));vascular disrupting agents and combretastatin A4, such as the compounds disclosed in WO 99 / 02166, WO 00 / 40529, WO 00 / 41669, WO 01 / 92224, WO 02 / 04434, and WO 02 / 08213; endothelin receptor antagonists, such as zibotentan and atrasentan;DNA damage repair regulators, for example, DNA-PK inhibitors (e.g., LY294002, NU7026, NU7441, IC86621, IC87102, IC87361, OK-1035, SU11752, vanillin, NK314, IC486241, BVAN08, M3814, AZD7648, VX-984, doxycycline), ATM inhibitors (e.g., caffeine, fortmannin, CP-466722, KU-55933, KU-6019, KU-559403), ATR inhibitors (e.g., schisandrin) B, NU6027, NVP-BEZ235, VE-821, VE-822, AZ20, Elimusertib, RP-3500, and AZD6738), CHK1 inhibitors (e.g., LY2606386, PF-0047736, SRA 737, SCH 900776, MK8776, CCT24477, and AZD6738), WEE1 inhibitors (e.g., AZD1775, ZN-c3, PD0166285), CDK1 (e.g., AZD5438, RO-3306, JNJ-7706621, and MER162), DNA LIG4 inhibitors (e.g., SCR7), HIF-1 inhibitors (e.g., LW6, PX-478), HDAC inhibitors (e.g., short-chain fatty acids, benzamides, hydroxamic acids, and cyclic tetrapeptides, suberoylanilide hydroxamic acid (SAHA), trichostatin A), RAD51 inhibitors (e.g., CYT-0851, SCR-6992, SAT-93 / 101, CAM833, JKYN-1 (IBR120 series, B02-iso), Pol θ inhibitors (e.g., ART558, ART4215, and WO 20 / 243459 No. WO 20 / 160213, WO 21 / 028644, WO 20160134, WO 22 / 026565, WO 22259204, WO 20 / 243459, WO 22 / 118210, CN115353512A, CN1159600779A, compounds disclosed in WO 19 / 079297), WRN (e.g., NCGC00029283, US200230046859A1, WO 22 / 249060), PKMYT1 (e.g., RP6306);Antisense therapy, e.g., therapy directed against the targets mentioned above, e.g., ISIS 2503, anti-ras antisense therapy; gene therapy, including methods for replacing abnormal genes such as abnormal p53 or abnormal BRCA1 or BRCA2, GDEPT (gene-directed enzyme prodrug therapy), e.g., methods using cytosine deaminase, thymidine kinase, or bacterial nitroreductase, and methods for increasing a patient's resistance to chemotherapy or radiation therapy, e.g., multidrug resistance gene therapy; immunotherapy, e.g., in vivo and ex vivo methods for improving the immunogenicity of a patient's tumor cells, e.g., reducing T-cell incompetence by transfection with cytokines such as interleukin-2, interleukin-4, or granulocyte-macrophage colony-stimulating factor, transfecting immune cells such as cytokine-transfected dendritic cells, using transfected immune cells, e.g., cytokine-transfected dendritic cells, using cytokine-transfected tumor cell lines, and using anti-specific antibodies;

[0421] synthesis The compounds described in this disclosure, and salts thereof, can be prepared using conventional organic synthesis techniques and can be synthesized according to any of a variety of possible synthetic routes, such as the schemes shown below.

[0422] The reactions for preparing the compounds of the present disclosure can be carried out in a suitable solvent that can be easily selected by those skilled in the art of organic synthesis. A suitable solvent can be one that does not substantially react with the starting materials (reactants), the intermediates, or the product at the temperature at which the reaction is carried out, for example, from the freezing temperature of the solvent to the boiling temperature of the solvent. A given reaction can be carried out in one solvent or a mixture of multiple solvents. A suitable solvent for a particular reaction step can be selected by those skilled in the art depending on the particular reaction step.

[0423] The preparation of compounds of the present disclosure may involve the protection and deprotection of various chemical groups. The need for such protection and deprotection and the selection of appropriate protecting groups can be easily determined by one skilled in the art. The chemical properties of such protecting groups are described, for example, in the following references: Kocienski, Protecting Groups, (Thieme, 2007); Robertson, Protecting Group Chemistry, (Oxford University Press, 2000); Smith el ah, March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 6th Ed. (Wiley, 2007); Peturssion et al., "Protecting Groups in Carbohydrate Chemistry," J. Chem. Educ., 1997, 74(11), 1297; and Wuts et al., Protective Groups in Organic Synthesis, 4th Ed. (Wiley, 2006).

[0424] The reaction can be monitored according to any suitable method known in the art. For example, product formation can be monitored by nuclear magnetic resonance spectroscopy (e.g., 1 H or 13 C), can be monitored by infrared spectroscopy, spectrophotometry (e.g., ultraviolet-visible) or mass spectrometry, or chromatography, such as high performance liquid chromatography (HPLC) or thin layer chromatography.

[0425] As used herein, the terms "ambient temperature," "room temperature," and "rt" generally refer to temperatures in the art. For example, reaction temperature refers to the ambient temperature at which a reaction is carried out, for example, about 20°C to about 30°C.

[0426] The compounds of the present disclosure can be prepared according to multiple preparation routes known from the literature.The following scheme provides a general guideline for preparing the compounds described in the present disclosure.It should be understood by those skilled in the art that, using general knowledge of organic chemistry, the preparation methods shown in the following scheme can be modified or optimized to prepare various compounds of the present disclosure.An exemplary synthetic method for preparing the compounds of the present disclosure is provided in the following scheme.

[0427] Below, some concepts described in this disclosure are illustrated with reference to examples, which are considered to provide an embodiment and should not be considered limitations of the more general embodiments described herein.

[0428] [Table 3-1] [Table 3-2] [Table 3-3]

[0429] Synthesis scheme A series of tricyclic derivatives represented by formulas 1-7 to 1-13 can be prepared by the method shown in Scheme 1. Here, compound 1-3 (where t and s are integers, e.g., 2, 3, or 4) can be prepared by the method shown in Scheme 1. Compound 1-1 (where W 1is a halogen such as Cl, Br, or I, or a pseudohalogen such as OTf or OMs) with an appropriate amine derivative 1-2 in the presence of a base such as Hunig's base. Compounds 1-3 can be converted to the appropriate 5- or 6-membered heteroaryl derivative Cy under standard Buchwald coupling conditions (e.g., in the presence of a palladium catalyst such as BrettPhosPdG3, t-BuXphosPd G3, RuPhosPd G4, or XantPhosPdG3, in the presence of a base such as t-BuOK, t-BuONa, Cs2CO3, or K2CO3) or Ullmann coupling conditions (e.g., CuI, CsF, and N1,N2-dimethylcyclohexane-1,2-diamine). 1 W1-4 (However, W 1 is a halogen such as Cl, Br, or I, or a pseudohalogen such as OTf or OMs) to give compound 1-5. Removal of the Boc group in compound 1-5 to give compound 1-6 can be achieved by treatment with an acid such as TFA in DCM, HCl in dioxane, or other acidic medium. Compound 1-6 can be converted to an acyl chloride R in the presence of a base (e.g., Hunig's base or KCO). b COCl to give the corresponding compounds 1-7, and the appropriate chloroformate R b OCOCl to give the corresponding compounds 1-8, and the isocyanate R c The corresponding compounds 1-9 can be obtained by reaction with N=C=O, and carbamyl chloride R c R d NCOCl to give the corresponding compounds 1-10, and the sulfinyl chloride R b The corresponding compounds 1-11 can be obtained by reaction with SOCl, and the sulfonyl chloride R b The corresponding compounds 1-12 can be obtained by reaction with SO2Cl, and the sulfamoyl chloride R c R dReaction with NSO2Cl can give the corresponding compounds 1-13.

[0430] [ka]

[0431] A series of tricyclic derivatives represented by formulae 2-2 to 2-4 can be prepared by the method shown in Scheme 2. Tricyclic derivative 2-2 can be prepared by the reaction of a suitable reagent R 10 -W (where W 1 is a halogen such as Cl, Br or I, or a pseudohalogen such as OTf or OMs) under alkylation conditions (e.g., in the presence of a base such as Hunig's base, NaH, t-BuOK, t-BuONa, CsCO or KCO). Correspondingly, tricyclic derivatives 2-3 can be prepared by N-alkylation of aldehydes, ketones or cycloketones R 10a C(O)R 10b (where R 10a and R 10b is H or an alkyl group, or R 10a and R 10b are C3 to C together with the carbon atoms connected to them. 10 Compounds 2-1 can be prepared by reductive amination under standard reductive amination conditions (e.g., in the presence of a reducing agent such as NaBH(OAc)3 or NaBH3CN) with an appropriate aryl or heteroaryl reagent Cy under standard Buchwald-Hartwig amination conditions (e.g., in the presence of a palladium catalyst such as XPhosPd G3, in the presence of a base such as Cs2CO3 or K3PO4). 3 By reacting with -W, compounds 2-4 can be prepared.

[0432] [ka]

[0433] A series of tricyclic derivatives represented by formulas 3-5 to 3-9 can be prepared by the method shown in Scheme 3. Compound 3-1 (wherein W 1 is a halogen such as Cl, Br, or I, or a pseudohalogen such as OTf or OMs) with vinyl boric acid or boric acid ester 3-2 (where R 10a and R 10b is H or an alkyl group, or R 10a and R 10b are C3 to C together with the carbon atoms connected to them. 10 Suzuki coupling of 3-5 with a cycloalkyl group or a 4- to 10-membered heterocycloalkyl group under standard Suzuki conditions (e.g., in the presence of a palladium catalyst such as [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) and a base such as KPO) can provide compound 3-5. Hydrogenation of 3-5 in the presence of a palladium catalyst such as Pd / C or Pd(OH) / C can provide compound 3-6.

[0434] Similarly, compound 3-1 can be converted to R under standard Suzuki coupling conditions (e.g., in the presence of a palladium catalyst such as Xanphos Pd or [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) and a base such as KPO), or under standard Negishi conditions (e.g., in the presence of a palladium catalyst such as tetrakis(triphenylphosphine)palladium(0) or [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)), or under standard Stille conditions (e.g., in the presence of a palladium(0) catalyst such as tetrakis(triphenylphosphine)palladium(0)). 10 Compound 3-7 can be obtained by coupling reaction with -Ar-M (where Ar is an aryl or heteroaryl group, and M is B(OH)2, Bpin, BF3K, Sn(Me)3, Sn(Bu)3, or ZnCl2). 10is a carbonate group, it can be saponified to acids 3-8 in the presence of a base such as LiOH, NaOH, or KOH. Compounds 3-8 can be converted to amines R under standard amide coupling conditions (e.g., in the presence of a coupling agent such as BOP, PyBOP, HATU, or HBTU and a base such as EtN or Hunig's base). c R d Compound 3-9 can be obtained by coupling with NH3-4.

[0435] [ka]

[0436] A series of tricyclic intermediates represented by formula 4-7 can be prepared by the method shown in Scheme 4. Sulfonamide 4-3 can be prepared by reacting sulfonyl chloride 4-1 with amine 4-2 in the presence of a base such as Hunig's base. Coupling of sulfonamide 4-3 with 2-cyanoacetamide in the presence of a base such as NaH, t-BuONa, or t-BuOK can give compound 4-4. Compound 4-4 can be further converted to indole derivative 4-5 by reduction of its nitro group using a reducing agent such as Zn / FeCl or Fe / NHCl in acidic medium, followed by ring closure. Reaction of indole derivative 4-5 with trialkyl orthoformate 4-6 in the presence of an acid such as p-TsOH or HCl can give the target product indole-pyrimidone 4-7. This product can be reacted with halogenating reagents such as SOCl2, POCl3 or POBr3 under DMF catalyzed or non-catalyzed conditions, or with TfCl or MsCl (where W 1 is OTf or OMs) to further prepare intermediate 4-8 (where W 1 is a halogen such as Cl or Br, or a pseudohalogen such as OTf or OMs).

[0437] [ka]

[0438] A series of tricyclic intermediates of formula 5-8 can be prepared by the method shown in Scheme 5. Compound 5-1 (wherein W 2 is a halogen such as Cl, Br or I, or a pseudohalogen such as OTf or OMs. 3 is a halogen such as Br or I, or a pseudohalogen such as OTf) can be coupled with compound 5-2 under 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, CsCO, or KCO), followed by intramolecular Heck ring closure under standard Heck reaction conditions (e.g., in the presence of a palladium catalyst such as dichlorobis(triphenylphosphine)palladium, palladium(II) acetate, or tetra(triphenylphosphine)palladium and a base such as NaCO, KCO, or NaOAc) to give tricyclic compound 5-3. The tricyclic compound 5-3 can be further converted to the corresponding sulfonyl chloride 5-4 by treatment with an oxidizing reagent such as N-chlorosuccinimide, sodium hypochlorite, or a suitable reagent such as 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione. The sulfonyl chloride 5-4 can be reacted with amine 5-5 in the presence of a base such as Hunig's base to give sulfonamide 5-6. The sulfonamide 5-6 can be further converted to 5-7 by treatment with an oxidizing agent such as hydrogen peroxide, ozone, or metachloroperbenzoic acid. The reaction of compound 5-7 with a halogenating agent such as SOCl, POCl, or POBr, or with TfCl or MsCl in the presence of a base such as Hunig's base, gives intermediate 5-8 (wherein W 1is a halogen such as Cl or Br, or a pseudohalogen such as OTf or OMs).

[0439] [ka]

[0440] Additionally, a series of tricyclic intermediates represented by formula 6-10 can be prepared by the method shown in Scheme 6. Tricyclic intermediate 6-3 can be prepared by reacting tricyclic compound 5-3 with the appropriate aniline 6-2, similar to Scheme 5. The benzyl group in compound 6-3 can be removed by hydrogenation in the presence of a catalyst such as Pd / C or Pd(OH)2 / C to generate the corresponding OH compound 6-4. Compound 6-4 can be treated with trifluoromethanesulfonic anhydride to generate compound 6-5. Compound 6-5 can be further prepared by reacting it with phenylmethanethiol or sodium phenylmethanethiol in the presence of a base such as Hunig's base, Cs2CO3, t-BuOK, or t-BuONa to generate compound 6-6. Compound 6-6 can be oxidized using an oxidizing agent such as N-chlorosuccinimide or sodium hypochlorite to generate sulfone chloride 6-7. The sulfone chloride 6-7 can be further converted to the target intermediate 6-10 by reacting with the appropriate amine 6-8 in the presence of a base such as Hunig's base, Na2CO3, or K2CO3, followed by removal of the protecting group Tf in the product 6-9 under basic conditions such as NaOH or KOH.

[0441] [ka]

[0442] Additionally, a series of tricyclic intermediates represented by formulas 7-3 and 7-5 can be prepared by the method shown in Scheme 7. Compounds 7-3 and 7-5 can be prepared by the reaction of compound 7-1 (wherein W 2is a halogen such as Cl, Br, or I, or a pseudohalogen such as OTf or Oms) with compounds 7-2 and 7-4, respectively, 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, CsCO, or KCO), followed by an intramolecular ring closure reaction in the presence of a Lewis acid such as AlCl, ZnCl, or other acidic medium such as polyphosphoric acid, POCl.

[0443] [ka]

[0444] In a similar manner, a series of tricyclic intermediates of formula 8-3 and 8-5 can be prepared by the method shown in Scheme 8. Compounds 8-3 and 8-5 can be prepared by the reaction of compound 8-1 (wherein W 3 is a halogen such as Cl, Br, or I, or a pseudohalogen such as OTf or Oms) with compounds 8-2 and 8-5, respectively, 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, CsCO, or KCO), followed by intramolecular Heck ring closure under standard reaction conditions (e.g., in the presence of a palladium catalyst such as dichlorobis(triphenylphosphine)palladium, palladium(II) acetate, or tetrakis(triphenylphosphine)palladium, and a base such as NaCO, KCO, or NaOAc).

[0445] [ka]

[0446] A series of tricyclic intermediates of formula 9-7, where A is O or S, can be prepared by the method shown in Scheme 9. Compound 9-3 can be prepared by the reaction of compound 9-1 (where W 2 Compounds 9-4 and 9-5 can be prepared by nucleophilic alkylation of 9-3 (where R is a halogen such as F, Cl, Br, or I, or a pseudohalogen such as OTf or Oms) with 2-cyanoacetate 9-2 (where R is an alkyl group such as Me, Et, or t-Bu) in the presence of a strong base such as t-BuOK, t-BuONa, or NaH. The nitro group in compound 9-3 can be reduced with a reducing agent such as zinc powder or iron powder under acidic conditions (such as acetic acid or HCl), followed by intramolecular ring closure to give compound 9-4. Compound 9-4 and acetal 9-5 bearing an alfa-H can be heated in the presence of a base such as NaOMe or NaOEt to give tricyclic compound 9-6. Compound 9-6 can be halogenated with a halogenating agent such as SOCl2, POCl3, or POBr3 to give the target intermediate 9-7 (where W is an alkyl group such as Me, Et, or t-Bu). 1 is Cl or Br), or by reacting compound 9-6 with TfCl or OMs under basic conditions of Hunig's base, the target intermediate 9-7 (where W is Cl or Br) can be obtained. 1 can be obtained by

[0447] [ka]

[0448] Example Example 1: 4-(4-(cyclopropanecarbonyl)piperazin-1-yl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1-methylcyclopropyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka]

[0449] Step 1: 4-(4-(cyclopropanecarbonyl)piperazin-1-yl)-N-(1-methylcyclopropyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] To a solution of 4-chloro-N-(1-methylcyclopropyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (111 mg, 0.330 mmol, Intermediate 2) and cyclopropyl(piperazin-1-yl)methanone (189 mg, 0.992 mmol) in MeCN (15 mL) was added NaHCO (1.11 g, 13.2 mmol). The solution was stirred under reflux overnight. The reaction mixture was diluted with HO (10 mL) and extracted with EtOAc (10 mL × 3). The combined organic phase was washed with saturated brine (20 mL × 2), dried over NaSO, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column eluted with EtOAc / PE (0-5%) to give 4-(4-(cyclopropanecarbonyl)piperazin-1-yl)-N-(1-methylcyclopropyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (100 mg, 66.5% yield) as a white solid. 1 H NMR: (400 MHz, DMSO-d6)δ 12.6 (s, 1H), 8.55 (s, 1H), 8.11 (s, 1H), 7.93-7.95 (m, 2H), 7.69-7.72 (m, 1H), 3.72-3.94 (m, 8H), 2.02-2.07 (m, 1H), 1.11 (s, 3H), 0.73-0.81 (m, 4H), 0.59-0.61 (m, 2H), 0.35-0.38 (m, 2H). LCMS calculated value C 22 H 25 N6O3S [MH] - : m / z = 453.2; Found: 453.1.

[0450] Step 2: 4-(4-(cyclopropanecarbonyl)piperazin-1-yl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1-methylcyclopropyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide A mixture of 4-(4-(cyclopropanecarbonyl)piperazin-1-yl)-N-(1-methylcyclopropyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (20 mg, 0.044 mmol), 2-bromo-5-(difluoromethyl)-1,3,4-thiadiazole (75.7 mg, 0.352 mmol), t-Bu3P (125 mg, 0.616 mmol), Pd2(dba)3 (60.4 mg, 0.066.0 mmol), and t-BuONa (123 mg, 1.28 mmol) in xylene (3 mL) was subjected to three cycles of degassing and filling with N2. The mixture was stirred overnight at 110 °C under a N2 atmosphere. The reaction mixture was cooled and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by prep-HPLC on a C18 column using ACN / water (30–60% (NH3·H2O + NH4HCO3)) to give 4-(4-(cyclopropanecarbonyl)piperazin-1-yl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1-methylcyclopropyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (1.8 mg, 3.47% yield) as a white solid. 1 H NMR: (400 MHz,DMSO-d6)δ 9.46 (s, 1H), 8.82 (s, 1H), 8.36 (s, 1H), 8.09 (d,J = 8.0 Hz, 1H), 7.99 (d,J = 8.0 Hz, 1H), 7.68 (t,J = 25.6 Hz, 1H), 3.73-4.04 (m, 8H), 1.44 (d,J = 13.2 Hz, 1H), 1.12 (s, 3H), 0.76-0.80 (m, 4H), 0.64-0.66 (m, 2H), 0.39-0.42 (m, 2H). LCMS calculated value C 25 H 25 F2N8O3S2[MH] -: m / z = 587.2; Found: 587.2.

[0451] The compounds shown in Table 1 below were prepared according to the same method as in Preparation Example 1, using Intermediate 1 (Int A, sulfonamide derivative) and appropriate Intermediates 10-55 (Int B, amine derivatives) or commercially available materials (CAM, amine derivatives) as starting materials.

[0452] [Table 4-1] [Table 4-2] [Table 4-3] [Table 4-4] [Table 4-5]

[0453] Example 22: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(4-(1-methyl-1H-imidazol-2-yl)piperazin-1-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide [ka]

[0454] Step 1: N-(1-cyanocyclopropyl)-4-(4-(1-methyl-1H-imidazol-2-yl)piperazin-1-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide [ka] This compound was prepared according to a similar method to Step 1 of Example 1, starting from 4-chloro-N-(1-cyanocyclopropyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (Intermediate 1) and 1-(1-methyl-1H-imidazol-2-yl)piperazine. LCMS calculated value: C 22 H 24 N9O2S [M+H] + : m / z = 478.2; Found: 478.1.

[0455] Step 2: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(4-(1-methyl-1H-imidazol-2-yl)piperazin-1-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide To a mixture of N-(1-cyanocyclopropyl)-4-(4-(1-methyl-1H-imidazol-2-yl)piperazin-1-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (75 mg, 0.16 mmol), 2-bromo-5-(difluoromethyl)-1,3,4-thiadiazole (169 mg, 0.78 mmol) in dioxane (10 mL) and DMF (0.5 mL) was added t-BuONa (90.6 mg, 0.94 mmol), followed by BrettPhos Pd G3 (85.4 mg, 0.094 mmol). The mixture was degassed and refilled with N gas three times and stirred at 110 °C for 12 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was purified by prep-HPLC on a C18 column and eluted with MeOH / water (40-65%, containing 1% HCl) to give the target compound (14.18 mg, 14.1% yield) as an off-white solid. 1H NMR: (400 MHz, DMSO-d6) δ9.53 (s, 1H), 9.47 (s, 1H), 8.90 (s, 1H), 8.15 (d,J = 8.4 Hz, 1H), 8.05-8.06 (d,J= 8.4 Hz, 1H), 7.71 (t,J = 7.37-7.39 (m, 2H), 4.06 (s, 4H), 3.70 (s, 3H), 3.54 (s, 3H), 1.43-1.47 (m, 2H), 1.29-1.32 (m, 2H).LCMS calculated value C 25 H 24 F2N 11 O2S2[M+H] + : m / z = 612.1; Found: 612.1.

[0456] The compounds shown in Table 2 below were prepared according to the same method as in Preparation Example 22, starting from Intermediate 1 (Int A, sulfonamide derivative) and appropriate Intermediates 10-55 (Int B, amine derivatives).

[0457] [Table 5-1] [Table 5-2] [Table 5-3] [Table 5-4] [Table 5-5]

[0458] Example 43: 4-(7-(N-(1-cyanocyclopropyl)sulfamoyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-9H-pyrimido-[4,5-b]indol-4-yl)-N,N-dimethylbenzamide [ka]

[0459] Step 1: 4-(7-(N-(1-cyanocyclopropyl)sulfamoyl)-9H-pyrimido-[4,5-b]indol-4-yl)-N,N-dimethylbenzamide [ka] A mixture of 4-chloro-N-(1-cyanocyclopropyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (300 mg, 0.86 mmol), [4-(dimethylcarbamoyl)phenyl]boronic acid (183 mg, 0.95 mmol), K3PO4 (549 mg, 2.59 mmol), and Pd(dppf)Cl2.CHCl2 (70.4 mg, 0.086 mmol) in dioxane (3 mL) and HO (0.5 mL) was degassed and backfilled with N2 gas three times and stirred under N2 atmosphere at 100 °C for 12 h. The reaction mixture was concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column eluted with EtOAc / PE (1-10%) to give the target compound (300 mg, 75.5% yield) as a yellow solid. LCMS calculated C 23 H 21 N6O3S [M+H] + : m / z = 461.1; Found: 461.0.

[0460] Step 2: 4-(7-(N-(1-cyanocyclopropyl)sulfamoyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-9H-pyrimido-[4,5-b]indol-4-yl)-N,N-dimethylbenzamide To a mixture of 4-(7-(N-(1-cyanocyclopropyl)sulfamoyl)-9H-pyrimido-[4,5-b]indol-4-yl)-N,N-dimethylbenzamide (85 mg, 0.18 mmol), 2-bromo-5-(difluoromethyl)-1,3,4-thiadiazole (198 mg, 0.92 mmol) in dioxane (10 mL) and DMF (0.5 mL) was added tBuXPhos Pd G3 (14.6 mg, 0.018 mmol) and t-BuONa (106 mg, 1.11 mmol) under a N atmosphere. The reaction mixture was degassed and refilled with N gas three times and stirred at 130 °C overnight. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was purified by prep-HPLC on a C18 column and eluted with MeCN / water (35-65%, containing 0.5% TFA) to give the target compound (11.7 mg, 10.6% yield) as an off-white solid. 1 H NMR: (400 MHz, DMSO-d6) δ9.57 (d,J = 1.6 Hz, 1H), 9.49 (s, 1H), 9.45 (s, 1H), 8.18 (d,J = 8.4 Hz, 1H), 8.04 (d,J = 8.0 Hz, 2H), 7.98-8.00 (m, 1H), 7.60-7.76 (m, 3H), 3.05 (d,J = 10.8 Hz, 6H), 1.42-1.45 (m, 2H), 1.24-1.27 (m, 2H). LCMS calculated value C 26 H 21 F2N8O3S2[M+H] + : m / z = 595.1; Found: 595.1.

[0461] Example 44: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(4-methoxypiperidin-1-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide [ka]

[0462] Step 1: N-(1-cyanocyclopropyl)-4-(4-methoxypiperidin-1-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] This compound was prepared in a similar manner to Step 1 of Example 1, starting from 4-chloro-N-(1-cyanocyclopropyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (Intermediate 1) and 4-methoxypiperidine. 1 H NMR: (400 MHz, DMSO-d6) δ 8.51 (s, 1H), 7.89-7.96 (m, 2H), 7.72-7.75 (m, 1H),5.76 (s, 1H), 3.98-4.03 (m, 2H), 3.43-3.60 (m, 2H), 2.03-2.06 (m, 2H), 1.63-1.67 (m, 2H), 1.35 (s, 2H), 1.18-1.26 (m, 2H).

[0463] Step 2: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(4-methoxypiperidin-1-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide CsCO (76.4 mg, 0.234 mmol) and XPhosPd G3 (4.96 mg, 0.006 mmol) were added to a mixture of N-(1-cyanocyclopropyl)-4-(4-methoxypiperidin-1-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (50.0 mg, 0.12 mmol), 2-bromo-5-(difluoromethyl)-1,3,4-thiadiazole (30.2 mg, 0.14 mmol) in dioxane (2 mL) under a N atmosphere. The mixture was degassed and refilled with N gas three times and stirred at 110 °C for 12 h. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The residue was purified by prep-HPLC on a C18 column and eluted with MeCN / water (45-75%, containing 0.5% TFA) to give the target compound (2.41 mg, 3.67% yield) as a pale yellow solid. 1 H NMR: (400 MHz, DMSO-d6) δ 9.49 (s, 1H), 9.39 (s, 1H), 8.79 (s, 1H), 8.03-8.10 (m, 2H),7.68 (t,J = 53.2 Hz, 1H), 4.04-4.08 (m, 2H), 3.56-3.65 (m, 3H), 2.03-2.06 (m, 2H), 1.65-1.70 (m, 2H), 1.41-1.45 (m, 2H), 1.26-1.29 (m, 2H).LCMS calculated value C 23 H 23 F2N8O3S2[M+H] + : m / z = 561.1; Found: 561.1.

[0464] The compounds shown in Table 3 below were prepared according to a similar method to that of Preparation Example 44, starting from Intermediates 1-3 (Int A, sulfonamide derivatives) and appropriate Intermediates 10-55 (Int B, amine derivatives) or commercially available materials (CAM, amine derivatives).

[0465] [Table 6-1] [Table 6-2] [Table 6-3] [Table 6-4] [Table 6-5]

[0466] Example 65: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(4-(1-methylazetidine-3-carbonyl)piperazin-1-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide [ka]

[0467] Step 1: tert-butyl 4-(7-(N-(1-cyanocyclopropyl)sulfamoyl)-9H-pyrimido-[4,5-b]indol-4-yl)piperazine-1-carboxylate [ka] To a solution of 4-chloro-N-(1-cyanocyclopropyl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide (0.30 g, 0.86 mmol, Intermediate 1) and tert-butyl piperazine-1-carboxylate (482 mg, 2.59 mmol) in MeCN (5 mL) was added NaHCO3 (2.90 g, 34.5 mmol). The reaction mixture was stirred under reflux for 12 hours. The solids were removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column eluted with EtOAc / PE (10-100%) to give the target compound (236 mg, 55% yield) as an off-white solid. LCMS calculated C 23 H28 N7O4S [M+H] + : m / z = 498.2; Found: 498.1.

[0468] Step 2: tert-butyl 4-(7-(N-(1-cyanocyclopropyl)sulfamoyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-9H-pyrimido-[4,5-b]indol-4-yl)piperazine-1-carboxylate [ka] A solution of tert-butyl 4-(7-(N-(1-cyanocyclopropyl)sulfamoyl)-9H-pyrimido-[4,5-b]indol-4-yl)piperazine-1-carboxylate (0.03 g, 0.06 mmol), 2-bromo-5-(difluoromethyl)-1,3,4-thiadiazole (64.8 mg, 0.3 mmol), BrettPhos Pd G3 (27.3 mg, 0.03 mmol), and t-BuONa (34.8 mg, 0.36 mol) in dioxane (4 mL) was degassed and backfilled with N2 for three cycles and stirred at 95 °C under N2 for 12 h. After cooling to room temperature, the solids were removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by prep-HPLC on a C18 column and eluted with MeCN / water (50-86%, containing 31% NH4HCO) to give the target compound (5 mg) as a brown solid. 1 H NMR:(400 MHz,DMSO-d6)δ 12.6 (s, 1H), 9.14 (s, 1H), 8.55 (s, 1H), 7.95-7.97 (m, 2H), 7.75 (d,J = 7.2 Hz, 1H), 3.70-3.71 (m, 7H), 3.58-3.59 (m, 4H), 1.45 (s, 9H), 1.40-1.41 (m, 2H), 1.23-1.25 (m, 2H). LCMS calculated value C 26 H 26 F2N9O4S2[MH] - : m / z = 630.2; Found: 630.2.

[0469] Step 3: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(4-(piperazin-1-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide [ka] A solution of tert-butyl 4-(7-(N-(1-cyanocyclopropyl)sulfamoyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-9H-pyrimido-[4,5-b]indol-4-yl)piperazine-1-carboxylate (0.08 g, 0.13 mmol) in HCl / MeOH (4 M, 32.0 mL) was stirred at 15° C. for 2 hours. The reaction mixture was concentrated under reduced pressure to give the hydrochloride salt of the target compound (0.08 g) as a brown oil. LCMS calculated value: C 21 H 20 F2N9O2S2[M+H] + : m / z = 532.1; Found: 532.0.

[0470] Step 4: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(4-(1-methylazatidine-3-carbonyl)piperazin-1-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide A mixture of N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(4-(piperazin-1-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide (0.02 g, 0.035 mmol) in DMF (1.00 mL) was treated with 1-methylazatidine-3-carboxylic acid (4.05 mg, 0.035 mmol) and DIEA (13.6 mg, 0.11 mmol). mol) was added. The reaction mixture was stirred at 25 °C for 30 min, then cooled to 10 °C, and TBTU (13.6 mg, 0.042 mmol) was added. The reaction mixture was stirred for 1 h and then directly concentrated under reduced pressure. The residue was purified by prep-HPLC on a C18 column and eluted with MeCN / water (30-60%, containing 31% NH4HCO) to give the target compound (2 mg, 8.68% yield) as an off-white solid. 1 H NMR:(400 MHz,DMSO-d6) δ9.49 (s, 1H), 8.83 (s, 1H), 8.10 (d,J=8.4 Hz, 1H), 8.02 (dd,J= 8.4 Hz, 1.6 Hz, 1H), 7.68 (t,J = 53.2 Hz, 1H), 3.82-3.83 (m, 4H), 3.69 (br.s, 2H), 3.51-3.52 (m, 2H), 3.44-3.47 (m, 3H), 3.12-3.15 (m, 2H), 2.18 (s, 3H), 1.40-1.43 (m, 2H), 1.23-1.27 (m, 2H). LCMS calculated value C 26 H 25 F2N 10 O3S2[MH] - : m / z = 627.2; Found: 627.2.

[0471] The compounds shown in Table 4 below were prepared following a similar method to Example 65, substituting the appropriate acid in place of 1-methylazatidine-3-carboxylic acid in step 4 above.

[0472] [Table 7]

[0473] [Table 8-1] [Table 8-2] [Table 8-3] [Table 8-4] [Table 8-5] [Table 8-6] [Table 8-7] [Table 8-8] [Table 8-9] [Table 8-10]

[0474] Example 69: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(4-(isopropylsulfinyl)piperazin-1-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide [ka]

[0475] Step 1: S-Isopropylpropane-2-thiosulfinate [ka] To a solution of 1,2-diisopropyldisulfane (5.00 g, 33.3 mmol) in MeCN (25.0 mL) was added HO (5.66 g, 49.9 mmol, 30%) dropwise at 0 °C. The mixture was stirred at 15 °C for 12 h and then quenched with HO (50 mL) at 0 °C. The mixture was extracted with DCM (50 mL × 3). The combined organic phase was washed with NaHSO (30 mL × 2), NaHCO (30 mL × 5), and saturated brine (30 mL × 2), dried over NaSO, filtered, and concentrated under reduced pressure to give the target compound (2.50 g, 45.2% yield) as a pale yellow oil. 1 H NMR:(400 MHz, CDCl3) δ 3.61-3.65 (m, 1H), 3.19-3.23 (m, 1H), 1.47-1.49 (m, 6H), 1.37-1.40 (m, 6H).

[0476] Step 2: Propane-2-sulfonyl chloride [ka] Sulfuryl chloride (40.6 mg, 0.30 mmol) was added dropwise to a solution of S-isopropylpropane-2-thiosulfinate (0.05 g, 0.30 mmol) in DCM (1 mL) at 0° C. The reaction was stirred for 2 hours at 0° C. The reaction was used directly in the next step without purification.

[0477] Step 3: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(4-(isopropylsulfinyl)piperazin-1-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide Propane-2-sulfonyl chloride (Step 2) was added dropwise to a mixture of N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(piperazin-1-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (Step 3 of Example 65) (0.02 g, 0.035 mmol), TEA (21.4 mg, 0.021 mmol), and DMAP (0.086 mg, 0.007 mmol) in DCM (1.0 mL) at 0 °C. The mixture was degassed and refilled with N gas three times and stirred under N atmosphere at 0 °C for 2 hours. The reaction mixture was directly concentrated under reduced pressure. The residue was purified by prep-HPLC on a C18 column and eluted with MeCN / water (50-70%, containing 31% NH4HCO) to give the target compound (1.80 mg, 8.22% yield) as an off-white solid. 1 H NMR:(400 MHz, DMSO-d6) δ 9.47 (s, 1H), 8.84 (s, 1H), 8.10 (d,J=8.0 Hz, 1H), 8.03 (d,J= 8.0 Hz, 1H), 7.68 (t,J = 53.2 Hz, 1H), 3.93-3.95 (m, 4H), 3.23-3.27 (m, 2H), 3.08-3.11 (m, 1H), 1.34-1.36 (m, 2H),1.21-1.23 (m, 5H), 1.15 (d,J = 6.8 Hz, 3H). LCMS calculated value C 24 H 24 F2N9O3S3[MH] - : m / z = 620.1; Found: 620.2.

[0478] Example 70: 4-(4-(tert-butylsulfinyl)piperazin-1-yl)-N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide [ka]

[0479] This compound was prepared in a similar manner to Step 3 of Example 69 using N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(piperazin-1-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide (Step 3 of Example 65) and 2-methylpropane-2-sulfinyl chloride as starting materials. 1 H NMR:(400 MHz,DMSO-d6)δ 9.49 (d,J= 1.2 Hz, 1H), 8.83 (s, 1H), 8.11 (d,J= 8.4 Hz, 1H), 8.03 (dd,J= 8.4 Hz, 1.6 Hz, 1H),7.68 (t,J = LCMS calculated value C 25 H 26 F2N9O3S3[MH] - : m / z = 634.1; Found: 633.9.

[0480] Example 71: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(5-(oxetane-3-carbonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide [ka]

[0481] Step 1: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide [ka] This compound was prepared in a manner similar to steps 1-3 of Example 65, using 4-chloro-N-(1-cyanocyclopropyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (Intermediate 1) and tert-butyl hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate as starting materials in step 1. LCMS calculated C 23 H 22 F2N9O2S2[M+H] + : m / z = 558.1; Found: 558.1.

[0482] Step 2: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(5-(oxetane-3-carbonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide This compound was prepared in a similar manner to Step 4 of Example 65 using N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide and oxetane-3-carboxylic acid as starting materials. 1 H NMR: (400 MHz, DMSO-d6) δ 9.51 (d,J= 2.0 Hz, 1 H), 9.37 (s, 1H), 8.67 (s, 1H), 8.50 (d,J= 8.8 Hz, 1H), 7.94 (dd,J = 6.8 Hz, 2.0 Hz, 1H), 7.68 (t,J = 53.2 Hz, 1H), 4.66-4.71 (m, 2H), 4.20-4.29 (m, 2H), 4.03-4.07 (s, 1H), 3.86-3.95 (m, 2H), 3.62-3.67 (m, 2H), 3.52-3.56 (m, 2H), 3.28-3.32 (m, 2H), 3.04-3.12 (m, 2H), 1.42-1.45 (m, 2H), 1.26-1.30 (m, 2H).LCMS calculated value C27 H 26 F2N9O4S2[M+H] + : m / z = 642.1; Found: 642.1.

[0483] Example 72: (S)-4-(7-(N-(1-cyanocyclopropyl)sulfamoyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-9H-pyrimido-[4,5-b]indol-4-yl)-N,N,3-trimethylpiperazine-1-carboxamide [ka]

[0484] Step 1: (S)—N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(2-methylpiperazin-1-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide [ka] This compound was prepared following a similar method to steps 1-3 of Example 65, using 4-chloro-N-(1-cyanocyclopropyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (Intermediate 1) and tert-butyl (3S)-3-methylpiperazine-1-carboxylate as the starting material in step 1. LCMS calculated for C22H22F2NO2S2 [M+H]+: m / z = 546.1; found: 546.0.

[0485] Step 2: (S)-4-(7-(N-(1-cyanocyclopropyl)sulfamoyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-9H-pyrimido-[4,5-b]indol-4-yl)-N,N,3-trimethylpiperazine-1-carboxamide To a solution of (S)—N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(2-methylpiperazin-1-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide (10 mg, 0.017 mmol) in DCM (2.5 mL), TEA (10.4 mg, 0.1 mmol) and DMAP (0.042 mg) were added, followed by the slow addition of dimethylcarbamyl chloride (1.83 mg, 0.017 mmol) at 0° C. The mixture was stirred at 20° C. for 6 hours and then concentrated under reduced pressure. The residue was purified by prep-HPLC on a C18 column and eluted with MeCN / water (45-75%, containing 0.5% TFA) to give the target compound (1.42 mg, 12.5% ​​yield) as an off-white solid. 1 H NMR (400 MHz, DMSO-d6) δ 9.54 (s, 1H), 9.50 (s, 1H), 8.82 (s,1H), 8.06 (s, 2H), 7.68 (t,J = 53.2 Hz, 1H), 4.79-4.81 (m, 1H), 3.97-4.00 (m, 1H), 3.80-3.83 (m, 1H), 3.67-3.77 (m, 1H), 3.54-3.57 (m, 1H), 3.01-3.04 (m, 1H), 2.82 (s, 6H), 1.42-1.45 (m, 2H), 1.36 (d,J = 6.8 Hz, 3H),1.27-1.29 (m, 3H). LCMS calculated value C 25 H 27 F2N 10 O3S2[M+H] + : m / z = 617.2; Found: 617.3.

[0486] Example 73: (R)-4-(7-(N-(1-cyanocyclopropyl)sulfamoyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-9H-pyrimido-[4,5-b]indol-4-yl)-N,N,3-trimethylpiperazine-1-carboxamide [ka]

[0487] Step 1: (R)—N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(2-methylpiperazin-1-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide [ka] This compound was prepared following a similar method to steps 1-3 of Example 65, using 4-chloro-N-(1-cyanocyclopropyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (Intermediate 1) and tert-butyl (3R)-3-methylpiperazine-1-carboxylate as the starting material in step 1. LCMS calculated: C 22 H 22 F2N9O2S2[M+H] + : m / z = 546.1; Found: 546.0.

[0488] Step 2: (R)-4-(7-(N-(1-cyanocyclopropyl)sulfamoyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-9H-pyrimido-[4,5-b]indol-4-yl)-N,N,3-trimethylpiperazine-1-carboxamide To a solution of (R)-N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(2-methylpiperazin-1-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (10 mg, 0.017 mmol, hydrochloride salt) in DCM (1 mL) was added TEA (10.4 mg, 0.1 mmol) and DMAP (0.042 mg, 0.344 mmol), followed by the slow addition of N,N-dimethylcarbamoyl chloride (2.77 mg, 0.026 mmol). The mixture was stirred at 20°C for 6 hours. The reaction mixture was concentrated under reduced pressure. The residue was purified by prep-HPLC on a C18 column and eluted with MeCN / water (45-75%, TFA) to give the target compound (2.11 mg, 8.91% yield) as an off-white solid. 1 H NMR: (400 MHz,DMSO) δ 9.50 (s, 1H), 9.41 (s, 1H), 8.82 (s, 1H), 8.05 (s, 2H), 7.68 (t,J = 53.2 Hz, 1H), 4.79-4.85 (m, 1H), 3.98 (d,J = 13.2 Hz, 2H), 3.80 (t,J = 11.6 Hz, 1H), 3.69 (t,J = 12.8 Hz, 1H), 3.25 (d,J = 3.2 Hz, 1H), 3.02 (t,J = 2.0 Hz, 1H), 2.82 (s, 6H), 1.45-1.41 (m, 2H), 1.36 (d,J = 36.4 Hz, 3H), 1.27 (t,J = 5.2 Hz, 3H). LCMS calculated value C 25 H 27 N 10 S2O3F2[M+H] + : m / z = 617.2; Found: 617.2.

[0489] Example 74: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(1-isobutyryl-1,2,3,6-tetrahydropyridin-4-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide [ka]

[0490] Step 1: tert-butyl 4-(7-(N-(1-cyanocyclopropyl)sulfamoyl)-9H-pyrimido-[4,5-b]indol-4-yl)-3,6-dihydropyridine-1(2H)-carboxylate [ka] To a mixture of 4-chloro-N-(1-cyanocyclopropyl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide (5.0 g, 14.4 mmol) in dioxane (50 mL) and HO (5 mL), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (5.8 g, 18.7 mmol), Pd(dppf)Cl (505 mg, 0.72 mmol), and NaCO (4.6 g, 43.2 mmol) were added. The mixture was degassed and backfilled with N gas three times and stirred at 100 °C for 6 h. The reaction mixture was then cooled to 25 °C, diluted with HO (30 mL), and extracted with DCM (30 mL × 3). The combined organic phase was washed with saturated brine (30 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by flash chromatography on a silica gel column eluted with EtOAc / PE (0-70%) to give the target compound (4.3 g, 60.5% yield). LCMS calculated C 24 H 27 N6O4S [M+H] + : m / z = 495.2; Found: 495.2.

[0491] Step 2: tert-butyl 4-(7-(N-(1-cyanocyclopropyl)sulfamoyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-9H-pyrimido[4,5-b]indol-4-yl)-3,6-dihydropyridine-1(2H)-carboxylate [ka] A mixture of tert-butyl 4-(7-(N-(1-cyanocyclopropyl)sulfamoyl)-9H-pyrimido-[4,5-b]indol-4-yl)-3,6-dihydropyridine-1(2H)-carboxylate (4.3 g, 8.7 mmol) in dioxane (85 mL) was treated with CsF (3.9 g, 25.7 mmol), CuI (0.98 g, 5.15 mmol), and (1R,2R)-N 1 ,N 2 1,2-Dimethylcyclohexane-1,2-diamine (1.46 g, 10.3 mmol) and 2-bromo-5-(difluoromethyl)-1,3,4-thiadiazole (5.5 g, 25.7 mmol) were added. The mixture was degassed and backfilled with N2 gas three times and stirred at 105 °C for 3 h. The reaction mixture was then cooled to 25 °C, diluted with H2O (250 mL), and extracted with DCM (300 mL x 3). The combined organic phase was washed with saturated brine (400 mL x 2), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by flash chromatography on a silica gel column eluted with EtOAc / PE (0-70%) to give the target compound (2.15 g, 39.8% yield). LCMS calculated value C 23 H 19 F2N8O4S2[M-56+H] + : m / z = 573.2; Found: 573.1.

[0492] Step 3: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(1,2,3,6-tetrahydropyridin-4-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide [ka] To a solution of tert-butyl 4-(7-(N-(1-cyanocyclopropyl)sulfamoyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-9H-pyrimido[4,5-b]indol-4-yl)-3,6-dihydropyridine-1(2H)-carboxylate (1.0 g, 1.59 mmol) in DCM (20 mL) was added TFA (7.0 mL). The mixture was stirred at room temperature for 2 hours. The reaction mixture was evaporated under reduced pressure. The residue was slurried in MTBE (30 mL), filtered, and the solid was dried in vacuo to give the target compound (0.99 g, 97.1% yield). LCMS calculated value C 22 H 19 F2N8O2S2[M+H] + : m / z = 529.1; Found: 529.2.

[0493] Step 4: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(1-isobutyryl-1,2,3,6-tetrahydropyridin-4-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide To a solution of N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(1,2,3,6-tetrahydropyridin-4-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide (0.99 g, 1.75 mmol) in THF (30 mL) and HO (2 mL) was added sodium bicarbonate (2.0 g, 23.8 mmol). Isobutyryl chloride (0.265 g, 2.49 mmol) was added dropwise to the mixture at 0 to 10°C, and the mixture was stirred at 0 to 10°C for 2 hours. The reaction mixture was poured into water (80 mL) and stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure. The residue was purified by prep-HPLC on a C18 column and eluted with MeCN / water (30-50%) to give the target compound (0.42 g, 44.6% yield) as a white solid. 1H NMR: (400 MHz, DMSO-d6) δ9.48 (d, J=1.6Hz, 1H), 9.43 (s, 1H), 9.24 (s, 1H), 8.49-8.54 (m, 1H), 7.97 (d,J = 8.0 Hz, 1H), 7.65 (t,J = 53.2 Hz, 1H), 6.60 (d,J=15.2 Hz, 1H), 4.45 (br s, 1H), 4.31 (br s, 1H), 3.81 (br s, 2H), 2.94-3.01 (m, 1H), 2.79 (br.s, 1H), 2.67 (br.s, 1H), 1.36-1.39 (m, 2H), 1.18-1.22 (m, 2H), 1.03 (d,J = 6.8 Hz, 6H). LCMS calculated value C 26 H 25 F2N8O3S2[M+H] + : m / z = 599.1; Found: 599.2. LCMS calculated value C 26 H 25 F2N8O3S2[M+H] + : m / z = 599.1; Found: 599.2.

[0494] Example 75: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(1-isobutyryl-1,2,3,4-tetrahydropyridin-4-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide [ka]

[0495] Cesium carbonate (870.8 mg, 2.67 mmol) was added to a solution of N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(1-isobutyryl-1,2,3,6-tetrahydropyridin-4-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (0.8 g, 1.34 mmol) in dioxane (16 mL). The mixture was stirred at 100 °C for 1 h, cooled to room temperature, and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column eluted with PE / EtOAc (0-100%) to give the crude product. The crude product was further purified by prep-HPLC, eluting with MeCN / H2O (10%-80%, containing 0.05% NH4HCO3) to give the target product (520 mg, 66% yield) as a white solid. 1 H NMR: (400 MHz, DMSO-d6) δ9.54 (d,J = 1.2 Hz, 1H), 9.29 (s, 1H), 8.65 (t,J = 8.4Hz, 1H), 8.10 (d,J = 9.6Hz, 1H), 7.70 (t,J = 53.2 Hz, 1H), 7.18-7.36 (m, 1H), 5.21-5.24 (m, 1H), 4.69 (brs, 1H), 4.02-4.06 (m, 1H), 3.71 (t,J = 2.8 Hz, 1H), 3.07-3.12 (m, 2H), 2.32-2.33 (t, 2H), 2.10-2.25 (m, 1H),1.42-1.46 (m, 2H), 1.25-1.29 (m, 2H), 1.08 (d,J = 6.4 Hz, 6H). LCMS calculated value C 26 H 25 F2N8O3S2[M+H] + : m / z = 599.1; Found: 599.2.

[0496] Example 76: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(1-isobutyrylpiperidin-4-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka]

[0497] To a mixture of N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(1-isobutyryl-1,2,3,6-tetrahydropyridin-4-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (20 mg, 0.034 mmol, Example 74) in THF (1 mL) was added Pd / C (36 mg, 10% wet). The mixture was degassed and refilled with H2 gas three times and stirred under H2 (15 psi) at 20 °C for 4 h. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by prep-HPLC on a C18 column eluted with MeCN / water (35-55%, 1% NH4HCO3) to give the title compound (3.59 mg, 3.59% yield) as an off-white solid. 1 H NMR: (400 MHz, DMSO-d6) δ9.53 (s, 1H), 9.30 (s, 1H),8.68 (d,J = 8.4 Hz, 1H), 8.08 (dd,J = 8.4 Hz, 1.6 Hz, 1H),7.72 (t,J = 53.6 Hz, 1H), 4.60-4.64 (m, 1H), 4.15-4.18 (m, 1H), 4.01-4.07 (m, 1H), 3.88 (br.s, 1H), 2.94-3.06 (m, 2H), 1.94-2.04 (m, 3H), 1.78-1.81 (m, 1H), 1.37 (br.s, 2H), 1.22 (t,J= 4.8 Hz, 2H), 1.10 (d,J= 6.8 Hz, 2H), 1.06 (s, 4H). LCMS calculated value C 26 H 27 F2N8O3S2[M+H] + : m / z = 601.2; Found: 601.2.

[0498] Example 77: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide [ka]

[0499] This compound was prepared following a similar method to steps 1-2 of Example 74, using 4-chloro-N-(1-cyanocyclopropyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (Intermediate 1) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)-1,2,3,6-tetrahydropyridine as starting materials in step 1. 1 H NMR (400 MHz, DMSO-d6) δ 9.55 (d,J= 1.6 Hz, 1 H), 9.29 (s, 1H), 8.54 (d, J = 8.4Hz, 1H), 8.04 (dd,J = 8.4 Hz, 1.6 Hz, 1H), 7.72 (t,J = LCMS calculated value C 23 H 21 F2N8O2S2[M+H] + : m / z = 543.1; Found: 543.1.

[0500] Example 78: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(3,6-dihydro-2H-pyran-4-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide [ka]

[0501] Step 1: N-(1-cyanocyclopropyl)-4-(3,6-dihydro-2H-pyran-4-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide [ka] This compound was prepared following a similar method to Step 1 of Example 74 using 4-chloro-N-(1-cyanocyclopropyl)-9H-pyrimido[4,5-b]indole-7-sulfonamide (Intermediate 1) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine. LCMS calculated C 19 H 18 N5O3S [M+H] - : m / z = 396.1; Found: 396.1.

[0502] Step 2: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(3,6-dihydro-2H-pyran-4-yl)-9H-pyrimido-[4,5-b]indole-7-sulfonamide This compound was prepared using N-(1-cyanocyclopropyl)-4-(3,6-dihydro-2H-pyran-4-yl)-9H-pyrimidido[4,5-b]indole-7-sulfonamide (Intermediate 1) and 2-bromo-5-(difluoromethyl)-1,3,4-thiadiazole as starting materials following a similar method to Step 1 of Example 74. 1H NMR (400 MHz, DMSO-d6) δ 9.54 (d,J = 1.6 Hz, 1H), 9.50 (s, 1H), 9.31 (s, 1H), 8.60 (d,J = 8.4 Hz, 1H), 8.035 (dd,J = 8.4 Hz, 1.6 Hz, 1H), 7.71 (t,J = 53.2 Hz, 1H), 6.72 (s, 1H), 4.48 (d,J = 2.4 Hz, 2H), 3.99 (t,J = 5.2 Hz, 2H), 2.76 (s, 2H), 1.43-1.47 (m, 2H), 1.25-1.29 (m, 2H). LCMS calculated value C 22 H 18 F2N7O3S2[M+H] + : m / z = 530.1; Found: 530.2.

[0503] Example 79: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(tetrahydro-2H-pyran-4-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka]

[0504] Step 1: N-(1-cyanocyclopropyl)-4-(3,6-dihydro-2H-pyran-4-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide [ka] This compound was prepared according to a method similar to Step 1 of Example 74, using 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxoborolane in place of tert-butyl 4-(4,4,5,5-tetramethyl-1,3,4-dioxoborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate. LCMS calculated for C19H18N5O3S [M+H]-: m / z = 396.1; found: 396.1.

[0505] Step 2: N-(1-cyanocyclopropyl)-4-(tetrahydro-2H-pyran-4-yl)-9H-pyrimidine-[4,5-b]indole-7-sulfonamide [ka] This compound was prepared according to the same method as in Example 76 using N-(1-cyanocyclopropyl)-4-(3,6-dihydro-2H-pyran-4-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide as starting material. LCMS calculated value C 19 H 18 N5O3S [MH] - : m / z = 396.1; Found: 396.1.

[0506] Step 3: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(tetrahydro-2H-pyran-4-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide This compound was prepared according to a similar method to Step 2 of Example 44, starting from N-(1-cyanocyclopropyl)-4-(tetrahydro-2H-pyran-4-yl)-9H-pyrimido[4,5-b]indole-7-sulfonamide and 2-bromo-5-(difluoromethyl)-1,3,4-thiadiazole. 1H NMR (400 MHz, DMSO-d6) δ 9.55 (d,J = 1.2 Hz, 1H), 9.52 (s, 1H), 9.33 (s, 1H), 8.67 (d,J = 8.4 Hz, 1H), 8.10 (dd,J = 8.4 Hz, 1.6 Hz, 1H), 7.71 (t,J = 53.2 Hz, 1H), 4.00-4.06 (m, 3H), 3.73-3.99 (m, 2H), 2.05-2.09 (m, 2H), 1.90 (d,J = 11.6 Hz, 2H), 1.45 (t,J = 2.8 Hz, 2H), 1.29 (t,J= 5.2 Hz, 2H). LCMS calculated value C 22 H 20 F2N7O3S2[M+H] + : m / z = 532.1; Found: 532.1.

[0507] Example 80: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(4-hydroxypiperidin-1-yl)-9H-pyridino[2,3-b]indole-7-sulfonamide [ka]

[0508] Step 1: N-(1-cyanocyclopropyl)-4-(4-hydroxypiperidin-1-yl)-9H-pyrido[2,3-b]indole-7-sulfonamide [ka] CsCO (4.66 g, 14.3 mmol) and t-BuXPhosPdG (569 mg, 0.72 mmol) were added to a mixture of 4-bromo-N-(1-cyanocyclopropyl)-9H-pyrido[2,3-b]indole-7-sulfonamide (2.80 g, 7.16 mmol, Intermediate 5) and piperidin-4-ol (1.45 g, 14.3 mmol) in dioxane (45 mL) at 20 °C under a N atmosphere. The mixture was degassed and backfilled with N gas three times and stirred at 100 °C overnight. The reaction mixture was cooled to room temperature, diluted with DMF (10 mL), and filtered through diatomaceous earth. The filtrate was concentrated under reduced pressure. The residue was purified by prep-HPLC on a C18 column and eluted with MeCN / water (5-40%, containing 0.5% TFA) to give the target compound (840 mg, 22.3% yield) as a white solid. 1 H NMR: (400 MHz, DMSO-d6) δ 12.6 (s, 1H), 9.16 (s, 1H), 8.32 (d,J = 4.0 Hz, 1H), 7.99-8.06 (m, 2H), 7.78 (d,J = 8.0 Hz, 1H), 6.98 (d,J LCMS calculated value C 20 H 22 N5O3S [M+H] - : m / z = 412.1; Found: 412.1.

[0509] Step 2: N-(1-cyanocyclopropyl)-9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-4-(4-hydroxypiperidin-1-yl)-9H-pyrido[2,3-b]indole-7-sulfonamide This compound was prepared according to a similar method to Step 2 of Example 44, starting from N-(1-cyanocyclopropyl)-4-(4-hydroxypiperidin-1-yl)-9H-pyrido[2,3-b]indole-7-sulfonamide and 2-bromo-5-(difluoromethyl)-1,3,4-thiadiazole. 1 H NMR: (400 MHz, DMSO-d6) δ9.53 (d,J = 1.2 Hz, 1H),δ 9.36 (s, 1H), 8.54 (d,J= 6.0 Hz, 1H), 8.07-8.14 (m, 2H), 7.67 (t,J = 53.2 Hz, 1H), 7.20 (d,J = 6.0 Hz, 1H), 4.90 (d,J = 3.6Hz, 1H), 3.84(t,J = 3.6 Hz, 1H),3.59(t,J = 8.4 Hz, 2H), 3.15-3.20 (m, 2H), 2.02-2.04 (m, 2H), 1.75-1.77 (m, 2H), 1.41-1.44 (m, 2H), 1.29 (t,J = 4.8 Hz, 2H). LCMS calculated value C 23 H 22 F2N7O3S2[M+H] + : m / z = 546.1; Found: 546.1.

[0510] Example 81: 4-(9-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-6-fluoro-7-(N-(1-methylcyclopropyl)sulfamoyl)-9H-pyrimido[4,5-b]indol-4-yl)-N,N-dimethyl-3,6-dihydropyridine-1(2H)-carboxamide [ka]

[0511] Step 1: N,N-Dimethyl-4-oxopiperidine-1-carboxamide [ka] Dimethylcarbamoyl chloride (3.17 g, 29.5 mmol) was added dropwise to a solution of piperidin-4-one hydrochloride (2 g, 14.8 mmol) and triethylamine (10.45 g, 103.2 mmol) in dichloromethane (30 mL) at 0 °C. The mixture was allowed to warm to room temperature and stirred at room temperature for 16 h. The resulting reaction mixture was poured into water (20 mL) and extracted with EtOAc (20 mL × 3). The combined organic phase was dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The concentrate was purified by flash chromatography on a silica gel column eluted with EtOAc / hexane (0-50%) to give the target compound (2.56 g, 94% yield). 1 H NMR (400 MHz, CDCl3)δ3.48 (t,J = 6.0 Hz, 4H), 2.85 (s, 6H), 2.44 (t,J = 6.0 Hz, 4H).

[0512] Step 2: 1-(dimethylcarbamoyl)-1,2,3,6-tetrahydropyridin-4-yl trifluoromethanesulfonate [ka] A solution of N,N-dimethyl-4-oxopiperidine-1-carboxamide (2 g, 11.8 mmol) in tetrahydrofuran (15 mL) was cooled to -78 °C and then lithium hexamethyldisilazide (17.6 mL, 1 M tetrahydrofuran solution) was added dropwise under a nitrogen atmosphere. The mixture was stirred for 0.5 h, and then 1,1,1-trifluoro-N-phenyl-N-((trifluoromethyl)sulfonyl)methanesulfonamide (6.3 g, 17.6 mmol) was added. The resulting solution was allowed to warm to room temperature and stirred for 16 h. The resulting reaction mixture was poured into ice water (20 mL) and extracted with EtOAc (20 mL × 3). The combined organic phase was dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column eluted with EtOAc / hexane (0-50%) to give the target compound (2.06 g, 58% yield).1 H NMR (400 MHz, CDCl3)δ5.91-5.62 (m, 1H), 3.88 (q,J = 2.8 Hz, 2H), 3.43 (t,J = 5.6 Hz, 2H), 2.86 (s, 6H), 2.52 (q,J = 2.8 Hz, 2H).

[0513] Step 3: N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxamide [ka] A mixture of 1-(dimethylcarbamoyl)-1,2,3,6-tetrahydropyridin-4-yl trifluoromethanesulfonate (2 g, 6.6 mmol), 4,4,4′,4′,5,5,5′,5′,5′-octamethyl-2,2′-bis(1,3,2-dioxoborolane) (2.52 g, 9.9 mmol), Pd(dppf)2Cl2 (960 mg, 1.3 mmol), and potassium acetate (1.95 g, 19.8 mmol) in dioxane (40 mL) was degassed and backfilled with N2 gas three times and stirred at 90 °C for 2 h. After filtration, the filtrate was diluted with water (20 mL) and extracted with EtOAc (20 mL × 3). The combined organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column eluted with EtOAc / hexane (0-30%) to give the target compound ...

Claims

1. A compound represented by the following formula (I), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotope variant, prodrug, or deuterated compound thereof. 【Chemistry 1】 [In the formula, X is O or NR ５ And, X １ is C, X ２ is N or C, X ３ is N or C, X ４ is C, 【Chemistry 2】 Y is N or CR １５ And, Y １ is N or CR ６ And, Y ２ is N or CR ７ and Y ３ is N or CR ８ And, Y ４ is N or CR ４ And, Y ５ is N or CR ４ And, Y ６ is S, O or NR １４ And, Y ７ is S, O or NR １６ And, Cy １ is R ９ A 5-10 membered heteroaryl group that is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the above, Cy ２ is C ６ ~C １０ Aryl group, C ３ ~C １０ Selected from the group consisting of cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-14 membered heterocycloalkyl groups (where the C ６ ~C １０ Aryl group, C ３ ~C １０ Cycloalkyl groups, 5-10 membered heteroaryl groups, or 4-14 membered heterocycloalkyl groups are R １０ (Optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the original molecule.) R １ , R ２ and R ３ These are H, D, CN, and C, respectively, independently. １ ~C ３ Alkyl alkyl group, C ２ ~C ３ Alkenyl group, C ２ ~C ３ Alkynyl group, C ３ ~C ７ Selected from the group consisting of cycloalkyl groups and 4- to 7-membered heterocycloalkyl groups (where the C １ ~C ３ Alkyl alkyl group, C ２ ~C ３ Alkenyl group, C ２ ~C ３ Alkynyl group, C ３ ~C ７ Cycloalkyl groups, or 4- to 7-membered heterocycloalkyl groups, are independently D, halogen, CN, OH, and C. １ ~C ６ Alkyl alkyl group, C １ ~C ６ Haloalkyl group, -O-C １ ~C ６ Alkyl alkyl groups, and -OC １ ~C ６ (Optionally substituted with 1 to 5 substituents selected from haloalkyl groups.) Or, R ２ and R ３ C ３ ~C ７ It forms a cycloalkyl group or a 4- to 7-membered heterocycloalkyl group (where the C ３ ~C ７ Cycloalkyl groups and 4- to 7-membered heterocycloalkyl groups are independently classified as D, halogens, CN, and NO. ２ , oxo group, OH, C １ ~C ６ Alkyl alkyl group, C １ ~C ６ Haloalkyl group, -O-C １ ~C ６ Alkyl alkyl group, -OC １ ~C ６ (Optionally substituted with one, two, three, or four substituents selected from haloalkyl groups.) R ４ is H, D, halogen, OH, CN, NO ２ , SF ５ , C １ ~C ３ alkyl group, C ２ ~C ３ alkenyl group, C ２ ~C ３ alkynyl group, -O-C １ ~C ３ alkyl group, and NR Ｃ R Ｄ selected from the group consisting of (wherein the C １ ~C ３ alkyl group, C ２ ~C ３ alkenyl group, C<000009​​​ R ５ is selected from the group consisting of H, D, CN, OR Ｂ and C １ to C ４ alkyl groups, where C １ to C ４ alkyl groups are optionally substituted with at least one in R ５Ａ and each R ５Ａ is independently D, F, Cl, CN, NH ２ , OH, -O-C １ to C ６ alkyl group, -OC １ to C ６ haloalkyl group, optionally substituted C ３ to C ７ cycloalkyl group, and optionally substituted 4- to 7-member heterocycloalkyl group, and further here, the optionally substituted means that it is substituted with any substituent selected from the group consisting of D, halogen, CN, OH, C １ to C ４ alkyl group, C １ to C ４ haloalkyl group, -O-C １ to C ４ alkyl group, -OC １ to C ４ haloalkyl group) Or, R １ and R ５ These, together with the atoms linked to them, form a 5-7 member partially saturated heterocycloalkyl group (where the 5-7 member partially saturated heterocycloalkyl group is independently D, halogen, CN, CF ３ NO ２ , oxo group, OH, C １ ~C ６ Alkyl alkyl group, C １ ~C ６ Haloalkyl group, -O-C １ ~C ６ Alkyl alkyl group, -OC １ ~C ６ (Optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of haloalkyl groups.) R ６ , R ７ and R １５ These are H, D, halogen, CN, and NO, respectively, independently. ２ , C １ ~C ６ Alkyl 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 , and NR Ｃ S(O)(=NR Ｂ ) R Ｂ Selected from the group consisting of (where C １ ~C ６ Alkyl alkyl group, C ２ ~C ６ Alkenyl group, or C ２ ~C ６ The alkynyl group is independently R １１ (Optionally substituted with one, two, or three substituents selected from) R ８ H, D, CN, halogen, OH, NH ２ , C １ ~C ３ Alkyl 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 Cyanoalkyl groups, and SF ５ Selected from the group consisting of, Each R ９ These are independently H, D, halogen, and C. １ ~C ６ Alkyl 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 , and SF ５ Selected from the group consisting of (where C １ ~C ６ Alkyl alkyl group, C ２ ~C ６ Alkenyl group, C ２ ~C ６ Alkynyl group or C ３ ~C ７ Cycloalkyl groups are R １１ (Optionally substituted with one, two, or three substituents independently selected from the original molecule.) Each R １０ These are independently H, D, halogen, CN, NO ２ , N ３ , oxo group, C １ ~C ６ Alkyl 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 , and O-C １ ~C ６ Alkyl-Cy ３ Selected from the group consisting of (where C １ ~C ６ Alkyl alkyl group, C ２ ~C ６ Alkenyl group, C ２ ~C ６ The alkynyl group is R １１ (Optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the original molecule.) Two R's １０ The oxo group, C, is formed along with the atoms linked to them. ３ ~C １０ It forms a cycloalkyl group or a 4- to 10-membered heterocycloalkyl group (where the C ３ ~C １０ Cycloalkyl groups or 4- to 10-membered heterocycloalkyl groups are independently classified as D, halogen, and C. １ ~C ６ Alkyl 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 group, 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 It is optionally substituted with one, two, or three substituents selected from, and further, Cy ４ is C ６ ~C １０ Aryl group, C ３ ~C １０ Selected from the group consisting of cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups, and further, here, the C ６ ~C １０ Aryl group, C ３ ~C １０ Cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups are D, halogens, CN, and NO. ２ OH, oxo group, NH ２ NHC １ ~C ４ alkyl group, N(C) １ ~C ４ (Alkyl group) ２ , C １ ~C ３ Alkyl 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 groups, and SF ５ (Optionally substituted with one, two, three, or four substituents independently selected from the original molecule.) Cy ３ C is independent ６ ~C １０ Aryl group, C ３ ~C １０ Selected from the group consisting of cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups (where the C ６ ~C １０ Aryl group, C ３ ~C １０ Cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups are either unsubstituted or R １２ (Optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the original molecule.) Each R １１ These are independently H, D, halogen, CN, NO ２ , N ３ , C １ ~C ６ Alkyl 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 the group consisting of cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups (where the C ６ ~C １０ Aryl group, C ３ ~C １０ Cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups are independently either unsubstituted or substituted with D, halogens, CN, or NO. ２ NH ２ NHC １ ~C ４ alkyl group, N(C) １ ~C ４ (Alkyl group) ２ , C １ ~C ３ Alkyl 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 groups, and SF ５ (Optionally substituted with 1, 2, 3, 4, or 5 substituents selected from) Each R １２ These are independently D, halogen, and C １ ~C ６ Alkyl 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 the group consisting of cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups (where the C ６ ~C １０ Aryl group, C ３ ~C １０ Unsubstituted with cycloalkyl groups, 5-10 membered heteroaryl groups, or 4-10 membered heterocycloalkyl groups, or independently of D, halogens, CN, and NO. ２ NH ２ NHC １ ~C ４ alkyl group, N(C) １ ~C ４ (Alkyl group) ２ , C １ ~C ３ Alkyl 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 groups, and SF ５ (Optionally substituted with 1, 2, 3, 4, or 5 substituents selected from) Each R １３ These are independently H, D, OH, CN, halogen, oxo group, C １ ~C ４ Alkyl alkyl group, C １ ~C ４ Haloalkyl group, C １ ~C ４ Cyanoalkyl groups, OC １ ~C ４ Alkyl alkyl groups, OC １ ~C ４ Haloalkyl groups, OC １ ~C ４ Alkyl-OH, OC １ ~C ４ Alkyl-O-C １ ~C ４ Alkyl alkyl groups, OC １ ~C ４ Alkyl-O-C １ ~C ４ Haloalkyl group, C １ ~C ４ Alkyl-O-C １ ~C ４ Alkyl alkyl group, C １ ~C ４ Alkyl-O-C １ ~C ４ Haloalkyl groups, optionally substituted C ３ ~C ７ Cycloalkyl groups, optionally substituted 4- to 7-membered heterocycloalkyl groups, SF ５ , OR ａ , SR ａ , C(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 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 , and B (OR ｃ ) ( OR ｄ ) selected from the group consisting of (where the arbitrarily selected substitutions refer to D, halogen, CN, OH, C １ ~C ４ Alkyl alkyl group, C １ ~C ４ Haloalkyl group, -O-C １ ~C ４ Alkyl alkyl group, -OC １ ~C ４ (It is substituted with a substitute group selected from the group consisting of haloalkyl groups.) R １４ and R １６ These are H, D, and C respectively. １ ~C ６ Alkyl 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-OH, C １ ~C ６ Alkyl-CN, C １ ~C ６ Alkyl-O-C １ ~C ６ Selected from the group consisting of alkyl groups, R Ａ These are H, D, and C, independently. １ ~C ６ Alkyl alkyl group, C ２ ~C ４ Alkenyl group, C ２ ~C ４ Alkynyl group, C ３ ~C １０ Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C ６ ~C １０ Selected from the group consisting of aryl groups, 5-10 membered heteroaryl groups, arylalkyl groups, heteroarylalkyl groups, cycloalkylalkyl groups, and heterocycloalkylalkyl groups (where the C １ ~C ６ Alkyl alkyl group, C ２ ~C ４ Alkenyl group, C ２ ~C ４ Alkynyl group, C ３ ~C １０ Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C ６ ~C １０ An aryl group, a 5- to 10-membered heteroaryl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, or a heterocycloalkylalkyl group can independently be D, OH, CN, halogen, or C. １ ~C ４ Alkyl alkyl, NO ２ , oxo group, 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 , and NR ｃ S(O)(=NR ｂ ) R ｂ (Optionally substituted with 1, 2, 3, 4, or 5 substituents selected from) R Ｂ These are H, D, and C, independently. １ ~C ６ Alkyl 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 Selected from the group consisting of aryl groups, 5-10 membered heteroaryl groups, arylalkyl groups, heteroarylalkyl groups, cycloalkylalkyl groups, and heterocycloalkylalkyl groups (where the C １ ~C ６ Alkyl 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 An aryl group, a 5-10 membered heteroaryl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, or a heterocycloalkylalkyl group can be independently classified as R １３ (Optionally substituted with 1, 2, 3, 4, or 5 substituents selected from) R Ｃ and R Ｄ These are H, D, and C, respectively, independently. １ ~C ６ Alkyl alkyl group, C ２ ~C ６ Alkenyl group, C ２ ~C ６ Alkynyl group, C ３ ~C ７ Selected from the group consisting of cycloalkyl groups, 4-7 membered heterocycloalkyl groups, phenyl groups, 5-6 membered heteroaryl groups, arylalkyl groups, heteroarylalkyl groups, cycloalkylalkyl groups, and heterocycloalkylalkyl groups (where the C １ ~C ６ Alkyl alkyl group, C ２ ~C ６ Alkenyl group, C ２ ~C ６ Alkynyl group, C ３ ~C ７ Cycloalkyl groups, 4-7 membered heterocycloalkyl groups, phenyl groups, 5-6 membered heteroaryl groups, arylalkyl groups, heteroarylalkyl groups, cycloalkylalkyl groups, or heterocycloalkylalkyl groups can independently be D, OH, CN, halogens, oxo groups, and C. １ ~C ４ Alkyl alkyl group, C １ ~C ４ Haloalkyl group, C １ ~C ４ Cyanoalkyl groups, OC １ ~C ４ Alkyl alkyl groups, OC １ ~C ４ Haloalkyl groups, OC ２ ~C ４ Alkyl-OH, OC ２ ~C ４ Alkyl-O-C １ ~C ４ Alkyl alkyl groups, OC ２ ~C ４ Alkyl-O-C １ ~C ４ Haloalkyl group, C １ ~C ４ Alkyl-O-C １ ~C ４ Alkyl alkyl group, C １ ~C ４ alkyl - O - C １ ~C ４ haloalkyl group, SF ５ , OC(O)NR ｃ R ｄ , NR ｃ R ｄ , NR ｃ C(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 , and optionally substituted with 1, 2, 3, 4 or 5 substituents selected from B(OR ｃ )(OR ｄ )) Or, R Ｃ and R Ｄ These, together with the N atoms linked to them, form a 4- to 7-membered heterocycloalkyl group (where the 4- to 7-membered heterocycloalkyl group is independently D, OH, oxo group, CN, -NH ２ ,-NH(C １ ~C ４ Alkyl alkyl group), -N(C １ ~C ４ (Alkyl group) ２ , halogen, C １ ~C ４ Alkyl alkyl group, C １ ~C ４ Haloalkyl group, C １ ~C ４ Cyanoalkyl groups, OC １ ~C ４ Alkyl alkyl groups, and OC １ ~C ４ Haloalkyl groups, OC ２ ~C ４ Alkyl-OH, OC ２ ~C ４ Alkyl-O-C １ ~C ４ Alkyl alkyl groups, OC ２ ~C ４ Alkyl-O-C １ ~C ４ (Optionally substituted with 1, 2, 3, 4, or 5 substituents selected from haloalkyl groups.) R ａ and R ａ１ are each independently selected from the group consisting of H, D, 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 group, 5- to 6-membered heteroaryl group, and 4- to 7-membered heterocycloalkyl group (wherein 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 group, 5- to 6-membered heteroaryl group, or 4- to 7-membered heterocycloalkyl group is independently D, OH, CN, -NH ２ , -NH(C １ ~C ４ alkyl group), -N(C １ ~C ４ alkyl group) ２ , halogen, C １ ~C ４ alkyl group, C １ ~C ４ alkoxy group, C １ ~C ４ haloalkyl group, and C １ ~C[[ID=, optionally substituted with one, two or three substituents selected from the group consisting of ４ haloalkoxy group). R ｂ and R ｂ１ These are H, D, and C, respectively, independently. １ ~C ４ Alkyl alkyl group, C ２ ~C ４ Alkenyl group, C ２ ~C ４ Alkynyl group, phenyl group, C ３ ~C ７ Selected from the group consisting of cycloalkyl groups, 5-6 membered heteroaryl groups, or 4-7 membered heterocycloalkyl groups, arylalkyl groups, heteroarylalkyl groups, cycloalkylalkyl groups, and heterocycloalkylalkyl groups (where the C １ ~C ４ Alkyl 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, 4-7 membered heterocycloalkyl groups, arylalkyl groups, heteroarylalkyl groups, cycloalkylalkyl groups, or heterocycloalkylalkyl groups are independently D, OH, CN, -NH ２ ,-NH(C １ ~C ４ Alkyl alkyl group), -N(C １ ~C ４ (Alkyl group) ２ , halogen, C １ ~C ４ Alkyl alkyl group, C １ ~C ４ Alkoxy group, C １ ~C ４ Haloalkyl group, C １ ~C ４ Haloalkoxy group, C ６ ~C １０ Aryl group, C ３ ~C １０ (Optionally substituted with one, two, or three substituents selected from cycloalkyl groups, 5- to 10-membered heteroaryl groups, and 4- to 10-membered heterocycloalkyl groups.) R ｃ and R ｄ These are H, D, and C, respectively, independently. １ ~C ４ Alkyl alkyl group, C １ ~C ４ Haloalkyl 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 the group consisting of cycloalkyl groups, 4-10 member heterocycloalkyl groups, arylalkyl groups, heteroarylalkyl groups, cycloalkylalkyl groups, heterocycloalkylalkyl groups, arylcycloalkyl groups, arylheterocycloalkyl groups, arylheteroaryl groups, diaryl groups, heteroarylcycloalkyl groups, heteroarylheterocycloalkyl groups, heteroarylaryl groups, and diheteroaryl groups (where the 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 membered heterocycloalkyl groups, arylalkyl groups, heteroarylalkyl groups, cycloalkylalkyl groups, heterocycloalkylalkyl groups, arylcycloalkyl groups, arylheterocycloalkyl groups, arylheteroaryl groups, diaryl groups, heteroarylcycloalkyl groups, heteroarylheterocycloalkyl groups, heteroarylaryl groups, or diheteroaryl groups are independently D, OH, CN, -NH ２ ,-NH(C １ ~C ４ Alkyl alkyl group), -N(C １ ~C ４ (Alkyl group) ２ , halogen, C １ ~C ４ Alkyl 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 Alkyl-O-C １ ~C ４ Alkyl alkyl groups, and C １ ~C ４ Alkyl-O-C １ ~C ４ (Optionally substituted with one, two, or three substituents selected from alkyl-O-) Or, R ｃ and R ｄ These, together with the N atoms linked to them, form a 4- to 7-membered heterocycloalkyl group (where the 4- to 7-membered heterocycloalkyl group is independently D, OH, CN, -NH ２ ,-NH(C １ ~C ４ Alkyl alkyl group), -N(C １ ~C ４ (Alkyl group) ２ , halogen, C １ ~C ４ Alkyl 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 alkyl groups, and C １ ~C ４ Alkoxy-C １ ~C ４ (Optionally substituted with one, two, or three substituents selected from the alkoxy group.) R ｃ１ and R ｄ１ These are H, D, and C, respectively, independently. １ ~C ４ Alkyl alkyl group, C １ ~C ４ Haloalkyl 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 the group consisting of cycloalkyl groups, 4-10 member heterocycloalkyl groups, arylalkyl groups, heteroarylalkyl groups, cycloalkylalkyl groups, and heterocycloalkylalkyl groups (where the C １ ~C ４ Alkyl alkyl group, C １ ~C ４ Haloalkyl 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- to 10-membered heterocycloalkyl groups, arylalkyl groups, heteroarylalkyl groups, cycloalkylalkyl groups, or heterocycloalkylalkyl groups are independently D, OH, CN, -NH ２ ,-NH(C １ ~C ４ Alkyl alkyl group), -N(C １ ~C ４ (Alkyl group) ２ , halogen, C １ ~C ４ Alkyl alkyl group, C １ ~C ４ Alkoxy group, C １ ~C ４ Haloalkyl groups and C １ ~C ４ (Optionally substituted with one, two, or three substituents selected from the haloalkoxy group.) Or, R ｃ１ and R ｄ１ These, together with the N atoms linked to them, form a 4- to 7-membered heterocycloalkyl group (where the 4- to 7-membered heterocycloalkyl group is D, OH, CN, -NH ２ ,-NH(C １ ~C ４ Alkyl alkyl group), -N(C １ ~C ４ (Alkyl group) ２ , halogen, C １ ~C ４ Alkyl alkyl group, C １ ~C ４ Alkoxy group, C １ ~C ４ Haloalkyl groups and C １－４ (Optionally substituted with one, two, or three substituents independently selected from the haloalkoxy group.) R Ｅ , R ｅ and R ｅ１ These are H, D, and C, respectively, independently. １ ~C ４ Alkyl alkyl group, C １ ~C ４ Haloalkyl group, C ２ ~C ４ Alkenyl group, (C １ ~C ４ Alkoxy)-C １ ~C ４ Alkyl 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, 3-10 member heterocycloalkyl groups, C ６ ~C １０ Aryl-C １ ~C ４ Alkyl alkyl group, C ３ ~C １０ Cycloalkyl-C １ ~C ４ Alkyl, 5-10 member heteroaryl-C １ ~C ４ Alkyl groups, and 4-10 member heterocycloalkyl-C １ ~C ４ Selected from the group consisting of alkyl groups, R Ｆ , R ｆ and R ｆ１ These are H, D, and C, respectively, independently. １ ~C ４ Alkyl 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 the group consisting of cycloalkyl groups and 4- to 10-membered heterocycloalkyl groups, R Ｇ , R Ｈ and R Ｉ Each is independent of C １ ~C ４ Selected from the group consisting of alkyl groups and phenyl groups.

2. The compound according to claim 1, characterized in that the compound represented by (I) is a compound represented by the following formulas (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), or (Iq), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotope variant, prodrug or deuterated compound thereof. 【Transformation 3】 【change】 (In the formula, R １ , R ２ , R ３ , X, X １ , X ２ , X ３ , X ４ , Y, Y １ , Y ２ , Y ３ , Y ４ , Y ５ , Y ６ , Y ７ Cy １ , and Cy ２ The definition is the same as in equation (I) above.

3. The compound represented by (I) above is the compound represented by the following formula (II), 【Chemistry 4】 [In the formula, X is O or NR ５ And, Y １ is N or CR ６ And, Y ２ is N or CR ７ and Y １ and Y ２ The largest of these is N, Y ３ is N or CR ８ And, n is 0, 1, or 2. Cy １ is R ９ A 5-10 membered heteroaryl group that is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the above, Cy ２ is C ６ ~C １０ Aryl group, C ３ ~C １０ Selected from the group consisting of cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-14 membered heterocycloalkyl groups (where the C ６ ~C １０ Aryl group, C ３ ~C １０ Cycloalkyl groups, 5-10 membered heteroaryl groups, or 4-14 membered heterocycloalkyl groups are R １０ (Optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the original molecule.) R １ , R ２ and R ３ These are H, D, CN, and C, respectively, independently. １ ~C ３ Alkyl alkyl group, C ２ ~C ３ Alkenyl group, C ２ ~C ３ Alkynyl group, C ３ ~C ７ Selected from the group consisting of cycloalkyl groups and 4- to 7-membered heterocycloalkyl groups (where the C １ ~C ３ Alkyl alkyl group, C ２ ~C ３ Alkenyl group, C ２ ~C ３ Alkynyl group, C ３ ~C ７ Cycloalkyl groups, or 4- to 7-membered heterocycloalkyl groups, are independently D, halogen, CN, OH, and C. １ ~C ６ Alkyl alkyl group, C １ ~C ６ Haloalkyl group, -O-C １ ~C ６ Alkyl alkyl group, -OC １ ~C ６ (Optionally substituted with 1 to 5 substituents selected from haloalkyl groups.) Or, R ２ and R ３ C ３ ~C ７ It forms a cycloalkyl group or a 4- to 7-membered heterocycloalkyl group (where the C ３ ~C ７ Cycloalkyl groups and 4- to 7-membered heterocycloalkyl groups are independently classified as D, halogens, CN, and NO. ２ , oxo group, OH, C １ ~C ６ Alkyl alkyl group, C １ ~C ６ Haloalkyl group, -O-C １ ~C ６ Alkyl alkyl group, -OC １ ~C ６ (Optionally substituted with one, two, three, or four substituents selected from haloalkyl groups.) R ４ H, D, halogen, OH, CN, NO ２ SF ５ , C １ ~C ３ Alkyl alkyl group, C ２ ~C ３ Alkenyl group, C ２ ~C ３ Alkynyl group, -O-C １ ~C ３ Alkyl groups, and NR Ｃ R Ｄ Selected from the group consisting of (where C １ ~C ３ Alkyl alkyl group, C ２ ~C ３ Alkenyl group, C ２ ~C ３ The alkynyl group is optionally substituted with a halogen or CN. R ５ is H, D, CN, OR Ｂ , and R ５Ａ At least one of them is optionally replaced by C １ ~C ４ Selected from the group consisting of alkyl groups (where R ５Ａ These are D, F, Cl, CN, and NH, respectively, independently. ２ OH, -O-C １ ~C ６ Alkyl alkyl group, -OC １ ~C ６ Haloalkyl groups, optionally substituted C ３ ~C ７ Selected from the group consisting of cycloalkyl groups and selectively substituted 4- to 7-membered heterocycloalkyl groups, wherein the selective substitution refers to D, halogen, CN, OH, C １ ~C ４ Alkyl alkyl group, C １ ~C ４ Haloalkyl group, -O-C １ ~C ４ Alkyl alkyl group, -OC １ ~C ４ (It is substituted with a substitute group selected from the group consisting of haloalkyl groups.) Or, R １ and R ５ These, together with the atoms linked to them, form a 5-7 member partially saturated heterocycloalkyl group (where the 5-7 member partially saturated heterocycloalkyl group is D, halogen, CN, CF ３ NO ２ , oxo group, OH, C １ ~C ６ Alkyl alkyl group, C １ ~C ６ Haloalkyl group, -O-C １ ~C ６ Alkyl alkyl group, -OC １ ~C ６ (Optionally substituted with one, two, three, or four substituents independently selected from the haloalkyl group.) R ６ and R ７ These are H, D, halogen, CN, and NO, respectively, independently. ２ , C １ ~C ６ Alkyl 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 , and NR Ｃ S(O)(=NR Ｂ ) R Ｂ Selected from the group consisting of (where C １ ~C ６ Alkyl alkyl group, C ２ ~C ６ Alkenyl group, or C ２ ~C ６ The alkynyl group is independently R １１ (Optionally substituted with one, two, or three substituents selected from) R ８ H, D, CN, halogen, OH, NH ２ , C １ ~C ３ Alkyl 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 Cyanoalkyl groups, and SF ５ Selected from the group consisting of, Each R ９ These are independently H, D, halogen, and C. １ ~C ６ Alkyl 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 , and SF ５ Selected from the group consisting of (where C １ ~C ６ Alkyl alkyl group, C ２ ~C ６ Alkenyl group, C ２ ~C ６ Alkynyl group, or C ３ ~C ７ Cycloalkyl groups are independently R １１ (Optionally substituted with one, two, or three substituents selected from) Each R １０ These are independently H, D, halogen, CN, NO ２ , N ３ , oxo group, C １ ~C ６ Alkyl 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 , and O-C １ ~C ６ Alkyl-Cy ３ Selected from the group consisting of (where C １ ~C ６ Alkyl alkyl group, C ２ ~C ６ Alkenyl group, C ２ ~C ６ The alkynyl group is independently R １１ (Optionally substituted with 1, 2, 3, 4, or 5 substituents selected from) Alternatively, two R's １０ The oxo group, C, is formed along with the atoms linked to them. ３ ~C １０ It forms a cycloalkyl group or a 4- to 10-membered heterocycloalkyl group (where the C ３ ~C １０ Cycloalkyl groups or 4- to 10-membered heterocycloalkyl groups are independently classified as D, halogen, and C. １ ~C ６ Alkyl 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 group, 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 It is optionally substituted with one, two, or three substituents selected from, and further, Cy ４ is C ６ ~C １０ Aryl group, C ３ ~C １０ Selected from the group consisting of cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups, and further, here, the C ６ ~C １０ Aryl group, C ３ ~C １０ Cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups are independently D, halogens, CN, and NO. ２ OH, oxo group, NH ２ NHC １ ~C ４ alkyl group, N(C) １ ~C ４ (Alkyl group) ２ , C １ ~C ３ Alkyl 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 groups, and SF ５ (Optionally substituted with 1, 2, 3, or 4 substituents selected from) Cy ３ C is independent ６ ~C １０ Aryl group, C ３ ~C １０ Selected from the group consisting of cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups (where the C ６ ~C １０ Aryl group, C ３ ~C １０ The cycloalkyl group, the 5-10 membered heteroaryl group, and the 4-10 membered heterocycloalkyl group are independently either unsubstituted or R １２ (Optionally substituted with 1, 2, 3, 4, or 5 substituents selected from) Each R １１ These are independently H, D, halogen, CN, NO ２ , N ３ , C １ ~C ６ Alkyl 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 the group consisting of cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups (where the C ６ ~C １０ Aryl group, C ３ ~C １０ Cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups are either unsubstituted or contain D, halogens, CN, or NO. ２ NH ２ NHC １ ~C ４ alkyl group, N(C) １ ~C ４ (Alkyl group) ２ , C １ ~C ３ Alkyl 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 groups, and SF ５ (Optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the original molecule.) Each R １２ These are independently D, halogen, and C １ ~C ６ Alkyl 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 the group consisting of cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups (where the C ６ ~C １０ Aryl group, C ３ ~C １０ Cycloalkyl groups, 5-10 membered heteroaryl groups, and 4-10 membered heterocycloalkyl groups are independently unsubstituted or contain D, halogens, CN, or NO. ２ NH ２ NHC １ ~C ４ alkyl group, N(C) １ ~C ４ (Alkyl group) ２ , C １ ~C ３ Alkyl 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 groups, and SF ５ (Optionally substituted with 1, 2, 3, 4, or 5 substituents selected from) R Ａ These are H, D, and C, independently. １ ~C ６ Alkyl alkyl group, C ２ ~C ４ Alkenyl group, C ２ ~C ４ Alkynyl group, C ３ ~C １０ Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C ６ ~C １０ Selected from the group consisting of aryl groups, 5-10 membered heteroaryl groups, arylalkyl groups, heteroarylalkyl groups, cycloalkylalkyl groups, and heterocycloalkylalkyl groups (where the C １ ~C ６ Alkyl alkyl group, C ２ ~C ４ Alkenyl group, C ２ ~C ４ Alkynyl group, C ３ ~C １０ Cycloalkyl groups, 4-10 member heterocycloalkyl groups, C ６ ~C １０ An aryl group, a 5- to 10-membered heteroaryl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, or a heterocycloalkylalkyl group can independently be D, OH, CN, halogen, or C. １ ~C ４ Alkyl alkyl, NO ２ , oxo group, 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 , and NR ｃ S(O)(=NR ｂ ) R ｂ (Optionally substituted with 1, 2, 3, 4, or 5 substituents selected from) R Ｂ These are H, D, and C, independently. １ ~C ６ Alkyl 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 Selected from the group consisting of aryl groups, 5-10 membered heteroaryl groups, arylalkyl groups, heteroarylalkyl groups, cycloalkylalkyl groups, and heterocycloalkylalkyl groups (where the C １ ~C ６ Alkyl 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 An aryl group, a 5-10 membered heteroaryl group, an arylalkyl group, a heteroarylalkyl group, a cycloalkylalkyl group, or a heterocycloalkylalkyl group can be independently classified as R １３ (Optionally substituted with 1, 2, 3, 4, or 5 substituents selected from) Each R １３ These are independently H, D, OH, CN, halogen, oxo group, C １ ~C ４ Alkyl alkyl group, C １ ~C ４ Haloalkyl group, C １ ~C ４ Cyanoalkyl groups, OC １ ~C ４ Alkyl alkyl groups, OC １ ~C ４ Haloalkyl groups, OC １ ~C ４ Alkyl-OH, OC １ ~C ４ Alkyl-O-C １ ~C ４ Alkyl alkyl groups, OC １ ~C ４ Alkyl-O-C １ ~C ４ Haloalkyl group, C １ ~C ４ Alkyl-O-C １ ~C ４ Alkyl alkyl group, C １ ~C ４ Alkyl-O-C １ ~C ４ Haloalkyl groups, optionally substituted C ３ ~C ７ Cycloalkyl groups, optionally substituted 4- to 7-membered heterocycloalkyl groups, SF ５ , OR ａ , SR ａ , C(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 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 , and B (OR ｃ ) ( OR ｄ ) selected from the group consisting of (where the arbitrarily selected substitutions refer to D, halogen, CN, OH, C １ ~C ４ Alkyl alkyl group, C １ ~C ４ Haloalkyl group, -O-C １ ~C ４ Alkyl alkyl group, -OC １ ~C ４ (It is substituted with a substitute group selected from the group consisting of haloalkyl groups.) R Ｃ and R Ｄ These are H, D, and C, respectively, independently. １ ~C ６ Alkyl alkyl group, C ２ ~C ６ Alkenyl group, C ２ ~C ６ Alkynyl group, C ３ ~C ７ Selected from the group consisting of cycloalkyl groups, 4-7 membered heterocycloalkyl groups, phenyl groups, 5-6 membered heteroaryl groups, arylalkyl groups, heteroarylalkyl groups, cycloalkylalkyl groups, and heterocycloalkylalkyl groups (where the C １ ~C ６ Alkyl alkyl group, C ２ ~C ６ Alkenyl group, C ２ ~C ６ Alkynyl group, C ３ ~C ７ Cycloalkyl groups, 4-7 membered heterocycloalkyl groups, phenyl groups, 5-6 membered heteroaryl groups, arylalkyl groups, heteroarylalkyl groups, cycloalkylalkyl groups, or heterocycloalkylalkyl groups can independently be D, OH, CN, halogens, oxo groups, and C. １ ~C ４ Alkyl alkyl group, C １ ~C ４ Haloalkyl group, C １ ~C ４ Cyanoalkyl groups, OC １ ~C ４ Alkyl alkyl groups, OC １ ~C ４ Haloalkyl groups, OC ２ ~C ４ Alkyl-OH, OC ２ ~C ４ Alkyl-O-C １ ~C ４ Alkyl alkyl groups, OC ２ ~C ４ Alkyl-O-C １ ~C ４ Haloalkyl group, C １ ~C ４ Alkyl-O-C １ ~C ４ Alkyl alkyl group, C １ ~C ４ Alkyl-O-C １ ~C ４ Haloalkyl groups, SF ５ , OC(O)NR ｃ R ｄ , NR ｃ R ｄ , NR ｃ C(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 , and B (OR ｃ ) ( OR ｄ (The substituents are optionally substituted with 1, 2, 3, 4, or 5 substituents selected from the above.) Or, R Ｃ and R Ｄ These, together with the N atoms linked to them, form a 4- to 7-membered heterocycloalkyl group (wherein the 4- to 7-membered heterocycloalkyl group, independently, D, OH, oxo group, CN, -NH ２ ,-NH(C １ ~C ４ Alkyl alkyl group), -N(C １ ~C ４ (Alkyl group) ２ , halogen, or C １ ~C ４ Alkyl alkyl group, C １ ~C ４ Haloalkyl group, C １ ~C ４ Cyanoalkyl groups, OC １ ~C ４ Alkyl alkyl group, or OC １ ~C ４ Haloalkyl groups, OC ２ ~C ４ Alkyl-OH, OC ２ ~C ４ Alkyl-O-C １ ~C ４ Alkyl alkyl groups, OC ２ ~C ４ Alkyl-O-C １ ~C ４ (Optionally substituted with 1, 2, 3, 4, or 5 substituents selected from haloalkyl groups.) R ａ and R ａ１ These are H, D, and C, respectively, independently. １ ~C ４ Alkyl alkyl group, C ２ ~C ４ Alkenyl group, C ２ ~C ４ Alkynyl group, phenyl group, C ３ ~C ７ Selected from the group consisting of cycloalkyl groups, 5-6 membered heteroaryl groups, and 4-7 membered heterocycloalkyl groups (where the C １ ~C ４ Alkyl 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 independently D, OH, CN, and -NH ２ ,-NH(C １ ~C ４ Alkyl alkyl group), -N(C １ ~C ４ (Alkyl group) ２ , halogen, C １ ~C ４ Alkyl alkyl group, C １ ~C ４ Alkoxy group, C １ ~C ４ Haloalkyl groups and C １ ~C ４ (Optionally substituted with one, two, or three substituents selected from the haloalkoxy group.) R ｂ and R ｂ１ These are H, D, and C, respectively, independently. １ ~C ４ Alkyl alkyl group, C ２ ~C ４ Alkenyl group, C ２ ~C ４ Alkynyl group, phenyl group, C ３ ~C ７ Selected from the group consisting of cycloalkyl groups, 5-6 membered heteroaryl groups, 4-7 membered heterocycloalkyl groups, arylalkyl groups, heteroarylalkyl groups, cycloalkylalkyl groups, and heterocycloalkylalkyl groups (where the C １ ~C ４ Alkyl 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, 4-7 membered heterocycloalkyl groups, arylalkyl groups, heteroarylalkyl groups, cycloalkylalkyl groups, or heterocycloalkylalkyl groups are independently D, OH, CN, -NH ２ ,-NH(C １ ~C ４ Alkyl alkyl group), -N(C １ ~C ４ (Alkyl group) ２ , halogen, C １ ~C ４ Alkyl alkyl group, C １ ~C ４ Alkoxy group, C １ ~C ４ Haloalkyl group, C １ ~C ４ Haloalkoxy group, C ６ ~C １０ Aryl group, C ３ ~C １０ (Optionally substituted with one, two, or three substituents selected from cycloalkyl groups, 5- to 10-membered heteroaryl groups, and 4- to 10-membered heterocycloalkyl groups.) R ｃ and R ｄ These are H, D, and C, respectively, independently. １ ~C ４ Alkyl alkyl group, C １ ~C ４ Haloalkyl 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 the group consisting of cycloalkyl groups, 4-10 member heterocycloalkyl groups, arylalkyl groups, heteroarylalkyl groups, cycloalkylalkyl groups, heterocycloalkylalkyl groups, arylcycloalkyl groups, arylheterocycloalkyl groups, arylheteroaryl groups, diaryl groups, heteroarylcycloalkyl groups, heteroarylheterocycloalkyl groups, heteroarylaryl groups, and diheteroaryl groups (where the 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 membered heterocycloalkyl groups, arylalkyl groups, heteroarylalkyl groups, cycloalkylalkyl groups, heterocycloalkylalkyl groups, arylcycloalkyl groups, arylheterocycloalkyl groups, arylheteroaryl groups, diaryl groups, heteroarylcycloalkyl groups, heteroarylheterocycloalkyl groups, heteroarylaryl groups, or diheteroaryl groups are independently D, OH, CN, -NH ２ ,-NH(C １ ~C ４ Alkyl alkyl group), -N(C １ ~C ４ (Alkyl group) ２ , halogen, C １ ~C ４ Alkyl 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 Alkyl-O-C １ ~C ４ Alkyl alkyl groups, and C １ ~C ４ Alkyl-O-C １ ~C ４ (Optionally substituted with one, two, or three substituents selected from alkyl-O-) Or, R ｃ and R ｄ These, together with the N atoms linked to them, form a 4- to 7-membered heterocycloalkyl group (where the 4- to 7-membered heterocycloalkyl group is D, OH, CN, -NH ２ ,-NH(C １ ~C ４ Alkyl alkyl group), -N(C １ ~C ４ (Alkyl group) ２ , halogen, C １ ~C ４ Alkyl 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 alkyl groups, and C １ ~C ４ Alkoxy-C １ ~C ４ (Optionally substituted with one, two, or three substituents independently selected from the alkoxy group.) R ｃ１ and R ｄ１ These are H, D, and C, respectively, independently. １ ~C ４ Alkyl alkyl group, C １ ~C ４ Haloalkyl 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 the group consisting of cycloalkyl groups, 4-10 member heterocycloalkyl groups, arylalkyl groups, heteroarylalkyl groups, cycloalkylalkyl groups, and heterocycloalkylalkyl groups (where the C １ ~C ４ Alkyl alkyl group, C １ ~C ４ Haloalkyl 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- to 10-membered heterocycloalkyl groups, arylalkyl groups, heteroarylalkyl groups, cycloalkylalkyl groups, or heterocycloalkyl groups are D, OH, CN, -NH ２ ,-NH(C １ ~C ４ Alkyl alkyl group), -N(C １ ~C ４ (Alkyl group) ２ , halogen, C １ ~C ４ Alkyl alkyl group, C １ ~C ４ Alkoxy group, C １ ~C ４ Haloalkyl groups and C １ ~C ４ (Optionally substituted with one, two, or three substituents independently selected from the haloalkoxy group.) Or, R ｃ１ and R ｄ１ These, together with the N atoms linked to them, form a 4- to 7-membered heterocycloalkyl group (where the 4- to 7-membered heterocycloalkyl group is D, OH, CN, -NH ２ ,-NH(C １ ~C ４ Alkyl alkyl group), -N(C １ ~C ４ (Alkyl group) ２ , halogen, C １ ~C ４ Alkyl alkyl group, C １ ~C ４ Alkoxy group, C １ ~C ４ Haloalkyl groups and C １－４ (Optionally substituted with one, two, or three substituents independently selected from the haloalkoxy group.) R Ｅ , R ｅ and R ｅ１ These are H, D, and C, respectively, independently. １ ~C ４ Alkyl alkyl group, C １ ~C ４ Haloalkyl group, C ２ ~C ４ Alkenyl group, (C １ ~C ４ Alkoxy)-C １ ~C ４ Alkyl 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, 3-10 member heterocycloalkyl groups, C ６ ~C １０ Aryl-C １ ~C ４ Alkyl alkyl group, C ３ ~C １０ Cycloalkyl-C １ ~C ４ Alkyl, 5-10 member heteroaryl-C １ ~C ４ Alkyl groups, and 4-10 member heterocycloalkyl-C １ ~C ４ Selected from the group consisting of alkyl groups, R Ｆ , R ｆ and R ｆ１ These are H, D, and C, respectively, independently. １ ~C ４ Alkyl 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 the group consisting of cycloalkyl groups and 4- to 10-membered heterocycloalkyl groups, R Ｇ , R Ｈ and R Ｉ Each is independent of C １ ~C ４ Selected from the group consisting of alkyl groups and phenyl groups. Preferably, X is O, Preferably, X is NR ５ And R ５ is H, D, CN, OR Ｂ , at least one R ５Ａ C is optionally replaced by １ ~C ４ Selected from the group consisting of alkyl groups (where R ５Ａ These are independently D, F, Cl, CN, NH ２ OH, -O-C １ ~C ６ Alkyl alkyl group, -OC １ ~C ６ Haloalkyl groups, optionally substituted C ３ ~C ７ Selected from the group consisting of cycloalkyl groups and optionally substituted 4- to 7-membered heterocycloalkyl groups, wherein the optionally substituted group is D, halogen, CN, OH, C １ ~C ４ Alkyl alkyl group, C １ ~C ４ Haloalkyl group, -O-C １ ~C ４ Alkyl alkyl group, -OC １ ~C ４ (It is substituted with a substituent selected from the group consisting of haloalkyl groups.) Preferably, Y ３ N is, Preferably, Y ３ CR ８ And R ８ H, D, CN, halogen, OH, NH ２ , C １ ~C ３ Alkyl 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 Cyanoalkyl groups, and SF ５ Selected from the group consisting of R ８ is H, D, F, Cl, OH, NH ２ , CN, CH ３ ,CH ２ CH ３ ,CH ２ CH ２ CH ３ , CH (CH ３ ) ２ CF ３ CHF ２ ,CH ２ F, OMe, OCH ２ CH ３ , OCH ２ CH ２ CH ３ , OCH(CH ３ ) ２ OCF ３ , and SF ５ Selected from the group consisting of, Preferably, Y １ If N and Y ２ CR ７ And, Preferably, Y １ CR ６ and Y ２ N is, Preferably, Y １ CR ６ and Y ２ CR ７ And, Preferably, R ６ H, D, halogen, CN, NO ２ , OR Ａ , SR Ａ SF ５ , C １ ~C ６ Alkyl alkyl groups, and C １ ~C ６ Selected from the group consisting of haloalkyl groups, preferably R ６ H, D, F, Cl, Br, I, CH ３ CF ３ ,-CHF ２ ien-CH ２ F, OH, -OCH ３ OCF ３ , -SMe, B(OH) ２ , CN, NO ２ , and SF ５ Selected from the group consisting of, preferably R ７ H, D, halogen, CN, NO ２ , OR Ａ SF ５ , C １ ~C ６ Alkyl alkyl groups, and C １ ~C ６ Selected from the group consisting of haloalkyl groups, preferably R ７ H, D, F, Cl, OH, CN, NO ２ SF ５ ,CH ３ CF ３ , and -OCH ３ Selected from the group consisting of, Preferably, Cy １ is 1, 2, 3 or 4 R ９ A 5-6 member heteroaryl group optionally substituted with Cy １ is 1, 2, or 3 R ９ It is a five-membered heteroaryl group that is optionally substituted with, Preferably, 【Transformation 5】 Preferably, 【change】 More preferably, Cy １ teeth 【Transformation 6】 And each R ９ These are independently H, D, halogen, and C. １ ~C ６ Alkyl 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 group, C １ ~C ６ Haloalkyl groups, OC ３ ~C ７ Cycloalkyl groups, C ３ ~C ７ Cycloalkyl groups, CN, NO ２ , N ３ , and SF ５ Selected from the group consisting of (where C １ ~C ６ Alkyl alkyl group, C ２ ~C ６ Alkenyl group, C ２ ~C ６ Alkynyl group, or C ３ ~C ７ Cycloalkyl groups are independently R １１ Preferably, each R is optionally substituted with one, two, or three substituents selected from the above. ９ These are independently H, D, halogen, and C. １ ~C ６ Alkyl alkyl group, C １ ~C ６ Selected from the group consisting of haloalkyl groups, more preferably each R ９ These are independently a methyl group, an ethyl group, an isopropyl group, a tert-butyl group, a cyclopropyl group, and CF ３ CHF ２ ,CH ２ F, and CDF ２ (Selected from a group consisting of) Preferably, Cy ２ is C ６ ~C １０ Aryl group, saturated C ３ ~C １０ Cycloalkyl groups, partially unsaturated C ３ ~C １０ Selected from the group consisting of cycloalkyl groups, 5-10 membered heteroaryl groups, 4-14 membered saturated heterocycloalkyl groups, and 4-14 membered partially unsaturated heterocycloalkyl groups (where the C ６ ~C １０ Aryl group, saturated C ３ ~C １０ Cycloalkyl groups, partially unsaturated C ３ ~C １０ Cycloalkyl groups, 5-10 membered heteroaryl groups, 4-14 membered saturated heterocycloalkyl groups, or 4-14 membered partially unsaturated heterocycloalkyl groups independently have 1, 2, 3, 4, or 5 R groups. １０ (Optionally replaced by), preferably Cy ２ is C ６ ~C １０ Aryl group, 5-10 membered heteroaryl group, saturated C ３－ C １０ Monocycloalkyl groups, saturated C ４ ~C １０ Dicycloalkyl group, saturated C ５－ C １０ Spirocycloalkyl group, saturated C ４ ~C １０ Cross-linked cycloalkyl groups, C ７ ~C １０ Condensed cycloalkyl groups, partially unsaturated C ３－ C １０ Monocycloalkyl groups, partially unsaturated C ４ ~C １０ Dicycloalkyl groups, partially unsaturated C ５－ C １０ Spirocycloalkyl groups, partially unsaturated C ４ ~C １０ The group consists of cross-linked cycloalkyl groups, 4-14 member saturated monocyclic heterocycloalkyl groups, 4-14 member saturated bicyclic heterocycloalkyl groups, 5-14 member saturated spiroheterocycloalkyl groups, 4-14 member saturated bridged heterocycloalkyl groups, 7-14 member condensed heterocycloalkyl groups, 4-14 member partially unsaturated monocyclic heterocycloalkyl groups, 4-14 member partially unsaturated bicyclic heterocycloalkyl groups, 4-14 member partially unsaturated spiroheterocycloalkyl groups, and 4-14 member partially unsaturated bridged heterocycloalkyl groups (where each ring has 1, 2, 3, 4, or 5 R atoms). １０ (which are optionally substituted by) are selected from, preferably Cy ２ These include phenyl group, pyrrolyl group, furanyl group, thiophenyl group, imidazolyl group, oxazolyl group, thiazolyl group, pyrazolyl group, triazolyl group, thiadiazolyl group, oxadiazolyl group, pyridinyl group, pyrimidinyl group, pyrazinyl group, pyridadinyl group, indolinyl group, indazolyl group, benzo[d]imidazolyl group, quinolyl group, quinoxalyl group, pyrrolo[3,2-b]pyridinyl group, indolyl group, cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclopropenyl group, and cyclobutenyl. Group, cyclopentenyl group, cyclopentadienyl group, cyclohexenyl group, azetidinyl group, oxetanyl group, thietanyl group, pyrrolidinyl group, tetrahydrofuranyl group, tetrahydrothiophenyl group, piperidinyl group, dioxanyl group, tetrahydropyranyl group, tetrahydrothiopyranyl group, piperazinyl group, morpholinyl group, azepanyl group, diazokanyl group, diazepanyl group, oxazepanyl group, azepanyl group, thiomorpholine 1,1-dioxydyl group, piperazinonyl group, tetrahydroxy-2H-thiopyran 1,1-dioxydyl group, Octahydropyrrolo[3,4-c]pyrrol group, hexahydrofloo[3,4-c]pyrrol group, hexahydrothieno[3,4-c]pyrrol group, octahydrocyclopenta[b]pyrrol group, octahydropyrrolo[3,2-b]pyrrol group, hexahydrofloo[3,2-b]pyrrol group, octahydropyrano[3,2-b]pyrrol group, octahydropyrrolo[3,2-b]pyridinyl group, hexahydropyrrolo[1,2-a]imidazolyl group, octahydropyrrolo[2,3-c]pyridinyl group, octahydropyrrolo[3,2-c]pyridinyl group, Octahydroimidazo[1,2-a]pyridinyl group, octahydropyrrolo[3,4-c]pyridinyl group, decahydroquinolyl group, octahydroclomenyl group, decahydroquinoxalyl group, octahydropyrido[1,2-a]pyridinyl group, octahydroxypyrazino[2,1-c][1,4]oxazinyl group, octahydropyrido[2,1-c][1,4]oxazinyl group, octahydropyrano[3,2-c]pyridinyl group, decahydro-2,6-naphthilidinyl group, octahydropyrano[3,4-c]pyridinyl group, octahydropyrrolo[1,2-a]pyrazinyl group, hexahydrooxazolo[3,4-a]pyrazinyl group, hexahydro-5H-cyclopenta[b][1,4]dioxynyl group, hexahydroimidazo[1,5-a]pyrazine-3(2H)-one group, hexahydro[1,4]dioxyno[2,3-c]pyrrolyl group, hexahydrooxazolo[3,4-a]pyrazine-3-one group, octahydro-2H-pyrazino[1,2-a]pyrazinyl group, hexahydropyrazino[2,1-c][1,4]oxazine-3(4H)-one group, hexahydropyrazino[2,1-c][1,4]oxadi n-4(3H)-one group, 2,6-diazaspiro[3.3]heptanyl group, 2-oxa-6-azaspiro[3.3]heptanyl group, 2,6-diazaspiro[3.4]octanyl group, 2,7-diazaspiro[3.5]nonanyl group, 2,7-diazaspiro[4.4]nonanyl group, 3,9-diazaspiro[5.5]undecanyl group, 2-oxa-7-azaspiro[3.5]nonanyl group, 2-oxa-6-azaspiro[3.4]octanyl group, 7-oxa-2-azaspiro[3.5]nonanyl group, 6-oxa-2-azaspiro[3.4]octanyl group, 1-oxa- 8-Azaspiro[4.5]decanyl group, 2-Oxa-8-Azaspiro[4.5]decanyl group, 2-Oxaspiro[3.5]nanyl group, 4,7-Diazaspiro[2.5]octanyl group, 1-Oxa-7-Azaspiro[3.5]nonanyl group, 5,8-Diazaspiro[3.5]nonanyl group, 7-Oxa-4-Azaspiro[2.5]octanyl group, 4-Oxa-7-Azaspiro[2.5]octanyl group, 8-Oxa-5-Azaspiro[3.5]nonanyl group, 5-Oxa-8-Azaspiro[3.5]nonanyl group, 2-Azabicyclo[1.1.1]pentanyl group, 5- Azabicyclo[2.1.1]hexanal group, 2-azabicyclo[2.2.1]heptanyl group, 2-azabicyclo[2.2.2]octanyl group, 6-azabicyclo[3.1.1]heptanyl group, 3-azabicyclo[3.2.1]octanyl group, 3-azabicyclo[3.3.1]nonanyl group, 3-azabicyclo[3.3.2]decanyl group, 3-azabicyclo[3.3.3]undecanyl group, 3,6-diazabicyclo[3.1.1]heptanyl group, 3,8-diazabicyclo[3.2.1]octanyl group, 2,5-diazabicyclo[2.2.2]octanyl group, 3,6-diazabicyclo[3.1.1]heptanyl group, 6-oxa-3-azabicyclo[3.1.1]heptanyl group, 3-oxa-6-azabicyclo[3.1.1]heptanyl group, 2,5-diazabicyclo[2.2.1]heptanyl group, 2-oxa-5-azabicyclo[2.2.1]heptanyl group, 2-oxa-5-azabicyclo[2.2.2]octanyl group, 3,8-diazabicyclo[3.2.1]octanyl group, 8-oxa-3-azabicyclo[3 2.1] Octanyl group, 3-oxa-8-azabicyclo[3.2.1]octanyl group, 5,6,7,8-tetrahydroimidazo[1,5-a]pyradinyl group, 5,6,7,8-tetrahydroimidazo[1,2-a]pyradinyl group, 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyradinyl group, 4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyradinyl group, 6,7,8,8a-tetrahydro-5H-[1 ,2,4]oxadiazolo[4,5-a]pyradinyl group, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridinyl group, 5,6,7,8-tetrahydro-1,7-naphthilidinyl group, 5,6,7,8-tetrahydro-1,6-naphthilidinyl group, 1,2,3,4-tetrahydro-2,7-naphthilidinyl group, 1,2,3,4-tetrahydroisoquinolyl group, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyradinyl group, 5, A group consisting of 6,7,8-tetrahydropyrillo[3,4-d]pyrimidinyl group, 1,2,3,6-tetrahydropyridinyl group, 3,6-dihydro-2H-pyranyl group, 1,2,3,4-tetrahydropyridinyl group, 3,4-dihydro-2H-pyranyl group, 2,3-dihydro-1H-pyrrolyl group, 2,5-dihydro-1H-pyrrolyl group, 2,3-dihydrofuranyl group, and 2,5-dihydrofuranyl group (where each ring has 1,2,3,4 or 5 R, １０ (which are arbitrarily substituted) are selected from Preferably, 【Chemistry 7-1】 【Chemistry 7-2】 【Transformation 7-3】 Selected from the group consisting of, Preferably, R １０ H, D, halogen, CN, NO ２ , N ３ , oxo group, C １ ~C ６ Alkyl 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)NR Ｃ OR Ａ , C(O)OR Ａ OC(O)R Ｂ , OC(O)NR Ｃ R Ｄ , 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 ), 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 , SiR Ｇ R Ｈ R Ｉ P(O)R Ｅ R Ｆ Cy ３ , C １ ~C ６ Alkyl-Cy ３ , OCy ３ , and O-C １ ~C ６ Alkyl-Cy ３ A group consisting of (where C １ ~C ６ Alkyl alkyl group, C ２ ~C ６ Alkenyl group, C ２ ~C ６ The alkynyl group consists of 1, 2, 3, 4, or 5 R groups. １１ (which are arbitrarily substituted) are selected from Preferably, each R １０ These are independently H, D, halogen, CN, NO ２ , N ３ , oxo group, SF ５ NHOH, methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, i-butyl group, tert-butyl group, pentyl group, hexyl group, CH ２ F, CHF ２ CF ３ ,CH ２ CH ２ F, CH ２ CHF ２ ,CH ２ CF ３ ,CH ２ OH, CH ２ OCH ３ ,CH ２ CH ２ OCH ３ ,CH ２ SCH ３ ,CH ２ CH ２ NCH ３ ,CH ２ CN, NH ２ , NHCH ３ , N (CH ３ ) ２ , N (CH ３ )CH ２ CH ３ , N (CH ３ )CH ２ CF ３ OH, OCH ３ , OCH ２ CH ３ OCF ３ , OCH ２ CF ３ , C(=S)CH ３ , C(=S)CH ２ CH ３ , C(=S)CH ２ CH ２ CH ３ , C(=S)CH(CH ３ ) ２ , C(=S)C(CH ３ ) ３ C(O)NH ２ C(O)NHCH ３ , C(O)N(CH ３ ) ２ 、C(O)N(CH ３ )CH ２ CH ３ 、C(O)N(CH ３ )CH ２ CF ３ 、C(O)N(CH ３ )CH ２ CH ２ OH、C(O)N(CH ３ )CH ２ CH ２ OCH ３ 、C(O)N(CH ３ )OCH ３ 、C(O)N(CH ３ )CH ２ CH(CH ３ )OH、C(O)OH、C(O)OCH ３ 、C(O)OCH ２ CH ３ 、C(O)OCH ２ CH ２ CH ３ 、C(O)OCH(CH ３ ) ２ 、C(O)OC(CH ３ ) ３ 、CHO、C(O)CH ３ 、C(O)CH ２ CH ３ 、C(O)CH ２ CH ２ CH ３ 、C(O)CH(CH ３ ) ２ 、C(O)CH ２ CH(CH ３ ) ２ 、C(O)C(CH ３ ) ３ 、C(O)CF ３ 、C(O)CH ２ CF ３ 、C(O)CH ２ OH, C(O)CH ２ OCH ３ S(O)CH ３ S(O)CH ２ CH ３ 、S(O)CH(CH ３ ) ２ S(O)C(CH) ３ ) ３ 、S(O) ２ CH ３ 、S(O) ２ CH ２ CH ３ 、S(O) ２ CH(CH ３ ) ２ 、S(O) ２ C(CH ３ ) ３ 、 【Chemistry 8-1】 【Chemistry 8-2】 Selected from the group consisting of, Preferably, R １ These are H, D, CN, and C, respectively, independently. １ ~C ３ Selected from the group consisting of alkyl groups (where C １ ~C ３ Alkyl alkyl groups are independently D, halogen, CN, OH, and C. １ ~C ６ Alkyl alkyl group, C １ ~C ６ Haloalkyl group, -O-C １ ~C ６ Alkyl alkyl group, -OC １ ~C ６ Preferably, R １ 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 , and CH ２ Selected from the group consisting of CN, preferably R ２ and R ３ These are H, D, CN, and C, respectively, independently. １ ~C ３ Alkyl alkyl group (where C １ ~C ３ Alkyl alkyl groups are D, halogen, CN, OH, C １ ~C ６ Alkyl alkyl group, C １ ~C ６ Haloalkyl group, -O-C １ ~C ６ Alkyl alkyl group, -OC １ ~C ６ Selected from the group consisting of (which are optionally substituted with 1 to 5 substituents independently selected from the haloalkyl group), preferably R ２ and R ３ C ３ -C ６ It forms a cycloalkyl group or a 4-6 member heterocycloalkyl group (where the C ３ -C ６ Cycloalkyl groups, or 4-6 member heterocycloalkyl groups, include D, halogens, CN, and NO. ２ , oxo group, OH, OMe, OCF ３ , and optionally substituted with 1, 2, 3 or 4 substituents independently selected from OEt), preferably R ２ and R ３ Together with the carbon atoms linked to them are cyclopropyl groups and cyclobutyl groups (where each ring is independently D, halogen, CN, NO). ２ , oxo group, OH, OMe, OCF ３ , and are optionally substituted with 1, 2, 3 or 4 substituents selected from OEt) Preferably, R ４ Each of these is independently H, D, OH, CN, NO ２ SF ５ , halogen, NR Ｃ R Ｄ , and C optionally substituted with halogen or CN １ ~C ３ Selected from the group consisting of alkyl groups, preferably R ４ Each is independently selected from the group consisting of H, D, OH, CN, and halogens. Preferably, the compound is a compound represented by the following formula (IIA), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotope variant, prodrug, or deuterated compound thereof. 【Chemistry 9】 (In the formula, each R １ , R ２ , R ３ , R ４ Cy １ Cy ２ , X, Y １ , Y ２ and Y ３ The definition is the same as in equation (I) above. Preferably, the compound is a compound represented by the following formula (IIa) or (IIb), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotope variant, prodrug or deuterated compound thereof. 【Chemistry 10】 (In the formula, each R １ , R ２ , R ３ , R ４ , R ５ Cy １ Cy ２ , Y １ , Y ２ and Y ３ The definition is the same as in equation (I) above. Preferably, the compound is a compound represented by the following formula (IIIa) or (IIIb), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotope variant, prodrug or deuterated compound thereof. 【Chemistry 11】 (In the formula, each R １ , R ２ , R ３ , R ５ Cy １ Cy ２ , Y １ , Y ２ and Y ３ The definition is the same as in equation (I) above. Preferably, the compound is a compound represented by the following formula (IV), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotope variant, prodrug, or deuterated compound thereof. 【Chemistry 12】 (In the formula, each R １ , R ２ , R ３ , R ８ Cy １ Cy ２ , X, Y １ and Y ２ The definition is the same as in equation (I) above. Preferably, the compound is a compound represented by the following formula (IVa) or formula (IVb), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotope variant, prodrug or deuterated compound thereof. 【Chemistry 13】 (In the formula, each R １ , R ２ , R ３ , R ５ , R ８ Cy １ Cy ２ , Y １ and Y ２ The definition is the same as in equation (I) above. Preferably, the compound is a compound represented by the following formula (Va), (Vb), or (Vc), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotope variant, prodrug, or deuterated compound thereof. 【Chemistry 14】 (In the formula, each R １ , R ２ , R ３ , R ６ , R ７ , R ８ Cy １ and Cy ２ The definition is the same as in equation (I) above. Preferably, the compound is a compound represented by the following formula (VI), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotope variant, prodrug, or deuterated compound thereof. 【Chemistry 15】 [In the formula, Cy １ This is a five-membered heteroaryl group having 1, 2, 3, or 4 heteroatoms selected independently from N, O, and S (where the five-membered heteroaryl group has 1, 2, 3, or 4 R ９ (It is optionally replaced by) Each R １ , R ２ , R ３ , R ９ Cy ２ , Y １ and Y ２ The definition is the same as in equation (I) above. Preferably, the compound is a compound represented by the following formula (VIa) or formula (VIb), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotope variant, prodrug or deuterated compound thereof. 【Chemistry 16】 [In the formula, Cy １ This is a five-membered heteroaryl group having 1, 2, 3, or 4 heteroatoms selected independently from N, O, and S (where the five-membered heteroaryl group has 1, 2, 3, or 4 R ９ (where it is arbitrarily replaced), each R １ , R ２ , R ３ , R ５ , R ９ Cy ２ , Y １ and Y ２ The definition is the same as in equation (I) above. Preferably, the compound is a compound represented by the following formula (VII), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotope variant, prodrug, or deuterated compound thereof. 【Chemistry 17】 (In the formula, each R １ , R ２ , R ３ , R ８ , R ９ Cy ２ , X, Y １ and Y ２ The definition is the same as in equation (I) above. Preferably, the compound is a compound represented by the following formula (VIIa) or formula (VIIb), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotope variant, prodrug or deuterated compound thereof. [Chemistry 18] (In the formula, each R １ , R ２ , R ３ , R ５ , R ８ , R ９ Cy ２ , Y １ and Y ２ The definition is the same as in equation (I) above. Preferably, the compound is a compound represented by the following formula (VIIIa), formula (VIIIb), or formula (VIIIc), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotope variant, prodrug, or deuterated compound thereof. 【Chemistry 19】 (In the formula, each R １ , R ２ , R ３ , R ６ , R ７ , R ８ , R ９ , and Cy ２ The definition is the same as in equation (I) above. Preferably, the compound is a compound represented by the following formula (IXa), formula (IXb), or formula (IXc), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotope variant, prodrug, or deuterated compound thereof. 【Chemistry 20】 (In the formula, each R １ , R ２ , R ３ , R ６ , R ７ , R ８ , R ９ and Cy ２ The definition is the same as in equation (I) above. Preferably, the compound is a compound represented by the following formula (Xa) or formula (Xb), or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotope variant, prodrug or deuterated compound thereof. 【Chemistry 21】 (In the formula, each R １ , R ５ , R ６ , R ８ , R ９ and Cy ２ The definition of is the same as that of formula (I) above.), and the compound according to claim 1.

4. The compound according to claim 1, characterized in that the compound represented by formula (I) is as follows, or a pharmaceutically acceptable salt, stereoisomer, solvate, N-oxide, tautomer, isotope variant, prodrug, or deuterated compound thereof. Table 1-1 Table 1-2 Table 1-3 Table 1-4 Table 1-5 Table 1-6 Table 1-7 Table 1-8 Table 1-9 Table 1-10 Table 1-11 Table 1-12

5. A pharmaceutical composition comprising a compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt, stereoisomer, prodrug, chelate compound, or non-covalent complex thereof, and at least one pharmaceutically acceptable carrier or excipient.

6. The use of a compound according to any one of claims 1 to 4, a pharmaceutically acceptable salt or stereoisomer thereof, a prodrug, a chelate compound, or a non-covalent complex in the manufacture of a pharmaceutical product, Preferably, the pharmaceutical product is used as a PARG inhibitor. Preferably, the pharmaceutical product is used to treat cancer, or Preferably, the cancer is breast cancer, ovarian cancer, stomach cancer, prostate cancer, pancreatic cancer, uterine cancer, cervical cancer, endometrial cancer, lung cancer, brain cancer, bile duct cancer, or hematological cancer.

7. A method for inhibiting PARG, comprising administering to a patient in need a compound according to any one of claims 1 to 4, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt thereof, a stereoisomer, a solvate thereof, an N-oxide thereof, or a prodrug.

8. This includes administering an effective amount of the compound described in any one of claims 1 to 4 to patients who require it, Preferably, the disease is cancer, or Preferably, a method for treating a disease related to PARG inhibition, wherein the cancer is breast cancer, ovarian cancer, gastric cancer, prostate cancer, pancreatic cancer, uterine cancer, cervical cancer, endometrial cancer, lung cancer, brain cancer, bile duct cancer, or hematological cancer.

9. The use of a compound according to any one of claims 1 to 4 in combination with surgery, chemotherapy, radiotherapy, targeted therapy, other DDR modifiers, immunotherapy, gene therapy, or cell therapy for the treatment of cancer, Preferably, the target-directed therapy is a kinase inhibitor, a growth factor inhibitor, a cyclin-dependent kinase inhibitor, or Preferably, the DDR modifier is a DNA-PK inhibitor, ATM inhibitor, ATR inhibitor, CHK1 inhibitor, WEE1 inhibitor, CDK1 inhibitor, LIG4 inhibitor, HIF-1 inhibitor, HDAC inhibitor, RAD51 inhibitor, Polθ inhibitor, WRN inhibitor, PRMT5 inhibitor, MAT2A inhibitor, and PKMYT1 inhibitor.

10. An intermediate compound represented by the following formula (A) or a salt thereof, 【Chemistry 22】 (In the formula, W １ R is a leaving group, １ , R ２ , R ３ , R ４ , X, Y １ , Y ２ The definitions of n and , are the same as in equation (I). Preferably, the intermediate compound of formula (A) is a compound represented by the following formula (Aa) or formula (Ab), 【Chemistry 23】 (In the formula, each R １ , R ２ , R ３ , R ４ , R ５ , Y １ , Y ２ , and W １ The definition is the same as in formula (A) above. ) or Preferably, the intermediate compound is as follows: Table 2 An intermediate compound or a salt thereof characterized by the above.

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