Compounds as BCL-2 inhibitors

Abstract

The present invention provides Bcl-2 inhibitors, pharmaceutical compositions thereof and methods of use thereof.

Description

[Technical Field]

[0001] This application claims priority to U.S. Provisional Patent Applications Nos. 63 / 021,816, 63 / 115,471, and 63 / 146,601, the entire contents of which are incorporated herein by reference.

[0002] The present invention relates to compounds or pharmaceutically acceptable salts thereof that can inhibit anti-apoptotic Bcl-2 family proteins and drug-resistant mutations thereof, and to the use of these compounds as drugs in the treatment of cancer, hyperproliferative diseases such as inflammation, immune diseases, and autoimmune diseases. [Background technology]

[0003] Hyperproliferative diseases such as cancer and inflammation have attracted the scientific community's attention in order to provide effective therapeutic approaches. In this context, efforts are being made to identify and target specific mechanisms that play a role in proliferative diseases.

[0004] Protein-protein interactions (PPIs) regulate various biological processes, such as cell proliferation, growth, differentiation, signal transduction, and apoptosis. Abnormal regulation of PPIs can lead to various diseases. Therefore, PPIs are important and novel molecular targets for the treatment of human diseases.

[0005] B-cell lymphoma-2 family proteins are important for regulating cell apoptosis, which is crucial for normal tissue development and maintaining cellular homeostasis. Apoptosis occurs through the activation of two distinct pathways: the extrinsic pathway is mediated by cell surface death receptors, and the intrinsic pathway involves Bcl-2 family proteins, such as Bcl-2, Bcl-X, and Bcl-X. L and anti-apoptotic proteins such as Mcl-1, and pro-apoptotic proteins such as Bid, Bim, Bad, Bak, and Bax.

[0006] Anti-apoptotic Bcl-2 family members were found to be upregulated in tumor cells and associated with staging and prognosis. Therefore, Bcl-2 proteins were investigated as potential drug therapeutic targets, and these targets include Bcl-2 and Bcl-X. L Bcl-2 protein expression can be an independent indicator of poor prognosis in tumors such as chronic lymphocytic leukemia (CLL), prostate cancer, and small cell lung cancer (SCLC). In other tumors, such as colon cancer, Bcl-X L Expression of Bcl-X is associated with disease grade and staging, and in hepatocellular carcinoma, L The expression of β-glucan (β-glucan) can be an independent indicator of short overall survival and disease-free survival. Venetolax, an effective first-generation Bcl-2 inhibitor, inhibits Bcl-2 highly selectively by binding to a critical hydrophobic groove in the Bcl-2 protein, which is the same site where physiological ligands (pro-apoptotic proteins containing BH3 domains) capture Bcl-2, thereby inhibiting tumor progression. However, after treatment with first-generation Bcl-2 inhibitors, cancer patients develop acquired drug resistance, creating a new unmet therapeutic need. Research has shown that mutations in the drug-binding site of Bcl-2, such as G101V, D103Y, F104L, and F104C, are one of the important mechanisms driving drug resistance.

[0007] Therefore, compounds with inhibitory activity against Bcl-2 and its drug-resistant mutations have important implications for the prevention and treatment of cancer. Although Bcl-2 inhibitors have been reported in literature, such as WO2011149492, many of them have short half-lives or are toxic. Therefore, there remains a need for novel Bcl-2 inhibitors that have advantages in at least one of solubility, drug interactions, therapeutic efficacy, stability, selectivity, toxicity, drug resistance, pharmacokinetics, and pharmacodynamics in the treatment of hyperproliferative diseases. Based on this, the present invention provides novel Bcl-2 inhibitors. Summary of the Invention

[0008] The present invention discloses new compounds, their pharmaceutically acceptable salts, their pharmaceutical compositions, and their use as medicines.

[0009] In one aspect, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof:

[0010] [ka] (I) (In the formula, X 1 N and CR 8 is selected from X 2 N and CR 9 is selected from X 3 N and CR 10 is selected from Y 1 , Y 2 and Y 3 is independently selected from N and CH; A and B are independently selected from N and CH; W is -CR 11 -, -NR 12 -, -O-, -S(O) r- and -S(O)(=NR 12 )-selected from Z is selected from N and CH; L 1 and L 2 are independently chemical bonds, -(CR C0 R D0 ) u -, -(CR C0 R D0 ) u O(CR C0 R D0 ) t -, -(CR C0 R D0 ) u NR A0 (CR C0 R D0 ) t-and-(CR C0 R D0 ) u S(O) r (CR C0 R D0 ) t - selected from R 1 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A1 R B1 , -OR A1 , -C(O)R A1 , -C(=NR E1 )R A1 , -C(=N-OR B1 )R A1 , -C(O)OR A1 , -OC(O)R A1 , -C(O)NR A1 R B1 , -NR A1 C(O)R B1 , -C(=NR E1 )NR A1 R B1 , -NR A1 C(=NR E1 )R B1 , -OC(O)NR A1 R B1 , -NR A1 C(O)OR B1 , -NR A1 C(O)NR A1 R B1 , -NR A1 C(S)NR A1 R B1 , -NR A1 C(=NR E1 )NR A1 R B1 , -S(O) r RA1 , -S(O)(=NR E1 )R B1 , -N=S(O)R A1 R B1 , -S(O)2OR A1 , -OS(O)2R A1 , -NR A1 S(O) r R B1 , -NR A1 S(O)(=NR E1 )R B1 , -S(O) r NR A1 R B1 , -S(O)(=NR E1 )NR A1 R B1 , -NR A1 S(O)NR A1 R B1 , -NR A1 S(O)(=NR E1 )NR A1 R B1 , -P(O)R A1 R B1 and -P(O)(OR A1 )(OR B1 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from R 2 and R 3 are independently selected from aryl groups, heteroaryl groups, and heterocyclic groups, wherein each of the aryl groups, heteroaryl groups, and heterocyclic groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Each R 4 are independently hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A4 R B4 , -OR A4 , -C(O)R A4 , -C(=NR E4 )R A4 , -C(=N-OR B4 )R A4 , -C(O)OR A4 , -OC(O)R A4 , -C(O)NR A4 R B4 , -NR A4 C(O)R B4 , -C(=NR E4 )NR A4 R B4 , -NR A4 C(=NR E4 )R B4 , -OC(O)NR A4 R B4 , -NR A4 C(O)OR B4 , -NR A4 C(O)NR A4 R B4 , -NR A4 C(S)NR A4 R B4 , -NR A4 C(=NR E4 )NR A4 R B4 , -S(O) r R A4 , -S(O)(=NR E4 )R B4 , -N=S(O)R A4 R B4 , -S(O)2OR A4 , -OS(O)2R A4 , -NR A4 S(O) r R B4 , -NR A4 S(O)(=NR E4 )R B4 , -S(O) r NR A4 R B4 , -S(O)(=NR E4 )NRA4 R B4 , -NR A4 S(O)NR A4 R B4 , -NR A4 S(O)(=NR E4 )NR A4 R B4 , -P(O)R A4 R B4 and -P(O)(OR A4 )(OR B4 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, any two R 4 or "R 4 and R 11 " or "R 4 and R 12 ", along with the atoms to which they are attached, are C 3-10 forming a cycloalkyl group or a 4- to 12-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, Each R 5 are independently hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A5 R B5 , -OR A5 , -C(O)R A5 , -C(=NR E5 )R A5 , -C(=N-OR B5 )RA5 、 -C(O)OR A5 、 -OC(O)R A5 、 -C(O)NR A5 R B5 、 -NR A5 C(O)R B5 、 -C(=NR E5 )NR A5 R B5 、 -NR A5 C(=NR E5 )R B5 、 -OC(O)NR A5 R B5 、 -NR A5 C(O)OR B5 、 -NR A5 C(O)NR A5 R B5 、 -NR A5 C(S)NR A5 R B5 、 -NR A5 C(=NR E5 )NR A5 R B5 、 -S(O) r R A5 、 -S(O)(=NR E5 )R B5 、 -N=S(O)R A5 ]>R B5 、 -S(O)2OR A5 、 -OS(O)2R A5 、 -NR A5 S(O) r R B5 、 -NR A5 S(O)(=NR E5 )R B5 、 -S(O) r NR A5 R B5 、 -S(O)(=NR E5 )NR A5 R B5 、 -NR A5 S(O)2NR A5 R B5 、 -NR A5 S(O)(=NR E5 )NR A5 R B5 、 -P(O)R A5 R B5 及び -P(O)(OR A5 )(ORB5 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, any two R 5 together with the carbon atoms to which they are attached, C 3-10 forming a cycloalkyl group or a 4- to 12-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, Each R 6 are independently hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A6 R B6 , -OR A6 , -C(O)R A6 , -C(=NR E6 )R A6 , -C(=N-OR B6 )R A6 , -C(O)OR A6 , -OC(O)R A6 , -C(O)NR A6 R B6 , -NR A6 C(O)R B6 , -C(=NR E6 )NR A6 R B6 , -NR A6 C(=NR E6 )R B6 , -OC(O)NR A6 R B6 , -NRA6 C(O)OR B6 , -NR A6 C(O)NR A6 R B6 , -NR A6 C(S)NR A6 R B6 , -NR A6 C(=NR E6 )NR A6 R B6 , -S(O) r R A6 , -S(O)(=NR E6 )R B6 , -N=S(O)R A6 R B6 , -S(O)2OR A6 , -OS(O)2R A6 , -NR A6 S(O) r R B6 , -NR A6 S(O)(=NR E6 )R B6 , -S(O) r NR A6 R B6 , -S(O)(=NR E6 )NR A6 R B6 , -NR A6 S(O)NR A6 R B6 , -NR A6 S(O)(=NR E6 )NR A6 R B6 , -P(O)R A6 R B6 and -P(O)(OR A6 )(OR B6 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, any two R 6 together with the carbon atoms to which they are attached, C 3-10forming a cycloalkyl group or a 4- to 12-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, Each R 7 are independently hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A7 R B7 , -OR A7 , -C(O)R A7 , -C(=NR E7 )R A7 , -C(=N-OR B7 )R A7 , -C(O)OR A7 , -OC(O)R A7 , -C(O)NR A7 R B7 , -NR A7 C(O)R B7 , -C(=NR E7 )NR A7 R B7 , -NR A7 C(=NR E7 )R B7 , -OC(O)NR A7 R B7 , -NR A7 C(O)OR B7 , -NR A7 C(O)NR A7 R B7 , -NR A7 C(S)NR A7 R B7 , -NR A7 C(=NR E7 )NR A7 R B7 , -S(O)r R A7 , -S(O)(=NR E7 )R B7 , -N=S(O)R A7 R B7 , -S(O)2OR A7 , -OS(O)2R A7 , -NR A7 S(O) r R B7 , -NR A7 S(O)(=NR E7 )R B7 , -S(O) r NR A7 R B7 , -S(O)(=NR E7 )NR A7 R B7 , -NR A7 S(O)NR A7 R B7 , -NR A7 S(O)(=NR E7 )NR A7 R B7 , -P(O)R A7 R B7 and -P(O)(OR A7 )(OR B7 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from R 8 are hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A8 R B8 , -OR A8 , -C(O)R A8 , -C(=NRE8 )R A8 、-C(=N-OR B8 )R A8 、-C(O)OR A8 、-OC(O)R A8 、-C(O)NR A8 R B8 、-NR A8 C(O)R B8 、-C(=NR E8 )NR A8 R B8 、-NR A8 C(=NR E8 )R B8 、-OC(O)NR A8 R B8 、-NR A8 C(O)OR B8 、-NR A8 C(O)NR A8 R B8 、-NR A8 C(S)NR A8 R B8 、-NR A8 C(=NR E8 )NR A8 R B8 、-S(O) r R A8 、-S(O)(=NR E8 )R B8 、-N=S(O)R A8 R B8 、-S(O)2OR A8 、-OS(O)2R A8 、-NR A8 S(O) r R B8 、-NR A8 S(O)(=NR E8 )R B8 、-S(O) r NR A8 R B8 、-S(O)(=NR E8 )NR A8 R B8 、-NR A8 S(O)2NR A8 R B8 、-NR A8 S(O)(=NR E8 )NR A8 R B8 、-P(O)RA8 R B8 and -P(O)(OR A8 )(OR B8 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, R 1 and R 8 together with the atoms to which they are attached, C 5-10 forming a cycloalkyl group or a 5- to 12-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, R 9 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A9 R B9 , -OR A9 , -C(O)R A9 , -C(=NR E9 )R A9 , -C(=N-OR B9 )R A9 , -C(O)OR A9 , -OC(O)R A9 , -C(O)NR A9 R B9 , -NR A9 C(O)R B9 , -C(=NR E9 )NR A9 R B9 , -NR A9 C(=NR E9 )RB9 , -OC(O)NR A9 R B9 , -NR A9 C(O)OR B9 , -NR A9 C(O)NR A9 R B9 , -NR A9 C(S)NR A9 R B9 , -NR A9 C(=NR E9 )NR A9 R B9 , -S(O) r R A9 , -S(O)(=NR E9 )R B9 , -N=S(O)R A9 R B9 , -S(O)2OR A9 , -OS(O)2R A9 , -NR A9 S(O) r R B9 , -NR A9 S(O)(=NR E9 )R B9 , -S(O) r NR A9 R B9 , -S(O)(=NR E9 )NR A9 R B9 , -NR A9 S(O)NR A9 R B9 , -NR A9 S(O)(=NR E9 )NR A9 R B9 , -P(O)R A9 R B9 and -P(O)(OR A9 )(OR B9 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from R 10 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A10 R B10 , -OR A10 , -C(O)R A10 , -C(=NR E10 )R A10 , -C(=N-OR B10 )R A10 , -C(O)OR A10 , -OC(O)R A10 , -C(O)NR A10 R B10 , -NR A10 C(O)R B10 , -C(=NR E10 )NR A10 R B10 , -NR A10 C(=NR E10 )R B10 , -OC(O)NR A10 R B10 , -NR A10 C(O)OR B10 , -NR A10 C(O)NR A10 R B10 , -NR A10 C(S)NR A10 R B10 , -NR A10 C(=NR E10 )NR A10 R B10 , -S(O) r R A10 , -S(O)(=NR E10 )R B10 , -N=S(O)R A10 R B10 , -S(O)2OR A10 , -OS(O)2R A10 , -NR A10 S(O) r R B10 , -NR A10 S(O)(=NRE10 )R B10 , -S(O) r NR A10 R B10 , -S(O)(=NR E10 )NR A10 R B10 , -NR A10 S(O)NR A10 R B10 , -NR A10 S(O)(=NR E10 )NR A10 R B10 , -P(O)R A10 R B10 and -P(O)(OR A10 )(OR B10 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from R 11 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, NR A11 R B11 , -OR A11 , -C(O)R A11 , -C(=NR E11 )R A11 , -C(=N-OR B11 )R A11 , -C(O)OR A11 , -OC(O)R A11 , -C(O)NR A11 R B11 , -NR A11 C(O)R B11 , -C(=NR E11 )NR A11 RB11 , -NR A11 C(=NR E11 )R B11 , -OC(O)NR A11 R B11 , -NR A11 C(O)OR B11 , -NR A11 C(O)NR A11 R B11 , -NR A11 C(S)NR A11 R B11 , -NR A11 C(=NR E11 )NR A11 R B11 , -S(O) r R A11 , -S(O)(=NR E11 )R B11 , -N=S(O)R A11 R B11 , -S(O)2OR A11 , -OS(O)2R A11 , -NR A11 S(O) r R B11 , -NR A11 S(O)(=NR E11 )R B11 , -S(O) r NR A11 R B11 , -S(O)(=NR E11 )NR A11 R B11 , -NR A11 S(O)NR A11 R B11 , -NR A11 S(O)(=NR E11 )NR A11 R B11 , -P(O)R A11 R B11 and -P(O)(OR A11 )(OR B11 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from R 12 is hydrogen, C1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl group, -C(O)R A12 , -C(=NR E12 )R A12 , -C(=N-OR B12 )R A12 , -C(O)OR A12 , -C(O)NR A12 R B12 , -C(=NR E12 )NR A12 R B12 , -S(O) r R A12 , -S(O)(=NR E12 )R B12 , -S(O)2OR A12 , -S(O) r NR A12 R B12 , -S(O)(=NR E12 )NR A12 R B12 , -P(O)R A12 R B12 and -P(O)(OR A12 )(OR B12 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from R A0 , R A1 , R A4 , R A5 , R A6 , R A7 , R A8 , R A9 , R A10 , R A11 , R A12 , R B1 , RB4 , R B5 , R B6 , R B7 , R B8 , R B9 , R B10 , R B11 and R B12 each independently represents hydrogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, "R A1 and R B1 " or "R A4 and R B4 " or "R A5 and R B5 " or "R A6 and R B6 " or "R A7 and R B7 " or "R A8 and R B8 " or "R A9 and R B9 " or "R A10 and R B10 " or "R A11 and R B11 " or "R A12 and R B12 " together with the atom or atoms to which they are attached constitute a 4- to 12-membered heterocyclic ring containing 0, 1, or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or X and is substituted with one, two or three substituents selected from R C0 and R D0 each independently represents hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, each "R C0 and R D0 " together with the carbon atom or atoms to which they are attached form a 3- to 12-membered ring containing zero, one, or two heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, R E1 , R E4 , R E5 , R E6 , R E7 , R E8 , R E9 , R E10 , R E11 and R E12 each independently represents hydrogen, C 1-10 Alkyl groups, CN, NO2, -OR a1 , -SR a1 , -S(O) r R a1 , -C(O)R a1 , C(O)OR a1 , -C(O)NR a1 R b1 and -S(O) r NR a1 R b1wherein the alkyl groups are unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Each R X are independently hydrogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, halogens, CN, -NO2, -(CR c1 R d1 ) t NR a1 R b1 , -(CR c1 R d1 ) t OR b1 , -(CR c1 R d1 ) t C(O)R a1 , -(CR c1 R d1 ) t C(=NR e1 )R a1 , -(CR c1 R d1 ) t C(=N-OR b1 )R a1 , -(CR c1 R d1 ) t C(O)OR b1 , -(CR c1 R d1 ) t OC(O)R b1 , -(CR c1 R d1 ) t C(O)NR a1 R b1 , -(CR c1 R d1 ) t NR a1 C(O)R b1 , -(CRc1 R d1 ) t C(=NR e1 )NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(=NR e1 )R b1 、-(CR c1 R d1 ) t OC(O)NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(O)OR b1 、-(CR c1 R d1 ) t NR a1 C(O)NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(S)NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(=NR e1 )NR a1 R b1 、-(CR c1 R d1 ) t S(O) r R b1 、-(CR c1 R d1 ) t S(O)(=NR e1 )R b1 、-(CR c1 R d1 ) t N=S(O)R a1 R b1 、-(CR c1 R d1 ) t S(O)2OR b1 、-(CR c1 R d1 ) t OS(O)2Rb1 , -(CR c1 R d1 ) t NR a1 S(O) r R b1 , -(CR c1 R d1 ) t NR a1 S(O)(=NR e1 )R b1 , -(CR c1 R d1 ) t S(O) r NR a1 R b1 , -(CR c1 R d1 ) t S(O)(=NR e1 )NR a1 R b1 , -(CR c1 R d1 ) t NR a1 S(O)NR a1 R b1 , -(CR c1 R d1 ) t NR a1 S(O)(=NR e1 )NR a1 R b1 , -(CR c1 R d1 ) t P(O)R a1 R b1 and -(CR c1 R d1 ) t P(O)(OR a1 )(OR b1 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Y and is substituted with at least one substituent selected from X 1 is CR 8 and X 2 is CR 9 and X 3 is CR 10 and R1 and R 8 together with the atoms to which they are attached, C 5-10 a cycloalkyl group or a 5- to 12-membered ring containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, and L 1 -(CR C0 R D0 ) u NR A0 (CR C0 R D0 ) t -L when selected from 2 is a chemical bond, -(CR C0 R D0 ) u O(CR C0 R D0 ) t -, -(CR C0 R D0 ) u S(O) r (CR C0 R D0 ) t - selected from L 2 is -O- and R 2 but [ka] If R 2 Each substituent R X is C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, halogens, CN, -NO2, -(CR c1 R d1 ) t NR a1 R b1 , -(CRc1 R d1 ) t OR b1 、-(CR c1 R d1 ) t C(O)R a1 、-(CR c1 R d1 ) t C(=NR e1 )R a1 、-(CR c1 R d1 ) t C(=N-OR b1 )R a1 、-(CR c1 R d1 ) t C(O)OR b1 、-(CR c1 R d1 ) t OC(O)R b1 、-(CR c1 R d1 ) t C(O)NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(O)R b1 、-(CR c1 R d1 ) t C(=NR e1 )NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(=NR e1 )R b1 、-(CR c1 R d1 ) t OC(O)NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(O)OR b1 、-(CR c1 R d1 ) t NR a1 C(O)NR a1 Rb1 、-(CR c1 R d1 ) t NR a1 C(S)NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(=NR e1 )NR a1 R b1 、-(CR c1 R d1 ) t S(O) r R b1 、-(CR c1 R d1 ) t S(O)(=NR e1 )R b1 、-(CR c1 R d1 ) t N=S(O)R a1 R b1 、-(CR c1 R d1 ) t S(O)2OR b1 、-(CR c1 R d1 ) t OS(O)2R b1 、-(CR c1 R d1 ) t NR a1 S(O) r R b1 、-(CR c1 R d1 ) t NR a1 S(O)(=NR e1 )R b1 、-(CR c1 R d1 ) t S(O) r NR a1 R b1 、-(CR c1 R d1 ) t S(O)(=NR e1 )NR a1 R b1 、-(CR c1 R d1 )t NR a1 S(O)NR a1 R b1 , -(CR c1 R d1 ) t NR a1 S(O)(=NR e1 )NR a1 R b1 , -(CR c1 R d1 ) t P(O)R a1 R b1 and -(CR c1 R d1 ) t P(O)(OR a1 )(OR b1 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Y and is substituted with at least one substituent selected from X 1 is CR 8 and X 2 is CR 9 and X 3 is CR 10 and R 1 and R 8 do not form a ring together with the atoms to which they are attached, A is CH and W is -CR 11 - selected from L 2 is -(CR C0 R D0 ) u O(CR C0 R D0 ) t -and-(CR C0 R D0 ) u S(O) r (CR C0 R D0 ) t - selected from R a1 and R b1 each independently represents hydrogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Y and is substituted with at least one substituent selected from Or, R a1 and R b1 together with the atom or atoms to which they are attached, form a 4-12 membered heterocyclic ring containing 0, 1, or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, and the ring is Y may be substituted with a group, R c1 and R d1 each independently represents hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Y and is substituted with at least one substituent selected from Or, R c1 and R d1together with the carbon atom or atoms to which they are attached, form a 3- to 12-membered ring containing 0, 1, or 2 heteroatoms independently selected from oxygen, sulfur, and nitrogen, and the ring is Y may be substituted with a group, Each R e1 are independently hydrogen, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl groups, CN, NO2, -OR a2 , -SR a2 , -S(O) r R a2 , -C(O)R a2 , -C(O)OR a2 , -S(O) r NR a2 R b2 and -C(O)NR a2 R b2 is selected from Each R Y independently, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, halogens, CN, NO2, -(CR c2 R d2 ) t NR a2 R b2 , -(CR c2 R d2 ) t OR b2 , -(CR c2 R d2 ) t C(O)R a2 , -(CR c2 R d2 ) t C(=NR e2 )R a2 , -(CRc2 R d2 ) t C(=N-OR b2 )R a2 、-(CR c2 R d2 ) t C(O)OR b2 、-(CR c2 R d2 ) t OC(O)R b2 、-(CR c2 R d2 ) t C(O)NR a2 R b2 、-(CR c2 R d2 ) t NR a2 C(O)R b2 、-(CR c2 R d2 ) t C(=NR e2 )NR a2 R b2 、-(CR c2 R d2 ) t NR a2 C(=NR e2 )R b2 、-(CR c2 R d2 ) t OC(O)NR a2 R b2 、-(CR c2 R d2 ) t NR a2 C(O)OR b2 、-(CR c2 R d2 ) t NR a2 C(O)NR a2 R b2 、-(CR c2 R d2 ) t NR a2 C(S)NR a2 R b2 、-(CR c2 R d2 ) t NR a2 C(=NR e2 )NR a2 Rb2 、-(CR c2 R d2 ) t S(O) r R b2 、-(CR c2 R d2 ) t S(O)(=NR e2 )R b2 、-(CR c2 R d2 ) t N=S(O)R a2 R b2 、-(CR c2 R d2 ) t S(O)2OR b2 、-(CR c2 R d2 ) t OS(O)2R b2 、-(CR c2 R d2 ) t NR a2 S(O) r R b2 、-(CR c2 R d2 ) t NR a2 S(O)(=NR e2 )R b2 、-(CR c2 R d2 ) t S(O) r NR a2 R b2 、-(CR c2 R d2 ) t S(O)(=NR e2 )NR a2 R b2 、-(CR c2 R d2 ) t NR a2 S(O)2NR a2 R b2 、-(CR c2 R d2 ) t NR a2 S(O)(=NR e2 )NR a2 R b2 、-(CR c2 R d2 )t P(O)R a2 R b2 and -(CR c2 R d2 ) t P(O)(OR a2 )(OR b2 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from hydroxy, CN, amino, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino groups and di(C 1-10 substituted with at least one substituent selected from the group consisting of alkyl)amino groups; R a2 and R b2 each independently represents hydrogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino group, di(C 1-10 Alkyl)amino group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups and heteroaryl-C 1-4alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, cycloalkoxy, alkylthio, cycloalkylthio, alkylamino, cycloalkylamino, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from halogen, CN, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl group, hydroxy group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, amino group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino groups and di(C 1-10 substituted with at least one substituent selected from the group consisting of alkyl)amino groups; Or, R a2 and R b2 together with the atom or atoms to which they are attached, form a 4-12 membered heterocyclic ring containing 0, 1 or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen and phosphorus, and the ring is independently selected from halogen, CN, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl group, hydroxy group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, amino group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino groups and di(C 1-10 optionally substituted with one or two substituents selected from: R c2 and R d2 each independently represents hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino group, di(C 1-10 Alkyl)amino group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, cycloalkoxy, alkylthio, cycloalkylthio, alkylamino, cycloalkylamino, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from halogen, CN, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl group, hydroxy group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, amino group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino groups and di(C 1-10 substituted with at least one substituent selected from the group consisting of alkyl)amino groups; Or, R c2 and R d2 together with the carbon atom or atoms to which they are attached, form a 3- to 12-membered ring containing 0, 1, or 2 heteroatoms independently selected from oxygen, sulfur, and nitrogen, and the ring is independently selected from halogen, CN, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10Cycloalkyl group, hydroxy group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, amino group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino groups and di(C 1-10 optionally substituted with one or two substituents selected from: Each R e2 are independently hydrogen, CN, NO2, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, -C(O)C 1-4 Alkyl group, -C(O)C 3-10 Cycloalkyl groups, -C(O)OC 1-4 Alkyl group, -C(O)OC 3-10 Cycloalkyl groups, -C(O)N(C 1-4 alkyl)2, -C(O)N(C 3-10 cycloalkyl)2, -S(O)2C 1-4 Alkyl group, -S(O)2C 3-10 Cycloalkyl groups, -S(O)N(C 1-4 alkyl)2 and -S(O)2N(C 3-10 cycloalkyl)2; m, m1, m2, n, n1, n2, p, p1, p2 and q are independently selected from 0, 1, 2 and 3; each r is independently selected from 0, 1, and 2; each t is independently selected from 0, 1, 2, 3, and 4; each u is independently selected from 0, 1, 2, 3, and 4

[0011] In another aspect, the present invention provides a compound of formula (I) wherein X 1 , X 2 , X 3wherein at least one of is N, or a pharmaceutically acceptable salt thereof.

[0012] In another aspect, the present invention provides a compound of formula (I) wherein X 3 is CH, A is N, B is CH, Z is N, and Y 1 , Y 2 and Y 3 is CH, and the compound is represented by formula (II), or a pharmaceutically acceptable salt thereof.

[0013] [ka] (In the formula, X 1 N and CR 8 and Y is selected from N and CR 9 Selected from X 1 and X 2 At least one of the groups is N, and W is -CR 11 -, -NR 12 -, -O- and -S(O) r - selected from L 1 , L 2 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 11 , R 12 The definitions of m, m1, m2, n, n1, n2, p, p1, p2 and q are the same as in formula (I). In another aspect, the present invention provides pharmaceutical compositions comprising a compound of formula (I) or at least one pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

[0014] In another aspect, the present invention provides a method of modulating Bcl-2, comprising administering to a system or individual in need thereof a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, thereby modulating Bcl-2.

[0015] The present invention also provides a method for treating, ameliorating, or preventing a condition responsive to Bcl-2 inhibition, comprising administering to a system or individual in need thereof an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, optionally in combination with a second therapeutic agent, to treat the condition.

[0016] Alternatively, the present invention provides the use of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating a condition mediated by Bcl-2. In certain embodiments, the compound may be used alone or in combination with a second therapeutic agent to treat a condition mediated by Bcl-2.

[0017] Alternatively, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof for the treatment of a condition mediated by Bcl-2.

[0018] In particular, such conditions include, but are not limited to, autoimmune diseases, transplant diseases, infectious diseases or cell proliferative disorders.

[0019] The present invention also provides a method for treating a cell proliferative disorder, the method comprising administering to a system or individual in need thereof an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or pharmaceutical composition thereof, optionally in combination with a second therapeutic agent, to treat the condition.

[0020] Alternatively, the present invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating a cell proliferative disorder. In certain embodiments, the compound may be used alone or in combination with a chemotherapeutic agent to treat a cell proliferative disorder.

[0021] Specifically, such cell proliferative disorders include, but are not limited to, lymphoma, osteosarcoma, melanoma, or tumors of the breast, kidney, prostate, colorectum, thyroid, ovary, pancreas, neuron, lung, uterus, or gastrointestinal tract.

[0022] In the above methods of using the above compounds of the present invention, the compound of formula (I) or a pharmaceutically acceptable salt thereof may be administered to a system containing a cell or tissue, or to an individual, including a mammalian individual, such as a human or animal individual.

[0023] term Unless otherwise defined, all technical and scientific terms used in this patent have the same meaning as commonly understood by one of ordinary skill in the art to which the claimed subject matter belongs. Unless otherwise explained, all patents, patent applications, disclosed materials, etc. referenced in this patent are incorporated by reference in their entirety. In the event of multiple definitions for the same term in this patent, the definitions in this section take precedence.

[0024] It should be understood that the foregoing general description and the following detailed description are explanatory only and do not limit any claims. In this patent application, the singular includes the plural unless specifically stated otherwise. Furthermore, in the specification and the appended claims, the singular references "a," "an," and "the" include the plural reference unless specifically stated otherwise. Furthermore, the term "or" refers to "and / or" unless specifically stated otherwise. Furthermore, the use of similar terms such as "comprises," "includes," and the like is non-limiting.

[0025] Unless otherwise specified, the mass spectroscopy, nuclear magnetic resonance, high performance liquid chromatography, infrared and ultraviolet / visible spectroscopy, and general pharmacological techniques used in this patent are conventional. Unless otherwise specified, the nomenclature, experimental methods, and techniques relating to analytical chemistry, organic synthetic chemistry, and drug and pharmaceutical chemistry in this patent are all known. Standard techniques can be used for chemical synthesis, chemical analysis, drug manufacture, formulation, administration, and patient treatment. Reactions and purification techniques can be performed with reference to manufacturer's instructions, known general techniques, or methods described in this patent. The techniques and manipulations described above can be performed by known general methods and methods in the documents cited herein. In the specification, groups and substituents can be selected by one of ordinary skill in the art to form stable structures and compounds.

[0026] When referring to substituents in a chemical formula, left-to-right and right-to-left representations of the substituents in the formula are equivalent. For example, CH2O and OCH2 are equivalent.

[0027] "Substituted" refers to the replacement of a hydrogen atom with a substituent, where the substituent on a particular atom is limited by its valence.

[0028] As used herein, the term "C i-j " or "i to j-membered" means that the moiety has i to j carbon atoms or i to j atoms. For example, "C 1-6 The term "alkyl group" refers to an alkyl group having 1 to 6 carbon atoms. 3-10 The cycloalkyl group refers to the above cycloalkyl group having 3 to 10 carbon atoms.

[0029] When any variable (e.g., R) appears more than once in a compound structure, it is defined independently at each occurrence. Thus, for example, if a group is substituted with zero to two R, that group may optionally be substituted with at most two R, each R being independently selected at each occurrence. Combinations of substituents and / or variants thereof are permissible only if such combinations result in stable compounds.

[0030] "One or more" or "at least one" refers to one, two, three, four, five, six, seven, eight, nine or more.

[0031] Unless otherwise stated, the term "hetero" refers to a heteroatom or heteroatom group (i.e., a group containing a heteroatom), i.e., an atom other than carbon or hydrogen atoms or a group containing such atoms. Preferably, the heteroatoms are independently selected from O, N, S, P, etc. In embodiments involving two or more heteroatoms, the two or more heteroatoms may be the same, some or all may be different.

[0032] The term "alkyl group," whether used alone or in combination with other terms, refers to a branched or straight-chain saturated aliphatic hydrocarbon group having the specified number of carbon atoms. Unless otherwise specified, "alkyl group" refers to a C 1-10 Refers to alkyl groups. For example, "C 1-6 "C" in "Alkyl group" 1-6 " refers to a group having 1, 2, 3, 4, 5, or 6 carbon atoms in a linear or branched arrangement. For example, "C 1-8 "Alkyl group" includes, but is not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, pentyl, hexyl, heptyl, and octyl groups.

[0033] The term "cycloalkyl group," whether used alone or in combination with other terms, refers to a saturated monocyclic or polycyclic (e.g., bicyclic or tricyclic) hydrocarbon ring system, typically having 3 to 16 ring atoms. All ring atoms of a cycloalkyl group are carbon, and the cycloalkyl group contains zero heteroatoms and zero double bonds. In polycyclic cycloalkyls, two or more rings may be fused, bridged, or spiro-fused. Examples of monocyclic systems include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. A "bridged cycloalkyl group" is a polycyclic system containing 3 to 10 carbon atoms and containing one or two alkylene bridges, each consisting of one, two, or three carbon atoms, respectively, linking two non-adjacent carbon atoms of the ring system. The cycloalkyl group can be fused with an aryl or heteroaryl group. In some embodiments, the cycloalkyl group is benzene-fused. Representative examples of bridged cycloalkyl systems include, but are not limited to, bicyclo[3.1.1]heptane, bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane, bicyclo[3.3.1]nonane, bicyclo[4.2.1]nonane, tricyclo[3.3.1.03,7]nonane, and tricyclo[3.3.1.13,7]decane (adamantane). The monocyclic and bridged hydrocarbon rings can be attached to the parent molecular moiety at any substitutable atom in the ring system.

[0034] The term "alkenyl group," whether used alone or in combination with other terms, refers to a straight-chain, branched, or cyclic non-aromatic hydrocarbon group containing 2 to 10 carbon atoms and having at least one carbon-carbon double bond. In some embodiments, cyclic refers to monocyclic or polycyclic. In polycyclic alkenyl groups, two or more rings may be joined by fused, bridged, or spirocyclic rings. In some examples, there is one carbon-carbon double bond, and possibly four non-aromatic carbon-carbon double bonds. Thus, "C" refers to a non-aromatic hydrocarbon group containing 2 to 10 carbon atoms and at least one carbon-carbon double bond. 2-6"Alkenyl group" refers to an alkenyl group containing 2 to 6 carbon atoms. Alkenyl groups include, but are not limited to, vinyl, propenyl, butenyl, 2-methylbutenyl, and cyclohexenyl groups. The straight, branched, or cyclic portions of the alkenyl group may contain double bonds, and if a substituted alkenyl group is specified, it indicates that it may be substituted.

[0035] The term "alkynyl group," whether used alone or in combination with other terms, refers to a straight-chain, branched, or cyclic hydrocarbon group containing 2 to 10 carbon atoms and having at least one carbon-carbon triple bond. In some embodiments, there may be three carbon-carbon triple bonds. Thus, "C 2-6 An "alkynyl group" refers to an alkynyl group containing 2 to 6 carbon atoms. Alkynyl groups include, but are not limited to, ethynyl, propynyl, butynyl, 3-methylbutynyl, and the like. The straight, branched, or cyclic portions of an alkynyl group may contain triple bonds, and if a substituted alkynyl group is specified, it indicates that it may be substituted.

[0036] "Halogen" refers to fluorine, chlorine, bromine, and iodine.

[0037] The term "alkoxy group," used alone or in combination with other terms, refers to an alkyl group, as defined above, that is bonded to an oxygen atom through a single bond. The alkoxy group and the molecule are bonded through an oxygen atom. An alkoxy group can be represented as an -O-alkyl group. 1-10 "Alkoxy" refers to an alkoxy group containing 1 to 10 carbon atoms and may be linear or branched. Alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, butoxy, pentyloxy, hexyloxy, and the like.

[0038] The term "cycloalkoxy group," used alone or in combination with other terms, refers to a cycloalkyl group, as defined above, connected to an oxygen atom by a single bond. The cycloalkoxy group and the molecule are connected by an oxygen atom. A cycloalkoxy group can be represented as -O-cycloalkyl group. "C 3-10 "Cycloalkoxy" refers to a cycloalkoxy group containing 3 to 10 carbon atoms. The cycloalkoxy group may be fused with an aryl or heteroaryl group. In some embodiments, the cycloalkoxy group is benzene-fused. Cycloalkoxy groups include, but are not limited to, cyclopropoxy, cyclobutoxy, cyclopentyloxy, cyclohexyloxy, and the like.

[0039] The term "alkylthio group," used alone or in combination with other terms, refers to an alkyl group, as defined above, that is bonded to a sulfur atom through a single bond. The alkylthio group and the molecule are bonded through the sulfur atom. The alkylthio group may be represented as -S-alkyl group. 1-10 "Alkylthio group" refers to an alkylthio group containing 1 to 10 carbon atoms and may be linear or branched. Alkylthio groups include, but are not limited to, methylthio, ethylthio, propylthio, isopropylthio, butylthio, and hexylthio groups.

[0040] The term "cycloalkylthio group," used alone or in combination with other terms, refers to a cycloalkyl group, as defined above, that is bonded to a sulfur atom through a single bond. The cycloalkylthio group and the molecule are bonded through the sulfur atom. A cycloalkylthio group can be represented as -S-cycloalkyl group. "C 3-10"Cycloalkylthio" refers to a cycloalkylthio group containing 3 to 10 carbon atoms. The cycloalkylthio group may be fused with an aryl or heteroaryl group. In some embodiments, the cycloalkylthio group is benzene-fused. Examples of cycloalkylthio groups include, but are not limited to, cyclopropylthio, cyclobutylthio, and cyclohexylthio.

[0041] The term "alkylamino group," used alone or in combination with other terms, refers to an alkyl group, as defined above, that is bonded to a nitrogen atom through a single bond. The alkylamino group and another molecule are bonded through the nitrogen atom. The alkylamino group can be represented as -NH(alkyl group). 1-10 "Alkylamino group" refers to an alkylamino group containing 1 to 10 carbon atoms, which may have a straight or branched structure. Alkylamino groups include, but are not limited to, methylamino, ethylamino, propylamino, isopropylamino, butylamino, and hexylamino groups.

[0042] The term "cycloalkylamino group," used alone or in combination with other terms, refers to a cycloalkyl group, as defined above, that is connected to a nitrogen atom through a single bond. The cycloalkylamino group is connected to another molecule through the nitrogen atom. The cycloalkylamino group can be represented as -NH(cycloalkyl group). "C 3-10 "Cycloalkylamino group" refers to a cycloalkylamino group containing 3 to 10 carbon atoms. The cycloalkylamino group may be fused with an aryl or heteroaryl group. In some embodiments, the cycloalkylamino group is benzene-fused. Cycloalkylamino groups include, but are not limited to, cyclopropaneamino, cyclobutylamino, and cyclohexylamino groups.

[0043] The term "di(alkyl)amino group," used alone or in combination with other terms, refers to two alkyl groups, as defined above, connected to a nitrogen atom by a single bond. The di(alkyl)amino group and the molecule are connected through the nitrogen atom. The di(alkyl)amino group can be represented as -N(alkyl). "Di(C 1-10 The term "di(C alkyl)amino group" refers to a group in which two alkyl moieties each contain 1 to 10 carbon atoms. 1-10 It refers to an amino group having a linear or branched structure.

[0044] An "aryl group," used alone or in combination with other terms, refers to an aryl group having 6, 7, 8, 9, 10, 11, 12, 13, or 14 carbon atoms ("C 6-14 "C6 aryl" refers to a monovalent, monocyclic, bicyclic or tricyclic aromatic hydrocarbon ring system having a ring with six carbon atoms (a "C6 aryl"), e.g., a phenyl group, or a ring with ten carbon atoms (a "C6 aryl"). 10 aryl group), such as a naphthyl group, or a ring having 14 carbon atoms ("C 14 An aryl group may be fused with a cycloalkyl group or a heterocyclic group.

[0045] Divalent groups formed from substituted benzene derivatives and having free valence electrons on ring atoms are named substituted phenylene groups. Divalent groups derived from monovalent polycyclic hydrocarbon groups whose names end in "-group" are obtained by removing one hydrogen atom from the carbon atom having the free valence electron, and their names are obtained by adding "-idene" to the name of the monovalent group; for example, a naphthyl group with two bonding sites is called a naphthylidene group.

[0046] The term "heteroaryl group," used alone or in combination with other terms, refers to a monovalent, monocyclic, bicyclic, or tricyclic aromatic ring system having 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 ring atoms ("5- to 14-membered heteroaryl group"), particularly 5, 6, 9, or 10 atoms, and including at least one heteroatom, which may be the same or different, selected from N, O, and S. The heteroaryl group may be fused with a cycloalkyl group or a heterocyclic group. In some embodiments, a "heteroaryl group" refers to: a 5- to 8-membered aromatic monocyclic ring containing 1 to 4 heteroatoms, and in some embodiments 1 to 3 heteroatoms, selected from N, O, and S, and the remainder being carbon atoms; an 8- to 12-membered bicyclic ring containing 1 to 6, in some embodiments 1 to 4, or in some embodiments 1 to 3 heteroatoms selected from N, O, and S, the remainder being carbon atoms, and at least one heteroatom being present in an aromatic ring; It refers to an 11- to 14-membered tricyclic ring that contains 1 to 8, in some embodiments 1 to 6, in some embodiments 1 to 4, or in some embodiments 1 to 3 heteroatoms selected from N, O, and S, and the remainder are carbon atoms.

[0047] When the total number of S and O in the heteroaryl group is greater than 1, these heteroatoms are not adjacent to one another. In some embodiments, the total number of S and O in the heteroaryl group is 2 or less. In some embodiments, the total number of S and O in the heteroaryl group is 1 or less.

[0048] Examples of heteroaryl groups include, but are not limited to, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 3-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 6-pyrimidinyl, 1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 1-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, pyridazinyl, triazinyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, triazolyl, tetrazolyl, thienyl, furanyl, and the like.

[0049] Additionally, heteroaryl groups include, but are not limited to, indolyl, benzothienyl, benzofuranyl, benzimidazolyl, benzotriazole, quinoxalyl, quinolyl, and isoquinolyl groups. "Heteroaryl groups" also include the N-oxide derivatives of any nitrogen-containing heteroaryl groups.

[0050] Divalent radicals derived from monovalent heteroaryl groups whose names end in "-radical" are obtained by removing one hydrogen atom from the carbon atom with the free valence electron and are named by adding "-idene" to the name of the monovalent radical; for example, a pyridyl group with two binding sites is called pyridylidene.

[0051] "Heterocycle" (and variations thereof, such as "heterocyclic" or "heterocyclic group") broadly refers to a saturated or unsaturated, monocyclic or polycyclic (e.g., bicyclic) cyclic aliphatic hydrocarbon system, typically having 3 to 12 ring atoms (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 4 to 12, 5 to 12, 4 to 8, 4 to 7, 4 to 6, 5 to 6, or 7 to 9 ring atoms) and containing at least one (e.g., 2, 3, or 4) heteroatom independently selected from oxygen, sulfur, nitrogen, and phosphorus (preferably oxygen, sulfur, or nitrogen). In polycyclic systems, two or more rings may be fused, bridged, or spirocyclic, and heterocycles may be fused with aryl or heteroaryl groups. In some embodiments, heterocycles are benzene-fused. Heterocycles further include ring systems substituted with one or more oxo or imino moieties. In some embodiments, the C, N, S, and P atoms in the heterocycle are optionally substituted with oxo. In some embodiments, the C, S, and P atoms in the heterocycle are optionally substituted with imino groups, and the imino groups may be unsubstituted or substituted. Any carbon atom or heteroatom in the heterocycle may be a bonding site, provided that a stable structure is formed. When a heterocycle has a substituent, the substituent may be bonded to any heteroatom or carbon atom in the heterocycle, provided that a stable chemical structure is formed.

[0052] Suitable heterocycles include, for example, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 1-imidazolidinyl, 2-imidazolidinyl, 3-imidazolidinyl, 4-imidazolidinyl, 5-imidazolidinyl, 1-pyrazolidinyl, 2-pyrazolidinyl, 3-pyrazolidinyl, 4-pyrazolidinyl, 5-pyrazolidinyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1-piperazinyl, 2-piperazinyl, 3-piperazinyl, 1-hexahydropyridazinyl, 3-hexahydropyridazinyl, and 4-hexahydropyridazinyl groups. Also included are morpholinyl groups, such as 1-morpholinyl, 2-morpholinyl, 3-morpholinyl, and 4-morpholinyl. Examples of heterocycles having one or more oxo moieties include, but are not limited to, piperidinyl-N-oxide, morpholinyl-N-oxide, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl. Bicyclic heterocycles include: [ka] Including, but not limited to:

[0053] As used herein, "aryl-alkyl group" refers to an alkyl group, as defined above, substituted with an aryl group, as defined above. Exemplary aralkyl groups include, but are not limited to, benzyl, phenethyl, naphthylmethyl, and the like. In some embodiments, the aralkyl group contains 7 to 20 or 7 to 11 carbon atoms. "Aryl C 1-4 When using "C alkyl group", 1-4 " refers to the number of carbon atoms in the alkyl group portion, not the aryl group portion.

[0054] As used herein, a "heterocycle-alkyl group" refers to an alkyl group, as defined above, substituted with a heterocycle group, as defined above. 1-4 When using "C alkyl group", 1-4 " refers to the number of carbon atoms in the alkyl group portion, not the heterocyclic group portion.

[0055] As used herein, "cycloalkyl-alkyl group" refers to an alkyl group, as defined above, substituted with a cycloalkyl group, as defined above. 3-10 Cycloalkyl-C 1-4 When using "C alkyl group", 3-10 " refers to the number of carbon atoms in the cycloalkyl group, not the alkyl group. 1-4 " refers to the number of carbon atoms in the alkyl group portion, not the cycloalkyl group portion.

[0056] As used herein, a "heteroaryl-alkyl group" refers to an alkyl group, as defined above, substituted with a heteroaryl group, as defined above. 1-4 When using "C alkyl group", 1-4 " refers to the number of carbon atoms in the alkyl group portion, not the heteroaryl group portion.

[0057] For the avoidance of doubt, when reference is made to substitution of, for example, alkyl, cycloalkyl, heterocyclic alkyl, aryl and / or heteroaryl groups thereof, this refers to the substitution of these groups singly or in combination, i.e., when R is an aryl-C 1-4 alkyl groups and unsubstituted, or independently R X When substituted with at least one substituent, such as one, two, three, or four, selected from X and the alkyl group portion is also unsubstituted or independently substituted with at least one substituent, such as one, two, three, or four, selected from R X It should be understood that the group is substituted with at least one, such as one, two, three or four, substituents selected from:

[0058] "Pharmaceutically acceptable salts" refers to salts prepared from pharmaceutically acceptable non-toxic bases or acids, including inorganic or organic bases and inorganic or organic acids. Salts of inorganic bases may be selected from, for example, aluminum, ammonium, calcium, copper, iron, ferrous, lithium, magnesium, manganese, divalent manganese, potassium, sodium, and zinc salts. Furthermore, pharmaceutically acceptable salts of inorganic bases may be selected from ammonium, calcium, magnesium, potassium, and sodium salts. Salts in solid form may exist in one or more crystalline forms or polymorphs, and may exist as solvates, such as in the form of hydrates. Pharmaceutically acceptable non-toxic organic base salts may be selected from, for example, salts of primary, secondary, and tertiary amines, substituted amines (including naturally occurring substituted amines), cyclic amines, and basic ion exchange resins, such as arginine, betaine, caffeine, choline, N,N'-dibenzylethylenediamine, diethylamine, 2-diethylaminoethanol, 2-dimethylaminoethanol, ethanolamine, ethylenediamine, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, histidine, hydrabamine, isopropylamine, lysine, methylglucamine, morpholine, piperazine, piperidine, polyamine resins, procaine, purines, theobromine, triethylamine, trimethylamine, tripropylamine, tromethamine.

[0059] When the compound referred to in this patent is a base, its salt must be prepared using at least one pharmaceutically acceptable non-toxic acid, which may be selected from inorganic and organic acids, such as acetic acid, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, citric acid, ethanesulfonic acid, fumaric acid, gluconic acid, glutamic acid, hydrobromic acid, hydrochloric acid, isethionic acid, lactic acid, maleic acid, malic acid, mandelic acid, methanesulfonic acid, mucic acid, nitric acid, pamoic acid, pantothenic acid, phosphoric acid, succinic acid, sulfuric acid, tartaric acid, and p-toluenesulfonic acid. In some embodiments, the acid may be selected from citric acid, hydrobromic acid, hydrochloric acid, maleic acid, phosphoric acid, sulfuric acid, fumaric acid, and tartaric acid.

[0060] "Administration of" or "administering" a compound or a pharmaceutically acceptable salt thereof refers to providing a compound of the invention or a pharmaceutically acceptable salt thereof to an individual in need of treatment.

[0061] "Effective amount" refers to that amount of a compound or pharmaceutically acceptable salt that elicits a biological or medical response in a tissue, system, animal or human that is observable by a researcher, veterinarian, clinician or other practitioner.

[0062] "Composition" includes products containing specific amounts of specific ingredients, and products made by combining these specific amounts of specific ingredients, any directly or indirectly. Pharmaceutical compositions include products containing active ingredients and inactive ingredients as carriers, and products resulting directly or indirectly from the combination, complexation, or aggregation of any two or more of the ingredients, or from the dissociation of one or more of the ingredients, or from any other type of reaction or interaction of one or more of the ingredients.

[0063] "Pharmaceutically acceptable" means compatible with the other ingredients of the formulation and not unacceptably harmful to the user.

[0064] "Individual" refers to an individual suffering from a disease, condition, etc., and includes mammals and non-mammals. Mammals include, but are not limited to, any member of the mammalian family, including humans, non-human primates such as chimpanzees, other apes, and monkeys, domestic animals such as cows, horses, sheep, goats, and pigs, livestock such as rabbits, dogs, and cats, and laboratory animals including rodents such as rats, mice, and guinea pigs. Non-mammals include, but are not limited to, birds, fish, and the like. In one embodiment of the present invention, the mammal is a human.

[0065] "Treatment" includes alleviating, reducing, or ameliorating a disease or symptom, preventing other symptoms, improving or preventing underlying metabolic factors of a symptom, inhibiting a disease or symptom, e.g., arresting the progression of a disease or symptom, alleviating a disease or symptom, promoting the remission of a disease or symptom, or arresting the symptoms of a disease or symptom, and broadly includes prevention. "Treatment" further includes achieving therapeutic benefit and / or prophylactic benefit. Therapeutic benefit refers to eradicating or ameliorating the condition being treated. Therapeutic benefit may also be achieved by eradicating or ameliorating one or more physiological symptoms associated with an underlying disease, such that an improvement in the disease is observed in a patient even though the patient still suffers from the underlying disease. Prophylactic benefit refers to the fact that the composition may be administered to a patient at risk of developing a particular disease or who reports one or more physiological symptoms of the disease, even if the disease has not been diagnosed.

[0066] A "protecting group" (PG) refers to a substituent that reacts with other functional groups in a compound to block or protect a particular functional group. For example, an "amino protecting group" refers to a substituent attached to an amino group that blocks or protects the amino functionality in a compound. Suitable amino protecting groups include acetyl, trifluoroacetyl, t-butoxycarbonyl (BOC), benzyloxycarbonyl (CBZ), and 9-fluorenylmethyloxycarbonyl (Fmoc) protecting groups. Similarly, a "hydroxyl protecting group" refers to a substituent of a hydroxy group that can effectively block or protect the functionality of the hydroxy group. Suitable protecting groups include, but are not limited to, acetyl and silyl groups. A "carboxyl protecting group" refers to a substituent of a carboxyl group that can effectively block or protect the functionality of the carboxyl group. Commonly used carboxyl protecting groups include -CHCHSOPh, cyanoethyl, 2-(trimethylsilyl)ethyl, 2-(trimethylsilyl)ethoxymethyl, 2-(p-toluenesulfonyl)ethyl, 2-(p-nitrophenylsulfinyl)ethyl, 2-(diphenylphosphino)-ethyl, nitroethyl, etc. For a general description and explanation of protecting groups, see reference: T.W. Greene, Protective Groups in Organic Synthesis, John Wiley & Sons, New York, 1991.

[0067] The "NH protecting group" includes a trichloroethoxycarbonyl group, a tribromoethoxycarbonyl group, a benzyloxycarbonyl group, a p-nitrobenzylformyl group, an o-bromobenzyloxycarbonyl group, a chloroacetyl group, a dichloroacetyl group, a trichloroacetyl group, a trifluoroacetyl group, a phenylacetyl group, a formyl group, an acetyl group, a benzoyl group, a t-pentyloxycarbonyl group, a t-butoxycarbonyl group, a p-methoxybenzyloxycarbonyl group, a 3,4-dimethoxybenzyloxycarbonyl group, a 4-(phenylazo)benzyloxycarbonyl group, a 2-furfuryloxycarbonyl group, a diphenylmethoxycarbonyl group, a 1,1-dimethylpropoxycarbonyl group, an isopropoxycarbonyl group, a phthaloyl group, a succinyl group, an alanyl group, a leucyl group, a 1-adamantyloxycarbonyl group, an 8-quinolyloxycarbonyl group, and a 2-hydroxybenzoyl group. Examples of suitable alkyl groups include, but are not limited to, a cycloalkyl group ...

[0068] The "C(O)OH" protecting group includes methyl, ethyl, n-propyl, isopropyl, 1,1-dimethylpropyl, n-butyl, t-butyl, phenyl, naphthyl, benzyl, diphenylmethyl, triphenylmethyl, p-nitrobenzyl, p-methoxybenzyl, bis(p-methoxyphenyl)methyl, acetylmethyl, phenacyl, p-nitrophenacyl, p-bromophenacyl, p-methanesulfonphenacyl, 2-tetrahydropyranyl, 2-tetrahydrofuranyl, 2,2,2-trichloroethyl, 2-(trimethylsilyl)ethyl, acetoxymethyl, propionyloxymethyl, pivaloyloxymethyl, phenacyl, methyl ... Examples of silyl groups include, but are not limited to, methylimidomethyl, succinimidomethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxymethyl, methoxyethoxymethyl, 2-(trimethylsilyl)ethoxymethyl, benzyloxymethyl, methylthiomethyl, 2-methylthioethyl, phenylthiomethyl, 1,1-dimethyl-2-propenyl, 3-methyl-3-butenyl, allyl, trimethylsilyl, triethylsilyl, triisopropylsilyl, diethylisopropylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, diphenylmethylsilyl, and t-butylmethoxyphenylsilyl groups.

[0069] The "OH or SH" protecting group is a benzyloxycarbonyl group, a 4-nitrobenzyloxycarbonyl group, a 4-bromobenzyloxycarbonyl group, a 4-methoxybenzyloxycarbonyl group, a 3,4-dimethoxybenzyloxycarbonyl group, a methoxycarbonyl group, an ethoxycarbonyl group, a t-butoxycarbonyl group, a 1,1-dimethylpropoxycarbonyl group, an isopropoxycarbonyl group, an isobutyloxycarbonyl group, a diphenylmethoxycarbonyl group, a 2,2,2-trichloroethoxy ... -Tribromoethoxycarbonyl group, 2-(trimethylsilyl)ethoxycarbonyl group, 2-(phenylsulfonyl)ethoxycarbonyl group, 2-(triphenylphosphonio)ethoxycarbonyl group, 2-furfuryloxycarbonyl group, 1-adamantyloxycarbonyl group, vinyloxycarbonyl group, allyloxycarbonyl group, 4-ethoxy-1-naphthyloxycarbonyl group, 8-quinolyloxycarbonyl group, acetyl group, formyl group, chloroacetyl group, dichloroacetyl group, trichloroacetyl group, triflic acid group, Oroacetyl, methoxyacetyl, phenoxyacetyl, pivaloyl, benzoyl, methyl, t-butyl, 2,2,2-trichloroethyl, 2-trimethylsilylethyl, 1,1-dimethyl-2-propenyl, 3-methyl-3-butenyl, allyl, benzyl (phenylmethyl), p-methoxybenzyl, 3,4-dimethoxybenzyl, diphenylmethyl, triphenylmethyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiopyranyl, methoxymethyl, methyl These include, but are not limited to, methylthiomethyl, benzyloxymethyl, 2-methoxyethoxymethyl, 2,2,2-trichloroethoxymethyl, 2-(trimethylsilyl)ethoxymethyl, 1-ethoxyethyl, methanesulfonyl, p-toluenesulfonyl, trimethylsilyl, triethylsilyl, triisopropylsilyl, diethylisopropylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, diphenylmethylsilyl, and t-butylmethoxyphenylsilyl groups.

[0070] The compounds of the present invention may exist as geometric isomers. The carbon-carbon or carbon-nitrogen double bonds of the compounds of the present invention may be in the E or Z configuration, where "E" indicates that the higher ranking substituent is on the opposite side of the carbon-carbon or carbon-nitrogen double bond according to the Cahn-Ingold-Prelog ranking rules, and "Z" indicates that the higher ranking substituent is on the same side of the carbon-carbon or carbon-nitrogen double bond. The compounds of the present invention may also exist as a mixture of "E" and "Z" isomers. Substituents around a cycloalkyl or heterocyclic group are referred to as being in the cis or trans configuration. The present invention also includes various isomers and mixtures thereof resulting from the arrangement of substituents around the adamantane ring system. Two substituents around a single ring in the adamantane ring system are referred to as being in the Z or E opposite configuration. See, for example, CD Jones, M. Kaselj, RN Salvatore, WJle Noble J. Org. Chem. 1998, 63, 2758-2760.

[0071] The compounds of the present invention may contain asymmetrically substituted carbon atoms in the R or S configuration. For the definitions of "R" and "S," see IUPAC 1974 Recommendations for Section E, Fundamental Stereochemistry, Pure Appl. Chem. (1976) 45, pp. 13-10. A compound containing asymmetrically substituted carbon atoms is racemic if the asymmetrically substituted carbon atoms in the R and S configurations are in equal amounts. When the amount of one configuration is greater than the amount of the other, the configuration of the chiral carbon atoms is represented by the configuration with the greater amount, and preferably has an enantiomeric excess of about 85-90%, more preferably about 95-99%, and even more preferably about 99% or greater. Therefore, the present invention includes racemic mixtures, relative and absolute stereoisomers, and mixtures of relative and absolute stereoisomers.

[0072] Isotopically enriched or isotopically labeled compounds The compounds of the present invention may exist in isotopically enriched or isotopically enriched form, containing one or more atoms with different atomic masses and mass numbers from the most common atomic masses in nature. The isotopes may be radioactive or non-radioactive. Isotopes of atoms such as hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, and iodine are 2 H, 3 H, 13 C. 14 C. 15 N, 18 O. 32 P, 35 S, 18 F, 36 Cl and 125 Compounds that contain other isotopes of these and / or other atoms are within the scope of this invention, including, but not limited to, I.

[0073] In another embodiment, the isotopically labeled compound is deuterium ( 2 H), tritium ( 3 H) or 14 The isotopically labeled compounds of the present invention include C isotopes. Isotopically labeled compounds of the present invention can be obtained by methods well known to those skilled in the art. These isotopically labeled compounds can be obtained by replacing non-labeled reagents with isotopically labeled reagents, with reference to the examples and reaction diagrams of the present invention. In some instances, compounds can be treated with an isotopically labeled reagent to replace atoms with their isotopic atoms, for example, hydrogen can be replaced with deuterium by the action of a deuterated acid such as DSO / D0.

[0074] The isotope-labeled compounds of the present invention can be used as standards in binding assays for Bcl-2 inhibitors. Compounds containing isotopes can be used in pharmaceutical research to study the in vivo metabolic fate of compounds by evaluating the mechanism of action and metabolic pathway of the non-isotopically labeled parent compound (Blake et al., J. Pharm. Sci. 64, 3, 367-391 (1975)). Such metabolic studies are very important for the design of safe and effective therapeutic drugs and can determine whether metabolites produced from in vivo active compounds or parent compounds used by patients have toxic or carcinogenic properties (Foster et al., Advances in Drug Research Vol. 14, pp. 2-36, Academic Press, London, 1985; Kato et al., J. Labeled Compounds. Radiopharmaceuticals., 36(10), 927-932 (1995); Kushner et al., Can. J. Physiol. Pharmacology, 77, 79-88 (1999)).

[0075] Additionally, drugs containing non-radioactive isotopes, such as deuterated drugs, also known as "heavy drugs," can be used to treat diseases and conditions associated with Bcl-2 activity. The proportion of a certain isotope in a compound that exceeds its natural abundance is referred to as enriched. Examples of enriched amounts include, but are not limited to, about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 21, 25, 29, 33, 37, 42, 46, 50, 54, 58, 63, 67, 71, 75, 79, 84, 88, 92, 96, and up to about 100 mol%.

[0076] Stable isotope labeling of a drug can change its physicochemical properties, such as pKa and liquid solubility. Isotopic substitution affects regions related to ligand-receptor interaction, and these effects and changes can affect the pharmacodynamic response of a drug molecule. Although some physical properties of stable isotope-labeled molecules differ from those of unlabeled molecules, their chemical and biological properties are the same, with one important distinction: due to the increased mass of the heavy isotope, any chemical bond containing the heavy isotope and another atom is stronger than the chemical bond between the heavy isotope and that atom. Due to the increased mass of the heavy isotope, any chemical bond containing the heavy isotope and another atom is stronger than the chemical bond between the light isotope. Accordingly, the presence of an isotope at a metabolic or enzymatic conversion site can slow down the reaction, thereby changing its pharmacokinetic profile or efficacy compared to a non-isotopically labeled compound.

[0077] In embodiment (1), the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof:

[0078] [ka] (In the formula, X 1 N and CR 8 is selected from X 2 N and CR 9 is selected from X 3 N and CR 10 is selected from Y 1 , Y 2 and Y 3 is independently selected from N and CH; A and B are independently selected from N and CH; W is -CR 11 -, -NR 12 -, -O-, -S(O) r- and -S(O)(=NR 12 )-selected from Z is selected from N and CH; L 1and L 2 are independently chemical bonds, -(CR C0 R D0 ) u -, -(CR C0 R D0 ) u O(CR C0 R D0 ) t -, -(CR C0 R D0 ) u NR A0 (CR C0 R D0 ) t -and-(CR C0 R D0 ) u S(O) r (CR C0 R D0 ) t - selected from R 1 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A1 R B1 , -OR A1 , -C(O)R A1 , -C(=NR E1 )R A1 , -C(=N-OR B1 )R A1 , -C(O)OR A1 , -OC(O)R A1 , -C(O)NR A1 R B1 , -NR A1 C(O)R B1 , -C(=NR E1 )NR A1 R B1 , -NR A1 C(=NR E1 )RB1 , -OC(O)NR A1 R B1 , -NR A1 C(O)OR B1 , -NR A1 C(O)NR A1 R B1 , -NR A1 C(S)NR A1 R B1 , -NR A1 C(=NR E1 )NR A1 R B1 , -S(O) r R A1 , -S(O)(=NR E1 )R B1 , -N=S(O)R A1 R B1 , -S(O)2OR A1 , -OS(O)2R A1 , -NR A1 S(O) r R B1 , -NR A1 S(O)(=NR E1 )R B1 , -S(O) r NR A1 R B1 , -S(O)(=NR E1 )NR A1 R B1 , -NR A1 S(O)NR A1 R B1 , -NR A1 S(O)(=NR E1 )NR A1 R B1 , -P(O)R A1 R B1 and -P(O)(OR A1 )(OR B1 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from R 2 and R 3are independently selected from aryl groups, heteroaryl groups, and heterocyclic groups, wherein each of the aryl groups, heteroaryl groups, and heterocyclic groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Each R 4 are independently hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A4 R B4 , -OR A4 , -C(O)R A4 , -C(=NR E4 )R A4 , -C(=N-OR B4 )R A4 , -C(O)OR A4 , -OC(O)R A4 , -C(O)NR A4 R B4 , -NR A4 C(O)R B4 , -C(=NR E4 )NR A4 R B4 , -NR A4 C(=NR E4 )R B4 , -OC(O)NR A4 R B4 , -NR A4 C(O)OR B4 , -NR A4 C(O)NR A4 R B4 , -NR A4 C(S)NR A4 R B4 , -NR A4 C(=NR E4 )NR A4 R B4 , -S(O) r RA4 , -S(O)(=NR E4 )R B4 , -N=S(O)R A4 R B4 , -S(O)2OR A4 , -OS(O)2R A4 , -NR A4 S(O) r R B4 , -NR A4 S(O)(=NR E4 )R B4 , -S(O) r NR A4 R B4 , -S(O)(=NR E4 )NR A4 R B4 , -NR A4 S(O)NR A4 R B4 , -NR A4 S(O)(=NR E4 )NR A4 R B4 , -P(O)R A4 R B4 and -P(O)(OR A4 )(OR B4 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, any two R 4 or "R 4 and R 11 " or "R 4 and R 12 ", along with the atoms to which they are attached, are C 3-10 forming a cycloalkyl group or a 4- to 12-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, Each R 5 are independently hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A5 R B5 , -OR A5 , -C(O)R A5 , -C(=NR E5 )R A5 , -C(=N-OR B5 )R A5 , -C(O)OR A5 , -OC(O)R A5 , -C(O)NR A5 R B5 , -NR A5 C(O)R B5 , -C(=NR E5 )NR A5 R B5 , -NR A5 C(=NR E5 )R B5 , -OC(O)NR A5 R B5 , -NR A5 C(O)OR B5 , -NR A5 C(O)NR A5 R B5 , -NR A5 C(S)NR A5 R B5 , -NR A5 C(=NR E5 )NR A5 R B5 , -S(O) r R A5 , -S(O)(=NR E5 )R B5 , -N=S(O)R A5 R B5 , -S(O)2OR A5 , -OS(O)2R A5 , -NR A5 S(O) r R B5 , -NR A5 S(O)(=NRE5 )R B5 , -S(O) r NR A5 R B5 , -S(O)(=NR E5 )NR A5 R B5 , -NR A5 S(O)NR A5 R B5 , -NR A5 S(O)(=NR E5 )NR A5 R B5 , -P(O)R A5 R B5 and -P(O)(OR A5 )(OR B5 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, any two R 5 together with the carbon atoms to which they are attached, C 3-10 forming a cycloalkyl group or a 4- to 12-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, Each R 6 are independently hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A6 R B6 , -OR A6 , -C(O)R A6 , -C(=NR E6 )RA6 、-C(=N-OR B6 )R A6 、-C(O)OR A6 、-OC(O)R A6 、-C(O)NR A6 R B6 、-NR A6 C(O)R B6 、-C(=NR E6 )NR A6 R B6 、-NR A6 C(=NR E6 )R B6 、-OC(O)NR A6 R B6 、-NR A6 C(O)OR B6 、-NR A6 C(O)NR A6 R B6 、-NR A6 C(S)NR A6 R B6 、-NR A6 C(=NR E6 )NR A6 R B6 、-S(O) r R A6 、-S(O)(=NR E6 )R B6 、-N=S(O)R A6 R B6 、-S(O)2OR A6 、-OS(O)2R A6 、-NR A6 S(O) r R B6 、-NR A6 S(O)(=NR E6 )R B6 、-S(O) r NR A6 R B6 、-S(O)(=NR E6 )NR A6 R B6 、-NR A6 S(O)2NR A6 R B6 、-NR A6 S(O)(=NR E6 )NR A6 R B6 、-P(O)R A6 R B6and -P(O)(OR A6 )(OR B6 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, any two R 6 together with the carbon atoms to which they are attached, C 3-10 forming a cycloalkyl group or a 4- to 12-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, Each R 7 are independently hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A7 R B7 , -OR A7 , -C(O)R A7 , -C(=NR E7 )R A7 , -C(=N-OR B7 )R A7 , -C(O)OR A7 , -OC(O)R A7 , -C(O)NR A7 R B7 , -NR A7 C(O)R B7 , -C(=NR E7 )NR A7 R B7 , -NR A7 C(=NR E7 )R B7 , -OC(O)NRA7 R B7 , -NR A7 C(O)OR B7 , -NR A7 C(O)NR A7 R B7 , -NR A7 C(S)NR A7 R B7 , -NR A7 C(=NR E7 )NR A7 R B7 , -S(O) r R A7 , -S(O)(=NR E7 )R B7 , -N=S(O)R A7 R B7 , -S(O)2OR A7 , -OS(O)2R A7 , -NR A7 S(O) r R B7 , -NR A7 S(O)(=NR E7 )R B7 , -S(O) r NR A7 R B7 , -S(O)(=NR E7 )NR A7 R B7 , -NR A7 S(O)NR A7 R B7 , -NR A7 S(O)(=NR E7 )NR A7 R B7 , -P(O)R A7 R B7 and -P(O)(OR A7 )(OR B7 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from R 8 are hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A8 R B8 , -OR A8 , -C(O)R A8 , -C(=NR E8 )R A8 , -C(=N-OR B8 )R A8 , -C(O)OR A8 , -OC(O)R A8 , -C(O)NR A8 R B8 , -NR A8 C(O)R B8 , -C(=NR E8 )NR A8 R B8 , -NR A8 C(=NR E8 )R B8 , -OC(O)NR A8 R B8 , -NR A8 C(O)OR B8 , -NR A8 C(O)NR A8 R B8 , -NR A8 C(S)NR A8 R B8 , -NR A8 C(=NR E8 )NR A8 R B8 , -S(O) r R A8 , -S(O)(=NR E8 )R B8 , -N=S(O)R A8 R B8 , -S(O)2OR A8 , -OS(O)2R A8 , -NR A8 S(O) r R B8 , -NR A8 S(O)(=NR E8 )RB8 , -S(O) r NR A8 R B8 , -S(O)(=NR E8 )NR A8 R B8 , -NR A8 S(O)NR A8 R B8 , -NR A8 S(O)(=NR E8 )NR A8 R B8 , -P(O)R A8 R B8 and -P(O)(OR A8 )(OR B8 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, R 1 and R 8 together with the atoms to which they are attached, C 5-10 forming a cycloalkyl group or a 5- to 12-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, R 9 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A9 R B9 , -OR A9 , -C(O)R A9 , -C(=NR E9 )R A9、-C(=N-OR B9 )R A9 、-C(O)OR A9 、-OC(O)R A9 、-C(O)NR A9 R B9 、-NR A9 C(O)R B9 、-C(=NR E9 )NR A9 R B9 、-NR A9 C(=NR E9 )R B9 、-OC(O)NR A9 R B9 、-NR A9 C(O)OR B9 、-NR A9 C(O)NR A9 R B9 、-NR A9 C(S)NR A9 R B9 、-NR A9 C(=NR E9 )NR A9 R B9 、-S(O) r R A9 、-S(O)(=NR E9 )R B9 、-N=S(O)R A9 R B9 、-S(O)2OR A9 、-OS(O)2R A9 、-NR A9 S(O) r R B9 、-NR A9 S(O)(=NR E9 )R B9 、-S(O) r NR A9 R B9 、-S(O)(=NR E9 )NR A9 R B9 、-NR A9 S(O)2NR A9 R B9 、-NR A9 S(O)(=NR E9 )NR A9 R B9 、-P(O)R A9 R B9and -P(O)(OR A9 )(OR B9 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from R 10 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A10 R B10 , -OR A10 , -C(O)R A10 , -C(=NR E10 )R A10 , -C(=N-OR B10 )R A10 , -C(O)OR A10 , -OC(O)R A10 , -C(O)NR A10 R B10 , -NR A10 C(O)R B10 , -C(=NR E10 )NR A10 R B10 , -NR A10 C(=NR E10 )R B10 , -OC(O)NR A10 R B10 , -NR A10 C(O)OR B10 , -NR A10 C(O)NR A10 R B10 , -NR A10 C(S)NR A10 R B10 , -NR A10 C(=NR E10 )NR A10R B10 , -S(O) r R A10 , -S(O)(=NR E10 )R B10 , -N=S(O)R A10 R B10 , -S(O)2OR A10 , -OS(O)2R A10 , -NR A10 S(O) r R B10 , -NR A10 S(O)(=NR E10 )R B10 , -S(O) r NR A10 R B10 , -S(O)(=NR E10 )NR A10 R B10 , -NR A10 S(O)NR A10 R B10 , -NR A10 S(O)(=NR E10 )NR A10 R B10 , -P(O)R A10 R B10 and -P(O)(OR A10 )(OR B10 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from R 11 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, NR A11 R B11 , -OR A11、-C(O)R A11 、-C(=NR E11 )R A11 、-C(=N-OR B11 )R A11 、-C(O)OR A11 、-OC(O)R A11 、-C(O)NR A11 R B11 、-NR A11 C(O)R B11 、-C(=NR E11 )NR A11 R B11 、-NR A11 C(=NR E11 )R B11 、-OC(O)NR A11 R B11 、-NR A11 C(O)OR B11 、-NR A11 C(O)NR A11 R B11 、-NR A11 C(S)NR A11 R B11 、-NR A11 C(=NR E11 )NR A11 R B11 、-S(O) r R A11 、-S(O)(=NR E11 )R B11 、-N=S(O)R A11 R B11 、-S(O)2OR A11 、-OS(O)2R A11 、-NR A11 S(O) r R B11 、-NR A11 S(O)(=NR E11 )R B11 、-S(O) r NR A11 R B11 、-S(O)(=NR E11 )NR A11 R B11 、-NR A11 S(O)2NR A11 R B11 、-NR A11 S(O)(=NR E11 )NR A11 RB11 , -P(O)R A11 R B11 and -P(O)(OR A11 )(OR B11 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from R 12 is hydrogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl group, -C(O)R A12 , -C(=NR E12 )R A12 , -C(=N-OR B12 )R A12 , -C(O)OR A12 , -C(O)NR A12 R B12 , -C(=NR E12 )NR A12 R B12 , -S(O) r R A12 , -S(O)(=NR E12 )R B12 , -S(O)2OR A12 , -S(O) r NR A12 R B12 , -S(O)(=NR E12 )NR A12 R B12 , -P(O)R A12 R B12 and -P(O)(OR A12 )(OR B12wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from R A0 , R A1 , R A4 , R A5 , R A6 , R A7 , R A8 , R A9 , R A10 , R A11 , R A12 , R B1 , R B4 , R B5 , R B6 , R B7 , R B8 , R B9 , R B10 , R B11 and R B12 each independently represents hydrogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, "R A1 and R B1 " or "R A4 and R B4 " or "R A5 and R B5 " or "R A6 and R B6 " or "R A7 and R B7 " or "RA8 and R B8 " or "R A9 and R B9 " or "R A10 and R B10 " or "R A11 and R B11 " or "R A12 and R B12 " together with the atom or atoms to which they are attached constitute a 4- to 12-membered heterocyclic ring containing 0, 1, or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or X and is substituted with one, two or three substituents selected from R C0 and R D0 each independently represents hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, each "R C0 and R D0 " together with the carbon atom or atoms to which they are attached form a 3- to 12-membered ring containing zero, one, or two heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, R E1 , R E4 , R E5 , R E6 , R E7 , RE8 , R E9 , R E10 , R E11 and R E12 each independently represents hydrogen, C 1-10 Alkyl groups, CN, NO2, -OR a1 , -SR a1 , -S(O) r R a1 , -C(O)R a1 , C(O)OR a1 , -C(O)NR a1 R b1 and -S(O) r NR a1 R b1 wherein the alkyl groups are unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Each R X are independently hydrogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, halogens, CN, -NO2, -(CR c1 R d1 ) t NR a1 R b1 , -(CR c1 R d1 ) t OR b1 , -(CR c1 R d1 ) t C(O)R a1 , -(CR c1 R d1 ) t C(=NR e1 )R a1 , -(CR c1 R d1 ) t C(=N-OR b1 )Ra1 、-(CR c1 R d1 ) t C(O)OR b1 、-(CR c1 R d1 ) t OC(O)R b1 、-(CR c1 R d1 ) t C(O)NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(O)R b1 、-(CR c1 R d1 ) t C(=NR e1 )NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(=NR e1 )R b1 、-(CR c1 R d1 ) t OC(O)NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(O)OR b1 、-(CR c1 R d1 ) t NR a1 C(O)NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(S)NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(=NR e1 )NR a1 R b1 、-(CR c1 R d1 ) t S(O)r R b1 ,-(CR c1 R d1 ) t S(O)(=NR e1 )R b1 ,-(CR c1 R d1 ) t N=S(O)R a1 R b1 ,-(CR c1 R d1 ) t S(O)2OR b1 ,-(CR c1 R d1 ) t OS(O)2R b1 ,-(CR c1 R d1 ) t NR a1 S(O) r R b1 ,-(CR[[ID=##**WARN**##]]The tag c1 is not closed. Please check the original text.##**WARN**##R d1 ) t NR a1 S(O)(=NR e1 )R b1 ,-(CR c1 R d1 ) t S(O) r NR a1 R b1 ,-(CR c1 R d1 ) t S(O)(=NR e1 )NR a1 R b1 ,-(CR c1 R d1 ) t NR a1 S(O)2NR a1 R b1 ,-(CR c1 R d1 ) t NR a1 S(O)(=NR e1 [[ID=1#**WARN**##]]The tag a1 is not closed. Please check the original text.##**WARN**##R b1 ,-(CR c1 R d1 ) t P(O)R a1 R b1 and -(CR c1 It should be noted that there seem to be some unclosed tags in the original text which may cause issues in a proper XML or similar context. The translation is done as accurately as possible based on the provided rules despite these potential errors.R d1 ) t P(O)(OR a1 )(OR b1 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Y and is substituted with at least one substituent selected from X 1 is CR 8 and X 2 is CR 9 and X 3 is CR 10 and R 1 and R 8 together with the atoms to which they are attached, C 5-10 a cycloalkyl group or a 5- to 12-membered ring containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, and L 1 -(CR C0 R D0 ) u NR A0 (CR C0 R D0 ) t -L when selected from 2 is a chemical bond, -(CR C0 R D0 ) u O(CR C0 R D0 ) t -, -(CR C0 R D0 ) u S(O) r (CR C0 R D0 ) t - selected from L 2 is -O- and R 2 but [ka] If R 2 Each substituent R X is C 1-10Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, halogens, CN, -NO2, -(CR c1 R d1 ) t NR a1 R b1 , -(CR c1 R d1 ) t OR b1 , -(CR c1 R d1 ) t C(O)R a1 , -(CR c1 R d1 ) t C(=NR e1 )R a1 , -(CR c1 R d1 ) t C(=N-OR b1 )R a1 , -(CR c1 R d1 ) t C(O)OR b1 , -(CR c1 R d1 ) t OC(O)R b1 , -(CR c1 R d1 ) t C(O)NR a1 R b1 , -(CR c1 R d1 ) t NR a1 C(O)R b1 , -(CR c1 R d1 ) t C(=NR e1 )NR a1 R b1 , -(CR c1 R d1 )t NR a1 C(=NR e1 )R b1 、-(CR c1 R d1 ) t OC(O)NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(O)OR b1 、-(CR c1 R d1 ) t NR a1 C(O)NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(S)NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(=NR e1 )NR a1 R b1 、-(CR c1 R d1 ) t S(O) r R b1 、-(CR c1 R d1 ) t S(O)(=NR e1 )R b1 、-(CR c1 R d1 ) t N=S(O)R a1 R b1 、-(CR c1 R d1 ) t S(O)2OR b1 、-(CR c1 R d1 ) t OS(O)2R b1 、-(CR c1 R d1 ) t NR a1 S(O) r R b1 、-(CR c1 Rd1 ) t NR a1 S(O)(=NR e1 )R b1 , -(CR c1 R d1 ) t S(O) r NR a1 R b1 , -(CR c1 R d1 ) t S(O)(=NR e1 )NR a1 R b1 , -(CR c1 R d1 ) t NR a1 S(O)NR a1 R b1 , -(CR c1 R d1 ) t NR a1 S(O)(=NR e1 )NR a1 R b1 , -(CR c1 R d1 ) t P(O)R a1 R b1 and -(CR c1 R d1 ) t P(O)(OR a1 )(OR b1 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Y and is substituted with at least one substituent selected from X 1 is CR 8 and X 2 is CR 9 and X 3 is CR 10 and R 1 and R 8 do not form a ring together with the atoms to which they are attached, A is CH and W is -CR 11 - selected from L 2 is -(CR C0 RD0 ) u O(CR C0 R D0 ) t -and-(CR C0 R D0 ) u S(O) r (CR C0 R D0 ) t - selected from R a1 and R b1 each independently represents hydrogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Y and is substituted with at least one substituent selected from Or, R a1 and R b1 together with the atom or atoms to which they are attached, form a 4-12 membered heterocyclic ring containing 0, 1, or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, and the ring is Y optionally substituted with a group, R c1 and R d1 each independently represents hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Y and is substituted with at least one substituent selected from Or, R c1 and R d1 together with the carbon atom or atoms to which they are attached, form a 3- to 12-membered ring containing 0, 1, or 2 heteroatoms independently selected from oxygen, sulfur, and nitrogen, and the ring is Y optionally substituted with a group, Each R e1 are independently hydrogen, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl groups, CN, NO2, -OR a2 , -SR a2 , -S(O) r R a2 , -C(O)R a2 , -C(O)OR a2 , -S(O) r NR a2 R b2 and -C(O)NR a2 R b2 is selected from Each R Y independently, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, halogens, CN, NO2, -(CR c2 R d2 ) t NR a2 Rb2 、-(CR c2 R d2 ) t OR b2 、-(CR c2 R d2 ) t C(O)R a2 、-(CR c2 R d2 ) t C(=NR e2 )R a2 、-(CR c2 R d2 ) t C(=N-OR b2 )R a2 、-(CR c2 R d2 ) t C(O)OR b2 、-(CR c2 R d2 ) t OC(O)R b2 、-(CR c2 R d2 ) t C(O)NR a2 R b2 、-(CR c2 R d2 ) t NR a2 C(O)R b2 、-(CR c2 R d2 ) t C(=NR e2 )NR a2 R b2 、-(CR c2 R d2 ) t NR a2 C(=NR e2 )R b2 、-(CR c2 R d2 ) t OC(O)NR a2 R b2 、-(CR c2 R d2 ) t NR a2 C(O)OR b2 、-(CR c2 R d2 ) t NR a2 C(O)NRa2 R b2 、-(CR c2 R d2 ) t NR a2 C(S)NR a2 R b2 、-(CR c2 R d2 ) t NR a2 C(=NR e2 )NR a2 R b2 、-(CR c2 R d2 ) t S(O) r R b2 、-(CR c2 R d2 ) t S(O)(=NR e2 )R b2 、-(CR c2 R d2 ) t N=S(O)R a2 R b2 、-(CR c2 R d2 ) t S(O)2OR b2 、-(CR c2 R d2 ) t OS(O)2R b2 、-(CR c2 R d2 ) t NR a2 S(O) r R b2 、-(CR c2 R d2 ) t NR a2 S(O)(=NR e2 )R b2 、-(CR c2 R d2 ) t S(O) r NR a2 R b2 、-(CR c2 R d2 ) t S(O)(=NR e2 )NR a2 R b2 、-(CR c2 Rd2 ) t NR a2 S(O)NR a2 R b2 , -(CR c2 R d2 ) t NR a2 S(O)(=NR e2 )NR a2 R b2 , -(CR c2 R d2 ) t P(O)R a2 R b2 and -(CR c2 R d2 ) t P(O)(OR a2 )(OR b2 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from hydroxy, CN, amino, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino groups and di(C 1-10 substituted with at least one substituent selected from the group consisting of alkyl)amino groups; R a2 and R b2 each independently represents hydrogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10Cycloalkylthio group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino group, di(C 1-10 Alkyl)amino group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, cycloalkoxy, alkylthio, cycloalkylthio, alkylamino, cycloalkylamino, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from halogen, CN, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl group, hydroxy group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, amino group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino groups and di(C 1-10 substituted with at least one substituent selected from the group consisting of alkyl)amino groups; Or, R a2 and R b2 together with the atom or atoms to which they are attached, form a 4- to 12-membered heterocyclic ring containing 0, 1, or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, and the ring is independently selected from halogen, CN, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl group, hydroxy group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, amino group, C 1-10 Alkylamino group, C 3-10Cycloalkylamino groups and di(C 1-10 optionally substituted with one or two substituents selected from: R c2 and R d2 each independently represents hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino group, di(C 1-10 Alkyl)amino group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, cycloalkoxy, alkylthio, cycloalkylthio, alkylamino, cycloalkylamino, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from halogen, CN, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl group, hydroxy group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, amino group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino groups and di(C 1-10 substituted with at least one substituent selected from the group consisting of alkyl)amino groups; Or, R c2 and R d2together with the carbon atom or atoms to which they are attached, form a 3- to 12-membered ring containing 0, 1, or 2 heteroatoms independently selected from oxygen, sulfur, and nitrogen, and the ring is independently selected from halogen, CN, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl group, hydroxy group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, amino group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino groups and di(C 1-10 optionally substituted with one or two substituents selected from: Each R e2 are independently hydrogen, CN, NO2, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, -C(O)C 1-4 Alkyl group, -C(O)C 3-10 Cycloalkyl groups, -C(O)OC 1-4 Alkyl group, -C(O)OC 3-10 Cycloalkyl groups, -C(O)N(C 1-4 alkyl)2, -C(O)N(C 3-10 cycloalkyl)2, -S(O)2C 1-4 Alkyl group, -S(O)2C 3-10 Cycloalkyl groups, -S(O)N(C 1-4 alkyl)2 and -S(O)2N(C 3-10 cycloalkyl)2; m, m1, m2, n, n1, n2, p, p1, p2 and q are independently selected from 0, 1, 2 and 3; each r is independently selected from 0, 1, and 2; each t is independently selected from 0, 1, 2, 3, and 4; each u is independently selected from 0, 1, 2, 3, and 4

[0079] In another embodiment (2), the compound of embodiment (1) of the present invention or a pharmaceutically acceptable salt thereof, wherein X 1 , X 2 , X 3 At least one of is N.

[0080] In another embodiment (3), the compound of embodiment (1) or (2) of the present invention, or a pharmaceutically acceptable salt thereof, is 3 is CH, A is N, B is CH, Z is N, and Y 1 , Y 2 and Y 3 is CH and the compound is a compound of formula (II).

[0081] [ka] (In the formula, X 1 N and CR 8 Selected from X 2 N and CR 9 Selected from X 1 and X 2 At least one of the groups is N, and W is -CR 11 -, -NR 12 -, -O- and -S(O) r - selected from L 1 , L 2 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 11 , R 12 , m, m1, m2, n, n1, n2, p, p1, p2 and q are defined as in formula (I).

[0082] In another embodiment (4), in the compound according to any one of embodiments (1) to (3) of the present invention or a pharmaceutically acceptable salt thereof, L 1 and L 2 are independently chemical bonds, -(CR C0 R D0 ) u -, -(CR C0 R D0 ) u O(CR C0 R D0 ) t -, -(CR C0 R D0 ) u NR A0 (CR C0 R D0 ) t - and S(O) r is selected from.

[0083] In another embodiment (5), in the compound according to any one of embodiments (1) to (4) of the present invention or a pharmaceutically acceptable salt thereof, L 1 is -(CR C0 R D0 ) u , -O-, -NH- and -S(O) r -, preferably L 1 is selected from -CH2-, -O-, -NH-, and -S-. In one embodiment, u is 1. In one embodiment, L 1 is selected from -CH2-, -O-, and -S-. 1 is -NH-.

[0084] In another embodiment (6), in the compound according to any one of embodiments (1) to (5) of the present invention or a pharmaceutically acceptable salt thereof, L 2 are chemical bonds, -O- and -S(O) r Preferably, L 2 is selected from a chemical bond and —O—.

[0085] In another embodiment (7), in the compound according to any one of embodiments (1) to (6) of the present invention, or a pharmaceutically acceptable salt thereof, R 1 is C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A1 R B1 , -OR A1 , -C(O)R A1 , -C(O)OR A1 , -OC(O)R A1 , -C(O)NR A1 R B1 , -NR A1 C(O)R B1 , -OC(O)NR A1 R B1 , -NR A1 C(O)OR B1 , -NR A1 C(O)NR A1 R B1 and -S(O) r R A1 wherein each of the alkyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0086] In another embodiment (8), in the compound according to any one of embodiments (1) to (7) of the present invention, or a pharmaceutically acceptable salt thereof, R 1 is C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4alkyl groups, wherein each of the alkyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X In one embodiment, R 1 is C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl groups, heterocyclic groups and heterocyclic-C 1-4 alkyl groups, wherein each of the alkyl groups, cycloalkyl groups, and heterocyclic groups is unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0087] In another embodiment (9), in the compound according to any one of embodiments (1) to (8) of the present invention, or a pharmaceutically acceptable salt thereof, R 1 teeth, [ka] and is unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0088] In another embodiment (10), in the compound according to any one of embodiments (1) to (9) of the present invention, or a pharmaceutically acceptable salt thereof, R 1 Each substituent R X independently, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, halogens, CN, NO2, -(CR c1 R d1 ) t NR a1 R b1 , -(CR c1 R d1 ) t OR b1 , -(CR c1 R d1 ) t C(O)R a1 and -(CR c1 R d1 )t N=S(O)R a1 R b1 wherein each of the alkyl and cycloalkyl groups is unsubstituted or independently selected from R Y is substituted with at least one substituent selected from

[0089] In another embodiment (11), in the compound according to any one of embodiments (1) to (10) of the present invention or a pharmaceutically acceptable salt thereof, each R a1 and each R b1 are independently hydrogen, C 1-10 Alkyl group, C 2-10 Alkenyl groups and C 2-10 alkynyl groups, wherein each of the alkyl, alkenyl, and alkynyl groups is unsubstituted or independently selected from R Y and is substituted with at least one substituent selected from Or, R a1 and R b1 together with the atom or atoms to which they are attached, form a 4-8 membered heterocyclic ring containing 0, 1, or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, and the ring is Y It may be substituted with a group.

[0090] In another embodiment (12), in the compound according to any one of embodiments (1) to (11) of the present invention, or a pharmaceutically acceptable salt thereof, R 1 Each substituent R X are independently OH, CN, halogen, C 1-10 Alkyl groups and [ka] is selected from.

[0091] In another embodiment (13), in the compound according to any one of embodiments (1) to (12) of the present invention, or a pharmaceutically acceptable salt thereof, R 1 teeth, [ka] is selected from.

[0092] In another embodiment (14), in the compound according to any one of embodiments (1) to (13) of the present invention, or a pharmaceutically acceptable salt thereof, R 8 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A8 R B8 , -OR A8 , -C(O)R A8 , -C(O)OR A8 , -OC(O)R A8 , -C(O)NR A8 R B8 , -NR A8 C(O)R B8 , -OC(O)NR A8 R B8 , -NR A8 C(O)OR B8 , -NR A8 C(O)NR A8 R B8 , -NR A8 C(S)NR A8 R B8 , -S(O) r R A8 , -S(O)2OR A8 , -OS(O)2R A8 , -NR A8 S(O) r R B8 and -S(O) r NR A8 R B8wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0093] In another embodiment (15), in the compound according to any one of embodiments (1) to (14) of the present invention, or a pharmaceutically acceptable salt thereof, R 8 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl groups, CN, NO2, -NR A8 R B8 , -OR A8 , -C(O)R A8 , -C(O)OR A8 , -OC(O)R A8 and -S(O) r R A8 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, and heterocyclic groups is unsubstituted or independently selected from R X and preferably, R 8 is hydrogen.

[0094] In another embodiment (16), in the compound according to any one of embodiments (1) to (15) of the present invention, or a pharmaceutically acceptable salt thereof, R 1 and R 8 together with the atoms to which they are attached, C 5-8 forming a cycloalkyl group or a 5- to 12-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X It is substituted with a substituent.

[0095] In another embodiment (17), in the compound according to any one of embodiments (1) to (16) of the present invention, or a pharmaceutically acceptable salt thereof, R 1 and R 8 together with the atoms to which they are attached form a 5- to 12-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X It is substituted with a substituent.

[0096] In another embodiment (18), the compound according to any one of the embodiments (1) to (17) of the present invention or a pharmaceutically acceptable salt thereof, is a compound of formula (I) [ka] moiety and of formula (II) [ka] The structure of the part is [ka] where R 1 and R 8 The heterocycle formed by R together with the atoms to which they are attached may be unsubstituted or contain one, two or three R X is substituted with a substituent, [ka] represents the point of attachment to the rest of the molecule. [ka] moiety and of formula (II) [ka] The structure of the part is [ka] where R 1 and R 8 The heterocycle formed by R together with the atoms to which they are attached may be unsubstituted or contain one, two or three R X is substituted with a substituent, [ka] represents the point of attachment to the rest of the molecule.

[0097] In another embodiment (19), in the compound according to any one of the embodiments (1) to (18) of the present invention or a pharmaceutically acceptable salt thereof, each substituent R of the 5- to 12-membered heterocyclic group X independently, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, halogens, CN, -NO2, -(CR c1 R d1 ) t NR a1 R b1 and -(CR c1 R d1 ) t OR b1 wherein each of the alkyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Y is substituted with at least one substituent selected from

[0098] In another embodiment (20), in the compound according to any one of the embodiments (1) to (19) of the present invention or a pharmaceutically acceptable salt thereof, each substituent R of the 5- to 12-membered heterocyclic group X are independently halogens, CN, NO2, OH, C 1-8 alkyl groups, [ka] In another embodiment, each substituent R of the 5- to 7-membered heterocyclic group is selected from X are independently halogens, CN, NO2, OH, C 1-8 alkyl groups, [ka] is selected from.

[0099] In another embodiment (21), in the compound according to any one of embodiments (1) to (20) of the present invention, or a pharmaceutically acceptable salt thereof, R 2 is selected from heterocyclic and heteroaryl groups, where the heterocyclic and heteroaryl groups are unsubstituted or independently selected from R X In one embodiment, R 2 is a heterocyclic or heteroaryl group, including a pyridopyrrolyl structure.

[0100] In another embodiment (22), in the compound according to any one of embodiments (1) to (21) of the present invention, or a pharmaceutically acceptable salt thereof, R 2 teeth, [ka] and is unsubstituted or independently selected from R X and preferably, R 2 teeth, [ka] and is unsubstituted or independently R X In another embodiment, R 2 teeth, [ka] and is unsubstituted or independently selected from R Xand preferably, R 2 teeth, [ka] is.

[0101] In another embodiment (23), in the compound according to any one of embodiments (1) to (22) of the present invention, or a pharmaceutically acceptable salt thereof, R 2 Each substituent R X independently, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, heterocyclic groups, heterocyclic-C 1-4 Alkyl groups, halogens, CN, -NO2, -(CR c1 R d1 ) t NR a1 R b1 , -(CR c1 R d1 ) t OR b1 , -(CR c1 R d1 ) t C(O)OR b1 , -(CR c1 R d1 ) t C(O)NR a1 R b1 , -(CR c1 R d1 ) t NR a1 C(O)R b1 , -(CR c1 R d1 ) t NR a1 C(O)OR b1 , -(CR c1 R d1 ) t NR a1 C(O)NR a1 R b1 , -(CR c1 R d1 ) t S(O)2OR b1 , -(CRc1 R d1 ) t S(O) r R b1 , -(CR c1 R d1 ) t NR a1 S(O) r R b1 , -(CR c1 R d1 ) t S(O) r NR a1 R b1 and -(CR c1 R d1 ) t NR a1 S(O)NR a1 R b1 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, and heterocyclic groups is unsubstituted or independently selected from R Y In another embodiment, R 2 Each substituent R X independently, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, heterocyclic groups, heterocyclic-C 1-4 Alkyl groups, halogens, CN, NO2, -(CR c1 R d1 ) t NR a1 R b1 , -(CR c1 R d1 ) t OR b1 , -(CR c1 R d1 ) t C(O)OR b1 , -(CR c1 R d1 ) t NR a1 C(O)R b1 , -(CR c1 R d1 ) t NR a1 C(O)OR b1 , -(CRc1 R d1 ) t NR a1 C(O)NR a1 R b1 , -(CR c1 R d1 ) t S(O)2OR b1 , -(CR c1 R d1 ) t S(O) r R b1 , -(CR c1 R d1 ) t NR a1 S(O) r R b1 , -(CR c1 R d1 ) t S(O) r NR a1 R b1 and -(CR c1 R d1 ) t NR a1 S(O)NR a1 R b1 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, and heterocyclic groups is unsubstituted or independently selected from R Y In another embodiment, R 2 Each substituent R X independently, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, halogens, CN, NO2, -(CR c1 R d1 ) t NR a1 R b1 and -(CR c1 R d1 ) t OR b1 wherein each of the alkyl and cycloalkyl groups is unsubstituted or independently selected from R Y and preferably, R 2 Each substituent R Xare independently selected from halogen, CN, NH2, methyl, trifluoromethyl, cyclopropyl, methoxy, methoxyethoxy, and difluoromethoxy.

[0102] In another embodiment (24), in the compound according to any one of embodiments (1) to (23) of the present invention, or a pharmaceutically acceptable salt thereof, R a1 and R b1 are independently hydrogen, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl groups, heterocyclic groups and heterocyclic-C 1-4 alkyl groups, wherein each of the alkyl groups, cycloalkyl groups, and heterocyclic groups is unsubstituted or independently selected from R Y is substituted with at least one substituent selected from

[0103] In another embodiment (25), in the compound according to any one of embodiments (1) to (24) of the present invention, or a pharmaceutically acceptable salt thereof, R 2 teeth, [ka] In another embodiment, R 2 teeth, [ka] In another embodiment, R 2 teeth, [ka] is selected from.

[0104] In another embodiment (26), in the compound according to any one of embodiments (1) to (25) of the present invention or a pharmaceutically acceptable salt thereof, W is -CH2-, -NR 12 -, -O-, -S(O) r - and -S(O)(=NR 12In another embodiment, W is selected from -CH-, -NR 12 -, -O-, -S(O) r - and -S(O)(=NR 12 )- is selected from.

[0105] In one embodiment, X 3 is CR 10 and X 1 is N. In one embodiment, X 3 is CR 10 and X 2 is N.

[0106] In another embodiment (27), the compound according to any one of embodiments (1) to (26) of the present invention, or a pharmaceutically acceptable salt thereof, is 1 is CR 8 and X 2 is CR 9 and X 3 is CR 10 is.

[0107] In another embodiment (28), the compound according to any one of embodiments (1) to (27) of the present invention, or a pharmaceutically acceptable salt thereof, is 1 , Y 2 and Y 3 is CH.

[0108] In another embodiment (29), in the compound according to any one of embodiments (1) to (28) of the present invention, or a pharmaceutically acceptable salt thereof, R 1 and R 8 together with the atoms to which they are attached, C 5-8 forming a cycloalkyl group or a 5- to 12-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X It is substituted with a substituent.

[0109] In another embodiment (30), in the compound according to any one of embodiments (1) to (29) of the present invention, or a pharmaceutically acceptable salt thereof, R 1 and R 8 together with the atoms to which they are attached form a 5- to 12-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X It is substituted with a substituent.

[0110] In another embodiment (31), the compound according to any one of the embodiments (1) to (30) of the present invention or a pharmaceutically acceptable salt thereof, [ka] The structure of the part is [ka] where R 1 and R 8 The heterocycle formed by R together with the atoms to which they are attached may be unsubstituted or contain one, two or three R X is substituted with a substituent, [ka] represents the point of attachment to the rest of the molecule. [ka] The structure of the part is [ka] where R 1 and R 8 The heterocycle formed by R together with the atoms to which they are attached may be unsubstituted or contain one, two or three R X is substituted with a substituent, [ka] represents the point of attachment to the rest of the molecule. [ka] The structure of the part is [ka] where R 1 and R 8 The heterocycle formed by R together with the atoms to which they are attached may be unsubstituted or contain one, two or three R X is substituted with a substituent, [ka] represents the point of attachment to the rest of the molecule.

[0111] In another embodiment (32), in the compound according to any one of the embodiments (1) to (31) of the present invention or a pharmaceutically acceptable salt thereof, each substituent R of the 5- to 12-membered heterocyclic group X independently, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, halogens, CN, -NO2, -(CR c1 R d1 ) t NR a1 R b1 and -(CR c1 R d1 ) t OR b1 wherein each of the alkyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Y is substituted with at least one substituent selected from

[0112] In another embodiment (33), in the compound according to any one of the embodiments (1) to (32) of the present invention or a pharmaceutically acceptable salt thereof, each substituent R of the 5- to 12-membered heterocyclic group X are independently halogens, CN, NO2, OH, C 1-8 alkyl groups, [ka] In another embodiment, each substituent R of the 5- to 7-membered heterocyclic group is selected from X are independently halogens, CN, NO2, OH, C 1-8 alkyl groups, [ka] is selected from.

[0113] In another embodiment (34), in the compound according to any one of embodiments (1) to (33) of the present invention, or a pharmaceutically acceptable salt thereof, L 1 is a chemical bond, -(CR C0 R D0 ) u -, -(CR C0 R D0 ) u O(CR C0 R D0 ) t -and-(CR C0 R D0 ) u S(O) r (CR C0 R D0 ) t -, preferably L 1 is selected from a chemical bond, —CH2—, —O—, and —S—.

[0114] In another embodiment (35), in the compound according to any one of embodiments (1) to (34) of the present invention, or a pharmaceutically acceptable salt thereof, L 1 is -(CR C0 R D0 ) u NR A0 (CRC0 R D0 ) t - selected from L 2 is a chemical bond, -(CR C0 R D0 ) u O(CR C0 R D0 ) t -and-(CR C0 R D0 ) u S(O) r (CR C0 R D0 ) t -, preferably L 2 is selected from a chemical bond and —O—.

[0115] In another embodiment (36), the compound according to any one of embodiments (1) to (35) of the present invention, or a pharmaceutically acceptable salt thereof, is 1 , Y 2 and Y 3 is CH and L 1 is -NH-, and L 2 is O, and the compound is a compound of formula (III), [ka] During the ceremony, W, A, B, Z, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , m, m1, m2, n, n1, n2, p, p1, p2 and q are defined as in formula (I).

[0116] In another embodiment (37), in the compound according to any one of embodiments (1) to (36) of the present invention, or a pharmaceutically acceptable salt thereof, R 2 is selected from heterocyclic and heteroaryl groups, where the heterocyclic and heteroaryl groups are unsubstituted or independently selected from R XIn one embodiment, R 2 is a heterocyclic or heteroaryl group, including a pyridopyrrolyl structure.

[0117] In another embodiment (38), in the compound according to any one of embodiments (1) to (37) of the present invention, or a pharmaceutically acceptable salt thereof, R 2 teeth, [ka] and is unsubstituted or independently selected from R X In another embodiment, R 2 Each substituent R X independently, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, halogens, CN, NO2, -(CR c1 R d1 ) t NR a1 R b1 , -(CR c1 R d1 ) t OR b1 , -(CR c1 R d1 ) t S(O)2OR b1 and -(CR c1 R d1 ) t NR a1 S(O) r R b1 wherein each of the alkyl, alkenyl, alkynyl, and cycloalkyl groups is unsubstituted or selected from the group consisting of R Y and preferably, R 2 Each substituent R X are independently selected from halogen, CN, NH2, a methyl group, a methoxy group, and a difluoromethoxy group.

[0118] In another embodiment (39), in the compound according to any one of embodiments (1) to (38) of the present invention, or a pharmaceutically acceptable salt thereof, L 2 is -O- and R 2 teeth, [ka] If R 2 is at least one R X is replaced by

[0119] In another embodiment (40), in the compound according to any one of embodiments (1) to (39) of the present invention, or a pharmaceutically acceptable salt thereof, R 2 Each substituent R X independently, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, heterocyclic groups, heterocyclic-C 1-4 Alkyl groups, halogens, CN, -NO2, -(CR c1 R d1 ) t NR a1 R b1 , -(CR c1 R d1 ) t OR b1 , -(CR c1 R d1 ) t C(O)OR b1 , -(CR c1 R d1 ) t C(O)NR a1 R b1 , -(CR c1 R d1 ) t NR a1 C(O)R b1 , -(CR c1 R d1 ) t NR a1 C(O)OR b1 , -(CR c1 R d1 ) t NR a1 C(O)NRa1 R b1 , -(CR c1 R d1 ) t S(O)2OR b1 , -(CR c1 R d1 ) t S(O) r R b1 , -(CR c1 R d1 ) t NR a1 S(O) r R b1 , -(CR c1 R d1 ) t S(O) r NR a1 R b1 and -(CR c1 R d1 ) t NR a1 S(O)NR a1 R b1 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, and heterocyclic groups is unsubstituted or independently selected from R Y In another embodiment, R 2 Each substituent R X independently, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, heterocyclic groups, heterocyclic-C 1-4 Alkyl groups, halogens, CN, NO2, -(CR c1 R d1 ) t NR a1 R b1 , -(CR c1 R d1 ) t OR b1 , -(CR c1 R d1 ) t C(O)OR b1 , -(CR c1 R d1 ) t NR a1 C(O)Rb1 , -(CR c1 R d1 ) t NR a1 C(O)OR b1 , -(CR c1 R d1 ) t NR a1 C(O)NR a1 R b1 , -(CR c1 R d1 ) t S(O)2OR b1 、 -(CR c1 R d1 ) t S(O) r R b1 , -(CR c1 R d1 ) t NR a1 S(O) r R b1 , -(CR c1 R d1 ) t S(O) r NR a1 R b1 and -(CR c1 R d1 ) t NR a1 S(O)NR a1 R b1 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, and heterocyclic groups is unsubstituted or independently selected from R Y is substituted with at least one substituent selected from

[0120] In another embodiment, L 2 is -O- and R 2 teeth, [ka] If R 2 is at least one R X where R 2 Each substituent R X independently, C 1-10 Alkyl group, C3-10 Cycloalkyl groups, halogens, CN, NO2, -(CR c1 R d1 ) t NR a1 R b1 and -(CR c1 R d1 ) t OR b1 wherein each of the alkyl and cycloalkyl groups is unsubstituted or independently selected from R Y and preferably, R 2 Each substituent R X are independently selected from halogen, CN, NH2, methyl, trifluoromethyl, cyclopropyl, methoxy, methoxyethoxy, and difluoromethoxy.

[0121] In another embodiment (41), in the compound according to any one of embodiments (1) to (40) of the present invention, or a pharmaceutically acceptable salt thereof, R 2 teeth, [ka] In another embodiment, R 2 teeth, [ka] In another embodiment, R 2 teeth, [ka] is selected from.

[0122] In another embodiment (42), in the compound according to any one of embodiments (1) to (41) of the present invention, or a pharmaceutically acceptable salt thereof, R 1 and R 8 do not form a ring together with the atoms to which they are attached.

[0123] In another embodiment (43), in the compound according to any one of embodiments (1) to (42) of the present invention, or a pharmaceutically acceptable salt thereof, A is CH and W is -CR 11 - is selected from.

[0124] In another embodiment (44), in the compound according to any one of embodiments (1) to (43) of the present invention, or a pharmaceutically acceptable salt thereof, L 2 is -(CR C0 R D0 ) u O(CR C0 R D0 ) t -and-(CR C0 R D0 ) u S(O) r (CR C0 R D0 ) t -, preferably L2 is selected from -O- and S(O) r is selected from.

[0125] In another embodiment (45), in the compound according to any one of embodiments (1) to (44) of the present invention, or a pharmaceutically acceptable salt thereof, R 1 is C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A1 R B1 , -OR A1 , -C(O)R A1 , -C(O)OR A1 , -OC(O)R A1 , -C(O)NR A1 R B1 , -NR A1 C(O)R B1 , -OC(O)NR A1 R B1 , -NRA1 C(O)OR B1 , -NR A1 C(O)NR A1 R B1 and -S(O) r R A1 wherein each of the alkyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X In one embodiment, R 1 is C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl groups, heterocyclic groups and heterocyclic-C 1-4 alkyl groups, wherein each of the alkyl groups, cycloalkyl groups, and heterocyclic groups is unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0126] In another embodiment (46), in the compound according to any one of embodiments (1) to (45) of the present invention, or a pharmaceutically acceptable salt thereof, R 1 is C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0127] In another embodiment (47), in the compound according to any one of embodiments (1) to (46) of the present invention, or a pharmaceutically acceptable salt thereof, R 1 teeth, [ka] and is unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0128] In another embodiment (48), in the compound according to any one of embodiments (1) to (47) of the present invention, or a pharmaceutically acceptable salt thereof, R 1 Each substituent R X independently, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, halogens, CN, NO2, -(CR c1 R d1 ) t NR a1 R b1 , -(CR c1 R d1 ) t OR b1 , -(CR c1 R d1 ) t C(O)R a1 and -(CR c1 R d1 ) t N=S(O)R a1 R b1 wherein each of the alkyl and cycloalkyl groups is unsubstituted or independently selected from R Y is substituted with at least one substituent selected from

[0129] In another embodiment (49), in the compound according to any one of embodiments (1) to (48) of the present invention, or a pharmaceutically acceptable salt thereof, each R a1 and each R b1 are independently hydrogen, C 1-10 Alkyl group, C 2-10 Alkenyl groups and C 2-10 alkynyl groups, wherein each of the alkyl, alkenyl, and alkynyl groups is unsubstituted or independently selected from R Y and is substituted with at least one substituent selected from Or, R a1 and R b1together with the atom or atoms to which they are attached, form a 4-8 membered heterocyclic ring containing 0, 1, or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, and the ring is Y It may be substituted with a group.

[0130] In another embodiment (50), in the compound according to any one of embodiments (1) to (49) of the present invention, or a pharmaceutically acceptable salt thereof, R 1 Each substituent R X are independently OH, CN, halogen, C 1-10 Alkyl groups and [ka] is selected from.

[0131] In another embodiment (51), in the compound according to any one of embodiments (1) to (50) of the present invention, or a pharmaceutically acceptable salt thereof, R 1 teeth, [ka] is selected from.

[0132] In another embodiment (52), in the compound according to any one of embodiments (1) to (51) of the present invention, or a pharmaceutically acceptable salt thereof, R 8 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A8 R B8 , -OR A8 , -C(O)R A8, -C(O)OR A8 , -OC(O)R A8 , -C(O)NR A8 R B8 , -NR A8 C(O)R B8 , -OC(O)NR A8 R B8 , -NR A8 C(O)OR B8 , -NR A8 C(O)NR A8 R B8 , -NR A8 C(S)NR A8 R B8 , -S(O) r R A8 , -S(O)2OR A8 , -OS(O)2R A8 , -NR A8 S(O) r R B8 and -S(O) r NR A8 R B8 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0133] In another embodiment (53), in the compound according to any one of embodiments (1) to (52) of the present invention, or a pharmaceutically acceptable salt thereof, R 8 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl groups, CN, NO2, -NR A8 R B8 , -OR A8 , -C(O)R A8 , -C(O)OR A8 , -OC(O)R A8 and -S(O) r RA8 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, and heterocyclic groups is unsubstituted or independently selected from R X and preferably, R 8 is hydrogen.

[0134] In another embodiment (54), in the compound according to any one of embodiments (1) to (53) of the present invention, or a pharmaceutically acceptable salt thereof, R 9 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl groups, CN, NO2, -NR A9 R B9 , -OR A9 and -C(O)R A9 wherein each of the alkyl, alkenyl, and cycloalkyl groups is unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0135] In another embodiment (55), in the compound according to any one of embodiments (1) to (54) of the present invention, or a pharmaceutically acceptable salt thereof, R 9 is selected from hydrogen, halogen, CN, OH, methyl, ethyl and trifluoromethyl.

[0136] In another embodiment (56), in the compound according to any one of embodiments (1) to (55) of the present invention, or a pharmaceutically acceptable salt thereof, R 10 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4alkyl group, CN, NO2, -NH2, and -OH, wherein each of the alkyl group, alkenyl group, and cycloalkyl group is unsubstituted or independently selected from R X and preferably, R 10 is hydrogen, halogen, C 1-10 alkyl groups, selected from CN, NO, —NH, and —OH, wherein the alkyl groups are unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0137] In another embodiment (57), in the compound according to any one of embodiments (1) to (56) of the present invention, or a pharmaceutically acceptable salt thereof, R 11 is hydrogen, C 1-10 Alkyl groups and C 3-10 cycloalkyl groups, wherein each of the alkyl and cycloalkyl groups is unsubstituted or independently selected from R X and preferably, R 11 is H.

[0138] In another embodiment (58), in the compound according to any one of embodiments (1) to (57) of the present invention, or a pharmaceutically acceptable salt thereof, R 12 is hydrogen, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, heterocyclic groups, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl group, heteroaryl group, -C(O)R A12 , -C(O)NR A12 R B12 , -C(O)OR A12 , -S(O) r R A12 and -S(O) r NR A12 R B12 wherein each of the alkyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R XIn another embodiment, R 12 is hydrogen, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, -C(O)R A12 , -C(O)OR A12 and -S(O) r R A12 wherein each of the alkyl and cycloalkyl groups is unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0139] In another embodiment (59)), in the compound according to any one of the embodiments (1) to (58) of the present invention, or a pharmaceutically acceptable salt thereof, R 12 is hydrogen, methyl group, ethyl group, cyclopropyl group, -C(O)CH3, -C(O)OCH3, -S(O)2CH3, [ka] In another embodiment, R 12 is selected from hydrogen, a methyl group, an ethyl group, a cyclopropyl group, —C(O)CH 3 , —C(O)OCH 3 , and —S(O) 2 CH 3 .

[0140] In another embodiment (60), in the compound according to any one of the embodiments (1) to (59) of the present invention or a pharmaceutically acceptable salt thereof, "R 4 and R 11 " or "R 4 and R 12 ", along with the carbon atoms to which they are attached, are C 3-10 forming a cycloalkyl group or a 4- to 12-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X It is substituted with a substituent.

[0141] In another embodiment (61), in the compound according to any one of the embodiments (1) to (60) of the present invention or a pharmaceutically acceptable salt thereof, "R 4 and R 11 " or "R 4 and R 12 ", along with the carbon atoms to which they are attached, are C 3-8 forming a cycloalkyl group or a 4- to 10-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X It is substituted with a substituent.

[0142] In another embodiment (62), in the compound according to any one of embodiments (1) to (61) of the present invention, or a pharmaceutically acceptable salt thereof, m1 and m2 are independently selected from 0 and 1.

[0143] In another embodiment (63), in the compound according to any one of embodiments (1) to (62) of the present invention, or a pharmaceutically acceptable salt thereof, R 3 is selected from aryl and heteroaryl groups, where the aryl and heteroaryl groups are unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0144] In another embodiment (64), in the compound according to any one of embodiments (1) to (63) of the present invention, or a pharmaceutically acceptable salt thereof, R 3 is selected from phenyl and pyridyl groups, wherein the phenyl and pyridyl groups are unsubstituted or independently selected from R X In one embodiment, the pyridine is selected from pyridin-3-yl and pyridin-4-yl.

[0145] In another embodiment (65), in the compound according to any one of embodiments (1) to (64) of the present invention, or a pharmaceutically acceptable salt thereof, R3 Each substituent R X is a halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 3-10 cycloalkyl groups, wherein each of the alkyl, alkenyl, and cycloalkyl groups is unsubstituted or independently selected from R Y is substituted with at least one substituent selected from

[0146] In another embodiment (66), in the compound according to any one of embodiments (1) to (65) of the present invention, or a pharmaceutically acceptable salt thereof, R 3 Each substituent R X is selected from halogen, methyl, ethyl, isopropyl, tert-butyl, propenyl, and cyclopropyl, wherein each of the methyl, ethyl, isopropyl, propenyl, and cyclopropyl groups is unsubstituted or independently selected from halogen, C 1-10 and substituted with at least one substituent selected from alkyl groups, CN, NO, -NH, and -OH. In one embodiment, the propylene group is 1-propylene-2-yl. In another embodiment, R 3 Each substituent R X is selected from halogen, methyl, ethyl, isopropyl, tert-butyl, propenyl, and cyclopropyl, wherein each of the methyl, ethyl, isopropyl, propenyl, and cyclopropyl groups is unsubstituted or substituted with at least one substituent independently selected from halogen.

[0147] In another embodiment (67), in the compound according to any one of embodiments (1) to (66) of the present invention, or a pharmaceutically acceptable salt thereof, R 3 teeth, [ka] In another embodiment, R 3 teeth, [ka] In another embodiment, R 3 teeth, [ka] is selected from.

[0148] In another embodiment (68), m is selected from 0, 1, and 2 in the compound according to any one of embodiments (1) to (67) of the present invention, or a pharmaceutically acceptable salt thereof.

[0149] In another embodiment (69), in the compound according to any one of embodiments (1) to (68) of the present invention, or a pharmaceutically acceptable salt thereof, each R 4 are independently hydrogen, halogen, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A4 R B4 , -OR A4 , -C(O)R A4 , -C(O)OR A4 , -OC(O)R A4 , -C(O)NR A4 R B4 and -S(O) r R A4 wherein each of the alkyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, any two R 4 together with the atoms to which they are attached, C 3-8forming a cycloalkyl group or a 4-8 membered heterocyclic group containing one, two or three heteroatoms independently selected from oxygen, sulfur, nitrogen and phosphorus, wherein the ring is unsubstituted or contains one, two or three R X It is substituted with a substituent.

[0150] In another embodiment (70), in the compound according to any one of embodiments (1) to (69) of the present invention, or a pharmaceutically acceptable salt thereof, each R 4 are independently selected from hydrogen, halogen, —OH, methyl, ethyl, isopropyl, and cyclopropyl, wherein each of the methyl, ethyl, isopropyl, and cyclopropyl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, any two R 4 together with the atom to which they are attached form a cyclopropyl group, where cyclopropyl is unsubstituted or contains one, two, or three R X It is substituted with a substituent.

[0151] In another embodiment, each R 4 are independently selected from hydrogen, halogen, methyl, ethyl, isopropyl, and cyclopropyl, wherein each of the methyl, ethyl, isopropyl, and cyclopropyl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, any two R 4 together with the atom to which they are attached form a cyclopropyl group, where cyclopropyl is unsubstituted or contains one, two, or three R X It is substituted with a substituent.

[0152] In another embodiment (71), the compound according to any one of the embodiments (1) to (70) of the present invention or a pharmaceutically acceptable salt thereof is a compound of formula (I) and formula (III) [ka] The structure of the part is [ka] wherein the symbol [ka] represents the point of attachment to the rest of the molecule. In one embodiment, [ka] The structure of the part is [ka] wherein the symbol [ka] represents the point of attachment to the rest of the molecule, and the carbon marked with * is an asymmetric center. In one embodiment, the asymmetric center is a carbon atom in the S configuration, a carbon atom in the enriched S configuration, a carbon atom in the R configuration, a carbon atom in the enriched R configuration, or a racemic carbon atom. In one embodiment, the asymmetric center is a carbon atom in the R configuration, a carbon atom in the enriched R configuration, or a racemic carbon atom, particularly a carbon atom in the R configuration. In one embodiment, the asymmetric center is a carbon atom in the S configuration, a carbon atom in the enriched S configuration, or a racemic carbon atom, particularly a carbon atom in the S configuration. In one embodiment, the compounds of formula (I) and formula (III) [ka] The structure of the part is [ka] wherein the symbol [ka] represents the point of attachment to the rest of the molecule.

[0153] In another embodiment (72), the compound according to any one of embodiments (1) to (71) of the present invention, or a pharmaceutically acceptable salt thereof, is a compound of formula (I) [ka] The structure of the part is [ka] wherein the symbol [ka] represents the point of attachment to the rest of the molecule.

[0154] In another embodiment (73), in the compound according to any one of embodiments (1) to (72) of the present invention, or a pharmaceutically acceptable salt thereof, each R 5 are independently hydrogen, halogen, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, CN, NO2, -NR A5 R B5 , -OR A5 and -C(O)R A5 wherein each of the alkyl and cycloalkyl groups is unsubstituted or independently selected from R X and each R is substituted with at least one substituent selected from 6 are independently hydrogen, halogen, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, CN, NO2, -NR A6 R B6 , -OR A6 and -C(O)R A6 wherein each of the alkyl and cycloalkyl groups is unsubstituted or independently selected from R X and preferably, each R 5 and each R 6 are independently hydrogen, halogen, C 1-10 Alkyl group, C 3-10and cycloalkyl groups selected from -CN, -NO, -NH, and -OH, wherein each of the alkyl and cycloalkyl groups is unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0155] In another embodiment (74), in the compound according to any one of embodiments (1) to (73) of the present invention, or a pharmaceutically acceptable salt thereof, R 5 and R 6 is H.

[0156] In another embodiment (75), the compound according to any one of embodiments (1) to (74) of the present invention, or a pharmaceutically acceptable salt thereof, is a compound of formula (I) and formula (III) [ka] The structure of the part is [ka] wherein the symbol [ka] represents the point of attachment to the rest of the molecule. In one embodiment, [ka] The structure of the part is [ka] wherein the symbol [ka] represents the point of attachment to the rest of the molecule.

[0157] In another embodiment (76), in the compound according to any one of embodiments (1) to (75) of the present invention, or a pharmaceutically acceptable salt thereof, each R 7are independently hydrogen, halogen, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, CN, NO2, -NR A7 R B7 , -OR A7 and -C(O)R A7 wherein each of the alkyl and cycloalkyl groups is unsubstituted or independently selected from R X and preferably, R 7 is hydrogen.

[0158] In another embodiment, the present invention provides a compound of formula (I'') or a pharmaceutically acceptable salt thereof.

[0159] [ka] (In the formula, X 1 N and CR 8 is selected from X 2 N and CR 9 is selected from X 3 N and CR 10 is selected from Y 1 , Y 2 and Y 3 is independently selected from N and CH; A and B are independently selected from N and CH; W is -CR 11 -, -NR 12 -, -O-, -S(O) r- and -S(O)(=NR 12 )-selected from Z is selected from N and CH; L 1 and L 2 are independently chemical bonds, -(CR C0 R D0 ) u -, -(CR C0 R D0 ) u O(CRC0 R D0 ) t -, -(CR C0 R D0 ) u NR A0 (CR C0 R D0 ) t -and-(CR C0 R D0 ) u S(O) r (CR C0 R D0 ) t - selected from R 1 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A1 R B1 , -OR A1 , -C(O)R A1 , -C(=NR E1 )R A1 , -C(=N-OR B1 )R A1 , -C(O)OR A1 , -OC(O)R A1 , -C(O)NR A1 R B1 , -NR A1 C(O)R B1 , -C(=NR E1 )NR A1 R B1 , -NR A1 C(=NR E1 )R B1 , -OC(O)NR A1 R B1 , -NR A1 C(O)OR B1 , -NR A1 C(O)NR A1 R B1, -NR A1 C(S)NR A1 R B1 , -NR A1 C(=NR E1 )NR A1 R B1 , -S(O) r R A1 , -S(O)(=NR E1 )R B1 , -N=S(O)R A1 R B1 , -S(O)2OR A1 , -OS(O)2R A1 , -NR A1 S(O) r R B1 , -NR A1 S(O)(=NR E1 )R B1 , -S(O) r NR A1 R B1 , -S(O)(=NR E1 )NR A1 R B1 , -NR A1 S(O)NR A1 R B1 , -NR A1 S(O)(=NR E1 )NR A1 R B1 , -P(O)R A1 R B1 and -P(O)(OR A1 )(OR B1 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from R 2 and R 3 are independently selected from aryl groups, heteroaryl groups, and heterocyclic groups, wherein each of the aryl groups, heteroaryl groups, and heterocyclic groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Each R 4 are independently hydrogen, halogen, C 1-10Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A4 R B4 , -OR A4 , -C(O)R A4 , -C(=NR E4 )R A4 , -C(=N-OR B4 )R A4 , -C(O)OR A4 , -OC(O)R A4 , -C(O)NR A4 R B4 , -NR A4 C(O)R B4 , -C(=NR E4 )NR A4 R B4 , -NR A4 C(=NR E4 )R B4 , -OC(O)NR A4 R B4 , -NR A4 C(O)OR B4 , -NR A4 C(O)NR A4 R B4 , -NR A4 C(S)NR A4 R B4 , -NR A4 C(=NR E4 )NR A4 R B4 , -S(O) r R A4 , -S(O)(=NR E4 )R B4 , -N=S(O)R A4 R B4 , -S(O)2OR A4 , -OS(O)2R A4 , -NR A4 S(O) r RB4 , -NR A4 S(O)(=NR E4 )R B4 , -S(O) r NR A4 R B4 , -S(O)(=NR E4 )NR A4 R B4 , -NR A4 S(O)NR A4 R B4 , -NR A4 S(O)(=NR E4 )NR A4 R B4 , -P(O)R A4 R B4 and -P(O)(OR A4 )(OR B4 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, any two R 4 or "R 4 and R 10 " or "R 4 and R 11 ", along with the atoms to which they are attached, are C 3-10 forming a cycloalkyl group or a 4- to 12-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, Each R 5 are independently hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4Alkyl group, CN, NO2, -NR A5 R B5 , -OR A5 , -C(O)R A5 , -C(=NR E5 )R A5 , -C(=N-OR B5 )R A5 , -C(O)OR A5 , -OC(O)R A5 , -C(O)NR A5 R B5 , -NR A5 C(O)R B5 , -C(=NR E5 )NR A5 R B5 , -NR A5 C(=NR E5 )R B5 , -OC(O)NR A5 R B5 , -NR A5 C(O)OR B5 , -NR A5 C(O)NR A5 R B5 , -NR A5 C(S)NR A5 R B5 , -NR A5 C(=NR E5 )NR A5 R B5 , -S(O) r R A5 , -S(O)(=NR E5 )R B5 , -N=S(O)R A5 R B5 , -S(O)2OR A5 , -OS(O)2R A5 , -NR A5 S(O) r R B5 , -NR A5 S(O)(=NR E5 )R B5 , -S(O) r NR A5 R B5 , -S(O)(=NR E5 )NR A5 R B5 , -NR A5 S(O)2NR A5 RB5 , -NR A5 S(O)(=NR E5 )NR A5 R B5 , -P(O)R A5 R B5 and -P(O)(OR A5 )(OR B5 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, any two R 5 together with the carbon atoms to which they are attached, C 3-10 forming a cycloalkyl group or a 4- to 12-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, Each R 6 are independently hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A6 R B6 , -OR A6 , -C(O)R A6 , -C(=NR E6 )R A6 , -C(=N-OR B6 )R A6 , -C(O)OR A6 , -OC(O)R A6 , -C(O)NR A6 R B6 , -NR A6 C(O)R B6, -C(=NR E6 )NR A6 R B6 , -NR A6 C(=NR E6 )R B6 , -OC(O)NR A6 R B6 , -NR A6 C(O)OR B6 , -NR A6 C(O)NR A6 R B6 , -NR A6 C(S)NR A6 R B6 , -NR A6 C(=NR E6 )NR A6 R B6 , -S(O) r R A6 , -S(O)(=NR E6 )R B6 , -N=S(O)R A6 R B6 , -S(O)2OR A6 , -OS(O)2R A6 , -NR A6 S(O) r R B6 , -NR A6 S(O)(=NR E6 )R B6 , -S(O) r NR A6 R B6 , -S(O)(=NR E6 )NR A6 R B6 , -NR A6 S(O)NR A6 R B6 , -NR A6 S(O)(=NR E6 )NR A6 R B6 , -P(O)R A6 R B6 and -P(O)(OR A6 )(OR B6 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Xand is substituted with at least one substituent selected from Or, any two R 6 together with the carbon atoms to which they are attached, C 3-10 forming a cycloalkyl group or a 4- to 12-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, Each R 7 are independently hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A7 R B7 , -OR A7 , -C(O)R A7 , -C(=NR E7 )R A7 , -C(=N-OR B7 )R A7 , -C(O)OR A7 , -OC(O)R A7 , -C(O)NR A7 R B7 , -NR A7 C(O)R B7 , -C(=NR E7 )NR A7 R B7 , -NR A7 C(=NR E7 )R B7 , -OC(O)NR A7 R B7 , -NR A7 C(O)OR B7 , -NR A7 C(O)NR A7 R B7 , -NR A7 C(S)NRA7 R B7 , -NR A7 C(=NR E7 )NR A7 R B7 , -S(O) r R A7 , -S(O)(=NR E7 )R B7 , -N=S(O)R A7 R B7 , -S(O)2OR A7 , -OS(O)2R A7 , -NR A7 S(O) r R B7 , -NR A7 S(O)(=NR E7 )R B7 , -S(O) r NR A7 R B7 , -S(O)(=NR E7 )NR A7 R B7 , -NR A7 S(O)NR A7 R B7 , -NR A7 S(O)(=NR E7 )NR A7 R B7 , -P(O)R A7 R B7 and -P(O)(OR A7 )(OR B7 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from R 8 are hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C1-4 Alkyl group, CN, NO2, -NR A8 R B8 , -OR A8 , -C(O)R A8 , -C(=NR E8 )R A8 , -C(=N-OR B8 )R A8 , -C(O)OR A8 , -OC(O)R A8 , -C(O)NR A8 R B8 , -NR A8 C(O)R B8 , -C(=NR E8 )NR A8 R[[ID=​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​R B8 , -NR A8 S(O)(=NR E8 )NR A8 R B8 , -P(O)R A8 R B8 and -P(O)(OR A8 )(OR B8 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, R 1 and R 8 together with the atoms to which they are attached, C 5-10 forming a cycloalkyl group or a 5- to 12-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, R 9 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A9 R B9 , -OR A9 , -C(O)R A9 , -C(=NR E9 )R A9 , -C(=N-OR B9 )R A9 , -C(O)OR A9 , -OC(O)R A9 , -C(O)NR A9 R B9 , -NR A9 C(O)R B9, -C(=NR E9 )NR A9 R B9 , -NR A9 C(=NR E9 )R B9 , -OC(O)NR A9 R B9 , -NR A9 C(O)OR B9 , -NR A9 C(O)NR A9 R B9 , -NR A9 C(S)NR A9 R B9 , -NR A9 C(=NR E9 )NR A9 R B9 , -S(O) r R A9 , -S(O)(=NR E9 )R B9 , -N=S(O)R A9 R B9 , -S(O)2OR A9 , -OS(O)2R A9 , -NR A9 S(O) r R B9 , -NR A9 S(O)(=NR E9 )R B9 , -S(O) r NR A9 R B9 , -S(O)(=NR E9 )NR A9 R B9 , -NR A9 S(O)NR A9 R B9 , -NR A9 S(O)(=NR E9 )NR A9 R B9 , -P(O)R A9 R B9 and -P(O)(OR A9 )(OR B9 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Xand is substituted with at least one substituent selected from R 10 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A10 R B10 , -OR A10 , -C(O)R A10 , -C(=NR E10 )R A10 , -C(=N-OR B10 )R A10 , -C(O)OR A10 , -OC(O)R A10 , -C(O)NR A10 R B10 , -NR A10 C(O)R B10 , -C(=NR E10 )NR A10 R B10 , -NR A10 C(=NR E10 )R B10 , -OC(O)NR A10 R B10 , -NR A10 C(O)OR B10 , -NR A10 C(O)NR A10 R B10 , -NR A10 C(S)NR A10 R B10 , -NR A10 C(=NR E10 )NR A10 R B10 , -S(O) r R A10 , -S(O)(=NR E10 )R B10 , -N=S(O)R A10 R B10 , -S(O)2ORA10 , -OS(O)2R A10 , -NR A10 S(O) r R B10 , -NR A10 S(O)(=NR E10 )R B10 , -S(O) r NR A10 R B10 , -S(O)(=NR E10 )NR A10 R B10 , -NR A10 S(O)NR A10 R B10 , -NR A10 S(O)(=NR E10 )NR A10 R B10 , -P(O)R A10 R B10 and -P(O)(OR A10 )(OR B10 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from R 11 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, NR A11 R B11 , -OR A11 , -C(O)R A11 , -C(=NR E11 )R A11 , -C(=N-OR B11 )R A11 , -C(O)OR A11 , -OC(O)R A11, -C(O)NR A11 R B11 , -NR A11 C(O)R B11 , -C(=NR E11 )NR A11 R B11 , -NR A11 C(=NR E11 )R B11 , -OC(O)NR A11 R B11 , -NR A11 C(O)OR B11 , -NR A11 C(O)NR A11 R B11 , -NR A11 C(S)NR A11 R B11 , -NR A11 C(=NR E11 )NR A11 R B11 , -S(O) r R A11 , -S(O)(=NR E11 )R B11 , -N=S(O)R A11 R B11 , -S(O)2OR A11 , -OS(O)2R A11 , -NR A11 S(O) r R B11 , -NR A11 S(O)(=NR E11 )R B11 , -S(O) r NR A11 R B11 , -S(O)(=NR E11 )NR A11 R B11 , -NR A11 S(O)2NR A11 R B11 , -NR A11 S(O)(=NR E11 )NR A11 R<000s979>, -P(O)R A11 R B11 and -P(O)(OR A11 )(OR B11wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from R 12 is hydrogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl group, -C(O)R A12 , -C(=NR E12 )R A12 , -C(=N-OR B12 )R A12 , -C(O)OR A12 , -C(O)NR A12 R B12 , -C(=NR E12 )NR A12 R B12 , -S(O) r R A12 , -S(O)(=NR E12 )R B12 , -S(O)2OR A12 , -S(O) r NR A12 R B12 , -S(O)(=NR E12 )NR A12 R B12 , -P(O)R A12 R B12 and -P(O)(OR A12 )(OR B12 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from R A0 , RA1 , R A4 , R A5 , R A6 , R A7 , R A8 , R A9 , R A10 , R A11 , R A12 , R B1 , R B4 , R B5 , R B6 , R B7 , R B8 , R B9 , R B10 , R B11 and R B12 each independently represents hydrogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, "R A1 and R B1 " or "R A4 and R B4 " or "R A5 and R B5 " or "R A6 and R B6 " or "R A7 and R B7 " or "R A8 and R B8 " or "R A9 and R B9 " or "R A10 and R B10 " or "R A11 and R B11 " or "R A12 and RB12 " together with the atom or atoms to which they are attached constitute a 4- to 12-membered heterocyclic ring containing 0, 1, or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or X and is substituted with one, two or three substituents selected from R C0 and R D0 each independently represents hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, each "R C0 and R D0 " together with the carbon atom or atoms to which they are attached form a 3- to 12-membered ring containing zero, one, or two heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, R E1 , R E4 , R E5 , R E6 , R E7 , R E8 , R E9 , R E10 , R E11 and R E12 each independently represents hydrogen, C 1-10 Alkyl groups, CN, NO2, -OR a1 , -SR a1 , -S(O)r R a1 , -C(O)R a1 , C(O)OR a1 , -C(O)NR a1 R b1 and -S(O) r NR a1 R b1 wherein the alkyl groups are unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Each R X are independently hydrogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, halogens, CN, -NO2, -(CR c1 R d1 ) t NR a1 R b1 , -(CR c1 R d1 ) t OR b1 , -(CR c1 R d1 ) t C(O)R a1 , -(CR c1 R d1 ) t C(=NR e1 )R a1 , -(CR c1 R d1 ) t C(=N-OR b1 )R a1 , -(CR c1 R d1 ) t C(O)OR b1 , -(CR c1 R d1 ) t OC(O)R b1 , -(CRc1 R d1 ) t C(O)NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(O)R b1 、-(CR c1 R d1 ) t C(=NR e1 )NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(=NR e1 )R b1 、-(CR c1 R d1 ) t OC(O)NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(O)OR b1 、-(CR c1 R d1 ) t NR a1 C(O)NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(S)NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(=NR e1 )NR a1 R b1 、-(CR c1 R d1 ) t S(O) r R b1 、-(CR c1 R d1 ) t S(O)(=NR e1 )R b1 、-(CR c1 R d1 ) tN=S(O)R a1 R b1 , -(CR c1 R d1 ) t S(O)2OR b1 , -(CR c1 R d1 ) t OS(O)2R b1 , -(CR c1 R d1 ) t NR a1 S(O) r R b1 , -(CR c1 R d1 ) t NR a1 S(O)(=NR e1 )R b1 , -(CR c1 R d1 ) t S(O) r NR a1 R b1 , -(CR c1 R d1 ) t S(O)(=NR e1 )NR a1 R b1 , -(CR c1 R d1 ) t NR a1 S(O)NR a1 R b1 , -(CR c1 R d1 ) t NR a1 S(O)(=NR e1 )NR a1 R b1 , -(CR c1 R d1 ) t P(O)R a1 R b1 and -(CR c1 R d1 ) t P(O)(OR a1 )(OR b1 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from RY and is substituted with at least one substituent selected from X 1 is CR 8 and X 2 is CR 9 and X 3 is CR 10 and R 1 and R 8 together with the atoms to which they are attached, C 5-10 a cycloalkyl group or a 5- to 12-membered ring containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, and L 1 -(CR C0 R D0 ) u NR A0 (CR C0 R D0 ) t -L when selected from 2 is a chemical bond, -(CR C0 R D0 ) u O(CR C0 R D0 ) t -, -(CR C0 R D0 ) u S(O) r (CR C0 R D0 ) t - selected from L 2 is -O- and R 2 but [ka] If R 2 Each substituent R X is C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, halogens, CN, -NO2, -(CR c1 R d1 ) t NR a1 R b1 , -(CR c1 R d1 ) t OR b1 , -(CR c1 R d1 ) t C(O)R a1 , -(CR c1 R d1 ) t C(=NR e1 )R a1 , -(CR c1 R d1 ) t C(=N-OR b1 )R a1 , -(CR c1 R d1 ) t C(O)OR b1 , -(CR c1 R d1 ) t OC(O)R b1 , -(CR c1 R d1 ) t C(O)NR a1 R b1 , -(CR c1 R d1 ) t NR a1 C(O)R b1 , -(CR c1 R d1 ) t C(=NR e1 )NR a1 R b1 , -(CR c1 R d1 ) t NR a1 C(=NR e1 )R b1 , -(CR c1 R d1 ) t OC(O)NR a1 R b1、-(CR c1 R d1 ) t NR a1 C(O)OR b1 、-(CR c1 R d1 ) t NR a1 C(O)NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(S)NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(=NR e1 )NR a1 R b1 、-(CR c1 R d1 ) t S(O) r R b1 、-(CR c1 R d1 ) t S(O)(=NR e1 )R b1 、-(CR c1 R d1 ) t N=S(O)R a1 R b1 、-(CR c1 R d1 ) t S(O)2OR b1 、-(CR c1 R d1 ) t OS(O)2R b1 、-(CR c1 R d1 ) t NR a1 S(O) r R b1 、-(CR c1 R d1 ) t NR a1 S(O)(=NR e1 )R b1 、-(CR c1 R d1 ) t S(O) rNR a1 R b1 , -(CR c1 R d1 ) t S(O)(=NR e1 )NR a1 R b1 , -(CR c1 R d1 ) t NR a1 S(O)NR a1 R b1 , -(CR c1 R d1 ) t NR a1 S(O)(=NR e1 )NR a1 R b1 , -(CR c1 R d1 ) t P(O)R a1 R b1 and -(CR c1 R d1 ) t P(O)(OR a1 )(OR b1 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Y and is substituted with at least one substituent selected from X 1 is CR 8 and X 2 is CR 9 and X 3 is CR 10 and R 1 and R 8 do not form a ring together with the atoms to which they are attached, A is CH and W is -CR 11 - selected from L 2 is -(CR C0 R D0 ) u O(CR C0 R D0 ) t -and-(CR C0 R D0 ) u S(O) r (CRC0 R D0 ) t - selected from R a1 and R b1 each independently represents hydrogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Y and is substituted with at least one substituent selected from Or, R a1 and R b1 together with the atom or atoms to which they are attached, form a 4-12 membered heterocyclic ring containing 0, 1, or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, and the ring is Y optionally substituted with a group, R c1 and R d1 each independently represents hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Yand is substituted with at least one substituent selected from Or, R c1 and R d1 together with the carbon atom or atoms to which they are attached, form a 3- to 12-membered ring containing 0, 1, or 2 heteroatoms independently selected from oxygen, sulfur, and nitrogen, and the ring is Y optionally substituted with a group, Each R e1 are independently hydrogen, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl groups, CN, NO2, -OR a2 , -SR a2 , -S(O) r R a2 , -C(O)R a2 , -C(O)OR a2 , -S(O) r NR a2 R b2 and -C(O)NR a2 R b2 is selected from Each R Y independently, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, halogens, CN, NO2, -(CR c2 R d2 ) t NR a2 R b2 , -(CR c2 R d2 ) t OR b2 , -(CR c2 R d2 ) t C(O)R a2、-(CR c2 R d2 ) t C(=NR e2 )R a2 、-(CR c2 R d2 ) t C(=N-OR b2 )R a2 、-(CR c2 R d2 ) t C(O)OR b2 、-(CR c2 R d2 ) t OC(O)R b2 、-(CR c2 R d2 ) t C(O)NR a2 R b2 、-(CR c2 R d2 ) t NR a2 C(O)R b2 、-(CR c2 R d2 ) t C(=NR e2 )NR a2 R b2 、-(CR c2 R d2 ) t NR a2 C(=NR e2 )R b2 、-(CR c2 R d2 ) t OC(O)NR a2 R b2 、-(CR c2 R d2 ) t NR a2 C(O)OR b2 、-(CR c2 R d2 ) t NR a2 C(O)NR a2 R b2 、-(CR c2 R d2 ) t NR a2 C(S)NR a2 R b2 、-(CR c2R d2 ) t NR a2 C(=NR e2 )NR a2 R b2 、-(CR c2 R d2 ) t S(O) r R b2 、-(CR c2 R d2 ) t S(O)(=NR e2 )R b2 、-(CR c2 R d2 ) t N=S(O)R a2 R b2 、-(CR c2 R d2 ) t S(O)2OR b2 、-(CR c2 R d2 ) t OS(O)2R b2 、-(CR c2 R d2 ) t NR a2 S(O) r R b2 、-(CR c2 R d2 ) t NR a2 S(O)(=NR e2 )R b2 、-(CR c2 R d2 ) t S(O) r NR a2 R b2 、-(CR c2 R d2 ) t S(O)(=NR e2 )NR a2 R b2 、-(CR c2 R d2 ) t NR a2 S(O)2NR a2 R b2 、-(CR c2 R d2 ) t NR a2S(O)(=NR e2 )NR a2 R b2 , -(CR c2 R d2 ) t P(O)R a2 R b2 and -(CR c2 R d2 ) t P(O)(OR a2 )(OR b2 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from hydroxy, CN, amino, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino groups and di(C 1-10 substituted with at least one substituent selected from the group consisting of alkyl)amino groups; R a2 and R b2 each independently represents hydrogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino group, di(C 1-10 Alkyl)amino group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, cycloalkoxy, alkylthio, cycloalkylthio, alkylamino, cycloalkylamino, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from halogen, CN, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl group, hydroxy group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, amino group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino groups and di(C 1-10 substituted with at least one substituent selected from the group consisting of alkyl)amino groups; Or, R a2 and R b2 together with the atom or atoms to which they are attached, form a 4- to 12-membered heterocyclic ring containing 0, 1, or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, and the ring is independently selected from halogen, CN, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl group, hydroxy group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, amino group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino groups and di(C 1-10 optionally substituted with one or two substituents selected from: R c2 and R d2 each independently represents hydrogen, halogen, C 1-10 Alkyl group, C2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino group, di(C 1-10 Alkyl)amino group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, cycloalkoxy, alkylthio, cycloalkylthio, alkylamino, cycloalkylamino, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from halogen, CN, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl group, hydroxy group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, amino group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino groups and di(C 1-10 substituted with at least one substituent selected from the group consisting of alkyl)amino groups; Or, R c2 and R d2 together with the carbon atom or atoms to which they are attached, form a 3- to 12-membered ring containing 0, 1, or 2 heteroatoms independently selected from oxygen, sulfur, and nitrogen, and the ring is independently selected from halogen, CN, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10Alkynyl group, C 3-10 Cycloalkyl group, hydroxy group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, amino group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino groups and di(C 1-10 optionally substituted with one or two substituents selected from: Each R e2 are independently hydrogen, CN, NO2, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, -C(O)C 1-4 Alkyl group, -C(O)C 3-10 Cycloalkyl groups, -C(O)OC 1-4 Alkyl group, -C(O)OC 3-10 Cycloalkyl groups, -C(O)N(C 1-4 alkyl)2, -C(O)N(C 3-10 cycloalkyl)2, -S(O)2C 1-4 Alkyl group, -S(O)2C 3-10 Cycloalkyl groups, -S(O)N(C 1-4 alkyl)2 and -S(O)2N(C 3-10 cycloalkyl)2; m, m1, m2, n, n1, n2, p, p1, p2 and q are independently selected from 0, 1, 2 and 3; each r is independently selected from 0, 1, and 2; each t is independently selected from 0, 1, 2, 3, and 4; each u is independently selected from 0, 1, 2, 3, and 4

[0160] In another embodiment, X 3 is CH, A is N, B is CH, Z is N, and Y 1 , Y2 and Y 3 is CH, providing a compound represented by formula (II″), which is represented by formula (I″).

[0161] [ka] (In the formula, X 1 N and CR 8 Selected from X 2 N and CR 9 Selected from X 1 and X 2 At least one of the groups is N, and W is -CR 10 -, -NR 11 -, -O- and -S(O) r - selected from L 1 , L 2 , W., R. 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , m, m1, m2, n, n1, n2, p, p1, p2 and q are defined as in formula (I''). In another embodiment (77), the compound of the present invention is [ka] [ka] [ka] [ka] [ka] [ka] [ka]

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

[0162] In another embodiment (78), the compound of the present invention is [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] and pharmaceutically acceptable salts thereof.

[0163] In another embodiment (79), the present invention provides a pharmaceutical composition comprising a compound according to any one of embodiments (1) to (78) or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

[0164] In another embodiment (80), the present invention provides a method for treating, ameliorating, or preventing a condition responsive to Bcl-2 inhibition, comprising administering to an individual in need thereof an effective amount of a compound according to any one of embodiments (1) to (78) or a pharmaceutically acceptable salt thereof, or at least one pharmaceutical composition thereof, optionally in combination with a second therapeutic agent.

[0165] In another embodiment (81), the present invention provides the use of a compound according to any one of embodiments (1) to (78), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating a cell proliferative disorder or an autoimmune disease.

[0166] In another embodiment (82), for use according to embodiment (71) of the present invention, the cell proliferative disorder includes, but is not limited to, breast cancer, ovarian cancer, bladder cancer, uterine cancer, prostate cancer, testicular cancer, lung cancer (including NSCLC, SCLC, squamous cell carcinoma or adenocarcinoma), esophageal cancer, head and neck cancer, colorectal cancer, renal cancer (including RCC), liver cancer (including HCC), pancreatic cancer, gastric cancer (i.e., cancer of the stomach), thyroid cancer, chronic lymphocytic leukemia (CLL), lymphoblastic leukemia, follicular lymphoma, lymphoid malignancies of T-cell or B-cell origin, melanoma, myeloid leukemia, and myeloma.

[0167] In another embodiment (83), in the use of embodiment (81) of the present invention, the autoimmune disease is selected from the group consisting of allergies, Alzheimer's disease, acute disseminated encephalomyelitis, Addison's disease, ankylosing spondylitis, antiphospholipid syndrome, asthma, atherosclerosis, autoimmune hemolytic anemia, autoimmune hemolytic and thrombocytopenic states, autoimmune hepatitis, autoimmune inner ear disease, bullous pemphigoid, celiac disease, Chagas' disease, chronic obstructive pulmonary disease, chronic idiopathic thrombocytopenic purpura (ITP), Churg-Strauss syndrome, Crohn's disease, dermatomyositis, type 1 diabetes, endometriosis, Goodpasture's syndrome (and associated glomerulonephritis and pulmonary hemorrhage), Graves' disease, Gila syndrome, and the like. These conditions include, but are not limited to, Levine-Barré syndrome, Hashimoto's disease, hidradenitis suppurativa, idiopathic thrombocytopenic purpura, interstitial cystitis, irritable bowel syndrome, lupus erythematosus, localized scleroderma, multiple sclerosis, myasthenia gravis, narcolepsy, neuromyotonia, Parkinson's disease, pemphigus vulgaris, pernicious anemia, polymyositis, primary biliary cirrhosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, schizophrenia, septic shock, scleroderma, Sjogren's disease, systemic lupus erythematosus (and associated glomerular nephritis), temporal arteritis, tissue transplant rejection and hyperacute rejection of transplanted organs, vasculitis (ANCA-associated and other vasculitis), vitiligo, and Wegener's granulomatosis.

[0168] Some examples may be described as follows.

[0169] Another embodiment <1> Now, the present invention provides a compound of formula<I′> or a pharmaceutically acceptable salt thereof.

[0170] [ka] (In the formula, X is N and CR 8 and Y is selected from N and CR 9 and at least one of X and Y is N; W is -CR 10 -, -NR11-, -O- and -S(O) r - selected from L1 and L2 are independently a chemical bond, -(CR C0 R D0 ) u -, -(CR C0 R D0 ) u O(CR C0 R D0 ) t -, -(CR C0 R D0 ) u NR A0 (CR C0 R D0 ) t -and-(CR C0 R D0 ) u S(O) r (CR C0 R D0 ) t - selected from R 1 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A1 R B1、-OR A1 、-C(O)R A1 、-C(=NR E1 )R A1 、-C(=N-OR B1 )R A1 、-C(O)OR A1 、-OC(O)R A1 、-C(O)NR A1 R B1 、-NR A1 C(O)R B1 、-C(=NR E1 )NR A1 R B1 、-NR A1 C(=NR E1 )R B1 、-OC(O)NR A1 R B1 、-NR A1 C(O)OR B1 、-NR A1 C(O)NR A1 R B1 、-NR A1 C(S)NR A1 R B1 、-NR A1 C(=NR E1 )NR A1 R B1 、-S(O) r R A1 、-S(O)(=NR E1 )R B1 、-N=S(O)R A1 R B1 、-S(O)2OR A1 、-OS(O)2R A1 、-NR A1 S(O) r R B1 、-NR A1 S(O)(=NR E1 )R B1 、-S(O) r NR A1 R B1 、-S(O)(=NR E1 )NR A1 R B1 、-NR A1 S(O)2NR A1 R B1 、-NR A1 S(O)(=NR E1)NR A1 R B1 , -P(O)R A1 R B1 and -P(O)(OR A1 )(OR B1 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from R 2 and R 3 are independently selected from aryl groups, heteroaryl groups, and heterocyclic groups, wherein each of the aryl groups, heteroaryl groups, and heterocyclic groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Each R 4 are independently hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A4 R B4 , -OR A4 , -C(O)R A4 , -C(=NR E4 )R A4 , -C(=N-OR B4 )R A4 , -C(O)OR A4 , -OC(O)R A4 , -C(O)NR A4 R B4 , -NR A4 C(O)R B4 , -C(=NR E4 )NR A4 R B4 , -NR A4 C(=NR E4 )RB4 , -OC(O)NR A4 R B4 , -NR A4 C(O)OR B4 , -NR A4 C(O)NR A4 R B4 , -NR A4 C(S)NR A4 R B4 , -NR A4 C(=NR E4 )NR A4 R B4 , -S(O) r R A4 , -S(O)(=NR E4 )R B4 , -N=S(O)R A4 R B4 , -S(O)2OR A4 , -OS(O)2R A4 , -NR A4 S(O) r R B4 , -NR A4 S(O)(=NR E4 )R B4 , -S(O) r NR A4 R B4 , -S(O)(=NR E4 )NR A4 R B4 , -NR A4 S(O)NR A4 R B4 , -NR A4 S(O)(=NR E4 )NR A4 R B4 , -P(O)R A4 R B4 and -P(O)(OR A4 )(OR B4 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, any two R 4 or "R 4 and R 10 " or "R 4and R 11 ", along with the carbon atoms to which they are attached, are C 3-10 forming a cycloalkyl group or a 4- to 12-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, Each R 5 are independently hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A5 R B5 , -OR A5 , -C(O)R A5 , -C(=NR E5 )R A5 , -C(=N-OR B5 )R A5 , -C(O)OR A5 , -OC(O)R A5 , -C(O)NR A5 R B5 , -NR A5 C(O)R B5 , -C(=NR E5 )NR A5 R B5 , -NR A5 C(=NR E5 )R B5 , -OC(O)NR A5 R B5 , -NR A5 C(O)OR B5 , -NR A5 C(O)NR A5 R B5 , -NR A5 C(S)NR A5 R B5 , -NR A5 C(=NRE5 )NR A5 R B5 , -S(O) r R A5 , -S(O)(=NR E5 )R B5 , -N=S(O)R A5 R B5 , -S(O)2OR A5 , -OS(O)2R A5 , -NR A5 S(O) r R B5 , -NR A5 S(O)(=NR E5 )R B5 , -S(O) r NR A5 R B5 , -S(O)(=NR E5 )NR A5 R B5 , -NR A5 S(O)NR A5 R B5 , -NR A5 S(O)(=NR E5 )NR A5 R B5 , -P(O)R A5 R B5 and -P(O)(OR A5 )(OR B5 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, any two R 5 together with the carbon atoms to which they are attached, C 3-10 forming a cycloalkyl group or a 4- to 12-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, Each R 6 are independently hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A6 R B6 , -OR A6 , -C(O)R A6 , -C(=NR E6 )R A6 , -C(=N-OR B6 )R A6 , -C(O)OR A6 , -OC(O)R A6 , -C(O)NR A6 R B6 , -NR A6 C(O)R B6 , -C(=NR E6 )NR A6 R B6 , -NR A6 C(=NR E6 )R B6 , -OC(O)NR A6 R B6 , -NR A6 C(O)OR B6 , -NR A6 C(O)NR A6 R B6 , -NR A6 C(S)NR A6 R B6 , -NR A6 C(=NR E6 )NR A6 R B6 , -S(O) r R A6 , -S(O)(=NR E6 )R B6 , -N=S(O)R A6 R B6 , -S(O)2OR A6 , -OS(O)2R A6 , -NR A6 S(O) r R B6 , -NR A6 S(O)(=NR E6)R B6 , -S(O) r NR A6 R B6 , -S(O)(=NR E6 )NR A6 R B6 , -NR A6 S(O)NR A6 R B6 , -NR A6 S(O)(=NR E6 )NR A6 R B6 , -P(O)R A6 R B6 and -P(O)(OR A6 )(OR B6 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, any two R 6 together with the carbon atoms to which they are attached, C 3-10 forming a cycloalkyl group or a 4- to 12-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, Each R 7 are independently hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A7 R B7 , -OR A7 , -C(O)R A7 , -C(=NR E7 )R A7、-C(=N-OR B7 )R A7 、-C(O)OR A7 、-OC(O)R A7 、-C(O)NR A7 R B7 、-NR A7 C(O)R B7 、-C(=NR E7 )NR A7 R B7 、-NR A7 C(=NR E7 )R B7 、-OC(O)NR A7 R B7 、-NR A7 C(O)OR B7 、-NR A7 C(O)NR A7 R B7 、-NR A7 C(S)NR A7 R B7 、-NR A7 C(=NR E7 )NR A7 R B7 、-S(O) r R A7 、-S(O)(=NR E7 )R B7 、-N=S(O)R A7 R B7 、-S(O)2OR A7 、-OS(O)2R A7 、-NR A7 S(O) r R B7 、-NR A7 S(O)(=NR E7 )R B7 、-S(O) r NR A7 R B7 、-S(O)(=NR E7 )NR A7 R B7 、-NR A7 S(O)2NR A7 R B7 、-NR A7 S(O)(=NR E7 )NR A7 R B7 、-P(O)R A7 R B7and -P(O)(OR A7 )(OR B7 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from R 8 are hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A8 R B8 , -OR A8 , -C(O)R A8 , -C(=NR E8 )R A8 , -C(=N-OR B8 )R A8 , -C(O)OR A8 , -OC(O)R A8 , -C(O)NR A8 R B8 , -NR A8 C(O)R B8 , -C(=NR E8 )NR A8 R B8 , -NR A8 C(=NR E8 )R B8 , -OC(O)NR A8 R B8 , -NR A8 C(O)OR B8 , -NR A8 C(O)NR A8 R B8 , -NR A8 C(S)NR A8 R B8 , -NR A8 C(=NR E8 )NR A8R B8 , -S(O) r R A8 , -S(O)(=NR E8 )R B8 , -N=S(O)R A8 R B8 , -S(O)2OR A8 , -OS(O)2R A8 , -NR A8 S(O) r R B8 , -NR A8 S(O)(=NR E8 )R B8 , -S(O) r NR A8 R B8 , -S(O)(=NR E8 )NR A8 R B8 , -NR A8 S(O)NR A8 R B8 , -NR A8 S(O)(=NR E8 )NR A8 R B8 , -P(O)R A8 R B8 and -P(O)(OR A8 )(OR B8 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, R 1 and R 8 together with the atoms to which they are attached, C 5-10 forming a cycloalkyl group or a 5- to 12-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, R 9 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A9 R B9 , -OR A9 , -C(O)R A9 , -C(=NR E9 )R A9 , -C(=N-OR B9 )R A9 , -C(O)OR A9 , -OC(O)R A9 , -C(O)NR A9 R B9 , -NR A9 C(O)R B9 , -C(=NR E9 )NR A9 R B9 , -NR A9 C(=NR E9 )R B9 , -OC(O)NR A9 R B9 , -NR A9 C(O)OR B9 , -NR A9 C(O)NR A9 R B9 , -NR A9 C(S)NR A9 R B9 , -NR A9 C(=NR E9 )NR A9 R B9 , -S(O) r R A9 , -S(O)(=NR E9 )R B9 , -N=S(O)R A9 R B9 , -S(O)2OR A9 , -OS(O)2R A9 , -NR A9 S(O) r R B9 , -NR A9 S(O)(=NR E9 )R B9 , -S(O)r NR A9 R B9 , -S(O)(=NR E9 )NR A9 R B9 , -NR A9 S(O)NR A9 R B9 , -NR A9 S(O)(=NR E9 )NR A9 R B9 , -P(O)R A9 R B9 and -P(O)(OR A9 )(OR B9 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from R 10 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A10 R B10 , -OR A10 , -C(O)R A10 , -C(=NR E10 )R A10 , -C(=N-OR B10 )R A10 , -C(O)OR A10 , -OC(O)R A10 , -C(O)NR A10 R B10 , -NR A10 C(O)R B10 , -C(=NR E10 )NR A10 R B10 , -NR A10 C(=NRE10 )R B10 , -OC(O)NR A10 R B10 , -NR A10 C(O)OR B10 , -NR A10 C(O)NR A10 R B10 , -NR A10 C(S)NR A10 R B10 , -NR A10 C(=NR E10 )NR A10 R B10 , -S(O) r R A10 , -S(O)(=NR E10 )R B10 , -N=S(O)R A10 R B10 , -S(O)2OR A10 , -OS(O)2R A10 , -NR A10 S(O) r R B10 , -NR A10 S(O)(=NR E10 )R B10 , -S(O) r NR A10 R B10 , -S(O)(=NR E10 )NR A10 R B10 , -NR A10 S(O)NR A10 R B10 , -NR A10 S(O)(=NR E10 )NR A10 R B10 , -P(O)R A10 R B10 and -P(O)(OR A10 )(OR B10 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from R 11 is hydrogen, C 1-10 Alkyl group, C 2-10Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl group, -C(O)R A11 , -C(=NR E11 )R A11 , -C(=N-OR B11 )R A11 , -C(O)OR A11 , -C(O)NR A11 R B11 , -C(=NR E11 )NR A11 R B11 , -S(O) r R A11 , -S(O)(=NR E11 )R B11 , -S(O)2OR A11 , -S(O) r NR A11 R B11 , -S(O)(=NR E11 )NR A11 R B11 , -P(O)R A11 R B11 and -P(O)(OR A11 )(OR B11 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from R A0 , R A1 , R A4 , R A5 , R A6 , R A7 , R A8 , R A9 , R A10 , R A11 , R B1 , R B4 , R B5 , R B6 , RB7 , R B8 , R B9 , R B10 and R B11 each independently represents hydrogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, "R A1 and R B1 " or "R A4 and R B4 " or "R A5 and R B5 " or "R A6 and R B6 " or "R A7 and R B7 " or "R A8 and R B8 " or "R A9 and R B9 " or "R A10 and R B10 " or "R A11 and R B11 " together with the atom or atoms to which they are attached constitute a 4- to 12-membered heterocyclic ring containing 0, 1, or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or X and is substituted with one, two or three substituents selected from R C0 and R D0 each independently represents hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Or, each "R C0 and R D0 " together with the carbon atom or atoms to which they are attached form a 3- to 12-membered ring containing zero, one, or two heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the ring is unsubstituted or contains one, two, or three R X is substituted with a substituent, R E1 , R E4 , R E5 , R E6 , R E7 , R E8 , R E9 , R E10 and R E11 each independently represents hydrogen, C 1-10 Alkyl groups, CN, NO2, -OR a1 , -SR a1 , -S(O) r R a1 , -C(O)R a1 , C(O)OR a1 , -C(O)NR a1 R b1 and -S(O) r NR a1 R b1 wherein the alkyl groups are unsubstituted or independently selected from R X and is substituted with at least one substituent selected from Each R X are independently hydrogen, C 1-10Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, halogens, CN, -NO2, -(CR c1 R d1 ) t NR a1 R b1 , -(CR c1 R d1 ) t OR b1 , -(CR c1 R d1 ) t C(O)R a1 , -(CR c1 R d1 ) t C(=NR e1 )R a1 , -(CR c1 R d1 ) t C(=N-OR b1 )R a1 , -(CR c1 R d1 ) t C(O)OR b1 , -(CR c1 R d1 ) t OC(O)R b1 , -(CR c1 R d1 ) t C(O)NR a1 R b1 , -(CR c1 R d1 ) t NR a1 C(O)R b1 , -(CR c1 R d1 ) t C(=NR e1 )NR a1 R b1 , -(CR c1 R d1 )t NR a1 C(=NR e1 )R b1 、-(CR c1 R d1 ) t OC(O)NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(O)OR b1 、-(CR c1 R d1 ) t NR a1 C(O)NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(S)NR a1 R b1 、-(CR c1 R d1 ) t NR a1 C(=NR e1 )NR a1 R b1 、-(CR c1 R d1 ) t S(O) r R b1 、-(CR c1 R d1 ) t S(O)(=NR e1 )R b1 、-(CR c1 R d1 ) t N=S(O)R a1 R b1 、-(CR c1 R d1 ) t S(O)2OR b1 、-(CR c1 R d1 ) t OS(O)2R b1 、-(CR c1 R d1 ) t NR a1 S(O) r R b1 、-(CR c1 Rd1 ) t NR a1 S(O)(=NR e1 )R b1 , -(CR c1 R d1 ) t S(O) r NR a1 R b1 , -(CR c1 R d1 ) t S(O)(=NR e1 )NR a1 R b1 , -(CR c1 R d1 ) t NR a1 S(O)NR a1 R b1 , -(CR c1 R d1 ) t NR a1 S(O)(=NR e1 )NR a1 R b1 , -(CR c1 R d1 ) t P(O)R a1 R b1 and -(CR c1 R d1 ) t P(O)(OR a1 )(OR b1 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Y and is substituted with at least one substituent selected from R a1 and R b1 each independently represents hydrogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Y and is substituted with at least one substituent selected from Or, R a1 and R b1 together with the atom or atoms to which they are attached, form a 4-12 membered heterocyclic ring containing 0, 1, or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, and the ring is Y optionally substituted with a group, R c1 and R d1 each independently represents hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Y and is substituted with at least one substituent selected from Or, R c1 and R d1 together with the carbon atom or atoms to which they are attached, form a 3- to 12-membered ring containing 0, 1, or 2 heteroatoms independently selected from oxygen, sulfur, and nitrogen, and the ring is Y optionally substituted with a group, Each R e1 are independently hydrogen, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10Cycloalkyl-C 1-4 Alkyl groups, CN, NO2, -OR a2 , -SR a2 , -S(O) r R a2 , -C(O)R a2 , -C(O)OR a2 , -S(O) r NR a2 R b2 and -C(O)NR a2 R b2 is selected from Each R Y independently, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, halogens, CN, NO2, -(CR c2 R d2 ) t NR a2 R b2 , -(CR c2 R d2 ) t OR b2 , -(CR c2 R d2 ) t C(O)R a2 , -(CR c2 R d2 ) t C(=NR e2 )R a2 , -(CR c2 R d2 ) t C(=N-OR b2 )R a2 , -(CR c2 R d2 ) t C(O)OR b2 , -(CR c2 R d2 ) t OC(O)R b2 , -(CRc2 R d2 ) t C(O)NR a2 R b2 、-(CR c2 R d2 ) t NR a2 C(O)R b2 、-(CR c2 R d2 ) t C(=NR e2 )NR a2 R b2 、-(CR c2 R d2 ) t NR a2 C(=NR e2 )R b2 、-(CR c2 R d2 ) t OC(O)NR a2 R b2 、-(CR c2 R d2 ) t NR a2 C(O)OR b2 、-(CR c2 R d2 ) t NR a2 C(O)NR a2 R b2 、-(CR c2 R d2 ) t NR a2 C(S)NR a2 R b2 、-(CR c2 R d2 ) t NR a2 C(=NR e2 )NR a2 R b2 、-(CR c2 R d2 ) t S(O) r R b2 、-(CR c2 R d2 ) t S(O)(=NR e2 )R b2 、-(CR c2 R d2 ) tN=S(O)R a2 R b2 、 -(CR c2 R d2 ) t S(O)2OR b2 、 -(CR c2 R d2 ) t OS(O)2R b2 、 -(CR c2 R d2 ) t NR a2 S(O) r ] R b2 、 -(CR c2 R d2 ) t NR a2 S(O)(=NR e2 )R b2 、 -(CR c2 R d2 ) t S(O) r NR a2 R b2 、 -(CR c2 R d2 ) t S(O)(=NR e2 )NR a2 R b2 、 -(CR c2 R d2 ] ) t NR<000 & 6970>S(O)2NR a2 R b2 、 -(CR c2 R d2 ) t NR a2 S(O)(=NR e2 )NR a2 [[ID=9 & 92]]R b2 、 -(CR c2 R d2 ) t P(O)R<0006 & 983>R b2 及び -(CR c2 R d2 ) t P(O)(OR a2 )(OR b2wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from hydroxy, CN, amino, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino groups and di(C 1-10 substituted with at least one substituent selected from the group consisting of alkyl)amino groups; R a2 and R b2 each independently represents hydrogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino group, di(C 1-10 Alkyl)amino group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, cycloalkoxy, alkylthio, cycloalkylthio, alkylamino, cycloalkylamino, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from halogen, CN, C 1-10 Alkyl group, C2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl group, hydroxy group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, amino group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino groups and di(C 1-10 substituted with at least one substituent selected from the group consisting of alkyl)amino groups; Or, R a2 and R b2 together with the atom or atoms to which they are attached, form a 4- to 12-membered heterocyclic ring containing 0, 1, or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, and the ring is independently selected from halogen, CN, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl group, hydroxy group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, amino group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino groups and di(C 1-10 optionally substituted with one or two substituents selected from: R c2 and R d2 each independently represents hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, C 1-10Alkylamino group, C 3-10 Cycloalkylamino group, di(C 1-10 Alkyl)amino group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups and heteroaryl-C 1-4 alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, cycloalkoxy, alkylthio, cycloalkylthio, alkylamino, cycloalkylamino, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from halogen, CN, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl group, hydroxy group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, amino group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino groups and di(C 1-10 substituted with at least one substituent selected from the group consisting of alkyl)amino groups; Or, R c2 and R d2 together with the carbon atom or atoms to which they are attached, form a 3- to 12-membered ring containing 0, 1, or 2 heteroatoms independently selected from oxygen, sulfur, and nitrogen, and the ring is independently selected from halogen, CN, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl group, hydroxy group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, C 1-10 Alkylthio group, C 3-10 Cycloalkylthio group, amino group, C 1-10 Alkylamino group, C 3-10 Cycloalkylamino groups and di(C 1-10optionally substituted with one or two substituents selected from: Each R e2 are independently hydrogen, CN, NO2, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, C 1-10 Alkoxy group, C 3-10 Cycloalkoxy group, -C(O)C 1-4 Alkyl group, -C(O)C 3-10 Cycloalkyl groups, -C(O)OC 1-4 Alkyl group, -C(O)OC 3-10 Cycloalkyl groups, -C(O)N(C 1-4 alkyl)2, -C(O)N(C 3-10 cycloalkyl)2, -S(O)2C 1-4 Alkyl group, -S(O)2C 3-10 Cycloalkyl groups, -S(O)N(C 1-4 alkyl)2 and -S(O)2N(C 3-10 cycloalkyl)2; m, m1, m2, n, n1, n2, p, p1, p2 and q are independently selected from 0, 1, 2 and 3; each r is independently selected from 0, 1, and 2; each t is independently selected from 0, 1, 2, 3, and 4; each u is independently selected from 0, 1, 2, 3, and 4

[0171] Another embodiment <2> Now, an embodiment of the present invention <1> or a pharmaceutically acceptable salt thereof, wherein X is N and Y is CR 9 is.

[0172] Another embodiment <3> Now, an embodiment of the present invention <2> or a pharmaceutically acceptable salt thereof, wherein X is N and Y is CH.

[0173] Another embodiment <4> Now, an embodiment of the present invention <1> or a pharmaceutically acceptable salt thereof, wherein X is N and Y is N.

[0174] Another embodiment <5> Now, an embodiment of the present invention <1> or a pharmaceutically acceptable salt thereof, X is CR 8 and Y is N.

[0175] Another embodiment <6> Now, an embodiment of the present invention <5> or a pharmaceutically acceptable salt thereof, 8 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A8 R B8 , -OR A8 , -C(O)R A8 , -C(=NR E8 )R A8 , -C(=N-OR B8 )R A8 , -C(O)OR A8 , -OC(O)R A8 , -C(O)NR A8 R B8 , -NR A8 C(O)R B8 , -C(=NR E8 )NR A8 R B8 , -NR A8 C(=NR E8 )R B8 , -OC(O)NR A8 R B8 , -NR A8 C(O)OR B8 , -NR A8 C(O)NR A8 R B8 , -NR A8 C(S)NR A8 R B8 , -NR A8C(=NR E8 )NR A8 R B8 , -S(O) r R A8 , -S(O)(=NR E8 )R B8 , -N=S(O)R A8 R B8 , -S(O)2OR A8 , -OS(O)2R A8 , -NR A8 S(O) r R B8 , -NR A8 S(O)(=NR E8 )R B8 and -S(O) r NR A8 R B8 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0176] Another embodiment <7> Now, an embodiment of the present invention <6> or a pharmaceutically acceptable salt thereof, 8 is hydrogen, halogen, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl groups, CN, NO2, -NR A8 R B8 , -OR A8 , -C(O)R A8 , -C(O)OR A8 , -OC(O)R A8 , -C(O)NR A8 R B8 , -NR A8 C(O)R B8 , -OC(O)NR A8 R B8 , -NR A8 C(O)OR B8 , -NRA8 C(O)NR A8 R B8 , -NR A8 C(S)NR A8 R B8 , -S(O) r R A8 , -S(O)2OR A8 , -OS(O)2R A8 and -NR A8 S(O) r R B8 wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0177] Another embodiment <8> Now, an embodiment of the present invention <1> ~ <7> In the compound or a pharmaceutically acceptable salt thereof according to any one of the above, L1 is -(CR C0 R D0 ) u -, -(CR C0 R D0 ) u O(CR C0 R D0 ) t -, -(CR C0 R D0 ) u NR A0 (CR C0 R D0 ) t -Japanese-(CR C0 R D0 ) u S(O) r (CR C0 R D0 ) t - is selected from.

[0178] Another embodiment <9> Now, an embodiment of the present invention <8> or a pharmaceutically acceptable salt thereof, L1 is -O-, -NH- and -S(O) r- is selected from.

[0179] Another embodiment <10> Now, an embodiment of the present invention <1> ~ <9> In the compound or a pharmaceutically acceptable salt thereof according to any one of the above, R 1 is C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A1 R B1 , -OR A1 , -C(O)R A1 , -C(O)OR A1 , -OC(O)R A1 , -C(O)NR A1 R B1 , -NR A1 C(O)R B1 , -OC(O)NR A1 R B1 , -NR A1 C(O)OR B1 , -NR A1 C(O)NR A1 R B1 and -S(O) r R A1 wherein each of the alkyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0180] Another embodiment <11> Now, an embodiment of the present invention <10> or a pharmaceutically acceptable salt thereof, 1 is C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4alkyl groups, wherein each of the alkyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0181] Another embodiment <12> Now, an embodiment of the present invention <11> or a pharmaceutically acceptable salt thereof, 1 teeth, [ka] and is unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0182] Another embodiment <13> Now, an embodiment of the present invention <1> ~ <12> In the compound or a pharmaceutically acceptable salt thereof according to any one of the above, R 1 The substituent R X independently, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, halogens, CN, NO2, -(CR c1 R d1 ) t NR a1 R b1 , -(CR c1 R d1 ) t OR b1 , -(CR c1 R d1 ) t C(O)R a1 and -(CR c1 R d1 ) t N=S(O)R a1 R b1 wherein each of the alkyl and cycloalkyl groups is unsubstituted or independently selected from R Y is substituted with at least one substituent selected from

[0183] Another embodiment <14> Now, an embodiment of the present invention <13> or a pharmaceutically acceptable salt thereof,a1 and each R b1 are independently hydrogen, C 1-10 Alkyl group, C 2-10 Alkenyl groups and C 2-10 alkynyl groups, wherein each of the alkyl, alkenyl, and alkynyl groups is unsubstituted or independently selected from R Y and is substituted with at least one substituent selected from Or, R a1 and R b1 together with the atom or atoms to which they are attached, form a 4-8 membered heterocyclic ring containing 0, 1, or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, and the ring is Y It may be substituted with a group.

[0184] Another embodiment <15> In the compound or a pharmaceutically acceptable salt thereof according to any one of the embodiments (1) to (11) of the present invention, R 1 The substituent R X are independently OH, halogen, C 1-10 Alkyl groups and [ka] is selected from.

[0185] Another embodiment <16> Now, an embodiment of the present invention <1> ~ <15> In the compound or a pharmaceutically acceptable salt thereof according to any one of the above, R 1 teeth, [ka] is selected from.

[0186] Another embodiment <17> Now, an embodiment of the present invention <1> ~ <10> In the compound or a pharmaceutically acceptable salt thereof according to any one of the above, R 1 and R 8together with the atoms to which they are attached form a cycloalkyl group or a 5- to 8-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X It is substituted with a substituent.

[0187] Another embodiment <18> Now, an embodiment of the present invention <17> or a pharmaceutically acceptable salt thereof, 1 and R 8 together with the atoms to which they are attached form a 5-6 membered heterocyclic group containing one, two or three heteroatoms independently selected from oxygen, sulfur, nitrogen and phosphorus, wherein the ring is unsubstituted or contains one, two or three R X It is substituted with a substituent.

[0188] Another embodiment <19> Now, an embodiment of the present invention <1> ~ <18> or a pharmaceutically acceptable salt thereof,<I’> of [ka] The structure of the part is [ka] where R 1 and R 8 The heterocycle formed by R together with the atoms to which they are attached may be unsubstituted or contain one, two or three R X is substituted with a substituent, [ka] represents the point of attachment to the rest of the molecule.

[0189] Another embodiment <20> Now, an embodiment of the present invention <19> In the compound of formula (I) or a pharmaceutically acceptable salt thereof, the substituent R of the 5- to 6-membered heterocyclic group X independently, C 1-10 Alkyl group, C 3-10Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, halogens, CN, -NO2, -(CR c1 R d1 ) t NR a1 R b1 and -(CR c1 R d1 ) t OR b1 wherein each of the alkyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Y is substituted with at least one substituent selected from

[0190] Another embodiment <21> Now, an embodiment of the present invention <20> In the compound of formula (I) or a pharmaceutically acceptable salt thereof, the substituent R of the 5- to 6-membered heterocyclic group X are halogens, CN, NO2, OH, C 1-8 Alkyl group, C 3-8 It is selected from cycloalkyl groups and benzyl groups.

[0191] Another embodiment <22> Now, an embodiment of the present invention <1> ~ <21> In the compound or a pharmaceutically acceptable salt thereof according to any one of the above, L2 is -(CR C0 R D0 ) u -, -(CR C0 R D0 ) u O(CR C0 R D0 ) t -and-(CR C0 R D0 ) u NR A0 (CR C0 R D0 ) t - is selected from.

[0192] Another embodiment <23> Now, an embodiment of the present invention <18> or a pharmaceutically acceptable salt thereof, L2 is selected from a chemical bond and -O-.

[0193] Another embodiment <24> Now, an embodiment of the present invention <1> ~ <23> In the compound or a pharmaceutically acceptable salt thereof according to any one of the above, R 2 is selected from heterocyclic and heteroaryl groups, where the heterocyclic and heteroaryl groups are unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0194] Another embodiment <25> Now, an embodiment of the present invention <24> or a pharmaceutically acceptable salt thereof, 2 teeth, [ka] is selected from.

[0195] Another embodiment <26> Now, an embodiment of the present invention <1> ~ <25> or a pharmaceutically acceptable salt thereof, W is -CR 10 -, -NR 11 - and -O-.

[0196] Another embodiment <27> Now, an embodiment of the present invention <26> or a pharmaceutically acceptable salt thereof, 10 and R 11 are independently hydrogen, C 1-10 Alkyl groups and C 3-10 cycloalkyl groups, wherein each of the alkyl and cycloalkyl groups is unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0197] Another embodiment <28> Now, an embodiment of the present invention <27> or a pharmaceutically acceptable salt thereof, 10 is H.

[0198] Another embodiment <29> Now, an embodiment of the present invention <27> or a pharmaceutically acceptable salt thereof, 11 is selected from H, a methyl group and an ethyl group.

[0199] Another embodiment <30> Now, an embodiment of the present invention <1> ~ <26> In the compound or a pharmaceutically acceptable salt thereof according to any one of the above, 4 and R 10 " or "R 4 and R 11 ", along with the carbon atoms to which they are attached, are C 3-10 forming a cycloalkyl group or a 4- to 12-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X It is substituted with a substituent.

[0200] Another embodiment <31> Now, an embodiment of the present invention <30> or a pharmaceutically acceptable salt thereof, 4 and R 10 " or "R 4 and R 11 ", along with the carbon atoms to which they are attached, are C 3-8 forming a cycloalkyl group or a 4- to 10-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R X It is substituted with a substituent.

[0201] Another embodiment <32> Now, an embodiment of the present invention <1> ~ <31> In the compound according to any one of the above or a pharmaceutically acceptable salt thereof, m1 and m2 are independently selected from 0 and 1.

[0202] Another embodiment <33> Now, an embodiment of the present invention <1> ~ <31> In the compound or a pharmaceutically acceptable salt thereof according to any one of the above, R 3is an aryl group, where the aryl group is unsubstituted or independently R X is substituted with at least one substituent selected from

[0203] Another embodiment <34> Now, an embodiment of the present invention <33> or a pharmaceutically acceptable salt thereof, 3 is a phenyl group, where the phenyl group is unsubstituted or independently R X is substituted with at least one substituent selected from

[0204] Another embodiment <35> Now, an embodiment of the present invention <34> or a pharmaceutically acceptable salt thereof, 3 The substituent R X is C 1-10 Alkyl groups and C 3-10 cycloalkyl groups, wherein each of the alkyl and cycloalkyl groups is unsubstituted or independently selected from R Y is substituted with at least one substituent selected from

[0205] Another embodiment <36> Now, an embodiment of the present invention <35> or a pharmaceutically acceptable salt thereof, 3 The substituent R X is selected from a methyl group, an ethyl group, an isopropyl group, and a cyclopropyl group, wherein each of the methyl group, the ethyl group, the isopropyl group, and the cyclopropyl group is unsubstituted or substituted with at least one substituent independently selected from halogen.

[0206] Another embodiment <37> Now, an embodiment of the present invention <1> ~ <36> In the compound according to any one of the above or a pharmaceutically acceptable salt thereof, m is selected from 0, 1 and 2.

[0207] Another embodiment <38> Now, an embodiment of the present invention <37> or a pharmaceutically acceptable salt thereof, 4 are independently hydrogen, halogen, C 1-10Alkyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkyl-C 1-4 Alkyl group, heterocyclic group, heterocyclic-C 1-4 Alkyl group, aryl group, aryl-C 1-4 Alkyl groups, heteroaryl groups, heteroaryl-C 1-4 Alkyl groups, CN, NO2, -NR A4 R B4 , -OR A4 , -C(O)R A4 , -C(O)OR A4 , -OC(O)R A4 , -C(O)NR A4 R B4 and -S(O) r R A4 wherein each of the alkyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0208] Another embodiment <39> Now, an embodiment of the present invention <38> or a pharmaceutically acceptable salt thereof, wherein any two R 4 together with the atoms to which they are attached, C 3-8 forming a cycloalkyl group or a 4-8 membered heterocyclic group containing one, two or three heteroatoms independently selected from oxygen, sulfur, nitrogen and phosphorus, wherein the ring is unsubstituted or contains one, two or three R X It is substituted with a substituent.

[0209] Another embodiment <40> Now, an embodiment of the present invention <39> or a pharmaceutically acceptable salt thereof, wherein any two R 4 together with the atom to which they are attached form a cyclopropyl group, where the cyclopropyl group is unsubstituted or contains one, two, or three R X It is substituted with a substituent.

[0210] Another embodiment <41> Now, an embodiment of the present invention <1> ~ <40> or a pharmaceutically acceptable salt thereof,<I’> Substructure of<II’> [ka] teeth, [ka] wherein the symbol [ka] represents the point of attachment to the rest of the molecule.

[0211] Another embodiment <42> Now, an embodiment of the present invention <1> ~ <41> In the compound or a pharmaceutically acceptable salt thereof according to any one of the preceding claims, 5 and each R 6 , independently, hydrogen, halogen, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, CN, NO2, -NR A7 R B7 , -OR A7 and -C(O)R A7 wherein each of the alkyl and cycloalkyl groups is unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0212] Another embodiment <43> Now, an embodiment of the present invention <41> or a pharmaceutically acceptable salt thereof, 5 and R 6 is H.

[0213] Another embodiment <44> Now, an embodiment of the present invention <1> ~ <43> or a pharmaceutically acceptable salt thereof,<I’> Substructure of<III’> [ka] teeth, [ka] wherein the symbol [ka] represents the point of attachment to the rest of the molecule.

[0214] Another embodiment <45> Now, an embodiment of the present invention <1> ~ <44> In the compound or a pharmaceutically acceptable salt thereof according to any one of the preceding claims, 7 are independently hydrogen, halogen, C 1-10 Alkyl group, C 3-10 Cycloalkyl groups, CN, NO2, -NR A7 R B7 , -OR A7 and -C(O)R A7 wherein each of the alkyl and cycloalkyl groups is unsubstituted or independently selected from R X is substituted with at least one substituent selected from

[0215] Another embodiment <46> Now, an embodiment of the present invention <45> or a pharmaceutically acceptable salt thereof, 7 is H.

[0216] Another embodiment <48> Now, the present invention is an embodiment <1> ~ <47> or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

[0217] Another embodiment <49> Thus, the present invention provides a method for treating, ameliorating, or preventing a condition responsive to Bcl-2 inhibition, comprising administering to an individual in need thereof an effective amount of an embodiment of the present invention. <1> ~ <47> or a pharmaceutically acceptable salt thereof, or at least one pharmaceutical composition thereof, optionally in combination with a second therapeutic agent.

[0218] Another embodiment <50> The present invention relates to a method for the manufacture of a medicament for treating a cell proliferative disorder or an autoimmune disease, in accordance with an embodiment. <1> ~ <47> The present invention provides a use of a compound according to any one of the above or a pharmaceutically acceptable salt thereof.

[0219] In another aspect, the present invention provides a kit containing a compound disclosed herein or a pharmaceutically acceptable salt thereof, and instructions containing one or more pieces of information selected from the group consisting of a disease state for which the component is to be administered, storage information for the component, administration information, and instructions regarding how to administer the component. In a particular variation, the kit contains the compound in a multi-dose form.

[0220] In another aspect, the present invention provides a product containing a compound disclosed herein or a pharmaceutically acceptable salt thereof, and packaging material. In one variation, the packaging material comprises a container. In a particular variation, the container comprises a label indicating one or more of the following: a disease state for which the compound is to be administered, storage information, administration information, and / or instructions regarding how to administer the compound. In another variation, the product comprises a multiple-dose form of the compound.

[0221] In another aspect, the invention provides a method of treatment comprising administering to an individual a compound disclosed herein or a pharmaceutically acceptable salt thereof.

[0222] In another aspect, the present invention provides methods of inhibiting Bcl-2 by contacting Bcl-2 with a compound disclosed herein, or a pharmaceutically acceptable salt thereof.

[0223] In another aspect, the present invention provides a method of inhibiting Bcl-2, comprising causing a compound disclosed herein, or a pharmaceutically acceptable salt thereof, to be present in an individual to inhibit the activity of Bcl-2 in vivo.

[0224] In another aspect, the invention provides a method of inhibiting Bcl-2 comprising administering to an individual a first compound that is converted in vivo to a second compound, wherein the second compound inhibits the activity of Bcl-2 in vivo, and wherein the second compound is a compound or variant described in any one of the above embodiments.

[0225] In another aspect, the present invention provides a method of treating a disease state in which activity of Bcl-2 contributes to the pathology and / or symptomology of the disease state, comprising causing to be present in an individual a therapeutically effective amount of a compound disclosed herein, or a pharmaceutically acceptable salt thereof, with respect to the disease state.

[0226] In another aspect, the present invention provides a method of treating a disease state in which activity of Bcl-2 contributes to the pathology and / or symptomology of the disease state, comprising administering to an individual a first compound that is converted in vivo to a second compound, wherein the second compound inhibits the activity of Bcl-2 in vivo. Note that the above compounds of the present invention may be the pre-conversion compound or the converted compound.

[0227] In variations of each of the above methods, the disease state is a cancerous proliferative disorder (e.g., brain, lung, squamous cell, bladder, stomach, pancreatic, breast, head, neck, renal, kidney, ovarian, prostate, colorectal, epidermal, esophageal, testicular, gynecological, or thyroid cancer), a non-cancerous proliferative disorder (e.g., benign hyperplasia of the skin (e.g., psoriasis), restenosis, and benign prostatic hyperplasia (BPH)), pancreatitis, kidney disease, pain, blastocyst prevention, angiogenesis or vascularization-related disorders (e.g., tumor angiogenesis, acute and chronic inflammatory disorders (e.g., rheumatoid arthritis, atherosclerosis, inflammatory bowel disease), skin conditions (e.g., psoriasis, eczema, and and scleroderma), diabetes, diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, hemangioma, glioma, melanoma, Kaposi's sarcoma, ovarian cancer, breast cancer, lung cancer, pancreatic cancer, prostate cancer, colon cancer, and epidermoid carcinoma), asthma, neutrophil chemotaxis (e.g., myocardial infarction and stroke reperfusion injury and inflammatory arthritis), septic shock, T cell mediated diseases in which immunosuppression is of value (e.g., prevention of organ transplant rejection, graft-versus-host disease, lupus erythematosus, multiple sclerosis, and rheumatoid arthritis), atherosclerosis, inhibition of keratinocyte response to growth factor cocktails, chronic obstructive pulmonary disease (COPD), and other diseases.

[0228] In another aspect, the present invention provides methods of treating disease states in which mutations in the Bcl-2 gene contribute to the pathology and / or symptoms of the disease state, including, for example, melanoma, lung cancer, colon cancer, and other types of tumors.

[0229] In another aspect, the invention relates to the use of the compounds and variants according to any one of the above embodiments as a medicament. In another aspect, the invention relates to the use of the compounds and variants according to any one of the above embodiments in the manufacture of a medicament for inhibiting Bcl-2.

[0230] In another aspect, the invention relates to the use of compounds and variants according to any one of the above embodiments in the manufacture of a medicament for the treatment of a disease state in which the activity of Bcl-2 contributes to the pathology and / or symptoms.

[0231] Administration and Pharmaceutical Compositions In general, the compounds of the present invention are administered alone or in combination with one or more therapeutic agents in a therapeutically effective amount in a commonly accepted manner known in the art.The therapeutically effective amount can vary widely depending on the severity of the disease, age and relative health of the subject, the efficacy of the compound used, and other factors known in the art.For example, for the treatment of tumor diseases and immune system diseases, the required dosage varies depending on the mode of administration, the specific condition to be treated, and the desired effect.

[0232] Generally, satisfactory results can be obtained at a daily dosage of 0.001 to 100 mg / kg body weight, specifically about 0.03 to 2.5 mg / kg body weight. For larger mammals, such as humans, the daily dosage may be about 0.5 mg to about 2000 mg, or more specifically, 0.5 mg to 1000 mg, conveniently administered, for example, in divided doses up to four times daily or in sustained-release form. Suitable unit dosage forms for oral administration contain about 1 to 50 mg of active ingredient.

[0233] The above compounds of the invention may be administered in the form of pharmaceutical compositions by any common route, for example enterally in the form of tablets or capsules, for example orally, parenterally in the form of injection solutions or suspensions, for example in the form of lotions, gels, ointments or creams, or topically in the form of nasal suppositories or suppositories.

[0234] Pharmaceutical compositions comprising the compounds of the present invention in the form of free base or pharmaceutically acceptable salts and at least one pharmaceutically acceptable carrier or diluent may be prepared in a conventional manner by mixing, granulating, coating, dissolving, or lyophilizing processes. For example, pharmaceutical compositions may be prepared in a conventional manner by combining the compounds of the present invention with at least one pharmaceutically acceptable carrier or diluent and mixing with a pharmaceutically acceptable carrier or diluent. A unit dosage form for oral administration may contain, for example, about 0.1 mg to about 500 mg of active substance.

[0235] In one embodiment, the pharmaceutical composition is a solution of the active ingredient, including a suspension or dispersion, e.g., an isotonic aqueous solution. In the case of a lyophilized composition containing the active ingredient alone or together with a carrier such as mannitol, a dispersion or suspension can be prepared before use. The pharmaceutical composition may be sterilized and / or contain auxiliary substances such as preservatives, stabilizers, wetting agents or emulsifiers, solubility enhancers, salts for regulating osmotic pressure, and / or buffers. Suitable preservatives include, but are not limited to, antioxidants such as ascorbic acid and microbicides such as sorbic acid or benzoic acid. The solution or suspension may further contain a viscosity enhancer, including, but not limited to, sodium carboxymethylcellulose, carboxymethylcellulose, dextran, polyvinylpyrrolidone, gelatin, or a solubilizer, such as Tween 80 (polyoxyethylene (20) sorbitan monooleate).

[0236] Suspensions in oil may contain, as the oily component, a vegetable oil, synthetic oil, or semi-synthetic oil commonly used for injection purposes. In some embodiments, the acid component includes a liquid fatty acid ester containing a long-chain fatty acid having 8 to 22 carbon atoms, or in some embodiments, 12 to 22 carbon atoms. Suitable liquid fatty acid esters include, but are not limited to, lauric acid, tridecylic acid, myristic acid, pentadecylic acid, palmitic acid, heptadecanoic acid, stearic acid, arachidic acid, behenic acid, or corresponding unsaturated acids such as oleic acid, elaidic acid, erucic acid, plandic acid, and linoleic acid, and may optionally contain an antioxidant such as vitamin E, 3-carotene, or 3,5-di-t-butyl-hydroxytoluene. The alcohol component of these fatty acid esters may have 6 carbon atoms and may be a monohydric or polyhydric alcohol, e.g., a monohydric, dihydric, or trihydric alcohol. Suitable alcohol components include, but are not limited to, methanol, ethanol, propanol, butanol, or pentanol, or isomers thereof, ethylene glycol, and glycerol.

[0237] Other suitable fatty acid esters include, but are not limited to, ethyl oleate, isopropyl myristate, isopropyl palmitate, LABRAFIL® M2375 (polyoxyethylene glycerol), LABRAFIL® M1944 CS (an unsaturated polyethylene glycolated glyceride containing glycerides and polyethylene glycol esters produced by the alcoholysis of apricot kernel oil), LABRASOL™ (a saturated polyethylene glycolated glyceride containing glycerides and polyethylene glycol esters produced by the alcoholysis of TCM, both available from GaKefosse, France), and / or MIGLYOL® 812 (a saturated fatty acid triglyceride with a chain length of C8 to C12 from Huls AG, Germany), and vegetable oils such as cottonseed oil, apricot kernel oil, olive oil, castor oil, sesame oil, soybean oil, or peanut oil.

[0238] Pharmaceutical compositions for oral administration can be obtained, for example, by mixing the active ingredient with one or more solid carriers, optionally pelletizing the resulting mixture, and processing the mixture or particles by adding further excipients to form tablets or tablet cores.

[0239] Suitable carriers include, but are not limited to, fillers (e.g., sugars (e.g., lactose, sucrose, mannitol, or sorbitol), cellulose preparations, and / or calcium phosphates (e.g., tricalcium phosphate or calcium hydrogen phosphate)), and binders (e.g., starches (e.g., corn, wheat, rice, or potato starch), methylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, and / or polyvinylpyrrolidone), and / or, optionally, disintegrating agents (e.g., the above-mentioned starches, carboxymethyl starch, cross-linked polyvinylpyrrolidone, alginic acid or a salt thereof (e.g., sodium alginate)). Further excipients include flow conditioners and lubricants, for example, silicic acid, talc, stearic acid or a salt thereof (e.g., magnesium stearate or calcium stearate), and / or polyethylene glycol, or derivatives thereof.

[0240] The tablet cores may be provided with a suitable, optionally enteric, coating, in particular by using concentrated sugar solutions which may contain gum arabic, talc, polyvinylpyrrolidone, polyethylene glycol and / or titanium dioxide, or coating solutions dissolved in suitable organic solvents or solvent mixtures, or solutions of cellulose preparations suitable for enteric coatings, such as cellulose acetate phthalate or hydroxypropylmethylcellulose phthalate. Dyes or pigments may be added to the tablets or tablet coatings, for example for identification purposes or to indicate different doses of active ingredient.

[0241] Pharmaceutical compositions for oral administration may also include hard capsules containing gelatin or soft, sealed capsules containing gelatin and a plasticizer (e.g., glycerol or sorbitol). Hard capsules may contain, for example, the active ingredient in particulate form mixed with a filler (e.g., corn starch), a binder and / or a glidant (e.g., talc or magnesium stearate), and optionally, a stabilizer. In soft capsules, the active ingredient may be dissolved or suspended in a suitable liquid excipient, such as fatty oils, paraffin oil, or liquid polyethylene glycol or a fatty acid ester of ethylene glycol or propylene glycol, to which stabilizers and detergents, for example, detergents of the fatty acid ester type of polyoxyethylene sorbitan, may be added.

[0242] Pharmaceutical compositions suitable for rectal administration are, for example, suppositories containing a combination of the active ingredient with a suppository base, such as natural or synthetic triglycerides, paraffin hydrocarbons, polyethylene glycols, or higher alkanols.

[0243] Pharmaceutical compositions suitable for parenteral administration may include aqueous solutions of the active ingredient in water-soluble form, for example, a water-soluble salt, or aqueous injection suspensions containing viscosity-increasing substances, for example, sodium carboxymethylcellulose, sorbitol, and / or dextran, and, if necessary, stabilizers. The active ingredient, optionally together with excipients, may also be in the form of a lyophilizate and can be made into a solution before parenteral administration by adding suitable solvents. The solution used may, for example, be used as an infusion solution for parenteral administration. The preparation of injection preparations is generally carried out under sterile conditions, for example, by filling ampoules or vials and sealing the containers.

[0244] The present invention further provides a pharmaceutical combination, e.g., a kit, containing a) a compound disclosed herein in free form or in the form of a pharmaceutically acceptable salt, and b) at least one auxiliary agent, and the kit may also contain instructions for use thereof.

[0245] Combination therapy The above compounds or pharmaceutically acceptable salts of this patent may be used alone or in combination with other therapeutic agents.

[0246] For example, the therapeutic effect of the compounds of the present invention can be improved by using an adjuvant (e.g., an adjuvant drug may have minimal therapeutic benefit when used alone, but may improve the therapeutic benefit to an individual when used in combination with another drug). Alternatively, for example, the compounds of the present invention can be used in combination with another therapeutic agent that has a similar therapeutic effect to improve the therapeutic effect to an individual. For example, when treating gout, the compounds of the present invention may be used in combination with another drug to treat gout to increase the clinical benefit. Alternatively, for example, if a side effect of using the compounds of the present invention is nausea, they may be used in combination with an antiemetic. Alternatively, combination therapies include, but are not limited to, physical therapy, psychotherapy, radiation therapy, compression therapy for the affected area, rest, dietary improvement, etc. Regardless of the disease, condition, or pathology, the two therapies can have additive or synergistic therapeutic benefits to an individual.

[0247] When the compounds of the present patent are used in combination with other therapeutic agents, the pharmaceutical compositions of the compounds of the present patent may be administered via the same route of administration as the other drugs, or may be administered via a different route due to their different physical and chemical properties. For example, the compounds of the present patent may be able to produce and maintain good blood levels when administered orally, while the other therapeutic agents may need to be administered intravenously. Therefore, the compounds of the present patent may be administered simultaneously with the other therapeutic agents, sequentially, or separately.

[0248] Example There are various methods for synthesizing the compound of formula (I) or a pharmaceutically acceptable salt thereof, and the methods listed in this example are representative. However, it should be noted that the compound of formula (I) or a pharmaceutically acceptable salt thereof can also be synthesized by other synthetic schemes.

[0249] In certain compounds of Formula (I), particular stereoisomers (e.g., chiral centers) may exist due to the bonds between atoms and other atoms. Synthesis of compounds of Formula (I) or pharmaceutically acceptable salts thereof may result in mixtures of different isomers (enantiomers, diastereomers). Unless a particular configuration is specifically described, all recited compounds include various possible stereoisomers.

[0250] The compounds of formula (I) can be prepared as pharmaceutically acceptable acid addition salts, for example, by reacting the free base form of the compounds of the present invention with a pharmaceutically acceptable inorganic or organic acid. Alternatively, the compounds of formula (I) can be prepared as pharmaceutically acceptable base addition salts by reacting the free acid form of the compounds of formula (I) with a pharmaceutically acceptable inorganic or organic base. Inorganic and organic acids and bases suitable for preparing pharmaceutically acceptable salts of compounds of formula (I) are described in the definitions section of this application. Salt forms of compounds of formula (I) can also be prepared using salts of starting materials or intermediates.

[0251] The free acid or free base of the compound of formula (I) can be prepared from the corresponding base addition salt or acid addition salt. The compound of formula (I) in the form of an acid addition salt can be converted to the corresponding free base, for example, by treating with a suitable base (e.g., ammonium hydroxide solution, sodium hydroxide, etc.). The compound of formula (I) in the form of a base addition salt can be converted to the corresponding free acid, for example, by treating with a suitable acid (e.g., hydrochloric acid, etc.).

[0252] The N-oxide of the compound of formula (I) or a pharmaceutically acceptable salt thereof can be prepared by a method known in the art. For example, the N-oxide can be obtained by reacting the non-oxidized form of the compound of formula (I) with an oxidizing agent (e.g., trifluoroperacetic acid, permaleic acid, perbenzoic acid, peracetic acid, metachloroperbenzoic acid, etc.) in an inert organic solvent (e.g., a halogenated hydrocarbon such as dichloromethane) at 0 to 80°C. Alternatively, the N-oxide of the compound of formula (I) can be prepared from the N-oxide of the starting material.

[0253] The unoxidized form of the compound represented by formula (I) can be prepared by reacting the N-oxide with a reducing agent (e.g., sulfur, sulfur dioxide, triphenylphosphine, lithium borohydride, sodium borohydride, phosphorus trichloride, phosphorus tribromide, etc.) in a corresponding inert organic solvent (e.g., acetonitrile, ethanol, aqueous dioxane, etc.) at 0 to 80°C.

[0254] Protected derivatives of compounds of formula (I) can be prepared by methods well known to those skilled in the art. For a detailed description of techniques for adding and removing protecting groups, see T.W. Greene, Protecting Groups in Organic Synthesis, 3rd edition, John Wiley & Sons, Inc. 1999.

[0255] All symbols and conventions used in these methods, routes, and examples are consistent with those used in the current scientific literature, e.g., the Journal of the American Chemical Society or the Journal of Biological Chemistry. Unless otherwise specified, standard single-letter or three-letter abbreviations generally refer to L-amino acid residues. Unless otherwise specified, all starting materials used were purchased from commercial suppliers and were not further purified before use.For example, the following abbreviations are used in the examples and throughout the specification: g (gram), mg (milligram), L (liter), mL (milliliter), μL (microliter), psi (pounds per square inch), M (mole), mM (millimolar), iv (intravenous), Hz (hertz), MHz (megahertz), mol (mole), mmol (millimol), RT (ambient temperature), min (minutes), h (hours), mp (melting point), TLC (thin layer chromatography), Rt (retention time), RP (reverse phase), MeOH( Methanol), i-PrOH (isopropanol), TEA (triethylamine), TFA (trifluoroacetic acid), TFAA (trifluoroacetic anhydride), THF (tetrahydrofuran), DMSO (dimethyl sulfoxide), EtOAc (ethyl acetate), DME (1,2-dimethoxyethane), DCM (dichloromethane), DCE (dichloroethane), DMF (N,N-dimethylformamide), DMPU (N,N'-dimethylpropyleneurea), CDI (1,1-carbonyldiimidazole), IBCF (isobutyl chloroformate), HOAc (acetic acid), HOSu (N-hydroxysuccinimide), HOBT (1-hydroxybenzotriazole), EtO (diethyl ether), EDCI (1-(3-dimethylaminopropyl) 3-ethylcarbodiimide hydrochloride), BOC (t-butoxycarbonyl group), FMOC (9-fluorenylmethoxycarbonyl group), DCC (dicyclohexylcarbodiimide), CBZ (benzyloxycarbonyl group), Ac (acetyl group), atm (atmospheric pressure), TMSE (2 -(trimethylsilyl)ethyl group), TMS (trimethylsilyl group), TIPS (triisopropylsilyl group), TBS (t-butyldimethylsilyl group), DMAP (4-dimethylaminopyridine), Me (methyl), OMe (methoxy), Et (ethyl), tBu (t-butyl), HPLC (high performance liquid chromatography), BOP (bis(2-oxo-3-oxazolidinyl)phosphinic chloride), TBAF (tetra-n-butylammonium fluoride), mCPBA (metachloroperbenzoic acid).

[0256] All references to ether or EtO refer to diethyl ether, and brine refers to saturated aqueous NaCl. Unless otherwise stated, all temperatures are in degrees Celsius and all reactions were conducted under an inert atmosphere at room temperature.

[0257] 1 H NMR spectra were recorded on a Varian Mercury Plus 400 nuclear magnetic resonance spectrometer. Chemical shifts are expressed in ppm. All coupling constants are in hertz (Hz). Splitting patterns describe the apparent multiplicity and are designated as s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), and br (broad).

[0258] Low-resolution mass spectra (MS) and compound purity data were acquired on a Shimadzu LC / MS single quadrupole system equipped with an electrospray ionization (ESI) detector, ultraviolet (UV) detectors (220 and 254 nm), and evaporative light scattering (ELSD) detector. Thin-layer chromatography was performed on 0.25 mm silica gel plates (60F-254) from the Superchem group using 5% ethanolic phosphomolybdic acid, ninhydrin, or p-methoxybenzaldehyde solutions and observed under a UV lamp. Flash column chromatography was performed on silica gel (200-300 mesh, Qingdao Ocean Chemical Industry Co., Ltd.).

[0259] Synthesis scheme The compounds of Formula I or pharmaceutically acceptable salts thereof can be synthesized in a variety of ways, some exemplary methods are provided in the following examples, and other synthetic methods can be readily provided by those skilled in the art based on the information disclosed in the present invention.

[0260] In each reaction described below, it may be necessary to protect the active groups, such as hydroxyl, amino, imine, thio, or carboxyl groups, contained in the final product to prevent them from participating in other undesired reactions. For common protecting groups, see T.W. Greene and P.G.M. Buts in "Protective Groups in Organic Chemistry," John Wiley and Sons, 1991.

[0261] The synthesis schemes for all compounds of the present invention are illustrated by the following schemes and examples. The starting materials used are either commercially available or can be prepared according to conventional process methods or as exemplified herein.

[0262] The intermediates shown in the schemes below are either known in the literature or can be prepared by analogous methods by one skilled in the art.

[0263] For illustrative purposes, Scheme 1 discloses one method for synthesizing the compound of formula I disclosed in the present invention. As shown in the scheme, the compound of formula I can be resolved into intermediates II to V in the synthetic methods reported in the literature, and the intermediate of formula III can be produced by a nucleophilic substitution reaction or a transition metal-catalyzed cross-coupling reaction between IV and intermediate V, as known in the literature. The intermediate of formula III and the intermediate of formula II are then subjected to a condensation reaction to obtain the compound of formula I.

[0264] [ka] Synthetic Scheme 1 As an illustration of the preparation of intermediates of Formula II, the synthesis of intermediates IIa & IIb is shown in Scheme 2. Starting with commercially available IIa-A, IIa is obtained by nucleophilic substitution with IIa-B to give IIa. Similarly, IIb-A can be subjected to a series of nucleophilic cross-coupling reactions followed by intramolecular cyclization using metal-catalyzed coupling reactions (e.g., Buchwald reaction) or other conditions known in the literature to produce intermediate IIb.

[0265] [ka] Synthetic Scheme 2 As an explanation of the method for preparing the intermediate of formula IV, the synthesis method of intermediate IVa is shown in Scheme 3. Starting from IVa-A, which is commercially available or reported in the literature, IVa-D can be prepared by converting the halogen group in IVa-A to a hydroxy group. IVa-D and IVa-E undergo a nucleophilic substitution reaction to give the intermediate of formula IVa.

[0266] [ka] Synthetic Scheme 3 As an illustration of the preparation of intermediates of formula V, the synthesis of intermediate Va is shown in Scheme 4. Intermediate Va can be prepared by a series of reductive amination and deprotection reactions on Va-A, which is commercially available or reported in the literature.

[0267] [ka] Synthetic Scheme 4 As another illustration of the method for preparing the intermediate of formula V, Scheme 5 provides a method for synthesizing intermediate Vb. Starting from Vb-A, which is commercially available or reported in the literature, the intermediate of formula Vb is prepared through three steps: intramolecular reductive amination, SN2 nucleophilic substitution, and deprotection.

[0268] [ka] Synthetic Scheme 5 In some situations, the sequence of the above synthetic schemes can be adjusted accordingly to facilitate the reaction or to avoid the formation of unwanted reaction products. In order to more fully understand the present invention, the following examples are provided. These examples are illustrative only and should not be construed as limiting the present invention.

[0269] Intermediate production Intermediate A (S)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)benzoic acid (Intermediate A) [ka] (R,E)-N-(2-bromophenylmethylene)-2-methylpropane-2-sulfenamide (A-1) A mixture of 2-bromobenzaldehyde (1.0 g, 5.0 mmol), (R)-2-methylpropane-2-sulfenamide (0.69 g, 5.6 mmol), and CsCO (1.1 g, 3.5 mmol) in DCM (10 mL) was stirred at 25 °C for 12 h. The mixture was concentrated and extracted with EtOAc, washed with saturated brine, dried over NaSO, and concentrated. The residue was purified by silica gel column chromatography eluting with PE / EtOAc (30:1 to 20:1) to give the title compound (R,E)-N-(2-bromophenylmethylene)-2-methylpropane-2-sulfenamide (A-1). MS-ESI (m / z): 288 [M+1] + .

[0270] (R)-N-((S)-1-(2-bromophenyl)-3-(1,3-dioxan-2-yl)propyl)-2-methylpropane-2-sulfenamide (A-2) (R,E)-N-(2-bromophenylmethylene)-2-methylpropane-2-sulfenamide (A-1) (1.3 g, 4.5 mmol) was dissolved in THF (30 mL), and then (2-(1,3-dioxan-2-yl)ethyl)magnesium bromide (0.5 M, 27 mL, 13.0 mmol) was added at −78° C. and stirred at −78° C. for 2 h. The mixture was then poured into NH4Cl solution (50 mL). The mixture was extracted with EtOAc, and the extract was washed with saturated brine, dried over Na2SO4, and concentrated. The residue was purified by silica gel column chromatography and eluted with DCM / MeOH (30:1) to obtain the title compound (R)-N-((S)-1-(2-bromophenyl)-3-(1,3-dioxan-2-yl)propyl)-2-methylpropane-2-sulfenamide (A-2). MS-ESI (m / z): 404 [M + 1] + . (S)-2-(2-bromophenyl)pyrrolidine (A-3) To a solution of (R)-N-((S)-1-(2-bromophenyl)-3-(1,3-dioxan-2-yl)propyl)-2-methylpropane-2-sulfenamide (A-2) (9.5 g, 2.3 mmol) in HCl (4 M, dioxane solution) (100 mL) was added HCl (concentrated, 15 mL) at 25 °C, and the mixture was stirred at 50 °C for 2.5. After that, NaBH (1.8 g, 4.6 mmol) and MeOH (50 mL) were added in several portions, and the mixture was stirred at 25 °C for 1 h. The mixture was then poured into ice water (200 g), extracted with EtOAc, washed with saturated brine, dried over Na SO , and concentrated to obtain the title compound (S)-2-(2-bromophenyl)pyrrolidine (A-3). MS-ESI (m / z): 226 [M + 1] + . (S)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)benzoic acid (Intermediate A) (S)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)benzoic acid (A) was prepared according to the method described in WO2019210828.

[0271] Intermediate B (S)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-isopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)benzoic acid (Intermediate B) [ka] (S)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-isopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)benzoic acid (B) was prepared according to the method described in WO2019210828.

[0272] Intermediate C 6-(((4-hydroxy-4-methylcyclohexyl)methyl)amino)-5-nitropyridine-3-sulfonamide (Intermediates Ca and Cb) [ka] 6-Amino-5-nitropyridine-3-sulfonic acid (C-1) A solution of 6-aminopyridine-3-sulfonic acid (3.5 g, 20 mmol) in HSO (14 mL) was heated to 50 °C, and fuming HNO was slowly added dropwise. The mixture was then stirred at 50 °C for 1.5 h. The mixture was then poured into ice water (50 mL) and filtered to obtain the title compound, 6-amino-5-nitropyridine-3-sulfonic acid (C-1). MS-ESI (m / z): 220 [M + 1] + . 6-Hydroxy-5-nitropyridine-3-sulfonic acid (C-2) At 0°C, a suspension of 6-amino-5-nitropyridine-3-sulfonic acid (C-1) (2.00 g, 9.13 mmol) in 3N HCl (35 mL) was added with NaNO2 solution (0.945 mg, 13.7 mmol). The mixture was stirred at 0°C for 1 h and then heated at 100°C for 1 h. The mixture was concentrated to give the title compound 6-hydroxy-5-nitropyridine-3-sulfonic acid (C-2). MS-ESI (m / z): 221 [M + 1] + . 6-Chloro-5-nitropyridine-3-sulfonyl chloride (C-3) To a solution of 6-hydroxy-5-nitropyridine-3-sulfonic acid (C-2) (2.00 g, 9.13 mmol) in sulfolane (20 mL) was added POCl (10 mL) at 25° C. The mixture was heated at 110° C. for 18 h and then poured into ice water (200 g). The mixture was extracted with DCM, washed with saturated brine, dried over NaSO, and concentrated to give the title compound 6-chloro-5-nitropyridine-3-sulfonyl chloride (C-3).

[0273] 6-Chloro-5-nitropyridine-3-sulfonamide (C-4) To a solution of 6-chloro-5-nitropyridine-3-sulfonyl chloride (C-3) (0.701 g, 2.74 mmol) in THF (14 mL) was added 37% aqueous ammonia at −10° C. and stirred at −10° C. for 0.5 h. The mixture was then extracted with DCM, washed with saturated brine, dried over NaSO, and concentrated to give the title compound 6-chloro-5-nitropyridine-3-sulfonamide (C-4). MS-ESI (m / z): 238 [M+1] + .

[0274] Benzyl((1,4-dioxaspiro[4.5]decan-8-yl)methyl)urethane (C-5) To a solution of (1,4-dioxaspiro[4.5]decan-8-yl)methylamine (0.092 g, 0.54 mmol) and TEA (0.082 g, 0.81 mmol) in DCM (3 mL) was added benzyl chloroformate (0.111 g, 0.65 mmol) at 0 °C and stirred at 0 °C for 0.5 h. The mixture was extracted with DCM, washed with saturated brine, dried over Na SO , and concentrated to give the title compound benzyl ((1,4-dioxaspiro[4.5]decan-8-yl)methyl)urethane (C-5). MS-ESI (m / z): 306 [M + 1] + . Benzyl((4-epoxycyclohexyl)methyl)urethane(C-6) To a solution of ((1,4-dioxaspiro[4.5]decan-8-yl)methyl)urethane (C-5) (0.10 g, 0.33 mmol) in THF (1 mL) was added 2N HCl (1 mL) and stirred at 40° C. for 2.5 h. The mixture was then extracted with EA, washed with saturated brine, dried over NaSO, and concentrated to give the title compound benzyl((4-epoxycyclohexyl)methyl)urethane (C-6). MS-ESI (m / z): 262 [M + 1] + . Benzyl((4-hydroxy-4-methylcyclohexyl)methyl)urethane (C-7) To a solution of benzyl((4-epoxycyclohexyl)methyl)urethane (C-6) (0.26 g, 1.0 mmol) in THF (4 mL) was added methylmagnesium bromide (3 M, 1 mL) at -70 °C. The mixture was stirred at -70 °C for 2.5 h. After quenching with NH4Cl solution, the mixture was extracted with EA, washed with saturated brine, dried over Na2SO4, and concentrated to give the title compound benzyl((4-hydroxy-4-methylcyclohexyl)methyl)urethane (C-7). MS-ESI (m / z): 278 [M + 1] + . 4-(aminomethyl)-1-methylcyclohexan-1-ol (C-8) To a solution of benzyl((4-hydroxy-4-methylcyclohexyl)methyl)urethane (C-7) (0.223 g, 0.805 mmol) in CHOH (8 mL) at RT, 10% Pd / C (67 mg) was added, and the mixture was stirred at RT for 2 h under a H atmosphere. The mixture was filtered and concentrated to give the title compound 4-(aminomethyl)-1-methylcyclohexan-1-ol (C-8). MS-ESI (m / z): 144 [M + 1] + . 6-(((4-hydroxy-4-methylcyclohexyl)methyl)amino)-5-nitropyridine-3-sulfonamide(Ca) To a solution of 4-(aminomethyl)-1-methylcyclohexan-1-ol (C-8) (0.070 g, 0.49 mmol) and 6-chloro-5-nitropyridine-3-sulfonamide (C-4) (0.116 g, 0.49 mmol) in CHCN (1 mL) was added DIPEA (0.095 g, 0.74 mmol) at RT and stirred at RT for 1 h. The mixture was then extracted with EA, washed with saturated brine, dried over NaSO, and concentrated. The residue was purified by preparative TLC to obtain the title compound 6-(((4-hydroxy-4-methylcyclohexyl)methyl)amino)-5-nitropyridine-3-sulfonamide (Ca) from the top spot on the chromatography plate. MS-ESI (m / z): 345 [M + 1] + . 6-(((4-hydroxy-4-methylcyclohexyl)methyl)amino)-5-nitropyridine-3-sulfonamide (Cb) To a solution of 4-(aminomethyl)-1-methylcyclohexan-1-ol (C-8) (0.070 g, 0.49 mmol) and 6-chloro-5-nitropyridine-3-sulfonamide (C-4) (0.116 g, 0.49 mmol) in CHCN (1 mL) was added DIPEA (0.095 g, 0.74 mmol) at RT and stirred at RT for 1 h. The mixture was then extracted with EA, washed with saturated brine, dried over NaSO, and concentrated. The residue was purified by preparative TLC to obtain the title compound 6-(((4-hydroxy-4-methylcyclohexyl)methyl)amino)-5-nitropyridine-3-sulfonamide (Cb) from the bottom of the chromatography plate. MS-ESI (m / z): 345 [M + 1] + . Intermediate D 6-(((4-((diethyl(oxo)-λ 6 -sulfanylidene)amino)cyclohexyl)methyl)amino)5-nitropyridine-3-sulfonamide (D) [ka] Diethyl(imino)-λ 6 -Sulfanone (D-1) The title compound, diethyl(imino)-λ 6 -sulfanone (D-1) was prepared according to the method described in WO2008 / 141843(A1).

[0275] Ethyl 4-((diethyl(oxo)-λ 6 -sulfanylidene)amino)cyclohexane-1-carboxylic acid ester (D-2) Diethyl(imino)-λ 6A solution of 4-oxocyclohexane-1-carboxylate (1.30 g, 7.68 mmol) in DCE (10 mL) was stirred at RT for 15 min, then NaBH(OAc) (1.82 g, 8.60 mmol) was added, and the resulting mixture was stirred at 0 °C overnight. The mixture was quenched with saturated aqueous NaHCO (15 mL), and extracted with DCM (3 × 30 mL), washed with saturated brine (30 mL), dried over NaSO, and concentrated. The residue was purified by silica gel column chromatography eluting with DCM / MeOH (15:1) to give the title compound ethyl 4-((diethyl(oxo)-λ). 6 -sulfanylidene)amino)cyclohexane-1-carboxylic acid ester (D-2) was obtained. MS-ESI (m / z): 276 [M + 1] + . Diethyl((4-(hydroxymethyl)cyclohexyl)imino)-λ 6 -Sulfanone (D-3) Ethyl 4-((diethyl(oxo)-λ 6 A solution of (4-(hydroxymethyl)cyclohexyl)imino)cyclohexane-1-carboxylic acid ester (D-2) (205 mg, 0.745 mmol) and LiAlH (142 mg, 3.73 mmol) in THF (5 mL) was stirred at 50 °C for 1 h. The mixture was quenched with 10% NaOH (165 μL) and water (165 μL). The mixture was filtered, the filtrate was concentrated, and the residue was purified by silica gel column chromatography eluting with DCM / MeOH (50:1 to 12:1) to give the title compound, diethyl((4-(hydroxymethyl)cyclohexyl)imino)-λ 6 -sulfanone (D-3) was obtained. MS-ESI (m / z): 234 [M + 1] + . (4-((diethyl(oxo)-λ 6 -Sulfanylidene)amino)cyclohexyl)methyl methanesulfonate (D-4) Diethyl((4-(hydroxymethyl)cyclohexyl)imino)-λ 6A solution of sulfanone (D-3) (46 mg, 0.197 mmol), MsCl (18 μL, 0.237 mmol) and TEA (33 μL, 0.237 mmol) in DCM (3 mL) was stirred at RT for 15 min, quenched with saturated aqueous NaHCO (15 mL) and the mixture was extracted with DCM (3 × 30 mL), dried over NaSO and concentrated to give the title compound (4-((diethyl(oxo)-λ 6 -sulfanylidene)amino)cyclohexyl)methyl methanesulfonate (D-4) was obtained. MS-ESI (m / z): 312 [M + 1] + . ((4-(azidomethyl)cyclohexyl)imino)diethyl-λ 6 -Sulfanone (D-5) (4-((diethyl(oxo)-λ 6 A solution of (4-(azidomethyl)cyclohexyl)amino)cyclohexylmethyl methanesulfonate (D-4) (106 mg, 0.341 mmol) and NaN (44 mg, 0.682 mmol) in DMF (2 mL) was stirred at 70 °C for 12 h, quenched with water, and the mixture was extracted with EtOAc (3 × 30 mL), washed with saturated brine (2 × 30 mL), dried over Na SO , and concentrated. The residue was purified by silica gel column chromatography eluting with DCM / MeOH (10:1) to give the title compound ((4-(azidomethyl)cyclohexyl)imino)diethyl-λ 6 -sulfanone (D-5) was obtained. MS-ESI (m / z): 259 [M + 1] + . ((4-(aminomethyl)cyclohexyl)imino)diethyl-λ6-sulfanone (D-6) ((4-(azidomethyl)cyclohexyl)imino)diethyl-λ 6A solution of α-sulfanone (D-5) (33 mg, 0.128 mmol) and PPh (44 mg, 0.166 mmol) in THF / HO (2 / 0.4 mL) was stirred at 30 °C overnight. The reaction mixture was oxidized with HCl (pH = 2) and extracted with DCM (2 × 30 mL). The extract was washed with saturated aqueous NaHCO (30 mL) and concentrated. The residue was dissolved in DCM / MeOH (5:1), dried over NaSO, and concentrated. The residue was purified by silica gel column chromatography eluting with DCM / MeOH (10:1 to 5:1) to give the title compound ((4-(aminomethyl)cyclohexyl)imino)diethyl-λ 6 -sulfanone (D-6) was obtained. MS-ESI (m / z): 233 [M + 1] + . 6-(((4-((diethyl(oxo)-λ 6 -sulfanylidene)amino)cyclohexyl)methyl)amino)5-nitropyridine-3-sulfonamide (D) ((4-(aminomethyl)cyclohexyl)imino)diethyl-λ 6 A solution of 6-(((4-((diethyl(oxo)-λ)-sulfanone (D-6) (10.0 mg, 0.043 mmol), 6-chloro-5-nitropyridine-3-sulfonamide (C-4) (12.0 mg, 0.052 mmol) and DIPEA (28.0 mg, 0.215 mmol) in acetonitrile (1 mL) was stirred at 80° C. overnight. The reaction mixture was cooled to RT and concentrated. The residue was purified by preparative TLC to obtain the title compound 6-(((4-((diethyl(oxo)-λ)-sulfanone (D-6) (10.0 mg, 0.043 mmol), 6-chloro-5-nitropyridine-3-sulfonamide (C-4) (12.0 mg, 0.052 mmol), and DIPEA (28.0 mg, 0.215 mmol). 6 -sulfanylidene)amino)cyclohexyl)methyl)amino)5-nitropyridine-3-sulfonamide (D) was obtained. MS-ESI (m / z): 433 [M + 1] + . Intermediate E (R)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)benzoic acid (Intermediate E) [ka] Based on the synthesis method of intermediate A, after replacing (R)-2-methylpropane-2-sulfenamide with (S)-2-methylpropane-2-sulfenamide, (R)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)benzoic acid (intermediate E) was prepared. MS-ESI (m / z): 563 [M + 1] + .

[0276] Intermediate F (S)-3-(4-hydroxy-4-methylcyclohexyl)-nitro-2,3-dihydrobenzo[b][1,4]quinoxaline-7-sulfonamide (Intermediate F) [ka] Intermediate F (R)-2-((t-butoxycarbonyl)amino)-2-(4-hydroxycyclohexyl)acetic acid (F-1) (R)-2-((t-butoxycarbonyl)amino)-2-(4-hydroxycyclohexyl)acetic acid (F-1) was prepared according to patent US2005 / 234065.

[0277] (R)-2-Bromo-2-(4-hydroxycyclohexyl)acetic acid (F-2) (R)-2-((t-butoxycarbonyl)amino)-2-(4-hydroxycyclohexyl)acetic acid (F-1) (7.0 g, 25.6 mmol) was dissolved in 48% aqueous HBr (56 mL) and stirred at room temperature for 0.5 h. After cooling to 0 °C, a solution of NaNO (2.82 g, 40.9 mmol) in water (28 mL) was added. The reaction mixture was then gradually warmed to room temperature and stirred overnight. After completion of the reaction, the mixture was diluted with saturated brine (50 mL) and extracted with ethyl acetate (2 × 70 mL). It was then washed with saturated aqueous sodium bisulfite (50 mL) and 15% saturated brine (50 mL), dried over NaSO, and concentrated. The residue was purified with dichloromethane (10 mL), filtered, and dried to give the target compound (R)-2-bromo-2-(4-hydroxycyclohexyl)acetic acid (F-2). MS-ESI (m / z): 235,237[M-1] - .

[0278] (R)-2-Bromo-2-(4-oxycyclohexyl)acetic acid (F-3) (R)-2-Bromo-2-(4-hydroxycyclohexyl)acetic acid (F-2) (1.9 g, 8.0 mmol) was dissolved in tetrahydrofuran (6 mL) and dichloromethane (80 mL), Dess-Martin periodinane (4.1 g, 9.7 mmol) was added, and the mixture was stirred at room temperature overnight. After the reaction was completed, the mixture was filtered, the filter cake was washed with 30 mL of dichloromethane, and the filtrate was concentrated to give crude (R)-2-bromo-2-(4-hydroxycyclohexyl)acetic acid (F-3). This crude product was used directly in the next reaction without further purification.

[0279] (R)-2-Bromo-2-(1,4-dioxaspiro[4.5]dec-8-yl)acetic acid (F-4) (R)-2-Bromo-2-(4-hydroxycyclohexyl)acetic acid (F-3) (6.0 g, 10.1 mmol) was added to toluene (90 mL), followed by the addition of ethylene glycol (0.038 g, 0.36 mmol), p-toluenesulfonic acid (150 mg), and 4A molecular sieves (6 g). The mixture was stirred at 100 °C for 3–4 hours. After the reaction was complete, the mixture was cooled to room temperature, filtered, and the filtrate was concentrated. The residue was purified by silica gel column chromatography using petroleum ether / ethyl acetate (5:1–1:1) as an eluent to obtain the desired product, (R)-2-bromo-2-(1,4-dioxaspiro[4.5]dec-8-yl)acetic acid (F-4). MS-ESI (m / z): 277, 279 [M-1] - .

[0280] (R)-2-Bromo-2-(1,4-dioxaspiro[4.5]dec-8-yl)methyl acetate (F-5) (R)-2-Bromo-2-(1,4-dioxaspiro[4.5]dec-8-yl)acetic acid (F-4) (250 mg, 0.896 mmol) was dissolved in N,N-dimethylacetamide (2 mL), potassium carbonate (150 mg, 1.08 mmol) and iodomethane (191 mg, 1.34 mmol) were added, and the mixture was stirred at room temperature for 1-2 hours. After the reaction was completed, the mixture was quenched by adding water (20 mL), extracted with ethyl acetate (3 × 20 mL), washed with water (10 mL) and saturated brine (10 mL), dried over NaSO, filtered, and concentrated to give crude (R)-2-bromo-2-(1,4-dioxaspiro[4.5]dec-8-yl)methyl acetate (F-5). This crude product was used in the next reaction without further purification. MS-ESI (m / z): 293,295 [M+1] + .

[0281] 3-Bromo-4-chloro-5-nitrobenzenesulfonamide (F-6) 3-Bromo-4-chloro-5-nitrobenzenesulfonamide (F-6) was prepared according to patent WO2018 / 192462.

[0282] (S)-2-((2-bromo-6-nitro-4-sulfonamidophenyl)thio)-2-(1,4-dioxaspiro[4.5]dec-8-yl)acetate methyl ester (F-7) 3-Bromo-4-chloro-5-nitrobenzenesulfonamide (F-6) (700 mg, 2.22 mmol) was dissolved in N,N-dimethylacetamide (7 mL), sodium sulfide (208 mg, 2.67 mmol) and 18-crown-6 (70 mg) were added, and the mixture was stirred overnight at room temperature. After the reaction was complete, (R)-2-bromo-2-(1,4-dioxaspiro[4.5]dec-8-yl)methyl acetate (F-5) (220 mg, 0.75 mmol) was added, and the mixture was stirred overnight at 40 °C. After the reaction was complete, the mixture was quenched with water (40 mL), extracted with ethyl acetate (3 × 20 mL), washed with water (2 × 10 mL) and saturated brine (10 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by silica gel column chromatography using dichloromethane / acetonitrile (20:1 to 10:1) as a developing solvent to obtain (S)-2-((2-bromo-6-nitro-4-sulfonamidophenyl)thio)-2-(1,4-dioxaspiro[4.5]dec-8-yl)methyl acetate (F-7). MS-ESI (m / z): 525, 527 [M+1] + .

[0283] (S)-3-Bromo-4-((2-hydroxy-1-(1,4-dioxa[4.5]dec-8-yl)ethyl)thio)-5-nitrophenylsulfonamide (F-8) (S)-2-((2-bromo-6-nitro-4-sulfonamidophenyl)thio)-2-(1,4-dioxaspiro[4.5]dec-8-yl)methyl acetate (F-7) (90 mg, 0.086 mmol) was dissolved in tetrahydrofuran (9 mL) under a nitrogen atmosphere, cooled to -60 °C, and a solution of DIBAL-H in normal hexane (4 mL) was slowly added dropwise. The mixture was stirred at -60 to -10 °C for 2 to 3 hours. After completion of the reaction, the mixture was quenched by adding methanol (2 mL) at -60 °C, diluted with dichloromethane (10 mL), gradually warmed to room temperature, and concentrated. The residue was purified by silica gel column chromatography using dichloromethane / acetonitrile (3:1) as a developing solvent to give (S)-3-bromo-4-((2-hydroxy-1-(1,4-dioxaspiro[4.5]dec-8-yl)ethyl)thio)-5-nitrophenylsulfonamide (F-8). MS-ESI (m / z): 495,497 [M-1] - .

[0284] (S)-5-Nitro-3-(1,4-dioxa[4.5]dec-8-yl)-2,3-dihydrobenzo[b][1,4]quinoxaline-7-sulfonamide (F-9) (S)-3-Bromo-4-((2-hydroxy-1-(1,4-dioxa[4.5]dec-8-yl)ethyl)thio)-5-nitrophenylsulfonamide (F-8) (35 mg, 0.0704 mmol) was dissolved in 1,4-dioxane (1.1 mL) and toluene (3.3 mL). Palladium acetate (3.2 mg, 0.014 mmol), Xantphos (0.028 mg, 0.0704 mmol), and potassium carbonate (19.5 mg, 0.14 mmol) were added under a nitrogen atmosphere. The mixture was heated to 90°C and stirred for 0.5 to 1 hour. After completion of the reaction, the mixture was cooled to room temperature, filtered, and concentrated. The residue was purified by PTLC using dichloromethane / acetonitrile (10:1) as the developer to give (S)5-nitro-3-(1,4-dioxaspiro[4.5]dec-8-yl)-2,3-dihydrobenzo[b][1,4]quinoxaline-7-sulfonamide (F-9). MS-ESI (m / z): 415 [M-1] - .

[0285] (S)-5-Nitro-3-(4-oxocyclohexyl)-2,3-dihydrobenzo[b][1,4]quinoxaline-7-sulfonamide (F-10) (S) 5-nitro-3-(1,4-dioxa[4.5]dec-8-yl)-2,3-dihydrobenzo[b][1,4]quinoxaline-7-sulfonamide (F-9) (30 mg, 0.072 mmol) was dissolved in tetrahydrofuran (2.5 mL). 3N aqueous hydrochloric acid (2 mL) was added at room temperature. The mixture was stirred at room temperature for 1-2 h. After the reaction was completed, the pH was adjusted to 7 with saturated aqueous sodium carbonate, extracted with ethyl acetate (3 × 10 mL), washed with water (5 mL) and saturated brine (5 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by PTLC using ethyl acetate / petroleum ether (1:1) as the eluent to give (S)-5-nitro-3-(4-oxocyclohexyl)-2,3-dihydrobenzo[b][1,4]quinoxaline-7-sulfonamide (F-10). MS-ESI (m / z): 371[M-1]-.

[0286] (S)-3-(4-hydroxy-4-methylcyclohexyl)-nitro-2,3-dihydrobenzo[b][1,4]quinoxaline-7-sulfonamide (F) (S)-5-Nitro-3-(4-oxocyclohexyl)-2,3-dihydrobenzo[b][1,4]quinoxaline-7-sulfonamide (F-10) (12.5 mg, 0.086 mmol) was dissolved in tetrahydrofuran (4 mL) under a nitrogen atmosphere, cooled to -78 °C, and a solution of methyllithium in ethyl ether (0.1 mL) was slowly added dropwise. The reaction was stirred at -78 °C for 0.5 hours. After completion of the reaction, the reaction was quenched by the addition of saturated aqueous ammonium chloride (2 mL) at -78 °C, extracted with ethyl acetate (3 × 10 mL), washed with water (5 mL) and saturated brine (5 mL), dried over Na SO , filtered, and concentrated. The residue was purified by PTLC using dichloromethane / acetonitrile (2:1) as the developer to give (S)-3-(4-hydroxy-4-methylcyclohexyl)-nitro-2,3-dihydrobenzo[b][1,4]quinoxaline-7-sulfonamide (Fa and Fb). MS-ESI (m / z): 387 [M-1] - .

[0287] Example A-1a (S)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)-N-((6-(((4-hydroxy-4-methylcyclohexyl)methyl)amino)-5-nitropyridin-3-yl)sulfonyl)benzamide (A-1a) [ka] A solution of 6-(((4-hydroxy-4-methylcyclohexyl)methyl)amino)-5-nitropyridine-3-sulfonamide (Ca) (4 mg, 0.012 mmol), EDCI (57 mg, 0.030 mmol) and DMAP (36 mg, 0.030 mmol) in DCM (1.5 mL) was stirred at RT for 15 min, followed by (S)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)benzoic acid (Intermediate A) (5 mg, 0.00 A solution of (S)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)-N-((6-(((4-hydroxy-4-methylcyclohexyl)methyl)amino)-5-nitropyridin-3-yl)sulfonyl)benzamide (A-1a) was added, and the resulting mixture was stirred at RT overnight and concentrated. The residue was purified by preparative TLC to give the title compound (S)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)-N-((6-(((4-hydroxy-4-methylcyclohexyl)methyl)amino)-5-nitropyridin-3-yl)sulfonyl)benzamide (A-1a). MS-ESI (m / z): 889 [M + 1] + .

[0288] Example A-1b (S)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)-N-((6-(((4-hydroxy-4-methylcyclohexyl)methyl)amino)-5-nitropyridin-3-yl)sulfonyl)benzamide (A-1b) [ka] A solution of 6-(((4-hydroxy-4-methylcyclohexyl)methyl)amino)-5-nitropyridine-3-sulfonamide (Cb) (4 mg, 0.012 mmol), EDCI (57 mg, 0.030 mmol), and DMAP (36 mg, 0.030 mmol) in DCM (1.5 mL) was stirred at RT for 15 min, followed by the addition of a solution of (S)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)benzoic acid (Intermediate A) (5 mg, 0.009 mmol) in TEA (4 mg, 0.04 mmol) in DCM (0.5 mL). The resulting mixture was stirred at RT overnight and concentrated, and the residue was purified by preparative TLC to give the title compound (S)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)-N-((6-(((4-hydroxy-4-methylcyclohexyl)methyl)amino)-5-nitropyridin-3-yl)sulfonyl)benzamide (A-1b). MS-ESI (m / z): 889 [M + 1] + .

[0289] Example A-1c (R)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)-N-((6-(((4-hydroxy-4-methylcyclohexyl)methyl)amino)-5-nitropyridin-3-yl)sulfonyl)benzamide (A-1c) [ka] (R)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)-N-((6-(((4-hydroxy-4-methylcyclohexyl)methyl)amino)-5-nitropyridin-3-yl)sulfonyl)benzamide (A-1c) Prepared according to the synthesis method of A-1a, after replacing (S)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)-pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)benzoic acid (intermediate A) with (R)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)benzoic acid (intermediate E). MS-ESI (m / z): 978 [M + 1] + .

[0290] Example A-2a (S)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)-N-((6-(((4-((diethyl(oxo)-λ 6 -sulfanylidene)amino)cyclohexyl)methyl)amino)5-nitropyridin-3-yl)sulfonyl)benzamide (A-2a) [ka] According to the synthesis method of A-1a, 6-(((4-hydroxy-4-methylcyclohexyl)methyl)amino)-5-nitropyridine-3-sulfonamide (Ca) was converted to 6-(((4-((diethyl(oxo)-λ 6-sulfanylidene)amino)cyclohexyl)methyl)amino)-5-nitropyridine-3-sulfonamide (intermediate D), followed by (S)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)-N-((6-(((4-((diethyl(oxo)-λ 6 -sulfanylidene)amino)cyclohexyl)methyl)amino)5-nitropyridin-3-yl)sulfonyl)benzamide (A-2a) was prepared. MS-ESI (m / z): 978 [M + 1] + .

[0291] Example A-2b (R)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)-N-((6-(((4-((diethyl(oxo)-λ 6 -sulfanylidene)amino)cyclohexyl)methyl)amino)5-nitropyridin-3-yl)sulfonyl)benzamide (A-2b) [ka] According to the synthesis method of A-1a, 6-(((4-hydroxy-4-methylcyclohexyl)methyl)amino)-5-nitropyridine-3-sulfonamide (Ca) and (S)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)benzoic acid (Intermediate A) were reacted with 6-(((4-((diethyl(oxo)-λ 6-sulfanylidene)amino)cyclohexyl)methyl)amino)-5-nitropyridine-3-sulfonamide (Intermediate D) and (R)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)benzoic acid (Intermediate E), followed by substitution of (R)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)-N-((6-(((4-((diethyl(oxo)-λ 6 -sulfanylidene)amino)cyclohexyl)methyl)amino)5-nitropyridin-3-yl)sulfonyl)benzamide (A-2b) was prepared. MS-ESI (m / z): 978 [M + 1] + .

[0292] Examples A-3 to A-173 listed in Table 1 are essentially synthesized according to the steps described in Examples A-1 to A-2 or similar synthetic policies or methods, using suitable intermediates that can be easily synthesized by methods known in the art and modified as necessary. The structures and names of Examples A-3 to A-173 are shown in Table 1.

[0293] [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]

[0294] Examples A-34 to A-173 listed in Table 2 are readily synthesized by methods known in the art and are prepared from appropriate intermediates, modified as necessary. The structures and names of Examples A-34 to A-173 are shown in Table 2.

[0295] [Table 2-1] [Table 2-2] [Table 2-3] [Table 2-4] [Table 2-5] [Table 2-6] [Table 2-7] [Table 2-8] [Table 2-9] [Table 2-10] [Table 2-11] Table 2-12 Table 2-13 Table 2-14 Table 2-15 Table 2-16 Table 2-17 Table 2-18 Table 2-19 Table 2-20 Table 2-21 Table 2-22 Table 2-23 Table 2-24 Table 2-25 Table 2-26 Table 2-27 Table 2-28 [Table 2-29] [Table 2-30] [Table 2-31]

[0296] Example B-1a (S)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)-N-((4-nitro-5-(((tetrahydro-2H-pyran-4-yl)methyl)amino)pyridin-2-yl)sulfonyl)benzamide (B-1a) [ka] 2-Chloro-5-fluoropyridine 1-oxide (B-1-a) 30% H2O2 was added dropwise to a solution of 2-chloro-5-fluoropyridine (7.7 g, 58 mmol) in TFA (180 ml) at 70 °C, and the mixture was stirred at this temperature overnight. The reaction mixture was concentrated to dryness under reduced pressure, and the residue was diluted with water, neutralized with 10% aqueous Na2CO3, and extracted with DCM / MeOH = 10:1, followed by concentration. The residue was purified by recrystallization from EA:PE = 1:9 to obtain the title compound 2-chloro-5-fluoropyridine 1-oxide (B-1-a). MS-ESI (m / z): 148 [M + 1] + .

[0297] 2-Chloro-5-fluoro-4-nitropyridine 1-oxide (B-1-b) A mixture of 2-chloro-5-fluoropyridine 1-oxide (B-1-a) (7.2 g, 49 mmol) and KNO (22.0 g, 217 mmol) in HSO (100 ml) was stirred at 120 °C for 3 h. After cooling to RT, the mixture was poured into ice water (400 g) and stirred for 10 min, filtered, and the wet filter cake was dissolved in DCM. The organic phase was washed with saturated brine, dried, and concentrated to give the title compound, 2-chloro-5-fluoro-4-nitropyridine 1-oxide (B-1-b). MS-ESI (m / z): 193 [M + 1] + .

[0298] 2-Chloro-4-nitro-5-(((tetrahydro-2H-pyran-4-yl)methyl)amino)pyridine 1-oxide (B-1-c) To a solution of 2-chloro-5-fluoro-4-nitropyridine 1-oxide (B-1-b) (542 mg, 2.82 mmol) in THF (25 ml), (tetrahydro-2H-pyran-4-yl)methylamine (487 mg, 4.23 mmol) and TEA (0.5 ml) were added, followed by stirring at 20 ° C. for 15 minutes. Water was added to the reaction mixture, which was diluted with EtOAc, acidified with 2N HCl, and filtered to obtain the title compound, 2-chloro-4-nitro-5-(((tetrahydro-2H-pyran-4-yl)methyl)amino)pyridine 1-oxide (B-1-c). MS-ESI (m / z): 288 [M + 1] + .

[0299] 5-((t-butoxycarbonyl)((tetrahydro-2H-pyran-4-yl)methyl)amino)-2-chloro-4-nitropyridine 1-oxide (B-1-d) A mixture of 2-chloro-4-nitro-5-(((tetrahydro-2H-pyran-4-yl)methyl)amino)-pyridine 1-oxide (B-1-c) (470 mg, 1.64 mmol), (Boc)2O (1.2 g, 5.5 mmol), and DMAP (300 mg, 2.46 mmol) in acetonitrile (10 ml) was stirred at 50 °C for 0.5 h. The mixture was concentrated, and the residue was purified by silica gel column chromatography eluting with EtOAc / PE (1:3) to give the title compound, 5-((tert-butoxycarbonyl)((tetrahydro-2H-pyran-4-yl)methyl)amino)-2-chloro-4-nitropyridine 1-oxide (B-1-d). MS-ESI (m / z): 388 [M + 1] + .

[0300] 2-(benzylthio)-5-((tert-butoxycarbonyl)((tetrahydro-2H-pyran-4-yl)methyl)amino)-4-nitropyridine 1-oxide (B-1-e) At 20°C, 5-((tert-butoxycarbonyl)((tetrahydro-2H-pyran-4-yl)methyl)amino)-2-chloro-4-nitropyridine 1-oxide (B-1-d) (10 mg, 0.025 mmol), NaS (6 mg, 0.077 mmol), and 18-crown-6 (10 mg, 0.038 mmol) were stirred with DMA (0.25 ml) for 0.5 h, then BnBr (30 mg, 0.175 mmol) was added, and the mixture was cooled to 20°C. After stirring at 0° C. for 10 minutes and quenching with water, the mixture was extracted with EtOAc, washed with saturated brine, dried over Na2SO4, and concentrated. The residue was purified by silica gel column chromatography and eluted with EtOAc / PE (1:1) to obtain the title compound 2-(benzylthio)-5-((tert-butoxycarbonyl)((tetrahydro-2H-pyran-4-yl)methyl)amino)-4-nitropyridine 1-oxide (B-1-e). MS-ESI (m / z): 476 [M + 1] + .

[0301] 5-((t-butoxycarbonyl)((tetrahydro-2H-pyran-4-yl)methyl)amino)-4-nitro-2-sulfamoylpyridine 1-oxide (B-1-f) Acetic acid (2 ml) and water (2 ml) were added to a solution of 2-(benzylthio)-5-((tert-butoxycarbonyl)((tetrahydro-2H-pyran-4-yl)methyl)amino)-4-nitropyridine 1-oxide (B-1-e) (167 mg, 0.35 mmol) in acetonitrile (10 ml) at 0° C., followed by the gradual addition of DCH (276 mg, 1.73 mmol), and the resulting mixture was stirred at 0° C. for 10 minutes. The mixture was gradually added to NH 3 .HO (15 ml) in an ice bath, extracted with EtOAc, and then concentrated. The residue was purified by silica gel column chromatography eluting with DCM / MeOH (50:1) to obtain the title compound, 5-((tert-butoxycarbonyl)((tetrahydro-2H-pyran-4-yl)methyl)amino)-4-nitro-2-sulfamoylpyridine 1-oxide (B-1-f). MS-ESI (m / z): 433 [M + 1] + .

[0302] 4-nitro-5-(((tetrahydro-2H-pyran-4-yl)methyl)amino)pyridine-2-sulfonamide (B-1-g) To a solution of 5-((tert-butoxycarbonyl)((tetrahydro-2H-pyran-4-yl)methyl)amino)-4-nitro-2-sulfamoylpyridine 1-oxide (B-1-f) (100 mg, 0.23 mmol) in DCM (10 ml) was added PCl (3 ml) and stirred at RT overnight. Then TFA (10 ml) was added and stirred at RT for 30 minutes. The mixture was concentrated, the residue was dissolved in DCM, the organic phase was washed with saturated NaHCO solution and saturated brine, dried over NaSO, and the residue was purified by P-TLC (DCM:MeOH=20:1) to give the title compound 4-nitro-5-(((tetrahydro-2H-pyran-4-yl)methyl)amino)pyridine-2-sulfonamide (B-1-g). MS-ESI (m / z): 315 [M-1] - . (S)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)-N-((4-nitro-5-(((tetrahydro-2H-pyran-4-yl)methyl)amino)pyridin-2-yl)sulfonyl)benzamide (B-1a) Following the synthesis method of 1, (S)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)-N-((4-nitro-5-(((tetrahydro-2H-pyran-4-yl)methyl)amino)pyridin-2-yl)sulfonyl)benzamide (B-1a) was prepared after replacing 6-(((4-hydroxy-4-methylcyclohexyl)methyl)amino)-5-nitropyridine-3-sulfonamide (Ca) with 4-nitro-5-(((tetrahydro-2H-pyran-4-yl)methyl)amino)pyridine-2-sulfonamide (B-1-g). MS-ESI (m / z): 861 [M + 1] + .

[0303] Example B-1b (R)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)-N-((4-nitro-5-(((tetrahydro-2H-pyran-4-yl)methyl)amino)pyridin-2-yl)sulfonyl)benzamide (B-1b) [ka] According to the synthesis method of B-1a, (S)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)benzoic acid (Intermediate A) was converted to (R)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3. After substituting (R)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)-N-((4-nitro-5-(((tetrahydro-2H-pyran-4-yl)methyl)amino)pyridin-2-yl)sulfonyl)benzamide (B-1b) was prepared. MS-ESI (m / z): 861 [M + 1] + .

[0304] Example B-2a 2-((1H-Pyrrolo[2,3-b]pyridin-5-yl)oxy)-N-(((S)-2-benzyl-8-nitro-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)sulfonyl)-4-(2-((S)-2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)benzamide (B-2a) [ka] 2,6-Dichloropyridin-4-amine (B-2-a) A solution of 2,6-dichloro-4-nitropyridine (2.0 g, 10 mmol), iron powder (5.80 g, 104 mmol), NH4Cl (1.1 g, 20.7 mmol), and water (8 ml) in EtOH (40) was stirred at 80 °C overnight, the mixture was filtered through diatomaceous earth and washed with MeOH, the filtrates were combined and concentrated, diluted with EtOAc and water, the organic phase was washed with brine, dried over Na2SO4, and concentrated to give the title compound 2,6-dichloropyridin-4-amine (B-2-a). MS-ESI (m / z): 163 [M + 1] + .

[0305] 2,6-Dichloro-3-fluoropyridin-4-amine (B-2-b) A solution of 2,6-dichloropyridin-4-amine (B-2-a) (1.0 g, 6.1 mmol) and Selectfluor (2.4 g, 6.8 mmol) in acetonitrile (10 ml) and DMF (10 ml) was stirred at 35 °C overnight. The mixture was quenched with water and then extracted with EtOAc. The organic phase was washed with saturated brine, dried, and concentrated. The residue was purified by silica gel column chromatography eluting with EtOAc / PE (1:9) to give the title compound, 2,6-dichloro-3-fluoropyridin-4-amine (B-2-b). MS-ESI (m / z): 181 [M + 1] + .

[0306] 2,6-Dichloro-3-fluoro-4-nitropyridine 1-oxide (B-2-c) To a solution of 2,6-dichloro-3-fluoropyridin-4-amine (B-2-b) (920 mg, 5.08 mmol) in H2SO4 (50 mL) was slowly added 30% H2O2 (20 mL) at 0 °C, and the resulting solution was diluted with 50 o C overnight. After cooling, the reaction mixture was quenched with ice and extracted with EtOAc, and the organic phase was washed with saturated brine, dried, and concentrated to give the title compound 2,6-dichloro-3-fluoro-4-nitropyridine 1-oxide (B-2-c).

[0307] (S)-2,6-Dichloro-3-((1-hydroxy-3-phenylpropan-2-yl)amino)-4-nitropyridine 1-oxide (B-2-d) Following the synthesis method of (B-1-c), 2-chloro-5-fluoro-4-nitropyridine 1-oxide (B-1-b) and (tetrahydro-2H-pyran-4-yl)methylamine were replaced with 2,6-dichloro-3-fluoro-4-nitropyridine 1-oxide (B-2-c) and (S)-2-amino-3-phenylpropan-1-ol, followed by the synthesis of (S)-2,6-dichloro-3-((1-hydroxy-3-phenylpropan-2-yl)amino)-4-nitropyridine 1-oxide (B-2-d). MS-ESI (m / z): 358 [M + 1] + .

[0308] (S)-2-Benzyl-6-chloro-8-nitro-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine 5-oxide (B-2-e) To a solution of (S)-2,6-dichloro-3-((1-hydroxy-3-phenylpropan-2-yl)amino)-4-nitropyridine 1-oxide (B-2-d) (600 mg, 1.68 mmol) in THF (20 ml) was added NaH (134 mg, 5.58 mmol), and the mixture was stirred at RT for 0.5 h. Quenched with ice water and extracted with EtOAc, the organic phase was washed with saturated brine, dried over Na2SO4, and concentrated to give the title compound (S)-2-benzyl-6-chloro-8-nitro-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine 5-oxide (B-2-e). MS-ESI (m / z): 322 [M + 1] + .

[0309] 2-((1H-Pyrrolo[2,3-b]pyridin-5-yl)oxy)-N-(((S)-2-benzyl-8-nitro-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)sulfonyl)-4-(2-((S)-2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)benzamide (B-2a) Following the synthesis method of (B-1a), 2-chloro-4-nitro-5-(((tetrahydro-2H-pyran-4-yl)methyl)amino)pyridine 1-oxide (B-1-c) was replaced with (S)-2-benzyl-6-chloro-8-nitro-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine 5-oxide (B-2-e), followed by the synthesis of 2-((1H-pyrrolo[ 2,3-b]pyridin-5-yl)oxy)-N-(((S)-2-benzyl-8-nitro-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)sulfonyl)-4-(2-((S)-2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)benzamide (B-2a) was prepared. MS-ESI (m / z): 895 [M + 1] + .

[0310] Example B-2b 2-((1H-Pyrrolo[2,3-b]pyridin-5-yl)oxy)-N-(((S)-2-benzyl-8-nitro-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)sulfonyl)-4-(2-((R)-2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)benzamide (B-2b) [ka] According to the synthesis method of (B-2a), (S)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)-pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)benzoic acid (Intermediate A) was converted to (R)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(2-(2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)benzoic acid. After substituting 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-N-(((S)-2-benzyl-8-nitro-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)sulfonyl)-4-(2-((R)-2-(2-cyclopropylphenyl)pyrrolidin-1-yl)-7-azaspiro[3.5]nonan-7-yl)benzamide (B-2b) was prepared. MS-ESI (m / z): 895 [M + 1] + .

[0311] Examples B-3 to B-68 listed in Table 3 are essentially synthesized according to the steps described in Examples B-1 to B-2 or similar synthetic policies or methods, using suitable intermediates that can be readily synthesized by methods known in the art and modified as necessary. The structures and names of Examples B-3 to B-68 are shown in Table 3.

[0312] [Table 3-1] [Table 3-2] [Table 3-3] [Table 3-4] [Table 3-5] [Table 3-6] [Table 3-7] [Table 3-8] [Table 3-9] [Table 3-10] [Table 3-11] [Table 3-12] [Table 3-13] [Table 3-14] [Table 3-15] [Table 3-16] Examples C-1 to C-7 listed in Table 4 are readily synthesized by methods known in the art and are prepared from appropriate intermediates obtained by modification as necessary. The structures and names of Examples C-1 to C-7 are shown in Table 4.

[0313] [Table 4-1] [Table 4-2] Examples D-1 to D-287 listed in Table 5 are readily synthesized by methods known in the art and are prepared from appropriate intermediates, modified as necessary. The structures and names of Examples D-1 to D-287 are shown in Table 5.

[0314] Table 5-1 Table 5-2 Table 5-3 Table 5-4 Table 5-5 Table 5-6 Table 5-7 Table 5-8 Table 5-9 Table 5-10 Table 5-11 Table 5-12 Table 5-13 Table 5-14 Table 5-15 Table 5-16 Table 5-17 Table 5-18 Table 5-19 Table 5-20 Table 5-21 Table 5-22 Table 5-23 Table 5-24 Table 5-25 Table 5-26 Table 5-27 Table 5-28 Table 5-29 Table 5-30 Table 5-31 Table 5-32 Table 5-33 Table 5-34 Table 5-35 Table 5-36 Table 5-37 Table 5-38 Table 5-39 Table 5-40 Table 5-41 Table 5-42 Table 5-43 Table 5-44 Table 5-45 Table 5-46 Table 5-47 Table 5-48 Table 5-49 Table 5-50 Table 5-51 Table 5-52 Table 5-53 Table 5-54 Table 5-55 Table 5-56 Table 5-57 Table 5-58 Table 5-59 Table 5-60 Table 5-61 Table 5-62 Table 5-63 Table 5-64 Table 5-65 Table 5-66 Table 5-67 Table 5-68 [Table 5-69] [Table 5-70] [Table 5-71] [Table 5-72] [Table 5-73] Examples E-1 to E-54 listed in Table 6 are readily synthesized by methods known in the art and are prepared from appropriate intermediates obtained by modification as necessary. The structures and names of Examples E-1 to E-54 are shown in Table 6.

[0315] [Table 6-1] [Table 6-2] [Table 6-3] [Table 6-4] [Table 6-5] [Table 6-6] [Table 6-7] [Table 6-8] [Table 6-9] [Table 6-10] [Table 6-11] [Table 6-12] Cell proliferation assay The MTS detection kit was purchased from Promega. RPMI-1640 medium, fetal bovine serum, and penicillin-streptomycin were purchased from Gibco. Dimethyl sulfoxide (DMSO) was purchased from Sigma.

[0316] Compound RS4;11 (ATCC® CRL-1873 TM The inhibitory effect of compounds on Bcl-2 was detected by measuring their inhibitory effect on cell proliferation. RS4;11 cells were cultured in RPMI-1640 medium containing 10% fetal bovine serum. When the cells reached 40%-80% confluence, they were digested and seeded into 96-well plates at a cell concentration of 30,000 RS4;11 cells / well and incubated overnight at 37°C with 5% CO2. Compounds were added to the 96-well plates at different concentrations (final concentrations of 10,000 nM, 3,333.3 nM, 1,111.1 nM, 270.4 nM, 123.5 nM, 41.2 nM, 13.7 nM, 4.6 nM, and 1.5 nM) and incubated at 37°C with 5% CO2 for 72 hours. 20 μl of MTS was added to each well, and after incubation for 2 hours, 25 μl of 10% SDS was added to each well to terminate the reaction. Absorbance was measured at 490 nm and 650 nm using a microplate reader. IC was calculated using GraphPad Prism 5.0. 50 was calculated.

[0317] The prepared compounds were tested according to the biological activity test method described above, and the results are shown in Table 7.

[0318] [Table 7] The MTS detection kit was purchased from Promega (Madison, WI, USA). RPMI-1640 medium, fetal bovine serum, and penicillin-streptomycin were purchased from BI (Biological Industries, Beit Haemek, Israel). Dimethyl sulfoxide (DMSO) was purchased from Sigma (St. Louis, MO, USA). DoHH2 (DSMZ catalog #:ACC47) cells were cultured in RPMI-1640 medium containing 10% fetal bovine serum and 100 U / mL penicillin-streptomycin.

[0319] The inhibitory effect of compounds on BCL-2 was detected by measuring their inhibitory effect on DoHH2 cell proliferation. DoHH2 cells ...

Claims

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof. 【Chemistry 1】 (In the formula, X １ is N and CR ８ is selected from X ２ is N and CR ９ is selected from X ３ is N and CR １０ where X is selected from １ , X ２ , X ３ at least one of is N, Y １ , Y ２ and Y ３ is CH, A and B are independently selected from N and CH; W is -CHR １１ -, -NR １２ -, -O-, -S(O) ｒ－ and -S(O)(=NR １２ ) - is selected from Z is selected from N and CH; L １ is a chemical bond, -CH ２ selected from —, —O—, —NH— and —S—; L ２ is selected from a chemical bond and —O—; R １ is C ３－１０ Cycloalkyl group, C ３－１０ Cycloalkyl-C １－４ Alkyl group, heterocyclic group, heterocyclic-C １－４ Alkyl group, aryl group, aryl-C １－４ Alkyl group, heteroaryl group, heteroaryl-C １－４ alkyl groups, wherein each of the alkyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Ｘ and is substituted with at least one substituent selected from R ２ teeth, 【Chemistry 2】 wherein these are unsubstituted or independently selected from R Ｘ and is substituted with at least one substituent selected from R ３ is a phenyl group, where the phenyl group is unsubstituted or independently R Ｘ and is substituted with at least one substituent selected from Each R ４ are independently selected from hydrogen, halogen, —OH, methyl, ethyl, isopropyl, and cyclopropyl, wherein each of the methyl, ethyl, isopropyl, and cyclopropyl groups is unsubstituted or independently selected from R Ｘ and is substituted with at least one substituent selected from Alternatively, any two R ４ together with the atom to which they are attached form a cyclopropyl group, where the cyclopropyl group is unsubstituted or contains one, two, or three R Ｘ is substituted with a substituent, Or, "R ４ and R １１ " or "R ４ and R １２ " together with the atoms to which they are attached, C ３－８ form a cycloalkyl group or a 4- to 10-membered heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the ring is unsubstituted or contains one, two, or three R Ｘ optionally substituted with substituents, Each R ５ and R ６ are independently hydrogen, halogen, C １－１０ Alkyl group, C ３－１０ Cycloalkyl groups, CN, NO ２ , -NH ２ and —OH, wherein each of the alkyl and cycloalkyl groups is unsubstituted or independently selected from R Ｘ and is substituted with at least one substituent selected from Each R ７ are independently hydrogen, halogen, C １－１０ Alkyl group, C ３－１０ Cycloalkyl groups, CN, NO ２ , -NR Ａ７ R Ｂ７ , -OR Ａ７ and -C(O)R Ａ７ wherein each of the alkyl and cycloalkyl groups is unsubstituted or independently selected from R Ｘ and is substituted with at least one substituent selected from R ８ is hydrogen, halogen, C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１０ Cycloalkyl group, C ３－１０ Cycloalkyl-C １－４ Alkyl group, heterocyclic group, heterocyclic-C １－４ Alkyl groups, CN, NO ２ , -NR Ａ８ R Ｂ８ , -OR Ａ８ , -C(O)R Ａ８ , -C(O)OR Ａ８ , -OC(O)R Ａ８ and -S(O) ｒ R Ａ８ wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, and heterocyclic groups is unsubstituted or independently selected from R Ｘ and is substituted with at least one substituent selected from Or, R １ and R ８ together with the atoms to which they are attached form a 5- to 12-membered heterocyclic group containing 1, 2, or 3 heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the ring is unsubstituted or contains 1, 2, or 3 R Ｘ is substituted with a substituent, R ９ is selected from hydrogen, halogen, CN, OH, methyl, ethyl and trifluoromethyl; R １０ is hydrogen, halogen, C １－１０ Alkyl groups, CN, NO ２ , -NH ２ and —OH, where the alkyl groups are unsubstituted or independently selected from R Ｘ and is substituted with at least one substituent selected from R １１ is hydrogen, C １－１０ Alkyl group and C ３－１０ cycloalkyl groups, wherein each of the alkyl and cycloalkyl groups is unsubstituted or independently selected from R Ｘ and is substituted with at least one substituent selected from R １２ is hydrogen, C １－１０ Alkyl group, C ３－１０ Cycloalkyl group, heterocyclic group, heterocyclic-C １－４ Alkyl group, aryl group, aryl-C １－４ Alkyl group, heteroaryl group, heteroaryl-C 1-4 alkyl, —C(O)R Ａ１２ , —C(O)NR Ａ１２ R Ｂ１２ , -C(O)OR Ａ１２ , -S(O) ｒ R Ａ１２ and -S(O) ｒ NR Ａ１２ R Ｂ１２ wherein each of the alkyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Ｘ and is substituted with at least one substituent selected from R Ａ７ , R Ａ８ , R Ａ１２ , R Ｂ７ , R Ｂ８ and R Ｂ１２ each independently represents hydrogen, C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１０ Cycloalkyl group, C ３－１０ Cycloalkyl-C １－４ Alkyl group, heterocyclic group, heterocyclic-C １－４ Alkyl group, aryl group, aryl-C １－４ Alkyl groups, heteroaryl groups and heteroaryl-C １－４ alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Ｘ and is substituted with at least one substituent selected from Or, "R Ａ７ and R Ｂ７ " or "R Ａ８ and R Ｂ８ " or "R Ａ１２ and R Ｂ１２ " together with the atom or atoms to which they are attached form a 4- to 12-membered heterocyclic ring containing 0, 1, or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, the ring being unsubstituted or containing 1, 2, or 3 R Ｘ is substituted with a substituent, Each R Ｘ are independently hydrogen, C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１０ Cycloalkyl group, C ３－１０ Cycloalkyl-C １－４ Alkyl group, heterocyclic group, heterocyclic-C １－４ Alkyl group, aryl group, aryl-C １－４ Alkyl group, heteroaryl group, heteroaryl-C １－４ Alkyl group, halogen, CN, -NO ２ , -(CR ｃ１ R ｄ１ ) ｔ NR ａ１ R ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ OR ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ C(O)R ａ１ , -(CR ｃ１ R ｄ１ ) ｔ C (=NR ｅ１ ) R ａ１ , -(CR ｃ１ R ｄ１ ) ｔ C(=N-OR ｂ１ ) R ａ１ , -(CR ｃ１ R ｄ１ ) ｔ C(O)OR ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ O.C.(O.)R. ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ C(O)NR ａ１ R ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ NR ａ１ C(O)R ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ C (=NR ｅ１ ) NR ａ１ R ｂ１ 、-(CR ｃ１ R ｄ１ ) ｔ NR ａ１ C(=NR ｅ１ )R ｂ１ 、-(CR ｃ１ R ｄ１ ) ｔ OC(O)NR ａ１ R ｂ１ 、-(CR ｃ１ R ｄ１ ) ｔ NR ａ１ C(O)OR ｂ１ 、-(CR ｃ１ R ｄ１ ) ｔ NR ａ１ C(O)NR ａ１ R ｂ１ 、-(CR ｃ１ R ｄ１ ) ｔ NR ａ１ C(S)NR ａ１ R ｂ１ 、-(CR ｃ１ R ｄ１ ) ｔ NR ａ１ C(=NR ｅ１ )NR ａ１ R ｂ１ 、-(CR ｃ１ R ｄ１ ) ｔ S(O) ｒ R ｂ１ 、-(CR ｃ１ R ｄ１ ) ｔ S(O)(=NR ｅ１ )R ｂ１ 、-(CR ｃ１ R ｄ１ ) ｔ N=S(O)R ａ１ R ｂ１ 、-(CR ｃ１ R ｄ１ ) ｔ S(O) ２ OR ｂ１ 、-(CR ｃ１ R ｄ１ ) ｔ OS(O) ２ R ｂ１ 、-(CR ｃ１ R ｄ１ ) ｔ NR ａ１ S (O) ｒ R ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ NR ａ１ S(O) (=NR ｅ１ ) R ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ S (O) ｒ NR ａ１ R ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ S(O) (=NR ｅ１ ) NR ａ１ R ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ NR ａ１ S (O) ２ NR ａ１ R ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ NR ａ１ S(O) (=NR ｅ１ ) NR ａ１ R ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ P(O)R ａ１ R ｂ１ and - (CR ｃ１ R ｄ１ ) ｔ P(O)(OR ａ１ ) (OR ｂ１ wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups is unsubstituted or independently selected from R Ｙ and is substituted with at least one substituent selected from R ａ１ and R ｂ１ each independently represents hydrogen, C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１０ Cycloalkyl group, C ３－１０ Cycloalkyl-C １－４ Alkyl group, heterocyclic group and heterocyclic ring-C １－４ alkyl groups, wherein each of the alkyl groups, alkenyl groups, alkynyl groups, cycloalkyl groups, and heterocyclic groups is unsubstituted or independently selected from R Ｙ and is substituted with at least one substituent selected from Or, R ａ１ and R ｂ１ together with the atom or atoms to which they are attached form a 4-12 membered heterocyclic ring containing 0, 1 or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen and phosphorus, and the ring is Ｙ optionally substituted with a group, R ｃ１ and R ｄ１ Each of the groups independently represents hydrogen, halogen, C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１０ Cycloalkyl group, C ３－１０ Cycloalkyl-C １－４ Alkyl group, heterocyclic group and heterocyclic ring-C １－４ alkyl groups, wherein each of the alkyl groups, alkenyl groups, alkynyl groups, cycloalkyl groups, and heterocyclic groups is unsubstituted or independently selected from R Ｙ and is substituted with at least one substituent selected from Each R ｅ１ are independently hydrogen, C １－１０ Alkyl group, C ３－１０ Cycloalkyl group, C ３－１０ Cycloalkyl-C １－４ Alkyl groups, CN, NO ２ , -OR ａ２ , -SR ａ２ , -S(O) ｒ R ａ２ , -C(O)R ａ２ , -C(O)OR ａ２ , -S(O) ｒ NR ａ２ R ｂ２ and -C(O)NR ａ２ R ｂ２ is selected from Each R Ｙ are independently １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１０ Cycloalkyl group, C ３－１０ Cycloalkyl-C １－４ Alkyl group, heterocyclic group, heterocyclic-C １－４ Alkyl groups, halogens, CN, NO ２ , -(CR ｃ２ R ｄ２ ) ｔ NR ａ２ R ｂ２ , -(CR ｃ２ R ｄ２ ) ｔ OR ｂ２ , -(CR ｃ２ R ｄ２ ) ｔ C(O)R ａ２ , -(CR ｃ２ R ｄ２ ) ｔ C (=NR ｅ２ ) R ａ２ , -(CR ｃ２ R ｄ２ ) ｔ C(=N-OR ｂ２ ) R ａ２ , -(CR ｃ２ R ｄ２ ) ｔ C(O)OR ｂ２ , -(CR ｃ２ R ｄ２ ) ｔ O.C.(O.)R. ｂ２ , -(CR ｃ２ R ｄ２ ) ｔ C(O)NR ａ２ R ｂ２ , -(CR ｃ２ R ｄ２ ) ｔ NR ａ２ C(O)R ｂ２ , -(CR ｃ２ R ｄ２ ) ｔ C (=NR ｅ２ ) NR ａ２ R ｂ２ , -(CR ｃ２ R ｄ２ ) ｔ NR ａ２ C(=NR ｅ２ )R ｂ２ 、-(CR ｃ２ R ｄ２ ) ｔ OC(O)NR ａ２ R ｂ２ 、-(CR ｃ２ R ｄ２ ) ｔ NR ａ２ C(O)OR ｂ２ 、-(CR ｃ２ R ｄ２ ) ｔ NR ａ２ C(O)NR ａ２ R ｂ２ 、-(CR ｃ２ R ｄ２ ) ｔ NR ａ２ C(S)NR ａ２ R ｂ２ 、-(CR ｃ２ R ｄ２ ) ｔ NR ａ２ C(=NR ｅ２ )NR ａ２ R ｂ２ 、-(CR ｃ２ R ｄ２ ) ｔ S(O) ｒ R ｂ２ 、-(CR ｃ２ R ｄ２ ) ｔ S(O)(=NR ｅ２ )R ｂ２ 、-(CR ｃ２ R ｄ２ ) ｔ N=S(O)R ａ２ R ｂ２ 、-(CR ｃ２ R ｄ２ ) ｔ S(O) ２ OR ｂ２ 、-(CR ｃ２ R ｄ２ ) ｔ OS(O) ２ R ｂ２ 、-(CR ｃ２ R ｄ２ ) ｔ NR ａ２ S(O) ｒ R ｂ２ 、-(CR ｃ２ R ｄ２ ) ｔ NR ａ２ S(O) (=NR ｅ２ ) R ｂ２ , -(CR ｃ２ R ｄ２ ) ｔ S (O) ｒ NR ａ２ R ｂ２ , -(CR ｃ２ R ｄ２ ) ｔ S(O) (=NR ｅ２ ) NR ａ２ R ｂ２ , -(CR ｃ２ R ｄ２ ) ｔ NR ａ２ S (O) ２ NR ａ２ R ｂ２ , -(CR ｃ２ R ｄ２ ) ｔ NR ａ２ S(O) (=NR ｅ２ ) NR ａ２ R ｂ２ , -(CR ｃ２ R ｄ２ ) ｔ P(O)R ａ２ R ｂ２ and - (CR ｃ２ R ｄ２ ) ｔ P(O)(OR ａ２ ) (OR ｂ２ wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, and heterocyclic groups is unsubstituted or independently selected from hydroxy, CN, amino, halogen, C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１０ Cycloalkyl group, C １－１０ Alkoxy group, C ３－１０ Cycloalkoxy group, C １－１０ Alkylthio group, C ３－１０ Cycloalkylthio group, C １－１０ Alkylamino group, C ３－１０ Cycloalkylamino groups and di(C １－１０ substituted with at least one substituent selected from the group consisting of: R ａ２ and R ｂ２ each independently represents hydrogen, C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１０ Cycloalkyl group, C ３－１０ Cycloalkyl-C １－４ Alkyl group, C １－１０ Alkoxy group, C ３－１０ Cycloalkoxy group, C １－１０ Alkylthio group, C ３－１０ Cycloalkylthio group, C １－１０ Alkylamino group, C ３－１０ Cycloalkylamino group, di(C １－１０ alkyl)amino group, heterocyclic group and heterocyclic-C １－４ alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, cycloalkoxy, alkylthio, cycloalkylthio, alkylamino, cycloalkylamino, and heterocyclic groups is unsubstituted or independently selected from halogen, CN, C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１０ Cycloalkyl group, hydroxy group, C １－１０ Alkoxy group, C ３－１０ Cycloalkoxy group, C １－１０ Alkylthio group, C ３－１０ Cycloalkylthio group, amino group, C １－１０ Alkylamino group, C ３－１０ Cycloalkylamino groups and di(C １－１０ substituted with at least one substituent selected from the group consisting of: Or, R ａ２ and R ｂ２ together with the atom or atoms to which they are attached form a 4- to 12-membered heterocyclic ring containing 0, 1, or 2 additional heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, and the ring is independently selected from halogen, CN, C １－１０ Alkyl group, C ３－１０ Cycloalkyl group, hydroxy group, C １－１０ Alkoxy group, C ３－１０ Cycloalkoxy group, C １－１０ Alkylthio group, C ３－１０ Cycloalkylthio group, amino group, C １－１０ Alkylamino group, C ３－１０ Cycloalkylamino groups and di(C １－１０ optionally substituted with one or two substituents selected from: R ｃ２ and R ｄ２ Each of the groups independently represents hydrogen, halogen, C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１０ Cycloalkyl group, C ３－１０ Cycloalkyl-C １－４ Alkyl group, C １－１０ Alkoxy group, C ３－１０ Cycloalkoxy group, C １－１０ Alkylthio group, C ３－１０ Cycloalkylthio group, C １－１０ Alkylamino group, C ３－１０ Cycloalkylamino group, di(C １－１０ alkyl)amino group, heterocyclic group and heterocyclic-C １－４ alkyl groups, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, cycloalkoxy, alkylthio, cycloalkylthio, alkylamino, cycloalkylamino, and heterocyclic groups is unsubstituted or independently selected from halogen, CN, C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１０ Cycloalkyl group, hydroxy group, C １－１０ Alkoxy group, C ３－１０ Cycloalkoxy group, C １－１０ Alkylthio group, C ３－１０ Cycloalkylthio group, amino group, C １－１０ Alkylamino group, C ３－１０ Cycloalkylamino groups and di(C １－１０ substituted with at least one substituent selected from the group consisting of: Each R ｅ２ are independently hydrogen, CN, NO ２ , C １－１０ Alkyl group, C ３－１０ Cycloalkyl group, C ３－１０ Cycloalkyl-C １－４ Alkyl group, C １－１０ Alkoxy group, C ３－１０ cycloalkoxy group, —C(O)C １－４ Alkyl group, —C(O)C ３－１０ Cycloalkyl groups, —C(O)OC １－４ Alkyl group, —C(O)OC ３－１０ Cycloalkyl groups, —C(O)N(C １－４ alkyl) ２ , -C(O)N(C ３－１０ cycloalkyl) ２ , -S(O) ２ C １－４ Alkyl group, —S(O) ２ C ３－１０ cycloalkyl group, —S(O) ２ N (C １－４ alkyl) ２ and -S(O) ２ N (C ３－１０ cycloalkyl) ２ is selected from m, n, p, and q are independently selected from 0, 1, 2, and 3; m1, m2, n1, n2, p1 and p2 are independently selected from 0 and 1; each r is independently selected from 0, 1, and 2; each t is independently selected from 0, 1, 2, 3, and 4; Here, the heterocycle is a monocyclic or bicyclic cycloaliphatic hydrocarbon system having 3 to 12 ring atoms, wherein at least one ring atom is independently a heteroatom selected from O, S, and N, wherein the heterocycle is unsubstituted or substituted with an oxo or imino moiety; Here, the aryl group is a monovalent, monocyclic or bicyclic aromatic hydrocarbon ring system having 6 or 10 carbon atoms; Here, heteroaryl is a 5- to 8-membered aromatic monocyclic ring containing 1 to 3 heteroatoms selected from N, O, and S, with the remaining ring atoms being carbon;

2. X ３ 2. The compound of claim 1, wherein A is CH, A is N, B is CH, Z is N, and the compound is a compound of formula (II), or a pharmaceutically acceptable salt thereof. 【Transformation 3】 (In the formula, X １ is N and CR ８ is selected from X ２ is N and CR ９ is selected from X １ and X ２ At least one of is N, and W is —CHR １１ -, -NR １２ -, -O- and -S(O) ｒ -, L １ , L ２ , R １ , R ２ , R ３ , R ４ , R ５ , R ６ , R ７ , R ８ , R ９ , R １１ , R １２ , m, m1, m2, n, n1, n2, p, p1, p2 and q are defined as in formula (I).

3. (i) R １ teeth, 【Chemistry 4】 and is unsubstituted or independently selected from R Ｘ and / or is substituted with at least one substituent selected from (ii) R １ The substituent R Ｘ Each of the groups independently represents C １－１０ Alkyl group, C ３－１０ Cycloalkyl groups, halogens, CN, NO ２ , -(CR ｃ１ R ｄ１ ) ｔ NR ａ１ R ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ OR ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ C(O)R ａ１ and - (CR ｃ１ R ｄ１ ) ｔ N=S(O)R ａ１ R ｂ１ wherein each of the alkyl and cycloalkyl groups is unsubstituted or independently selected from R Ｙ and is substituted with at least one substituent selected from 3. The compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof.

4. (i) R １ The substituent R Ｘ each independently represents OH, CN, a halogen, C １－１０ alkyl groups, 【Transformation 5】 and / or (ii) R １ teeth, 【Transformation 6】 and / or (iii) R ８ is hydrogen, halogen, C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１０ Cycloalkyl group, C ３－１０ Cycloalkyl-C １－４ Alkyl group, heterocyclic group, heterocyclic-C １－４ Alkyl groups, CN, NO ２ , -NR Ａ８ R Ｂ８ , -OR Ａ８ , -C(O)R Ａ８ , -C(O)OR Ａ８ , -OC(O)R Ａ８ and -S(O) ｒ R Ａ８ wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, and heterocyclic groups is unsubstituted or independently selected from R Ｘ and is substituted with at least one substituent selected from The compound according to any one of claims 1 to 3 or a pharmaceutically acceptable salt thereof.

5. R １ and R ８ together with the atoms to which they are attached form a 5- to 12-membered heterocyclic group containing 1, 2, or 3 heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the ring is unsubstituted or contains 1, 2, or 3 R Ｘ The compound according to any one of claims 1 to 2, or a pharmaceutically acceptable salt thereof, which is substituted with a substituent.

6. (i) a compound of formula (I) 【Transformation 7】 moiety and of formula (II) 【Transformation 8】 The structure of the part is 【Chemistry 9】 wherein R １ and R ８ The heterocycle formed by is unsubstituted or contains one, two or three R Ｘ is substituted with a substituent, 【Chemistry 10】 represents the point of attachment to the rest of the molecule; and / or (ii) Substituent R of 5- to 12-membered heterocyclic group Ｘ each independently represents a halogen, CN, NO ２ , O.H., C. １－８ alkyl groups, 【Chemistry 11】 Selected from:

6. The compound of claim 5 or a pharmaceutically acceptable salt thereof.

7. R ２ The substituent R Ｘ Each of the groups independently represents C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１０ Cycloalkyl group, heterocyclic group, heterocyclic-C １－４ Alkyl group, halogen, CN, -NO ２ , -(CR ｃ１ R ｄ１ ) ｔ NR ａ１ R ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ OR ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ C(O)OR ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ C(O)NR ａ１ R ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ NR ａ１ C(O)R ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ NR ａ１ C(O)OR ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ NR ａ１ C(O)NR ａ１ R ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ S (O) ２ OR ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ S (O) ｒ R ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ NR ａ１ S (O) ｒ R ｂ１ , -(CR ｃ１ R ｄ１ ) ｔ S (O) ｒ NR ａ１ R ｂ１ and - (CR ｃ１ R ｄ１ ) ｔ NR ａ１ S (O) ２ NR ａ１ R ｂ１ wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, and heterocyclic groups is unsubstituted or independently selected from R Ｙ is substituted with at least one substituent selected from The compound according to any one of claims 1 to 6 or a pharmaceutically acceptable salt thereof.

8. (i) R ２ teeth, 【Chemistry 12】 【Chemistry 13】 and / or (ii) W is —CH ２ -, -NR １２ -, -O-, -S(O) ｒ - and -S(O)(=NR １２ ) - selected from 8. The compound according to any one of claims 1 and 3 to 7, or a pharmaceutically acceptable salt thereof.

9. R １２ is hydrogen, a methyl group, an ethyl group, a cyclopropyl group, or —C(O)CH ３ , —C(O)OCH ３ , -S(O) ２ CH ３ , 【Chemistry 14】 The compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof, selected from:

10. R ３ The substituent R Ｘ are each selected from halogen, methyl, ethyl, isopropyl, tert-butyl, propenyl, and cyclopropyl, wherein each of the methyl, ethyl, isopropyl, propenyl, and cyclopropyl groups is unsubstituted or independently selected from halogen, C １－１０ Alkyl groups, CN, NO ２ , -NH ２ and -OH, The compound according to any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof.

11. R ３ teeth, 【Chemistry 15】 Selected from: The compound according to any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof.

12. of formula (I) 【Chemistry 16】 The structure of the part is 【Chemistry 17】 wherein the symbol [Chemistry 18] 9. The compound of any one of claims 1 and 3 to 8, or a pharmaceutically acceptable salt thereof, wherein represents the point of attachment to the remainder of the molecule.

13. (i) R ５ and R ６ is H; and / or (ii) of formula (I) 【Chemistry 19】 The structure of the part is 【Chemistry 20】 wherein the symbol 【Chemistry 21】 represents the point of attachment to the rest of the molecule 13. The compound according to any one of claims 1 and 3 to 12, or a pharmaceutically acceptable salt thereof. 【Request Item 14】 【Chemistry 22】 【Chemistry 23】 【Chemistry 24】 【Chemistry 25】 【Chemistry 26】 【Chemistry 27】 【Chemistry 28】 【Chemistry 29】 【Transformation 30】 【Chemistry 31】 【Chemistry 32】 【Transformation 33】 【Transformation 34】 【Chemistry 35】 【Transformation 36】 【Chemistry 37】 and pharmaceutically acceptable salts thereof.

15. A pharmaceutical composition comprising the compound according to any one of claims 1 to 14 or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier.

16. 16. The pharmaceutical composition of claim 15 for use in the treatment of a cell proliferative disorder or an autoimmune disease.

17. (i) the cell proliferative disorder is selected from breast cancer, ovarian cancer, bladder cancer, uterine cancer, prostate cancer, testicular cancer, lung cancer, esophageal cancer, head and neck cancer, colorectal cancer, kidney cancer, liver cancer, pancreatic cancer, gastric cancer, thyroid cancer, chronic lymphocytic leukemia (CLL), lymphoblastic leukemia, follicular lymphoma, lymphoid malignancies of T-cell or B-cell origin, melanoma, myeloid leukemia, and myeloma; and / or (ii) Autoimmune diseases include allergies, Alzheimer's disease, acute disseminated encephalomyelitis, Addison's disease, ankylosing spondylitis, antiphospholipid syndrome, asthma, atherosclerosis, autoimmune hemolytic anemia, autoimmune hemolytic and thrombocytopenic states, autoimmune hepatitis, autoimmune inner ear disease, bullous pemphigoid, celiac disease, Chagas' disease, chronic obstructive pulmonary disease, chronic idiopathic thrombocytopenic purpura (ITP), Churg-Strauss syndrome, Crohn's disease, dermatomyositis, type 1 diabetes, endometriosis, Goodpasture's syndrome and associated glomerulonephritis and pulmonary hemorrhage, Graves' disease, Guillain-Barré syndrome, and the like. - selected from Barre syndrome, Hashimoto's disease, hidradenitis suppurativa, idiopathic thrombocytopenic purpura, interstitial cystitis, irritable bowel syndrome, lupus erythematosus, localized scleroderma, multiple sclerosis, myasthenia gravis, narcolepsy, neuromyotonia, Parkinson's disease, pemphigus vulgaris, pernicious anemia, polymyositis, primary biliary cirrhosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, schizophrenia, septic shock, scleroderma, Sjogren's disease, systemic lupus erythematosus and associated glomerular nephritis, temporal arteritis, tissue transplant rejection and hyperacute rejection of transplanted organs, vasculitis, vitiligo, and Wegener's granulomatosis, 17. The pharmaceutical composition of claim 16.

Images