Isoindolinone compounds and uses thereof

Abstract

Provided is an isoindolinone compound represented by structural formula (I) or a pharma- ceutically acceptable salt thereof, and its use in the treatment of proliferative diseases. Also provided is a pharmaceutical composition comprising the compound or a salt thereof and a medicamentous carrier. JPEG2024531465000490.jpg60150

Description

[Technical Field]

[0001] The present application relates to the field of medicine. The present application provides an isoindolinone compound represented by structural formula (I) or a pharmaceutically acceptable salt thereof, and its use in the treatment of proliferative diseases. The present application also provides a pharmaceutical composition comprising the compound or a salt thereof described herein and a pharmaceutically acceptable carrier. [Background technology]

[0002] Cancer is a malignant disease that affects human health. There is a huge medical demand for the treatment of various types of cancer. Research has shown that cancer development is complex, involving many factors and multiple steps.

[0003] Cereblon (CRBN) is a cerebron-associated protein. CRBN has multiple functions. It interacts with the ubiquitin ligase E3 regulator Cullins to activate the activity of ubiquitin ligase E3, promoting the ligation of ubiquitin molecules to substrate proteins, thereby achieving ubiquitination. Ubiquitinated proteins are recognized and degraded by the proteasome. For example, CRBN can induce the ubiquitination and degradation of the zinc-finger transcription factors Ikaros (IKZF1) and Aiolos (IKZF3). These two transcription factors function in the proliferation process of cancer cells, and their degradation has a toxic effect on cancer cells. CRBN is a direct target of domides, which can enhance the degradation of tumor-associated factors by CRBN (Science, 2014, 343, 301-305). Domides are also known as CRBN molecular glue. However, domides have numerous toxic and adverse effects, limiting their use as anticancer drugs. For example, thalidomide can cause fetal malformations.

[0004] SALL4 (Spalt-like transcription factor 4) is an embryonic Cys2-His2 (C2H2) zinc finger transcription factor involved in fetal limb development. CRBN molecular glue also degrades SALL4, which can potentially cause toxicity in the body (Nature Chemical Biology, 2018, 14, 981-987). However, the ability of CRBN molecular glue to degrade other factors (SALL4) cannot be predicted from its chemical structure. Therefore, careful analysis of the activity of IKZF degradants against SALL4 is essential during the development process.

[0005] Therefore, the development of more effective and safer cancer treatment methods is urgently needed. IKZF digests with low or no activity against SALL4 appear to be attractive. Summary of the Invention

[0006] The inventors of the present application have surprisingly found that the compound of the present application or a pharmaceutically acceptable salt thereof effectively decomposes IKZF, while significantly reducing the degradation of SALL4, and therefore the compound of the present application or a pharmaceutically acceptable salt thereof has excellent anticancer activity and reduced toxicity and side effects. [Brief explanation of the drawings]

[0007] [Figure 1] Test results of the kinetics experiment of IKZF1 protein degradation.

[0008] Detailed Description of the Invention The present application provides an isoindolinone compound represented by structural formula (I) or a pharmaceutically acceptable salt thereof:

[0009] A first embodiment of the present application is a compound having structural formula (I) or a pharmaceutically acceptable salt thereof:

[0010] [ka] (however, R 1 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl groups, heterocyclic groups, aryl groups, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogen atoms, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups, and wherein the cycloalkyl groups, heterocyclic groups, aryl groups, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogen atoms, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0011] R 1’is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0012] R 2 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0013] R 2’ is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0014] R 3is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0015] R 4 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0016] R 5 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups. a is 0, 1 or 2. b is 0, 1 or 2. X 1 appears each time, independently, 14 Or selected from N. X 2 appears each time, independently, 14’ Or selected from N. X 3 appears each time, independently, 14’’ Or selected from N. X 4 appears each time, independently,14’’’ Or selected from N. R 14 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0017] R 14’ is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0018] R 14’’ is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0019] R 14’’’is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0020] L, when it occurs each time, is independently O, NR 21 , C.R. 22 , C.R. 23 R 24 , N.R. 25 -CR 26 , C.R. 27 -CR 28 Selected from.

[0021] R 21is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0022] R 22 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0023] L is CR 23 R 24 In the case of R 23 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally substituted with 1, 2, 3 or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH or C1-C6 alkyl groups; R 24is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally substituted with 1, 2, 3 or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups; or R 23 and R 24 are joined together with the carbon atoms to which they are attached to form a monocyclic, bicyclic or tricyclic saturated or unsaturated system having 5-14 ring atoms, wherein 0, 1, 2, 3 or 4 of the ring atoms are heteroatoms selected from N, O and S, and the remainder are carbon atoms, and the ring system is optionally substituted with 1, 2, 3 or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0024] L is NR 25 -CR 26 In the case of R 25is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally substituted with 1, 2, 3 or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH or C1-C6 alkyl groups; R 26 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally substituted with 1, 2, 3 or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups; or R 25 and R 26 together with the attached nitrogen and carbon atoms form a monocyclic, bicyclic or tricyclic saturated or unsaturated system having 5-14 ring atoms, in which 0, 1, 2, 3 or 4 of the other ring atoms other than the nitrogen atom are heteroatoms selected from N, O and S, the remainder being carbon atoms, and the ring system is optionally substituted with 1, 2, 3 or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0025] L is CR 27 -CR 28 In the case of R 27 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally substituted with 1, 2, 3 or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH or C1-C6 alkyl groups; R 28 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally substituted with 1, 2, 3 or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups; or R 27 and R 28 are joined together with the carbon atoms to which they are attached to form a monocyclic, bicyclic or tricyclic saturated or unsaturated system having 5-14 ring atoms, wherein 0, 1, 2, 3 or 4 of the ring atoms are heteroatoms selected from N, O and S, and the remainder are carbon atoms, and the ring system is optionally substituted with 1, 2, 3 or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups. J is NR 31 , C.R. 32 R 33 is. g is 0, 1 or 2. K is NR 34 , C.R. 35 R 36 is. h is 0, 1 or 2. R 31is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0026] R 32 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0027] R 33 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0028] R 34is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0029] R 35 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0030] R 36 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl groups, heterocyclic groups, aryl groups, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0031] In a second aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (II) or a pharmaceutically acceptable salt thereof:

[0032] [ka] (however, T is N or CH.

[0033] P, when occurring each time, is independently selected from the group consisting of: absent, hydrogen, halogen, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C2-C6 alkanoyl, C2-C6 alkyl ester, C1-C6 alkylthio, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), -O-C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0034] Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0035] In a third aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (III) or a pharmaceutically acceptable salt thereof:

[0036] [ka] (However, the base

[0037] [ka] represents a mono-, bi- or tricyclic saturated or unsaturated ring system having 5-14 ring atoms, U is N, C or O, Y is N, C or O, said ring system further containing 0, 1, 2, 3 or 4 heteroatoms selected from N, O and S, and said ring system is optionally substituted with 1, 2, 3 or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH or C1-C6 alkyl groups.

[0038] Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0039] In a fourth aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (IV) or a pharmaceutically acceptable salt thereof:

[0040] [ka] (however, R 6 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0041] R 7 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0042] R 8is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups.

[0043] R 9 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0044] R 10 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0045] R 11is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups. c is 0, 1 or 2. d is 0, 1 or 2. e is 0, 1 or 2. Q is CR 12 R 13 where n is 0, 1, or 2. X 5 , O, CR 15 R 16 , or NR 17 Selected from. R 12is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups.

[0046] R 13 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0047] R 15 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0048] R 16is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0049] R 17 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0050] R 18 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups. T is N or CH. X 6 is N or C. X 7 is N or C. X 8 is N or C. X 9 is N or C.

[0051] Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0052] In a fifth aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (V) or a pharmaceutically acceptable salt thereof:

[0053] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0054] In a sixth aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (VI) or a pharmaceutically acceptable salt thereof:

[0055] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0056] In a seventh aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (VII) or a pharmaceutically acceptable salt thereof:

[0057] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0058] In an eighth aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (VIII) or a pharmaceutically acceptable salt thereof:

[0059] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0060] In a ninth aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (IX) or a pharmaceutically acceptable salt thereof:

[0061] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0062] In a tenth aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (X):

[0063] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0064] In an eleventh aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XI) or a pharmaceutically acceptable salt thereof:

[0065] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0066] In a twelfth aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XII) or a pharmaceutically acceptable salt thereof:

[0067] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0068] In a thirteenth aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XIII) or a pharmaceutically acceptable salt thereof:

[0069] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0070] In a fourteenth aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XIV) or a pharmaceutically acceptable salt thereof:

[0071] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0072] In a fifteenth aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XV) or a pharmaceutically acceptable salt thereof:

[0073] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0074] In a sixteenth aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XVI) or a pharmaceutically acceptable salt thereof:

[0075] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0076] In a seventeenth aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XVII) or a pharmaceutically acceptable salt thereof:

[0077] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0078] In an eighteenth aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XVIII) or a pharmaceutically acceptable salt thereof:

[0079] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0080] In a nineteenth aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XIX) or a pharmaceutically acceptable salt thereof:

[0081] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0082] In a twentieth aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XX) or a pharmaceutically acceptable salt thereof:

[0083] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0084] In a twenty-first aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XXI) or a pharmaceutically acceptable salt thereof:

[0085] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0086] In a twenty-second aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XXII) or a pharmaceutically acceptable salt thereof:

[0087] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0088] In a twenty-third aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XXIII) or a pharmaceutically acceptable salt thereof:

[0089] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0090] In a twenty-fourth aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XXIV) or a pharmaceutically acceptable salt thereof:

[0091] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0092] In a twenty-fifth aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XXV) or a pharmaceutically acceptable salt thereof:

[0093] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0094] In a twenty-sixth aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XXVI) or a pharmaceutically acceptable salt thereof:

[0095] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0096] In a twenty-seventh aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XXVII) or a pharmaceutically acceptable salt thereof:

[0097] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0098] In a twenty-eighth aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XXVIII) or a pharmaceutically acceptable salt thereof:

[0099] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0100] In a twenty-ninth aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XXIX) or a pharmaceutically acceptable salt thereof:

[0101] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0102] In a thirtieth aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XXX) or a pharmaceutically acceptable salt thereof:

[0103] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0104] In a thirty-first aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XXXI) or a pharmaceutically acceptable salt thereof:

[0105] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0106] In a thirty-second aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XXXII) or a pharmaceutically acceptable salt thereof:

[0107] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0108] In a thirty-third aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XXXIII) or a pharmaceutically acceptable salt thereof:

[0109] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0110] In a thirty-fourth aspect of the first embodiment of the present application, the compound of structural formula (I) is a compound of structural formula (XXXIV) or a pharmaceutically acceptable salt thereof:

[0111] [ka] (Other variables are as described and defined in the first embodiment and any aspect thereof.)

[0112] In any embodiment and any aspect of the present application, R 1 , R 1’ , R 2 , R 2’ , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 14’ , R 14’’ , R 14’’’ , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28, R 29 , R 30 , R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , R 37 , R 38 , R 39 and P are each independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, a hydroxy group, a nitro group, a cyano group, an amino group, a mercapto group, -COOH, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkyl group, a C1-C6 haloalkoxy group, a hydroxyC1-C6 alkyl group, an aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, a C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. Preferably, any of them, when occurring each time, is independently either absent or selected from hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, and the like.

[0113] [ka] trifluoromethyl, monofluoromethyl, difluoromethyl, 2-fluoroethyl, pentafluoroethyl, and cyanofluorobenzyl groups, more preferably, any of which, when present each time, is independently hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0114] [ka] trifluoromethyl, monofluoromethyl, difluoromethyl, 2-fluoroethyl, pentafluoroethyl, and cyanofluorobenzyl, most preferably any of which, when present each time, is independently hydrogen, fluorine, cyano, methyl, isopropyl, morpholyl,

[0115] [ka] Selected from.

[0116] In any embodiment and any aspect of the present application, R 1 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 1 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0117] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 1 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0118] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 1 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0119] In any embodiment and any aspect of the present application, R 1’ each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 1’each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0120] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 1’ each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0121] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 1 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0122] In any embodiment and any aspect of the present application, R 2 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 2 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0123] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 2 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0124] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 2 is independently selected from hydrogen, fluorine, chlorine, bromine, cyano, trifluoromethyl, methoxy, ethoxy, methyl, and isopropyl in each occurrence.

[0125] In any embodiment and any aspect of the present application, R 2’each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 2’ each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0126] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 2’ each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0127] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 2’is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0128] In any embodiment and any aspect of the present application, R 3 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 3 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0129] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 3 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0130] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 3 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0131] In any embodiment and any aspect of the present application, R 4 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 4 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0132] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 4each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0133] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 4 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0134] In any embodiment and any aspect of the present application, R 5 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 5 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0135] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 5 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0136] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 5 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0137] In any embodiment and any aspect of the present application, R 6 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 6each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0138] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 6 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0139] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 6 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0140] In any embodiment and any aspect of the present application, R 7 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 7 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0141] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 7 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0142] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 7 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0143] In any embodiment and any aspect of the present application, R 8each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 8 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0144] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 8 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0145] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 8is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0146] In any embodiment and any aspect of the present application, R 9 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 9 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0147] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 9 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0148] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 9 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0149] In any embodiment and any aspect of the present application, R 10 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 10 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0150] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 10each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0151] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 10 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0152] In any embodiment and any aspect of the present application, R 11 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 11 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0153] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 11 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0154] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 11 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0155] In any embodiment and any aspect of the present application, R 12 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 12each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0156] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 12 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0157] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 12 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0158] In any embodiment and any aspect of the present application, R 13 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 13 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0159] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 13 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0160] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 13 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0161] In any embodiment and any aspect of the present application, R 14each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 14 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0162] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 14 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0163] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 14is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0164] In any embodiment and any aspect of the present application, R 14’ each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 14’ each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0165] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 14’ each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0166] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 14’ is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0167] In any embodiment and any aspect of the present application, R 14’’ each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 14’’ each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0168] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 14’’each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0169] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 14’’ is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0170] In any embodiment and any aspect of the present application, R 14’’’ each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 14’’’ each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0171] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 14’’’ each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0172] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 14’’’ is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0173] In any embodiment and any aspect of the present application, R 15 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 15each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0174] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 15 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0175] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 15 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0176] In any embodiment and any aspect of the present application, R 16 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 16 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0177] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 16 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0178] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 16 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0179] In any embodiment and any aspect of the present application, R 17each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 17 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0180] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 17 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0181] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 17is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0182] In any embodiment and any aspect of the present application, R 18 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 18 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0183] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 18 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0184] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 18 is independently selected from hydrogen, fluorine, chlorine, cyano, methyl, or isopropyl at each occurrence.

[0185] In any embodiment and any aspect of the present application, R 21 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 21 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0186] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 21each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0187] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 21 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0188] In any embodiment and any aspect of the present application, R 22 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 22 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0189] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 22 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0190] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 22 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0191] In any embodiment and any aspect of the present application, R 23 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 23each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0192] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 23 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0193] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 23 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0194] In any embodiment and any aspect of the present application, R 24 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 24 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0195] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 24 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0196] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 24 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0197] In any embodiment and any aspect of the present application, R 25each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 25 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0198] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 25 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0199] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 25is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0200] In any embodiment and any aspect of the present application, R 26 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 26 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0201] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 26 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0202] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 26 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0203] In any embodiment and any aspect of the present application, R 27 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 27 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0204] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 27each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0205] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 27 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0206] In any embodiment and any aspect of the present application, R 28 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 28 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0207] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 28 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0208] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 28 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0209] In any embodiment and any aspect of the present application, R 31 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 31each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0210] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 31 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0211] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 31 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0212] In any embodiment and any aspect of the present application, R 32 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 32 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0213] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 32 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0214] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 32 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0215] In any embodiment and any aspect of the present application, R 33each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 33 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0216] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 33 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0217] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 33is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0218] In any embodiment and any aspect of the present application, R 34 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 34 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0219] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 34 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0220] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 34 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0221] In any embodiment and any aspect of the present application, R 35 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 35 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0222] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 35each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0223] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 35 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0224] In any embodiment and any aspect of the present application, R 36 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. 36 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0225] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. More preferably, R 36 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0226] [ka] It is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group. Most preferably, R 36 is independently selected from hydrogen, fluorine, cyano, methyl, and isopropyl when it occurs each time.

[0227] In any embodiment and any aspect of the present application, a is 0. In any embodiment and any aspect of the present application, a is 1. In any embodiment and any aspect of the present application, a is 2.

[0228] In any embodiment and any aspect of the present application, b is 0. In any embodiment and any aspect of the present application, b is 1. In any embodiment and any aspect of the present application, b is 2.

[0229] In any embodiment and any aspect of the present application, c is 0. In any embodiment and any aspect of the present application, c is 1. In any embodiment and any aspect of the present application, c is 2.

[0230] In any embodiment and any aspect of the present application, d is 0. In any embodiment and any aspect of the present application, d is 1. In any embodiment and any aspect of the present application, d is 2.

[0231] In any embodiment and any aspect of the present application, e is 0. In any embodiment and any aspect of the present application, e is 1. In any embodiment and any aspect of the present application, e is 2.

[0232] In any embodiment and any aspect of the present application, n is 0. In any embodiment and any aspect of the present application, n is 1. In any embodiment and any aspect of the present application, n is 2.

[0233] In any embodiment and any aspect of the present application, g is 0. In any embodiment and any aspect of the present application, g is 1. In any embodiment and any aspect of the present application, g is 2.

[0234] In any embodiment and any aspect of the present application, h is 0. In any embodiment and any aspect of the present application, h is 1. In any embodiment and any aspect of the present application, h is 2.

[0235] In any embodiment and any aspect of the present application, X 1 is N. In any embodiment and any aspect of the present application, X 1 is CR 14 is.

[0236] In any embodiment and any aspect of the present application, X 2 is N. In any embodiment and any aspect of the present application, X 2 is CR 14’ is.

[0237] In any embodiment and any aspect of the present application, X 3 is N. In any embodiment and any aspect of the present application, X 3 is CR 14’’ is.

[0238] In any embodiment and any aspect of the present application, X 4 is N. In any embodiment and any aspect of the present application, X 4 is CR 14’’’ is.

[0239] In any embodiment and any aspect of the present application, X 5 is O. In any embodiment and any aspect of the present application, X 5 is CR 15 R 16 In any embodiment and any aspect of the present application, X 5 is NR 17 is.

[0240] In any embodiment and any aspect of the present application, X 6 is N. In any embodiment and any aspect of the present application, X 6 is C.

[0241] In any embodiment and any aspect of the present application, X 7 is N. In any embodiment and any aspect of the present application, X 7 is C.

[0242] In any embodiment and any aspect of the present application, X 8 is N. In any embodiment and any aspect of the present application, X 6 is C.

[0243] In any embodiment and any aspect of the present application, X 9 is N. In any embodiment and any aspect of the present application, X 9 is C.

[0244] In any embodiment and any aspect of the present application, T is N. In any embodiment and any aspect of the present application, T is CH.

[0245] In any embodiment and any aspect of the present application, U is N. In any embodiment and any aspect of the present application, U is C. In any embodiment and any aspect of the present application, U is O.

[0246] In any embodiment and any aspect of the present application, Y is N. In any embodiment and any aspect of the present application, Y is C. In any embodiment and any aspect of the present application, Y is O.

[0247] In any embodiment and any aspect of the present application, J is NR 31 In any embodiment and any aspect of the present application, J is CR 32 R 33 is.

[0248] In any embodiment and any aspect of the present application, K is NR 34 In any embodiment and any aspect of the present application, K is CR 35 R 36 is.

[0249] In any embodiment and any aspect of the present application, L is O. In any embodiment and any aspect of the present application, L is NR 21 In any embodiment and any aspect of the present application, L is CR 22 In any embodiment and any aspect of the present application, L is CR 23 R 24 In any embodiment and any aspect of the present application, L is NR 25 -CR 26 In any embodiment and any aspect of the present application, L is CR 27 -CR 28 is.

[0250] In any embodiment and any aspect of the present application,

[0251] [ka] is a five-membered monocyclic ring. In any embodiment and any aspect of the present application,

[0252] [ka] is a 6-membered monocyclic ring. In any embodiment and any aspect of the present application,

[0253] [ka] is a 7-membered monocyclic ring. In any embodiment and any aspect of the present application,

[0254] [ka] is substituted with one substituent. In any embodiment and any aspect of the present application,

[0255] [ka] is substituted with two substituents. In any embodiment and any aspect of the present application,

[0256] [ka] teeth

[0257] [ka] In any embodiment and any aspect of the present application,

[0258] [ka] is a five-membered monocyclic ring. In any embodiment and any aspect of the present application,

[0259] [ka] is a 6-membered monocyclic ring. In any embodiment and any aspect of the present application,

[0260] [ka] is a 7-membered monocyclic ring. In any embodiment and any aspect of the present application,

[0261] [ka] is substituted with one substituent. In any embodiment and any aspect of the present application,

[0262] [ka] is substituted with two substituents. In any embodiment and any aspect of the present application,

[0263] [ka] teeth

[0264] [ka] is.

[0265] In any embodiment and any aspect thereof of the present application, P, at each occurrence, is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, —COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, —C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups. Preferably, P, in each occurrence, is independently absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, or

[0266] [ka] Preferably, P is selected from the group consisting of trifluoromethyl, monofluoromethyl, difluoromethyl, 2-fluoroethyl, pentafluoroethyl, and cyanofluorobenzyl. More preferably, P, when present in each occurrence, is independently hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0267] [ka] Preferably, P is selected from the group consisting of trifluoromethyl, monofluoromethyl, difluoromethyl, 2-fluoroethyl, pentafluoroethyl, and cyanofluorobenzyl. Most preferably, P, in each occurrence, is independently selected from hydrogen, fluorine, cyano, methyl, isopropyl, t-butyl, trifluoromethyl, morpholyl,

[0268] [ka]

[0269] Selected from.

[0270] In one aspect, the compound of the present application has the following structural formula (I): or a pharmaceutically acceptable salt thereof:

[0271] [ka] (however, R 1 , R 3 , R 1’ , R 2’ , R 4 , R 5 are both hydrogen. a and b are both 2. g and h are both 2. J and K are both CH2. L is O. X 2 and X 4 are both CH. X 1 are N, CH, CF, and C-CH3. X 3 is N, CH, CF, C-CH3, and R 2 is hydrogen, fluorine, cyano, trifluoromethyl, methoxy, ethoxy or methyl.

[0272] In one aspect, the compound of the present application is a compound of structural formula (XIII) or a pharmaceutically acceptable salt thereof:

[0273] [ka] (however, T is N. R 2 is hydrogen, fluorine, a cyano group, a trifluoromethyl group, a methoxy group, an ethoxy group, or a methyl group. X 8 is C and R 18 is hydrogen, fluorine, chlorine, a cyano group, or a methyl group. -(Q) n - is -(CH2)- or -(CH2)2-. X 5 is O. X1 are N, CH, CF, and C-CH3. X 2 are N, CH, CF, and C-CH3. X 3 are N, CH, CF, and C-CH3. X 4 are N, CH, CF, and C-CH3. X 6 are N, CH, CF, and C-CH3. X 7 are N, CH, CF, and C-CH3. X 9 are N, CH, CF, and C-CH3.

[0274] In one aspect, the compound of the present application is a compound of structural formula (XIV) or a pharmaceutically acceptable salt thereof:

[0275] [ka] (however, T is N. R 2 is hydrogen, fluorine, cyano, trifluoromethyl, methoxy, ethoxy or methyl. X 8 is C and R 18 is hydrogen, fluorine, chlorine, a cyano group, or a methyl group. -(Q) n - is -(CH2)- or -(CH2)2-. X 5 is O. X 1 are N, CH, CF, and C-CH3. X 2 are N, CH, CF, and C-CH3. X 3 are N, CH, CF, and C-CH3. X 4 are N, CH, CF, and C-CH3. X 6 are N, CH, CF, and C-CH3. X 7are N, CH, CF, and C-CH3. X 9 are N, CH, CF, and C-CH3.

[0276] In one aspect, the compound of the present application is a compound of structural formula (XV) or a pharmaceutically acceptable salt thereof:

[0277] [ka] (however, T is N. R 2 is hydrogen, fluorine, a cyano group, a trifluoromethyl group, a methoxy group, an ethoxy group, or a methyl group. X 8 is C and R 18 is hydrogen, fluorine, chlorine, a cyano group, or a methyl group. -(Q) n - is -(CH2)- or -(CH2)2-. X 5 is O. X 1 are N, CH, and CF. X 2 are N, CH, CF, and C-CH3. X 3 are N, CH, CF, and C-CH3. X 4 are N, CH, CF, and C-CH3. X 6 are N, CH, CF, and C-CH3. X 7 are N, CH, CF, and C-CH3. X 9 are N, CH, CF, and C-CH3.

[0278] In one aspect, the compound of the present application is a compound of structural formula (XVI) or a pharmaceutically acceptable salt thereof:

[0279] [ka] (however, T is N. R 2 is hydrogen, fluorine, a cyano group, a trifluoromethyl group, a methoxy group, an ethoxy group, or a methyl group. X 8 is C and R 18 is hydrogen, fluorine, chlorine, a cyano group, or a methyl group. -(Q) n - is -(CH2)- or -(CH2)2-. X 5 is O. X 1 are N, CH, CF, and C-CH3. X 2 are N, CH, CF, and C-CH3. X 3 are N, CH, CF, and C-CH3. X 4 are N, CH, CF, and C-CH3. X 6 are N, CH, CF, and C-CH3. X 7 are N, CH, CF, and C-CH3. X 9 are N, CH, CF, and C-CH3.

[0280] In one aspect, the compound of the present application is a compound of structural formula (XVII) or a pharmaceutically acceptable salt thereof:

[0281] [ka] (however, T is N. R 2 is hydrogen, fluorine, a cyano group, a trifluoromethyl group, a methoxy group, an ethoxy group, or a methyl group. R 18 is hydrogen, fluorine, chlorine, a cyano group, or a methyl group. X 1 are N, CH, CF, and C-CH3. X 3 are N, CH, CF, and C-CH3. X 6 are N, CH, CF, and C-CH3.

[0282] In one aspect, the compound of the present application is a compound of structural formula (XVIII) or a pharmaceutically acceptable salt thereof:

[0283] [ka] (however, T is N. R 2 is hydrogen, fluorine, a cyano group, a trifluoromethyl group, a methoxy group, an ethoxy group, or a methyl group. R 18 is hydrogen, fluorine, chlorine, a cyano group, or a methyl group. X 1 are N, CH, CF, and C-CH3. X 3 are N, CH, CF, and C-CH3. X 6 are N, CH, CF, and C-CH3.

[0284] In one aspect, the compound of the present application is a compound of structural formula (XIX) or a pharmaceutically acceptable salt thereof:

[0285] [ka] (however, T is N. R 2 is hydrogen, fluorine, a cyano group, a trifluoromethyl group, a methoxy group, an ethoxy group, or a methyl group. R 18 is hydrogen, fluorine, chlorine, a cyano group, or a methyl group. X 1 are N, CH, CF, and C-CH3. X 3 are N, CH, CF, and C-CH3. X 6 are N, CH, CF, and C-CH3.

[0286] In one aspect, the compound of the present application is a compound of structural formula (XX) or a pharmaceutically acceptable salt thereof:

[0287] [ka] (however, T is N. R 2 is hydrogen, fluorine, a cyano group, a trifluoromethyl group, a methoxy group, an ethoxy group, or a methyl group. R 18 is hydrogen, fluorine, chlorine, a cyano group, or a methyl group. X 1 are N, CH, CF, and C-CH3. X 3 are N, CH, CF, and C-CH3. X 6 are N, CH, CF, and C-CH3.

[0288] In one aspect, the compound of the present application is a compound of structural formula (XXIII) or a pharmaceutically acceptable salt thereof:

[0289] [ka] (however, R 2 is hydrogen, fluorine, chlorine, bromine, cyano, trifluoromethyl, methoxy, ethoxy or methyl. X 1 are N, CH, CF, and C-CH3. X 3 are N, CH, CF, and C-CH3. -(J) g - is -(CH2)- or -(CH2)2-. -(K) h - is -(CH2)- or -(CH2)2-.

[0290] [ka] is a 5-, 6- or 7-membered monocyclic ring. U is C, N or O. Y is C, N, or O. In this aspect,

[0291] [ka] teeth

[0292] [ka] is preferred.

[0293] In one aspect, the compound of the present application is a compound of structural formula (XXIV) or a pharmaceutically acceptable salt thereof:

[0294] [ka] (however, R 2 is hydrogen, fluorine, chlorine, bromine, cyano, trifluoromethyl, methoxy, ethoxy or methyl. X 1 are N, CH, CF, and C-CH3. X 3 are N, CH, CF, and C-CH3. -(J) g - is -(CH2)- or -(CH2)2-. -(K) h - is -(CH2)- or -(CH2)2-.

[0295] [ka] is a 5-, 6- or 7-membered monocyclic ring. U is C, N or O. Y is C, N, or O. In this aspect,

[0296] [ka] teeth

[0297] [ka]

[0298] In one aspect, the compound of the present application is a compound of structural formula (XXV) or a pharmaceutically acceptable salt thereof:

[0299] [ka] (however, R 2 is hydrogen, fluorine, chlorine, bromine, cyano, trifluoromethyl, methoxy, ethoxy or methyl. X 1 are N, CH, CF, and C-CH3. X 3 are N, CH, CF, and C-CH3.

[0300] [ka] is a 5-, 6- or 7-membered monocyclic ring. Y is C, N, or O. In this aspect,

[0301] [ka] teeth

[0302] [ka] is preferred.

[0303] In one aspect, the compound of the present application is a compound of structural formula (XXVI) or a pharmaceutically acceptable salt thereof:

[0304] [ka] (however, R 2 is hydrogen, fluorine, chlorine, bromine, cyano, trifluoromethyl, methoxy, ethoxy or methyl. X 1 are N, CH, CF, and C-CH3. X 3 are N, CH, CF, and C-CH3.

[0305] [ka] is a 5-, 6- or 7-membered monocyclic ring. Y is C, N, or O. In this aspect,

[0306] [ka] teeth

[0307] [ka] is preferred.

[0308] In one aspect, the compound of the present application is a compound of structural formula (XXIX) or a pharmaceutically acceptable salt thereof:

[0309] [ka] (however, T is C or N. -(J) g - is -(CH2)- or -(CH2)2-. -(K) h - is -(CH2)- or -(CH2)2-. R 2 is hydrogen, fluorine, chlorine, bromine, cyano, trifluoromethyl, methoxy, ethoxy or methyl. X 1 are N, CH, CF, and C-CH3. X 3 are N, CH, CF, and C-CH3.

[0310] P is hydrogen, fluorine, cyano group, methyl group, isopropyl group, t-butyl group, trifluoromethyl group, morpholyl group,

[0311] [ka] )

[0312] In one aspect, the compound of the present application is a compound of structural formula (XXX) or a pharmaceutically acceptable salt thereof:

[0313] [ka] (however, T is C or N. -(J) g - is -(CH2)- or -(CH2)2-. -(K) h - is -(CH2)- or -(CH2)2-. R 2 is hydrogen, fluorine, chlorine, bromine, cyano, trifluoromethyl, methoxy, ethoxy or methyl. X 1 are N, CH, CF, and C-CH3. X 3 are N, CH, CF, and C-CH3. P is hydrogen, fluorine, cyano group, methyl group, isopropyl group, t-butyl group, trifluoromethyl group, morpholyl group,

[0314] [ka] )

[0315] In one aspect, the compound of the present application is a compound of structural formula (XXXI) or a pharmaceutically acceptable salt thereof:

[0316] [ka] (however, T is C or N. R 2 is hydrogen, fluorine, chlorine, bromine, cyano, trifluoromethyl, methoxy, ethoxy or methyl. X 1 are N, CH, CF, and C-CH3. X 3 are N, CH, CF, and C-CH3. P is hydrogen, fluorine, cyano group, methyl group, isopropyl group, t-butyl group, trifluoromethyl group, morpholyl group,

[0317] [ka] )

[0318] In one aspect, the compound of the present application is a compound of structural formula (XXXII) or a pharmaceutically acceptable salt thereof:

[0319] [ka] (however, T is C or N. R 2 is hydrogen, fluorine, chlorine, bromine, cyano, trifluoromethyl, methoxy, ethoxy or methyl. X 1 are N, CH, CF, and C-CH3. X 3 are N, CH, CF, and C-CH3. P is hydrogen, fluorine, cyano group, methyl group, isopropyl group, t-butyl group, trifluoromethyl group, morpholyl group,

[0320] [ka] )

[0321] In one aspect, the compound of the present application is a compound of structural formula (XXXIII) or a pharmaceutically acceptable salt thereof:

[0322] [ka] (however, T is C or N. R 2 is hydrogen, fluorine, chlorine, bromine, cyano, trifluoromethyl, methoxy, ethoxy or methyl. X 1 are N, CH, CF, and C-CH3. X 3 are N, CH, CF, and C-CH3. P is hydrogen, fluorine, cyano group, methyl group, isopropyl group, t-butyl group, trifluoromethyl group, morpholyl group,

[0323] [ka] )

[0324] In one aspect, the compound of the present application is a compound of structural formula (XXXIV) or a pharmaceutically acceptable salt thereof:

[0325] [ka] (however, T is C or N. R 2 is hydrogen, fluorine, chlorine, bromine, cyano, trifluoromethyl, methoxy, ethoxy or methyl. X 1 are N, CH, CF, and C-CH3. X 3 are N, CH, CF, and C-CH3. P is hydrogen, fluorine, cyano group, methyl group, isopropyl group, t-butyl group, trifluoromethyl group, morpholyl group,

[0326] [ka] )

[0327] The term "pharmaceutically acceptable salt" refers to a pharmaceutically acceptable organic or inorganic salt of a compound of the present invention. Exemplary salts include, but are not limited to, sulfate, citrate, acetate, oxalate, chloride, bromide, iodide, nitrate, bisulfate, phosphate, acid phosphate, isonicotinate, lactate, salicylate, acid citrate, tartrate, oleate, tannate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisate, fumarate, gluconate, glucuronate, saccharate, formate, benzoate, glutamate, methanesulfonate "mesylate," ethanesulfonate, benzenesulfonate, p-toluenesulfonate, pamoate (i.e., 1,1'-methylenebis(2-hydroxy-3-naphthoate)), alkali metal (e.g., sodium or potassium) salts, alkaline earth metal (e.g., magnesium) salts, and ammonium salts. Pharmaceutically acceptable salts may also contain another molecule, such as an acetate ion, succinate ion, or other counterion. The counterion may be any organic or inorganic moiety that stabilizes the charge on the parent compound. Pharmaceutically acceptable salts may also have more than one charged atom in their structure. Multiple charged atoms are an example of some pharmaceutically acceptable salts, which may have multiple counterions. Thus, a pharmaceutically acceptable salt may have one or more charged atoms and / or one or more counterions.

[0328] When the compound of the present invention is a base, the desired pharmaceutically acceptable salt can be prepared by any suitable method available in the art, for example, by treating the free base with an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, methanesulfonic acid, phosphoric acid, or an organic acid such as acetic acid, maleic acid, succinic acid, mandelic acid, fumaric acid, malonic acid, pyruvic acid, oxalic acid, glycolic acid, salicylic acid, pyranosidyl acids such as glucuronic acid and galacturonic acid, α-hydroxy acids such as citric acid and tartaric acid, amino acids such as aspartic acid or glutamic acid, aromatic acids such as benzoic acid and cinnamic acid, or sulfonic acids such as p-toluenesulfonic acid and ethanesulfonic acid.

[0329] If the compound of the invention is an acid, the desired pharmaceutically acceptable salt can be prepared by any suitable method, for example, by treating the free acid with an inorganic or organic base, such as an amine (primary, secondary, or tertiary), alkali metal hydroxide, or alkaline earth metal hydroxide. Illustrative examples of suitable salts include, but are not limited to, organic salts derived from amino acids such as glycine and arginine, ammonia, primary, secondary, and tertiary amines, and cyclic amines such as piperidine, morpholine, and piperazine, and inorganic salts derived from sodium, calcium, potassium, magnesium, manganese, iron, copper, zinc, aluminum, and lithium.

[0330] The term "pharmaceutically acceptable" means that the substance or composition is chemically and / or toxicologically suitable for use with other ingredients in the formulation and / or the mammal being treated therewith.

[0331] The compounds of the present application may exist in various stereoisomeric forms. The term "stereoisomer" refers to compounds with similar chemical constitution and connectivity, but with different orientations of their atoms in space that cannot be converted into each other by rotating a single bond. "Stereoisomer" may also include "diastereomers" and "enantiomers." "Diastereomers" are stereoisomers with two or more chiral centers whose molecules are non-mirror images of each other. "Enantiomers" are two stereoisomers of a compound that are non-superimposable mirror images of each other. "R" and "S" refer to the configuration of substituents around one or more chiral atoms. The compounds of the present application can be prepared as single isomers by chiral synthesis or resolution from an isomeric mixture. The disclosed compounds may have one or more chiral centers, and each chiral center may independently exist in the R or S configuration. If the absolute stereochemistry of a chiral center has not been determined, the stereochemical configuration may be indicated by an (*) at the given center. In one embodiment, the compounds described herein may exist in optically active or racemic form. It should be noted that the compounds described herein include racemic, optically active, positional and stereoisomeric forms or combinations thereof that possess the therapeutically useful properties described herein.

[0332] In one embodiment, the compounds described herein contain one or more chiral centers. These compounds can be prepared by any means, including stereoselective synthesis, enantioselective synthesis, or resolution of enantiomeric or diastereomeric mixtures. Resolution of the compounds and their isomers can be achieved by any means, including, but not limited to, chemical processes, enzymatic catalysis, fractional crystallization, distillation, and chromatography.

[0333] definition The term "substituted" refers to the replacement of any one or more hydrogens on a given atom or group with a moiety selected from a given group, provided that the normal valence of the given atom is not exceeded.

[0334] An "alkyl group" is a branched or straight-chain saturated aliphatic hydrocarbon group. In one embodiment, an alkyl group contains 1 to about 12 carbon atoms, more typically 1 to about 6 carbon atoms or 1 to about 4 carbon atoms. In one embodiment, an alkyl group contains 1 to about 8 carbon atoms. In some embodiments, an alkyl group is C1-C2, C1-C3, or C1-C6. As used herein, a range refers to any one of the ranges, each of which is an independent type of alkyl group. For example, as used herein, the term C1-C6 alkyl group refers to any one of the ranges, each of which is an independent type of alkyl group. For example, as used herein, the term C1-C4 alkyl group refers to any one of the ranges, each of which is an independent type of alkyl group. When a CO-Cn alkyl group is used herein in combination with another group, such as a (C3-C7 cycloalkyl)CO-C4 alkyl group or a group represented by a —CO-C4 alkyl(C3-C7 cycloalkyl) group, the cycloalkyl group may be directly attached via a single covalent bond (CO alkyl) or may be linked via an alkyl chain (in this case, 1, 2, 3, or 4 carbon atoms). The alkyl group may also be linked via another group, e.g., a heteroatom, such as an —O—CO-C4 alkyl(C3-C7 cycloalkyl) group. Illustrative examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, n-pentyl, isopentyl, t-pentyl, neopentyl, n-hexyl, 2-methylpentane, 3-methylpentane, 2,2-dimethylbutane, and 2,3-dimethylbutane. In one embodiment, the alkyl group is optionally substituted as described above.

[0335] An "alkenyl group" is a branched or straight-chain aliphatic hydrocarbon group containing one or more carbon-carbon double bonds, which may occur at any stable point along the chain. Non-limiting examples include C2-C8 alkenyl groups, C2-C6 alkenyl groups, and C2-C4 alkenyl groups. As used herein, a given range refers to each independent type of alkenyl group, as described above for alkyl groups. Examples of alkenyl groups include, but are not limited to, vinyl and propenyl groups. In one embodiment, an alkenyl group is optionally substituted as described above.

[0336] An "alkynyl group" is a branched or straight-chain aliphatic hydrocarbon group containing one or more carbon-carbon triple bonds, which may occur at any stable point along the chain, such as a C2-C8 alkynyl group or a C2-C6 alkynyl group. As used herein, a range refers to each independent type of alkynyl group, as described above for alkyl groups. Examples of alkynyl groups include, but are not limited to, ethynyl, propargyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, and 5-hexynyl. In one embodiment, an alkynyl group is optionally substituted as described above.

[0337] An "alkoxy group" is an alkyl group as defined above covalently bonded through an oxygen bridge (-O-). Illustrative examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, 2-butoxy, t-butoxy, n-pentoxy, 2-pentoxy, 3-pentoxy, isopentoxy, neopentoxy, n-hexoxy, 2-hexoxy, 3-hexoxy, and 3-methylpentoxy. Similarly, an "alkylthio group" or "thioalkyl group" is an alkyl group as defined above having the specified number of carbon atoms covalently bonded through a sulfur bridge (-S-). In one embodiment, the alkoxy group is optionally substituted as defined above.

[0338] An "alkenyloxy group" is an alkenyl group as defined above covalently linked via an oxygen bridge (-O-) to the group substituted thereby.

[0339] An "alkanoyl group" is an alkyl group as defined above covalently bonded via a carbonyl (C=O) bridge. The carbon of the carbonyl group is included in the carbon number, i.e., a C2 alkanoyl group is a CH3(C=O)- group. In one embodiment, the alkanoyl group is optionally substituted as defined above.

[0340] An "alkyl ester" is an alkyl group, as described herein, covalently attached via an ester bond. The ester bond may be in any orientation, and includes, for example, a group of the formula -O(C=O)alkyl or a group of the formula -(C=O)Oalkyl.

[0341] A "carbocyclic group," "carbocycle," or "cycloalkyl group" is a saturated or partially unsaturated (i.e., non-aromatic) group containing all carbon ring atoms. A carbocyclic group is typically a single ring containing 3 to 7 carbon atoms or two fused rings each containing 3 to 7 carbon atoms. The cycloalkyl substituent may be pendant from a substituted nitrogen or carbon atom, or two optionally substituted carbon atoms may have a cycloalkyl linked as a spirocyclic group. Illustrative carbocyclic rings include cyclohexenyl, cyclohexyl, cyclopentenyl, cyclopentyl, butyl, and propyl rings. In one embodiment, the carbocyclic ring is optionally substituted as described above. In one embodiment, a cycloalkyl group is a partially unsaturated (i.e., non-aromatic) group containing all carbon ring atoms.

[0342] A "carbocycle-oxy group" is a monocyclic carbocycle or a mono- or bicyclic carbocycle group as defined above linked through an oxygen -O- to the group it replaces.

[0343] A "haloalkyl group" is a branched or straight-chain alkyl group substituted with one or more halogen atoms, up to the maximum allowable number of halogen atoms. Examples of haloalkyl groups include, but are not limited to, trifluoromethyl, monofluoromethyl, difluoromethyl, 2-fluoroethyl, and pentafluoroethyl groups.

[0344] A "haloalkoxy group" is a haloalkyl group as defined herein linked through an oxygen bridge (the oxygen of the alcohol radical).

[0345] A "hydroxyalkyl group" is an alkyl group as defined above substituted with at least one hydroxy group.

[0346] An "aminoalkyl group" is an alkyl group as defined above that is substituted with at least one amino substituent.

[0347] "Halogen" refers independently to any of fluorine, chlorine, bromine and iodine.

[0348] An "aryl group" is an aromatic ring or rings containing only carbon atoms. In one embodiment, an aryl group contains 1 to 3 single or fused rings and 6 to 18 (e.g., 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18) ring atoms, with no heteroatoms. Where specified, such aryl groups may be substituted with carbon or non-carbon atoms or groups. Such substitution may include fusion to a 5- to 7-membered saturated ring group, optionally containing one or two heteroatoms independently selected from N, O, and S, to form, for example, a 3,4-methylenedioxyphenyl group. Examples of aryl groups include phenyl and naphthyl groups (including 1-naphthyl and 2-naphthyl groups). In one embodiment, an aryl group is a side group. An example of a side ring is a phenyl group substituted with a phenyl group. In one embodiment, an aryl group is optionally substituted as described above. Aryl groups include bicyclic groups, which include saturated, partially unsaturated rings or aromatic rings fused with aromatic carbocyclic or heterocyclic rings. Typical aryl groups include, but are not limited to, groups derived from benzene (phenyl), substituted benzene, naphthalene, anthracene, indenyl, indanyl, 1,2-dihydronaphthalene, 1,2,3,4-tetrahydronaphthyl, and the like. Preferably, the aryl group is a phenyl group.

[0349] As used herein, the term "heterocycle" refers to a saturated or partially unsaturated (i.e., having one or more double and / or triple bonds in the ring and not being aromatic) carbocyclic ring group having 3 to 18 (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18) ring atoms, at least one ring atom of which is a heteroatom selected from nitrogen, oxygen, phosphorus, and sulfur, the remaining ring atoms being C, and one or more of which ring atoms are optionally independently substituted with one or more of the above-described substituents. A heterocycle may be a monocycle having 3 to 7 ring members (2 to 6 carbon atoms and 1 to 4 heteroatoms selected from N, O, P, and S) or a bicycle having 6 to 10 ring members (4 to 9 carbon atoms and 1 to 6 heteroatoms selected from N, O, P, and S), such as a bicyclo[4,5], [5,5], [5,6], or [6,6] system. In one embodiment, the only heteroatom is nitrogen. In one embodiment, the only heteroatom is oxygen. In one embodiment, the only heteroatom is sulfur. Heterocycles are described in Paquette, Leo A.; "Principles of Modern Heterocyclic Chemistry" (WA Benjamin, New York, 1968), especially Chapters 1, 3, 4, 6, 7, and 9; "The Chemistry of Heterocyclic Compounds, A series of Monographs" (John Wiley & Sons, New York, 1950 to present), especially Chapters 13, 14, 16, 19, and 28; and J. Am. Chem. Soc. (1960) 82:5566.Illustrative examples of heterocycles are pyrrolidyl, dihydrofuryl, tetrahydrothienyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidyl, piperidinonyl, morpholyl, thiomorpholyl, thioxanyl, piperazinyl, homopiperazinyl, azetidyl, oxetanyl, thietanyl, homopiperidinyl, oxepanyl, thiepanyl, oxazepinyl, diazepinyl, thiazepinyl, 2-pyrrolinyl, 3-pyrrolinyl, indolinyl, 2H-pyranyl, 4H-pyranyl, dioxanyl, 1,3-dioxolanyl, pyrazolyl, and the like. nyl group, dithianyl group, dithiolanyl group, dihydropyranyl group, dihydrothienyl group, dihydrofuranyl group, tetrahydroisoquinolinyl group, pyrazolinyl group, imidazolinyl group, imidazolidinyl group, 2-oxa-5-azabicyclo[2.2.2]hexane, 3-oxa-8-azabicyclo[3.2.1]hexane, 8-oxa-3-azabicyclo[3.2.1]hexane, 6 Examples of heterocyclic groups include, but are not limited to, -oxa-3-azabicyclo[3.1.1]heptane, 2-oxa-5-azabicyclo[2.2.1]heptane, 3-azabicyclo[3.1.0]hexanyl, 3-azabicyclo[4.1.0]heptanyl, azabicyclo[2.2.2]hexanyl, 3H-indolyl, quinolizidinyl, N-pyridyl urea, and pyrrolopyrimidine. Spiro moieties are also included within the scope of this definition. Illustrative examples of heterocyclic groups in which one or two ring carbon atoms are substituted with oxo (=O) moieties are pyrimidinonyl and 1,1-dioxothiomorpholyl. Heterocyclic groups herein are optionally independently substituted with one or more substituents described herein. "Heterocyclic group" includes "heterocycloalkyl group." "Heterocycloalkyl group" is a saturated ring group. For example, it may have 1, 2, 3, or 4 heteroatoms independently selected from N, S, and O, with the remaining ring atoms being carbon. In one exemplary embodiment, nitrogen is the heteroatom. Monocyclic heterocycloalkyl groups typically have 3 to about 8 ring atoms, or 4 to 6 ring atoms.Illustrative examples of heterocycloalkyl groups include morpholyl, piperazyl, piperidyl, and pyrrolinyl groups. A "heterocyclic group" may contain 1, 2, 3, 4, or 5 heteroatoms selected from N, O, or S.

[0350] A "heterocycle-oxy group" is a monocyclic or bicyclic heterocyclic group, as defined above, linked via an oxygen-O- linking group to the group it replaces.

[0351] A "heteroaryl group" refers to a stable monocyclic aromatic ring containing 1 to 3, or in some embodiments, 1 to 2, heteroatoms selected from N, O, and S, with the remaining ring atoms being carbon, or a stable bicyclic or tricyclic ring system containing at least one, 1 to 3, or in some embodiments, 1 to 2, heteroatoms selected from N, O, and S, with the remaining ring atoms being carbon. In one embodiment, the only heteroatom is nitrogen. In one embodiment, the only heteroatom is oxygen. In one embodiment, the only heteroatom is sulfur. Monocyclic heteroaryl groups typically have 5 to 8, or in some embodiments, 5, 6, 7, or 8, ring atoms. In some embodiments, bicyclic heteroaryl groups are 9-10-membered heteroaryl groups, i.e., groups containing 9 or 10 ring atoms, in which one 5- to 7-membered aromatic ring is fused to another aromatic or non-aromatic ring. When the total number of S and O atoms in the heteroaryl group exceeds 1, these heteroatoms are not adjacent to one another. In one embodiment, the total number of S and O atoms in the heteroaryl group is 2 or less. In another embodiment, the total number of S and O atoms in the aromatic heterocycle is 1 or less. Illustrative examples of heteroaryl groups are pyridyl (including, for example, 2-hydroxypyridyl), imidazolyl, imidazolopyridyl, pyrimidyl (for example, 4-hydroxypyrimidyl), pyrazolyl, thiazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxadiazolyl, oxazolyl, isothiazolyl, pyrrolyl, quinolyl, isoquinolyl, tetrahydroisoquinolyl, indolyl, and benzimidazolyl. , benzofuryl, cinnolinyl, indolizinyl, phthalazinyl, pyridazyl, triazyl, isoindolyl, pteridinyl, purinyl, oxadiazolyl, triazolyl, thiadiazolyl, thiadiazolyl, furazanyl, benzofurazanyl, benzothienyl, benzothiazolyl, benzoxazolyl, quinazolinyl, quinoxalinyl, naphthyridinyl, tetrahydrofuryl and furopyridyl groups.Heteroaryl groups are optionally substituted independently with one or more substituents described herein. A "heteroaryloxy group" is a heteroaryl group as defined above attached to the group it substitutes via an oxygen-O-linking group. A "heteroaryl group" may contain 1, 2, 3, 4, or 5 heteroatoms selected from N, O, or S.

[0352] The present application further includes polycyclic ring systems, such as bicyclic, tricyclic, tetracyclic, pentacyclic, etc., formed by one or more monocyclic rings selected from "cycloalkyl groups," "aryl groups," and "heteroaryl groups," in a valence-allowed manner.

[0353] The term cyano is -CN.

[0354] The term "mono-, bi-, or tricyclic saturated or unsaturated ring system having 5 to 14 ring atoms" means that the ring system has 5 to 14 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14) ring atoms, the ring system contains one, two, or three rings, any of which may independently be saturated, unsaturated, or aromatic. Preferably, any of the saturated, unsaturated, and aromatic rings may contain ring heteroatoms.

[0355] The applicant has found that the compounds of the present application or pharmaceutically acceptable salts thereof can effectively degrade IKZF. Therefore, the compounds of the present application or salts thereof are useful for treating proliferative diseases. The applicant has further found that the compounds described herein or salts thereof degrade IKZF without inhibiting / degrading SALL4. In other words, the compounds of the present application or salts thereof can selectively degrade IKZF and have reduced or no effect on other proteins / kinases, resulting in reduced or no toxicity or side effects compared to conventional IKZF decomposers / inhibitors.

[0356] The compounds of the present application or pharmaceutically acceptable salts thereof are useful for treating proliferative diseases. The present application also provides use of the compounds of the present application or pharmaceutically acceptable salts thereof in the manufacture of a medicament for treating a proliferative disease. The present application also provides the compounds or pharmaceutically acceptable salts thereof for treating a proliferative disease. The present application also provides a method for treating a proliferative disease, comprising administering a therapeutically effective amount of the compounds or pharmaceutically acceptable salts thereof to a subject in need thereof.

[0357] The term "proliferative disorder" or "cell proliferative disorder" refers to a disorder associated with some degree of abnormal cell proliferation, which may be malignant or benign. In some embodiments, the proliferative disorder is cancer. In some aspects, the cancer is a solid tumor. In some aspects, the cancer is a hematological malignancy. The terms "proliferative disorder," "cell proliferative disorder," "cancer," "cancerous," and "tumor" are not mutually exclusive when referred to herein.

[0358] The term "cancer" includes cancer cells and / or benign or pre-cancerous cells. Exemplary cancers include breast cancer, colon cancer, brain cancer, prostate cancer, kidney cancer, pancreatic adenocarcinoma, ovarian cancer, head and neck cancer, melanoma, colorectal cancer, gastric cancer, squamous cell carcinoma, small cell lung cancer, non-small cell lung cancer, testicular cancer, Merkel cell carcinoma, glioblastoma, neurocytoma, leukemia (acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute monocytic leukemia (AMOL), hairy cell leukemia (HCL), T-cell prolymphocytic leukemia (T-PLL), large granular lymphocytic leukemia (LLL), and leukemia (LLL). Hemocytes, adult T-cell disease), lymphomas (small lymphocytic lymphoma (SLL), Hodgkin's lymphoma (nodular sclerosing, mixed cell, lymphocyte-rich, lymphocyte-reduced or non-reduced and nodular lymphocyte-dominated Hodgkin's lymphoma), non-Hodgkin's lymphoma (all subtypes), chronic lymphocytic leukemia / small lymphocytic lymphoma, precursor B lymphoblastic leukemia, lymphoplasmacytic lymphoma (e.g., Waldenstrom macroglobulinemia), splenic marginal zone lymphoma, plasma cell neoplasms (plasmacytic bone tumors) Myeloma, plasmacytoma, monoclonal gammopathy, heavy chain disease), extranodal marginal zone B-cell lymphoma (MALT lymphoma), nodal marginal zone B-cell lymphoma (NMZL), follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt lymphoma / leukemia, T-cell prolymphocytic leukemia, T-cell large granular lymphocytic leukemia, aggressive NK-cell leukemia, adult T-cell leukemia / Cancers of the lymphoid organs and myeloid malignancies, including, but not limited to, lymphoma, extranodal NK / T-cell lymphoma (nasal type), enteropathic T-cell lymphoma, hepatosplenic T-cell lymphoma, blastic NK-cell lymphoma, mycosis fungoides / Sezary syndrome, primary cutaneous CD30-positive T-lymphoproliferative disease, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma (non-specific), anaplastic large cell lymphoma, multiple myeloma (plasma cell myeloma or Kahler's disease), etc. The term "cancer" further includes leukemia, carcinoma, and sarcoma.Exemplary cancers include brain cancer, breast cancer, cervical cancer, colon cancer, head and neck cancer, liver cancer, kidney cancer, lung cancer, non-small cell lung cancer, melanoma, mesothelioma, ovarian cancer, sarcoma, gastric cancer, uterine cancer, and medulloblastoma. Other examples include Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, neuroblastoma, ovarian cancer, rhabdomyosarcoma, essential thrombocythemia, primary macroglobulinemia, primary brain tumor, cancer, malignant insulinoma, malignant cancer, bladder cancer, advanced skin lesions, testicular cancer, lymphoma, thyroid cancer, neuroblastoma, esophageal cancer, genitourinary tract cancer, malignant hypercalcemia, endometrial cancer, adrenocortical carcinoma, tumors of the endocrine and exocrine pancreatic glands, and prostate cancer. The term cancer further includes leukemia, multiple myeloma, lymphoma, liver cancer, gastric cancer, breast cancer, cholangiocarcinoma, pancreatic adenocarcinoma, lung cancer, colon cancer, osteosarcoma, melanoma, human cervical cancer, glioma, nasopharyngeal carcinoma, laryngeal carcinoma, esophageal cancer, middle ear tumors, prostate cancer, etc.

[0359] The present application also provides a pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable carrier. The pharmaceutical composition may be in the form of tablets, capsules, granules, syrup, suspension, solution, dispersion, sustained-release formulation for oral or parenteral administration, intravenous injection formulation, subcutaneous injection formulation, inhalation formulation, transdermal formulation, or rectal or vaginal suppository.

[0360] The pharmaceutically acceptable carriers referred to herein are pharmaceutically acceptable carriers familiar to those skilled in the art, and include, but are not limited to, fillers, wetting agents, binding agents, disintegrants, lubricants, binders, flow agents, flavoring agents, surfactants, preservatives, etc. Fillers include, but are not limited to, lactose, microcrystalline cellulose, starch, powdered sugar, dextrin, mannitol, and calcium sulfate. Wetting agents and binding agents include, but are not limited to, carmellose sodium, hydroxypropyl cellulose, hydroxypropylmethylcellulose, gelatin, sucrose, and polyvinylpyrrolidone. Disintegrants include, but are not limited to, carboxymethyl starch sodium, crospovidone, croscarmellose sodium, and low-substituted hydroxypropyl cellulose. Lubricants include, but are not limited to, magnesium stearate, Aerosil, talc powder, hydrogenated vegetable oil, polyethylene glycol, and magnesium lauryl sulfate. Binders include, but are not limited to, gum arabic, alginic acid, carboxymethylcellulose calcium, carmellose sodium, glucose binder, dextrin, dextrose, ethylcellulose, gelatin, liquid glucose, guar gum, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, magnesium aluminum silicate, maltose dextrin, methylcellulose, polymethacrylate, polyvinylpyrrolidone, pregelatinized starch, sodium alginate, sorbitol, starch, syrup, and tragacanth. Flow agents include, but are not limited to, colloidal silica, powdered cellulose, magnesium trisilicate, silica, and talc powder. Flavoring agents include, but are not limited to, aspartame, stevioside, fructose, glucose, syrup, honey, xylitol, mannitol, lactose, sorbitol, maltitol, and glycyrrhizin. Surfactants include, but are not limited to, Tween 80 and poloxamer. Preservatives include, but are not limited to, nipagin esters, sodium benzoate, potassium sorbate, and the like.

[0361] Methods for preparing various drug combinations containing various ratios of active ingredients are known or readily apparent to those skilled in the art based on the disclosures herein, e.g., as described in REMINGTON'S PHARMACEUTICAL SCIENCES, Martin, EW, ed., Mack Publishing Company, 19th ed. (1995). Methods for preparing the drug compositions include incorporating appropriate pharmaceutical excipients, carriers, diluents, etc. The drug compositions described herein are prepared by known methods, including conventional mixing, dissolving, or freeze-drying techniques.

[0362] In the pharmaceutical compositions of the present application, the proportion of the active ingredient may vary but may comprise from about 0.01% to about 99% of the weight of a given unit dosage form. In the formulation of such therapeutically useful pharmaceutical compositions, the amount of active ingredient is such that an effective dosage level will be obtained.

[0363] Tablets, capsules, and the like of the present application may contain binders such as tragacanth, gum arabic, cornstarch, or gelatin; excipients such as dicalcium hydrogen phosphate; disintegrating agents such as cornstarch, potato starch, or alginic acid; lubricants such as magnesium stearate; and sweeteners such as sucrose, pectin, lactose, or aspartame, or flavorings such as peppermint, oil of wintergreen, or cherry flavor. When the unit dosage form is a capsule, in addition to the above-mentioned ingredients, it may also contain a liquid carrier, such as vegetable oil or polyethylene glycol. Various other materials may also be present, serving as coatings or otherwise modifying the physical form of the solid unit dosage form. For example, tablets or capsules may be coated with gelatin, wax, lacquer, or sugar. Syrups may contain the active ingredient, sucrose or pectin as a sweetener, methyl or propyl p-hydroxybenzoate as a preservative, a dye, and a flavoring agent (e.g., cherry or orange flavor). Of course, any material used in preparing any unit dosage form would be pharmaceutically acceptable and used in non-toxic amounts. The active ingredient may also be incorporated into sustained-release preparations or devices.

[0364] The active ingredient may be administered intravenously or intraperitoneally by infusion or injection. Aqueous solutions of the active ingredient or its salts may be prepared, optionally containing a nontoxic surfactant. Dispersions may also be prepared in glycerin, liquid polyethylene glycol, glycerin triacetate, and mixtures thereof, and oils. Under normal conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms.

[0365] Dosage forms of pharmaceutical compositions suitable for injection or infusion include sterile aqueous solutions or dispersions or sterile powders containing the active ingredient (optionally encapsulated in liposomes) suitable for the extemporaneous preparation of sterile injectable or infusible solutions or dispersions. In all cases, the final dosage form must be sterile, fluid, and stable under the conditions of manufacture and storage. The liquid carrier may be a solvent or liquid dispersion medium, and includes, for example, water, ethanol, polyols (e.g., glycerin, propylene glycol, liquid polyethylene glycol, etc.), vegetable oils, non-toxic glycerol esters, and suitable mixtures thereof. Proper fluidity can be maintained, for example, by the formation of liposomes, the maintenance of the required particle size in the case of dispersions, or the use of surfactants. Prevention of microorganisms can be achieved by various antibacterial and antifungal agents (e.g., p-hydroxybenzoates, chlorobutanol, phenol, sorbic acid, thimerosal, etc.). In many cases, it is preferable to include isotonic agents, for example, sugars, buffers, and sodium chloride. Prolonged absorption of the injectable compositions can be brought about by the use in the compositions of agents delaying absorption, for example, aluminum monostearate or gelatin.

[0366] The required amount of active ingredient in a suitable solvent is mixed with various other ingredients as listed above, and then filtered to produce a sterile injectable solution. When used to prepare sterile powders for sterile injectable solutions, the preferred preparation methods are vacuum drying and freeze-drying techniques, which yield powders of the active ingredient and any other ingredients that may be present in the sterile-filtered solution.

[0367] Useful solid carriers include finely divided solids (e.g., talc, clay, microcrystalline cellulose, silica, aluminum oxide, etc.). Useful liquid carriers include water, ethanol, or ethylene glycol or water-ethanol / ethylene glycol mixtures, in which the pharmaceutical compositions of the present application can be dissolved or dispersed at an effective content, optionally with the aid of a nontoxic surfactant. Adjuvants (e.g., flavors) and other antimicrobial agents can be included to optimize the properties for a given use.

[0368] Thickeners (e.g., synthetic polymers, fatty acids, fatty acid salts and esters, fatty alcohols, modified cellulose, or modified inorganic materials) can be used with liquid carriers to form pastes, gels, ointments, soaps, etc. that can be coated or applied directly to the user's skin.

[0369] The therapeutically effective amount of the active ingredient will depend not only on the particular salt chosen, but also on the mode of administration, the nature of the disease being treated, and the age and condition of the patient, and will ultimately be determined by the attending physician or clinician.

[0370] The above-mentioned preparations may be in unit dosage form, which is a physically dispersed unit containing a unit dosage amount suitable for administration to humans and other mammals. The unit dosage form may be a capsule or tablet. Depending on the specific treatment involved, the unit dosage amount of the active ingredient may vary or be adjusted from about 0.01 to about 1000 mg or more.

[0371] As used herein, the term "treatment" generally refers to achieving a desired pharmacological and / or physiological effect. Such an effect may be prophylactic, by completely or partially preventing a disease or its symptoms, and / or therapeutic, by partially or completely stabilizing or curing a disease and / or its side effects. As used herein, "treatment" includes any treatment of a patient, including (a) preventing a disease or condition from occurring in a patient susceptible to, but not yet diagnosed with, the disease or condition; (b) suppressing the symptoms of a disease, i.e., arresting its development; or (c) alleviating the symptoms of a disease, i.e., inducing regression of the disease or condition. The compounds of the present application, or pharmaceutically acceptable salts thereof, may also be administered in combination with other therapeutic agents for the treatment of one or more types of cancer. Such other therapeutic agents include, but are not limited to, anthracyclines, cyclophosphamide, 5-fluorouracil, cisplatin, and the like.

[0372] Unless otherwise stated, any percentage, ratio, or part used herein is calculated by weight or volume. The amounts used herein are amounts by weight or volume and can be readily determined by one of ordinary skill in the art.

[0373] In another aspect of this application, this application further includes compounds resulting from the combination of any of the groups defined in any of the variables herein, or pharmaceutically acceptable salts thereof.

[0374] The present application also includes the following exemplary compounds:

[0375] [ka]

[0376] The present application will now describe the beneficial effects of the present application in examples. Those skilled in the art will recognize that these examples are illustrative and non-limiting. These examples do not limit the scope of the present application in any way. Unless otherwise specified, all experimental methods described in the following examples are conventional methods. Unless otherwise specified, all reagents and materials are commercially available.

[0377] Example The compounds of the present application can be synthesized by the following exemplary general synthetic methods or similar methods. Each intermediate may have each substituent described in the present application, provided that valences allow.

[0378] [ka] Compound 1B is obtained from compound 1A and chlorotoluene in the presence of a base, or compound 1C is obtained from compound 1A and an aromatic aldehyde by a reductive amination reaction. Compound 1D (or 1E) is obtained from compound 1B (or 1C) and compound 1L by a coupling reaction in the presence of a catalyst, and then compound 1G (or 1H) is obtained from compound 1D (or 1E) and compound 1F in the presence of a base.

[0379] Compound 1A may be a commercially available spiro or bridged ring system, a spiro or bridged ring system synthesized by known methods, or a ring system synthesized by the following exemplary general synthetic method or similar methods.

[0380] [ka] Compound 1A1 and phenol are subjected to a Mitsunobu reaction to give 1A2, which is then deprotected and subjected to a coupling reaction to give 1A4, which is then further deprotected to give compound 1A.

[0381] Synthesis of Key Intermediate B1

[0382] [ka]

[0383] Step 1: Synthesis of Intermediate B1-2

[0384] [ka]

[0385] At 0°C, aluminum trichloride (22.0 g, 165 mmol) was slowly added to a solution of intermediate B1-1 (10 g, 89.2 mmol) in fluorobenzene (51.0 g, 531 mmol, 50 mL). The reaction mixture was stirred at 0°C for 1 hour, then slowly heated to 75°C and stirred at 75°C for 18 hours. The reaction mixture was cooled to room temperature, poured into 500 mL of 2N aqueous hydrochloric acid, and extracted three times with 300 mL of ethyl acetate. The organic phase was washed with 300 mL of water and then with 300 mL of saturated sodium bicarbonate three times. The aqueous phase was then adjusted to pH 2-3 and extracted three times with 300 mL of ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, filtered, and rotary evaporated to give crude intermediate B1-2 (7.30 g, yield: 43.0%) as a yellow solid, which was used directly in the next step without further purification. 1H NMR (400MHz,CDCl3)δ 9.04 - 8.62 (m,1H),8.32 - 8.11 (m,1H),8.04 - 7.78 (m,1H),7.54 - 7.40 (m,2H),7.36 - 7.29 (m,1H).

[0386] Step 2: Synthesis of Intermediate B1-3

[0387] [ka] Diphenylphosphoryl azide (1.55 g, 5.62 mmol, 1.22 mL) was added to a solution of intermediate B1-2 (1.00 g, 5.26 mmol) and triethylamine (1.65 g, 16.3 mmol, 2.27 mL) in t-butanol (10 mL) at 20 °C. The reaction mixture was stirred at 100 °C for 17 hours under nitrogen gas protection. The reaction mixture was rotary evaporated to give the crude product. The crude product was separated by column chromatography (petroleum ether / ethyl acetate = 1 / 0 to 10 / 1) to give intermediate B1-3 (1.10 g, yield: 80.1%) as a white solid.

[0388] LCMS (ESI + ): m / z 206.99 [M+H-56] + .

[0389] Step 3: Synthesis of Intermediate B1-4

[0390] [ka] To a solution of intermediate B1-3 (1.10 g, 4.21 mmol) in dichloromethane (10 mL) was added 4 M hydrochloric acid in dioxane (10 mL). The reaction mixture was reacted at 20 °C for 2 hours. The reaction mixture was rotary evaporated to give intermediate B1-4 (770 mg, crude product) as a white solid. This was used directly in the next step without further purification.

[0391] LCMS (ESI + ): m / z 161.96 [M+H] + .

[0392] Step 4: Synthesis of Intermediate B1-5

[0393] [ka] A solution of pyridine-2-carboxylic acid (500 mg, 4.06 mmol), the hydrochloride salt of intermediate B1-4 (770 mg, 3.90 mmol), and N,N-diisopropylethylamine (1.51 g, 11.7 mmol, 2.04 mL) in dichloromethane (5 mL) was added with 50% tri-n-propylphosphonic anhydride (3.72 g, 5.84 mmol, 3.48 mL). The reaction mixture was allowed to react at 20 °C for 18 hours. The reaction mixture was then rotary evaporated to give the crude product. The crude product was separated by column chromatography (petroleum ether / ethyl acetate = 1 / 0 to 5 / 1) to give intermediate B1-5 (860 mg, yield: 69.6%) as a white solid.

[0394] LCMS (ESI + ): m / z 267.1 [M+H] + .

[0395] Step 5: Synthesis of Intermediate B1-6

[0396] [ka] A solution of intermediate B1-5 (840 mg, 3.15 mmol), isopropyl chloroformate (1.16 g, 9.46 mmol, 1.31 mL), palladium acetate (70 mg, 311.79 μmol), sodium iodide (480 mg, 3.20 mmol), and sodium acetate (520 mg, 6.34 mmol) in toluene (10 mL) was purged with nitrogen gas three times and stirred at 120 °C under nitrogen gas protection for 24 h. The reaction mixture was filtered and rotary evaporated to give the crude product. The crude product was subjected to column chromatography (petroleum ether / ethyl acetate = 1 / 0 to 5 / 2) to give intermediate B1-6 (660 mg, yield: 44.6%) as a yellow solid.

[0397] LCMS (ESI +): m / z 353.0 [M+H] + .

[0398] Step 6: Synthesis of Intermediate B1-7

[0399] [ka] Sodium hydroxide (224.75 mg, 5.62 mmol) was added to a solution of intermediate B1-6 (660 mg, 1.87 mmol) in ethanol (15 mL). The reaction mixture was stirred at 80 °C for 18 hours. The reaction mixture was rotary evaporated to obtain a crude product, and then water (5 mL) was added. The pH was adjusted to 2 with 1N hydrochloric acid. The mixture was extracted three times with 15 mL of ethyl acetate. The organic phase was washed twice with 15 mL of saturated sodium bicarbonate, dried over anhydrous sodium sulfate, filtered, and rotary evaporated to obtain a crude product. The crude product was separated by column chromatography (petroleum ether / ethyl acetate = 1 / 0 to 3 / 1) to obtain intermediate B1-7 (110 mg, yield: 27.3%) as a yellow solid.

[0400] Step 7: Synthesis of Intermediate B1-8

[0401] [ka] A solution of intermediate B1-7 (110 mg, 588 μmol) in trichloromethane (5 mL) was added dropwise over 3 minutes to a solution of liquid bromine (93.9 mg, 588 μmol, 30.30 μL) in trichloromethane (3 mL) at 0° C. The reaction mixture was stirred at 20° C. for 20 hours. The reaction mixture was rotary evaporated to give intermediate B1-8 (156 mg, crude) as a yellow solid, which was used directly in the next step reaction without further purification.

[0402] Step 8: Synthesis of Intermediate B1-9

[0403] [ka] A dioxane solution (5 mL) of intermediate B1-8 (150 mg, 564 μmol), bis(pinacolato)diboron (150 mg, 591 μmol), potassium acetate (166 mg, 1.69 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (41.3 mg, 56.4 μmol) was stirred at 100 °C for 16 h under nitrogen gas protection. The reaction mixture was filtered and rotary evaporated to give the crude product. The crude product was separated by column chromatography (petroleum ether / ethyl acetate = 8 / 1 to 5 / 1) to give crude yellow solid B1-9 (134 mg, yield: 56.2%). This product was used directly in the next step without further purification.

[0404] LCMS (ESI + ): m / z 314.0 [M+H] + .

[0405] Synthesis of intermediate B2

[0406] [ka] Step 1: Synthesis of Intermediate B2-2

[0407] [ka] Intermediate B2-1 (5.00 g, 24.4 mmol), vinyl pinacol boronate (5.63 g, 36.6 mmol), potassium carbonate (10.3 g, 74.4 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (1.07 g, 1.46 mmol) were dissolved in dioxane (50 mL) and water (5 mL). The mixture was purged with nitrogen three times and stirred at 90 °C for 16 h. The reaction mixture was cooled to room temperature and quenched with water (30 mL). The mixture was extracted three times with ethyl acetate (50 mL × 3). The combined organic phase was washed twice with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give the crude product. Purification by column chromatography (petroleum ether / ethyl acetate = 1 / 0 to 3 / 1) gave intermediate B2-2 (2.86 g, yield: 73%) as a yellow oil.

[0408] Step 2: Synthesis of Intermediate B2-3

[0409] [ka] Intermediate B2-2 (2.86 g, 18.8 mmol) was dissolved in tetrahydrofuran (30 mL) and water (8 mL). The reaction mixture was cooled to 0 °C, followed by the addition of potassium osmate monohydrate (360 mg, 0.977 mmol) and sodium periodate (16.1 g, 75.2 mmol). After the addition, the reaction mixture was stirred at 0 °C for 1 h. The mixture was then quenched with water (10 mL) and extracted three times with ethyl acetate (10 mL × 3). The combined organic phase was washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product. Purification by column chromatography (petroleum ether / ethyl acetate = 1 / 0 to 3 / 1) afforded intermediate B2-3 (1.47 g, 51% yield) as a pale red oil.

[0410] Step 3: Synthesis of Intermediate B2-4

[0411] [ka] Intermediate B2-3 (210 mg, 1.36 mmol), 1-oxa-8-azaspiro[4.5]decane (242 mg, 1.36 mmol), and acetic acid (8.18 mg, 0.136 mmol) were dissolved in dichloromethane (10 mL), and the reaction mixture was stirred at 25 °C for 0.5 h. Sodium cyanoborohydride (128 mg, 2.04 mmol) was added to the reaction mixture. The reaction mixture was stirred at 25 °C for 12 h. The reaction mixture was quenched with saturated sodium bicarbonate solution (10 mL) and extracted with dichloromethane (20 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and rotary evaporated to obtain the crude product. The crude product was separated by column chromatography (dichloromethane:methanol = 1 / 0 to 20 / 1) to obtain compound B2-4 (160 mg, yield: 39.9%) as a colorless oil.

[0412] LCMS (ESI+): m / z 279.6 [M+H]+.

[0413] Step 4: Synthesis of Intermediate B2

[0414] [ka] Intermediate B2-4 (160 mg, 573 μmol) was dissolved in dichloromethane (5 mL), and thionyl chloride (681 mg, 5.73 mmol) was added dropwise to the reaction mixture. The reaction mixture was stirred at 25° C. for 12 hours. The reaction mixture was spun down to give the crude white solid intermediate B2 (190 mg, crude). LCMS (ESI+): m / z 298.11 [M+H]+.

[0415] Intermediate B3, Intermediate B4, and Intermediate B5 were synthesized by a method similar to that for Intermediate B2.

[0416] Example 2: Compound Intermediate B3

[0417] [ka] LCMS (ESI + ): m / z 298.8 [M+H]+ .

[0418] Example 3: Intermediate B4

[0419]

change

[0420] Example 4: Intermediate B5

[0421]

change

[0422] Synthesis of intermediate B6

[0423]

change

[0424] Process 1: Synthesis of intermediate B6-2

[0425]

change

[0426] 1 H NMR (400MHz,DMSO-d6)δ 11.00 (s,1H),8.91 - 8.75 (m,1H),8.24 - 8.17 (m,1H),8.15 - 8.07 (m,2H),8.03 (d,J = 8.4Hz,1H),7.99 - 7.92 (m,2H),7.81 - 7.68 (m,2H),7.51 (dd,J = 7.6,8.4Hz,1H)

[0427] Step 2: Synthesis of intermediate B6-3

[0428] [ka] A toluene solution (300 mL) of intermediate B6-2 (10.0 g, 30.6 mmol), isopropyl chloroformate (11.2 g, 91.7 mmol), sodium acetate (6.01 g, 73.3 mmol), sodium iodide (4.58 g, 30.6 mmol), and palladium acetate (1.37 g, 6.11 mmol) was purged with nitrogen gas three times and stirred under nitrogen gas protection at reflux at 135 °C for 3 h. The reaction mixture was then cooled to room temperature, diluted with 300 mL of dichloromethane, and adjusted to a pH greater than 7 with triethylamine. The reaction mixture was filtered and rotary evaporated to obtain the crude product. The crude product was subjected to column chromatography (petroleum ether / dichloromethane / ethyl acetate = 1 / 0 to 1 / 1) to obtain intermediate B6-3 (7.10 g, yield: 56.2%) as a pale yellow solid.

[0429] Step 3: Synthesis of intermediate B6-4

[0430] [ka] Sodium hydroxide (1.03 g, 25.8 mmol) was added to a solution of intermediate B6-3 (7.10 g, 17.2 mmol) in ethanol (80 mL), and the reaction mixture was stirred for 16 hours at 80° C. The pH of the reaction mixture was adjusted to approximately 6 with 1 M aqueous hydrochloric acid, and the product precipitated. The solid was filtered to obtain intermediate B6-4 (3.6 g, yield: 84.5%) as a yellow solid.

[0431] 1 H NMR (400MHz,DMSO-d6)δ 10.88 (br.s.,1H),8.07 (d,J = 7.2Hz,1H),7.89 (d,J = 7.2Hz,1H),7.67 - 7.59 (m,1H),7.57 - 7.51 (m,1H),7.05 (d,J = 6.8Hz, 1H).

[0432] [ka] A dioxane solution (20 mL) of intermediate B6-4 (2.00 g, 8.06 mmol), t-butyl aminoformate (3.78 g, 32.3 mmol), cesium carbonate (7.88 g, 24.2 mmol), and XPhos Pd G3 (1.36 g, 1.61 mmol) was purged with nitrogen gas three times and stirred at 110 °C for 6 h under nitrogen gas protection. The reaction mixture was filtered and rotary evaporated to give the crude product. The crude product was purified by column chromatography (ISCO®; 40 g SepaFlash® Silica Flash Column, petroleum ether / ethyl acetate = 1 / 0 to 1 / 2) to give intermediate B6-5 (1.50 g, yield: 65.4%) as a yellow solid.

[0433] LCMS (ESI + ): m / z 285.3 [M+H] + .

[0434] Step 2: Synthesis of intermediate B6-6

[0435] [ka] A solution of intermediate B6-5 (1.47 g, 5.17 mmol) in dichloromethane (4 mL) was added to 4 M hydrochloric acid in dioxane (10 mL). The reaction mixture was allowed to react at 25 °C for 10 minutes. The reaction mixture was then rotary evaporated to give the crude product. The crude product was diluted with dichloromethane (20 mL) and saturated sodium bicarbonate solution (20 mL). The layers were separated, and the aqueous phase was extracted twice with 20 mL of dichloromethane. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and rotary evaporated to give intermediate B6-6 (950 mg, yield: 99.8%) as a golden yellow solid.

[0436] LCMS (ESI + ): m / z 185.1 [M+H] + .

[0437] 1H NMR (400MHz,DMSO-d6)δ 10.18 (br.s.,1H),7.70 (d,J = 8.4Hz,1H),7.64 (d,J = 7.6Hz,1H),7.28 - 7.21 (m,1H),7.04 - 6.93 (m,2H),6.83 (d,J = 6.8Hz,1H),6.70 (d,J = 8.0Hz,1H) Step 3: Synthesis of Intermediate B6-7

[0438] [ka] A solution of intermediate B6-6 (550 mg, 2.99 mmol) in ethylene glycol dimethyl ether (12 mL) was slowly added dropwise over 10 min to a solution of boron trifluoride ethyl ether (1.47 g, 4.78 mmol, 48%) in ethylene glycol dimethyl ether (20 mL) at -5 °C. The mixture was reacted at 0 °C for 1 h, and then a solution of t-butyl nitrite (370 mg, 3.58 mmol) in ethylene glycol dimethyl ether (8 mL) was slowly added dropwise to the mixture. The mixture was reacted at 25 °C for 2 h. The solvent was removed by rotary evaporation under reduced pressure, and chlorobenzene (10 mL) was added to the reaction flask. The flask was heated to 140 °C and refluxed for 50 min. The reaction mixture was then returned to room temperature, and the solvent was removed by rotary evaporation under reduced pressure to obtain the crude product. The crude product was purified by column chromatography (petroleum ether / ethyl acetate = 1 / 0 to 1 / 2) to obtain intermediate B6-7 (200 mg, yield: 35.8%) as a yellow solid.

[0439] LCMS (ESI + ): m / z 188.1 [M+H] + .

[0440] 1 H NMR (500MHz,DMSO-d6)δ 10.97 - 10.76 (m,1H),8.05 - 8.01 (m,1H),7.64 - 7.54 (m,3H),7.06 (d,J = 6.5Hz,1H).

[0441] Step 4: Synthesis of intermediate B6-8

[0442] [ka] NBS (190 mg, 1.07 mmol) was added to a DMF (2 mL) solution of intermediate B6-7 (200 mg, 1.07 mmol) and the mixture was allowed to react at room temperature for 2 hours. The reaction mixture was poured into saturated sodium bicarbonate, filtered, and the cake was dried to obtain the crude product. The crude product was purified by column chromatography (petroleum ether / ethyl acetate = 1 / 0 to 1 / 2) to obtain intermediate B6-8 (135 mg, yield: 39.41%) as a yellow solid.

[0443] LCMS (ESI + ): m / z 268.0 [M+H] + .

[0444] 1 H NMR (400MHz,DMSO-d6)δ 11.26 - 10.62 (m,1H),8.13 - 8.07 (m,1H),7.82 - 7.76 (m,1H),7.70 - 7.61 (m,1H),6.99 - 6.92 (m,1H).

[0445] Step 5: Synthesis of Intermediate B6

[0446] [ka] A dioxane solution (5 mL) of intermediate B6-8 (135 mg, 507 μmol), bis(pinacolato)diboron (193 mg, 761 μmol), potassium acetate (149 mg, 1.52 mmol), and Pd(dppf)Cl2 (37.1 mg, 50.7 μmol) was purged with nitrogen gas three times and stirred at 90 °C for 4 h under nitrogen gas protection. The reaction mixture was filtered and rotary evaporated to give the crude product. The crude product was purified by column chromatography (petroleum ether / ethyl acetate = 1 / 0 to 1 / 2) to give intermediate B6 (230 mg, crude product) as a yellow solid.

[0447] LCMS (ESI +): m / z 314.1 [M+H] + .

[0448] Synthesis of intermediate B8

[0449] [ka]

[0450] Step 1: Synthesis of intermediate B8-2

[0451] [ka] At 20°C, methanol (40 mL) was slowly added to a solution of intermediate B8-1 (5.00 g, 27.7 mmol), methoxyamine hydrochloride (3.01 g, 36.0 mmol), and pyridine (3.28 g, 41.5 mmol). The atmosphere was purged with nitrogen gas three times, and the mixture was stirred at 20°C for 16 hours under nitrogen gas protection. The reaction mixture was rotary evaporated to obtain the crude product. The crude product was separated by column chromatography (petroleum ether / ethyl acetate = 1 / 0) to obtain intermediate B8-2 (5.48 g, yield: 94.4%) as a yellow oil.

[0452] 1 H NMR (400MHz,CDCl3)δ 7.92 (d,J = 8.4Hz,1H),7.19 - 7.09 (m,2H),3.99 (s,3H),2.78 - 2.65 (m,4H),1.90 - 1.78 (m,2H).

[0453] Step 2: Synthesis of intermediate B8-3

[0454] [ka] Palladium acetate (58.7 mg, 261 μmol) was added to a solution of intermediate B8-2 (5.48 g, 26.1 mmol) and N-bromosuccinimide (5.44 g, 30.6 mmol) in acetic acid (30 mL) at 20 °C. The atmosphere was purged with nitrogen gas three times, and the reaction mixture was stirred at 80 °C under nitrogen gas protection for 0.5 h. The reaction mixture was rotary evaporated to give the crude product. The crude product was separated by column chromatography (petroleum ether / ethyl acetate = 1 / 0) to give intermediate B8-3 (7.48 g, yield: 99.2%) as a yellow oil.

[0455] Step 3: Synthesis of intermediate B8-4

[0456] [ka] 6M hydrochloric acid (70mL) was added to a solution of intermediate B8-3 (7.48g, 25.9mmol) in dioxane (50mL). The reaction mixture was reacted at 100°C for 1 hour. The reaction mixture was cooled to room temperature, and the pH was adjusted to 7 with 10% sodium hydroxide solution. The mixture was then extracted twice with 100mL of ethyl acetate. The separated organic phase was washed twice with 80mL of saturated brine. The organic phase was dried over anhydrous sodium sulfate, filtered, and rotary evaporated to obtain the crude product. The crude product was separated by column chromatography (petroleum ether / ethyl acetate = 1 / 0 to 10 / 1) to obtain intermediate B8-4 (3.4g, yield: 50.5%) as a yellow oil.

[0457] 1 H NMR (500MHz,DMSO-d6)δ 7.70 (d,J = 2.0Hz,1H),7.55 - 7.51 (m,1H),2.97 (t,J = 6.0Hz,2H),2.63 (t,J = 7.0Hz,2H),2.02 - 1.96 (m,2H).

[0458] Step 4: Synthesis of intermediate B8-5

[0459] [ka] Cuprous cyanide (173 mg, 1.93 mmol) was added to a solution of intermediate B8-4 (500 mg, 1.93 mmol) in N,N-dimethylformamide (2 mL), water (1 mL), and t-butanol (2 mL). The reaction mixture was heated at 110 °C for 48 hours. The reaction mixture was cooled to room temperature and quenched by adding 20 mL of water. The mixture was extracted three times with 60 mL of dichloromethane, and the organic phase was washed once with 10 mL of saturated brine. The organic phase was dried over anhydrous sodium sulfate and rotary evaporated to obtain the crude product. The crude product was separated by column chromatography (petroleum ether / ethyl acetate = 1 / 0 to 1 / 1) to obtain intermediate B8-5 (172 mg, yield: 43.4%) as a yellow solid.

[0460] 1 H NMR (500MHz,DMSO-d6)δ 10.50 (s,1H),7.53 - 7.42 (m,2H),5.45 (t,J = 4.4Hz,1H),2.95 (t,J = 8.0Hz,2H),2.64 (t,J = 8.0Hz,2H).

[0461] Step 5: Synthesis of intermediate B8-6

[0462] [ka] Dichlorodicyanobenzoquinone (188 mg, 827 μmol) was added to a solution of intermediate B8-5 (170 mg, 827 μmol) in dichloromethane (4 mL), and the reaction mixture was stirred at 20 °C for 16 hours. The reaction mixture was rotary evaporated to give a crude product. The crude product was subjected to column chromatography (petroleum ether / ethyl acetate = 1 / 0 to 3 / 1) to give intermediate B8-6 (360 mg, crude product) as a yellow solid.

[0463] LCMS (ESI + ): m / z 204.1 [M+H] + .

[0464] 1H NMR (400MHz,DMSO-d6)δ 10.92 (s,1H),8.30 (d,J = 1.2Hz,1H),8.01 (d,J = 1.2Hz,1H),7.59 - 7.50 (m,2H),7.00 (dd,J = 1.2,6.4Hz,1H).

[0465] Step 6: Synthesis of intermediate B8-7

[0466] [ka] N-Bromosuccinimide (262 mg, 1.47 mmol) was added to a solution of intermediate B8-6 (300 mg, 1.47 mmol) in N,N-dimethylformamide (7 mL) at 0 °C. The reaction mixture was stirred at 0 °C for 2 h. The reaction mixture was extracted three times with 60 mL of ethyl acetate, and the organic phase was washed twice with 40 mL of saturated brine, dried over anhydrous sodium sulfate, filtered, and rotary evaporated to obtain the crude product. The crude product was separated by column chromatography (petroleum ether / ethyl acetate = 1 / 0 to 3 / 1) to obtain intermediate B8-7 (300 mg, yield: 50.5%) as a yellow solid.

[0467] 1 H NMR (400MHz,DMSO-d6)δ 11.05 (s,1H),8.14 (s,1H),8.11 (s,1H),7.81 (d,J = 7.6Hz,1H),6.93 (d,J = 8.0Hz,1H).

[0468] Step 7: Synthesis of Intermediate B8

[0469] [ka] A solution of intermediate B8-7 (240 mg, 850 μmol), bis(pinacolato)diboron (324 mg, 1.27 mmol), and potassium acetate (250 mg, 2.55 mmol) in dioxane (4 mL) was charged with [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (62.2 mg, 85.0 μmol). The mixture was purged with nitrogen gas three times and stirred at 90 °C for 2 h under nitrogen gas protection. The reaction mixture was extracted twice with 40 mL of ethyl acetate. The organic phase was washed twice with 60 mL of saturated brine, dried over anhydrous sodium sulfate, filtered, and rotary evaporated to obtain the crude product. The crude product was separated by column chromatography (petroleum ether / ethyl acetate = 1 / 0 to 3 / 1) to obtain intermediate B8 (198 mg, yield: 57.4%) as a yellow solid.

[0470] LCMS (ESI + ): m / z 330.1 [M+H] + .

[0471] Synthesis of intermediate B9

[0472] [ka] Intermediate B9 could be synthesized by the method of step 7 of intermediate B8.

[0473] LCMS (ESI + ): m / z 296.3 [M+H] + .

[0474] Synthesis of intermediate B10

[0475] [ka]

[0476] Step 1: Synthesis of Intermediate B10-3

[0477] [ka] To a solution of intermediate B10-2 (2 g, 9.75 mmol) and B10-1 (1.50 g, 9.75 mmol) in dichloromethane (3 mL), triethylamine (4.93 g, 48.7 mmol, 6.78 mL) was added, followed by AcOH (2.93 g, 48.7 mmol, 2.79 mL). The reaction mixture was stirred at 20 °C for 0.5 h. Sodium cyanoborohydride (1.84 g, 29.2 mmol) was then added. The reaction mixture was stirred at 20 °C for 16 h. Water (30 mL) was added to the reaction mixture, and the mixture was extracted with three 90 mL portions of dichloromethane. The combined organic phase was washed with saturated brine (150 mL), dried over anhydrous sodium sulfate, filtered, and rotary evaporated to give the crude product. The crude product was separated by column chromatography (petroleum ether / ethyl acetate = 1 / 0 to 1 / 1) to obtain intermediate B10-3 (2.9 g, yield: 86.7%) as a white solid.

[0478] LCMS (ESI + ): m / z 343.9 [M+H] + .

[0479] Step 2: Synthesis of Intermediate B10

[0480] [ka] Thionyl chloride (6.8 mL) was added to a solution of intermediate B10-3 (750 mg, 2.18 mmol) in dichloromethane (3 mL), and the reaction mixture was stirred at 25 °C for 16 hours. The reaction mixture was concentrated under reduced pressure to remove the thionyl chloride, then diluted with ethyl acetate (50 mL), and washed with saturated sodium bicarbonate solution (20 mL). The separated organic phase was dried over anhydrous sodium sulfate, filtered, and rotary evaporated to obtain the crude product. The crude product was purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1 to 1 / 1) to obtain intermediate B10 (445 mg, yield: 52.4%) as a yellow oil.

[0481] LCMS (ESI + ): m / z 363.2 [M+H] + .

[0482] Synthesis of intermediate B11

[0483] [ka] Intermediate B10 was synthesized by the synthesis method of B10.

[0484] LCMS (ESI + ): m / z 343.8 [M+H] + .

[0485] Example 1: Compound 1

[0486] [ka]

[0487] Step 1: Synthesis of Intermediate 1-2

[0488] [ka] A black suspension of Intermediate 1-1 (110 mg, 311 μmol), Intermediate B1-9 (195 mg, 622 μmol), potassium phosphate (198 mg, 933 μmol), tris(dibenzylideneacetone)dipalladium (42.7 mg, 46.6 μmol), and tri(o-methylphenyl)phosphine (18.9 mg, 62.2 μmol) in toluene (3 mL) and ethanol (0.5 mL) was bubbled with nitrogen gas for 1 minute and stirred at 80 °C for 16 hours. The reaction mixture was rotary evaporated to dryness to obtain the crude product. The crude product was subjected to plate chromatography (petroleum ether / ethyl acetate = 1 / 1) to obtain Intermediate 2-2 (105 mg, yield: 62.8%) as a yellow solid. LCMS (ESI + ): m / z 505.0 [M+H] + .

[0489] Step 2: Synthesis of Compound 1

[0490] [ka] A yellow solution of intermediate 1-2 (105 mg, 208.10 μmol) in tetrahydrofuran (2 mL) was added to a gray suspension of 60% sodium hydride (83.2 mg, 2.08 mmol) and THF (1 mL) at 0 °C. Then, 3-bromopiperidine-2,6-dione (199.79 mg, 1.04 mmol, 5.0 eq) in colorless tetrahydrofuran (1 mL) was added at 0 °C. The yellow suspension was then stirred at 60 °C for 1 h. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with ice water (50 mL). The organic phase was washed with 30 mL of saturated brine. The mixture was dried over anhydrous sodium sulfate, filtered, and rotary evaporated to give the crude product. The crude product was separated by plate chromatography (petroleum ether / ethyl acetate = 1 / 1) to give compound 1 (32.0 mg, yield: 23.8%) as a yellow solid.

[0491] LCMS (ESI + ): m / z 616.2 [M+H] + .

[0492] 1 H NMR (400MHz,DMSO-d6)δ 11.15 (s,1H),8.16 (d,J = 11.2Hz,1H),8.03 (d,J = 7.6Hz,1H),7.45 (d,J = 7.2Hz,1H),7.30 - 7.16 (m,5H),7.13 - 7.01 (m,2H),6.94 (d,J = 8.8Hz,1H),5.44 (dd,J = 5.2,12.8Hz,1H),4.35 (s,2H),4.25 (dd,J = 2.8,10.8Hz,1H),3.95 - 3.77 (m,2H),3.55 - 3.41 (m,2H),3.21 - 3.14 (m,1H),3.00 - 2.82 (m,2H),2.81 - 2.72 (m,2H),2.64 - 2.58 (m,1H),2.43 - 2.42 (m,1H),2.16 - 2.01 (m,2H),1.79 - 1.60 (m,1H).

[0493] Examples 2 to 19 were synthesized by methods similar to those for compound 1.

[0494] Example 2: Compound 2

[0495]

change

[0496] 1 H NMR (400MHz, DMSO-d6)δ 11.15 (s,1H),8.57 (d,J = 1.6Hz,1H),8.25 (dd,J = 1.6,11.2Hz,1H),8.05 (dd,J = 1.6,7.6Hz,1H),7.65 (dd,J = 2.0,8.0Hz,1H),7.48 (d,J = 7.6Hz,1H),7.36 (d,J = 8.0Hz,1H),7.21 (dd,J = 2.0,8.4Hz,1H),7.11 (d,J = 7.2Hz,1H),7.07 (d,J = 2.0Hz,1H),6.94 (d,J = 8.8Hz,1H),5.44 (dd,J = 5.2,12.8Hz,1H),4.38 (s,2H),4.29 - 4.18 (m,1H),3.93 - 3.77 (m,2H),3.66 - 3.51 (m,2H),3.24 - 3.17 (m,1H),2.90 (d,J = 9.6Hz,2H),2.83 - 2.69 (m,2H),2.53 - 2.47 (m,1H),2.45 - 2.42 (m,1H),2.23 - 2.14 (m,1H),2.13 - 2.04 (m,1H),1.81 (t,J = 10.8Hz,1H).

[0497] Example 3: Compound 3

[0498]

change

[0499] 1 H NMR (400MHz, DMSO-d6)δ 11.15 (s,1H),8.46 - 8.27 (m,1H),8.19 - 8.04 (m,2H),7.89 - 7.73 (m,1H),7.43 (d,J = 7.2Hz,1H),7.34 (d,J = 2.0Hz,1H),7.29 - 7.17 (m,4H),7.12 (d,J = 7.2Hz,1H),5.45 (dd,J = 5.2,12.8Hz,1H),4.52 - 4.34 (m,3H),4.33 - 4.25 (m,1H),3.94 - 3.81 (m,1H),3.58 - 3.49 (m,1H),3.45 (d,J = 7.2Hz,1H),3.34 - 3.33 (m,1H),3.01 - 2.82 (m,4H),2.81 - 2.70 (m,1H),2.44 - 2.36 (m,1H),2.15 - 1.97 (m,2H),1.74 (t,J = 10.8Hz,1H).

[0500] Example 4: Compound 4

[0501]

change

[0502] 1H NMR (400MHz, DMSO-d6)δ 11.14 (s,1H),8.37 (d,J = 8.4Hz,1H),8.19 - 7.98 (m,2H),7.91 - 7.76 (m,1H),7.40 - 7.31 (m,2H),7.25 - 6.99 (m,4H),5.56 - 5.40 (m,1H),4.52 - 4.36 (m,3H),4.30 (s,1H),3.87 (dd,J = 8.4,11.2Hz,1H),3.57 - 3.49 (m,2H),3.03 - 2.83 (m,4H),2.82 - 2.71 (m,1H),2.64 - 2.56 (m,1H),2.47 - 2.43 (m,1H),2.14 - 1.99 (m,2H),1.77 (t,J = 10.8Hz,1H).

[0503] Example 5: Compound 5

[0504]

change

[0505] 1 H NMR (400MHz, DMSO-d6)δ 11.15 (br s,1H),8.37 - 8.31 (m,1H),8.13 - 8.04 (m,1H),7.85 - 7.78 (m,1H),7.49 - 7.40 (m,1H),7.29 - 7.25 (m,2H),7.24 - 7.20 (m,3H),7.14 - 7.10 (m,1H),7.09 - 7.03 (m,1H),6.96 - 6.91 (m,1H),5.49 - 5.39 (m,1H),4.39 (s,2H),4.27 - 4.22 (m,1H),3.88 - 3.80 (m,2H),3.45 - 3.42 (m,2H),3.22 - 3.17 (m,1H),2.98 - 2.79 (m,4H),2.70 - 2.61 (m,2H),2.15 - 2.03 (m,2H),1.76 - 1.66 (m,1H).

[0506] Example 6: Compound 6

[0507]

change

[0508] 1 H NMR (400MHz, DMSO-d6)δ 11.15 (br s,1H),8.24 - 8.13 (m,1H),8.10 - 8.01 (m,1H),7.38 - 7.29 (m,1H),7.21 (t,J = 8.0Hz,1H),7.10 - 6.99 (m,3H),5.50 - 5.39 (m,1H),4.35 (s,2H),3.56 - 3.50 (m,6H),3.33 - 3.27 (m,5H),2.99 - 2.89 (m,1H),2.75 - 2.62 (m,2H),2.25 - 2.15 (m,4H),2.13 - 2.05 (m,1H).

[0509] Example 7: Compound 7

[0510]

change

[0511] 1H NMR (400MHz, DMSO-d6)δ 11.14 (s,1H),8.18 (dd,J = 1.6,11.2Hz,1H),8.05 (dd,J = 1.6,7.6Hz,1H),7.33 (d,J = 7.2Hz,1H),7.21 (t,J = 7.6Hz,1H),7.14 - 7.00 (m,3H),5.44 (dd,J = 5.2,12.8Hz,1H),4.35 (s,2H),3.66 (t,J = 6.8Hz,2H),3.41 (s,2H),3.00 - 2.88 (m,1H),2.79 - 2.60 (m,2H),2.43 - 2.26 (m,4H),2.14 - 2.05 (m,1H),1.86 - 1.76 (m,2H),1.64 - 1.56 (m,2H),1.54 - 1.47 (m,4H).

[0512] Example 8: Compound 8

[0513]

change

[0514] 1 H NMR (400MHz, DMSO-d6)δ 11.15 (s,1H),8.24 - 8.15 (m,1H),8.10 - 7.98 (m,1H),7.42 - 7.31 (m,1H),7.28 - 7.19 (m,1H),7.17 - 6.95 (m,3H),5.53 - 5.35 (m,1H),4.36 (s,2H),3.66 - 3.49 (m,4H),3.43 (s,2H),3.01 - 2.88 (m,1H),2.80 - 2.59 (m,2H),2.38 - 2.21 (m,4H),2.15 - 2.04 (m,1H).

[0515] Example 9: Compound 9

[0516]

change

[0517] 1 H NMR (400MHz,DMSO-d6)δ 11.16 (s,1H),8.22 - 8.12 (m,1H),8.08 - 7.99 (m,1H),7.73 - 7.64 (m,1H),7.60 - 7.51 (m,1H),7.45 (d,J = 7.2Hz,1H),7.32 - 7.19 (m,4H),7.14 - 7.04 (m,2H),5.50 - 5.39 (m,1H),4.35 (s,2H),3.46 (s,2H),3.14 (br s,4H),3.01 - 2.88 (m,1H),2.82 - 2.71 (m,1H),2.68 (br s,1H),2.47 (br s,4H), 2.16 - 2.05 (m,1H).

[0518] Chiral SFC separation conditions: DAICEL CHIRALPAK Ia (250 mm × 30 mm, 10 μm); mobile phase: A: supercritical CO2, B: ethanol (neutral), A:B = 15:85 at 80 mL / min; column temperature: 38 °C; nozzle pressure: 100 Bar; nozzle temperature: 60 °C; evaporator temperature: 20 °C; trimmer temperature: 25 °C; wavelength: 220 nm.

[0519] In the order in which the peaks appear, the first compound peak (Peak-1) is compound 9-B, and the second compound peak (Peak-2) is compound 9-A. Compound 9-A-Peak-2-SFC RT:7.689 min Compound 9-B-Peak-1-SFC RT:5.503min Compound 9-A

[0520] [ka] LCMS (ESI+): m / z 606.4 [M+H] + .

[0521] 1 H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 8.19 - 8.12 (m, 1H), 8.03 (d, J = 7.6 Hz, 1H), 7.67 (dd, J = 1.6, 13.2 Hz, 1H), 7.60 - 7.53 (m, 1H), 7.44 (d, J = 7.2 Hz, 1H), 7.30 - 7.18 (m, 4H), 7.15 - 7.03 (m, 2H), 5.44 (dd, J = 5.2, 12.8 Hz, 1H), 4.35 (s, 2H), 3.45 (s, 2H), 3.14 (br s, 4H), 3.03 - 2.88 (m, 1H), 2.81 - 2.71 (m, 1H), 2.66 - 2.56 (m, 1H), 2.47 (br s, 4H), 2.14 - 2.04 (m, 1H).

[0522] Compound 9-B

[0523]

Chem.

[0524] 1H NMR (400MHz, DMSO-d6) δ11.14 (s,1H),8.22 - 8.19 (s,0.07 H),8.15 (dd,J = 2.0,11.2Hz,1H),8.02 (dd,J = 2.0,7.6Hz,1H),7.67 (dd,J = 2.0,13.2Hz,1H),7.55 (dd,J = 1.6,8.4Hz,1H),7.44 (d,J = 7.6Hz,1H),7.31 - 7.19 (m,4H),7.14 - 6.96 (m,2H),5.44 (dd,J = 5.2,12.8Hz,1H),4.35 (s,2H),3.45 (s,2H),3.14 (br s,4H),2.99 - 2.86 (m,1H),2.81 - 2.70 (m,1H),2.62 (br s,1H),2.48 - 2.42 (m,4H),2.16 - 2.01 (m,1H).

[0525] Example 10: Compound 10

[0526]

change

[0527] 1 H NMR (400MHz, DMSO-d6)δ 11.15 (br s,1H),8.26 - 8.00 (m,3H),7.44 - 7.32 (m,2H),7.27 (t,J = 8.0Hz,1H),7.15 (d,J = 11.2Hz,1H),7.08 (d,J = 7.6Hz,2H),5.52 - 5.37 (m,1H),4.45 (d,J = 13.2Hz,1H),4.39 - 4.22 (m,3H),3.94 - 3.82 (m,1H),3.58 - 3.52 (m,2H),2.98 - 2.86 (m,4H),2.78 - 2.70 (m,1H),2.64 - 2.59 (m,1H),2.43 - 2.40 (m,1H),2.17 - 2.02 (m,2H),1.85 - 1.71 (m,1H).

[0528] Example 11: Compound 11

[0529]

change

[0530] 1 H NMR (400MHz, DMSO-d6)δ 11.15 (s,1H),8.17 (dd,J = 1.6,11.2Hz,1H),8.04 (dd,J = 1.6,7.6Hz,1H),7.32 (d,J = 7.6Hz,1H),7.22 (t,J = 8.0Hz,1H),7.12 - 7.05 (m,2H),7.03 (d,J = 8.0Hz,1H),5.48- 5.37 (m,1H),4.34 (s,2H),3.56 - 3.52 (m,4H),3.36 - 3.35 (m,1H),2.81 - 2.62 (m,4H),2.42 - 2.37 (m,4H),2.13 - 2.02 (m,2H),1.93 - 1.82 (m,2H),1.73 - 1.65 (m,2H),1.40 - 1.29 (m,2H),0.81 - 0.68 (m,2H).

[0531] Example 12: Compound 12

[0532]

change

[0533] 1H NMR (400MHz, DMSO-d6)δ 11.16 (s,1H),8.15 (dd,J = 1.6,11.2Hz,1H),8.03 (dd,J = 1.6,7.6Hz,1H),7.44 (d,J = 7.6Hz,1H),7.25 (d,J = 8.0Hz,2H),7.21 (d,J = 8.0Hz,2H),7.10 (d,J = 7.6Hz,1H),5.44 (dd,J = 5.2,12.8Hz,1H),4.34 (s,2H),3.57 - 3.49 (m,4H),3.36 - 3.27 (m,2H),3.00 -2.89 (m,1H),2.81 - 2.65 (m,2H),2.34 - 2.25 (m,4H),2.15 - 2.06 (m,1H).

[0534] Example 13: Compound 13

[0535]

change

[0536] 1 H NMR (400MHz, DMSO-d6)δ 11.15 (s,1H),8.31 (s,0.952,FA),8.18 (d,J = 11.20Hz,1H),8.05 (d,J = 7.60Hz,1H),7.32 (d,J = 7.60Hz,1H),7.22 (t,J = 8.0Hz,1H),7.06 - 7.11 (m,2H),7.03 (d,J = 8.0Hz,1H),5.44 (d,J = 1.20Hz,1H),4.35 (s,2H),3.39 (s,2H),2.84 - 3.04 (m,2H),2.69 -2.80 (m,1H),2.59 - 2.68 (m,2H),2.56 (br s,3H),2.22-2.40 (m,3H),2.05- 2.14 (m,1H),0.97 (s,9H).

[0537] Example 14: Compound 14

[0538]

change

[0539] 1 H NMR (400MHz, DMSO-d6)δ 11.15 (br.s.,1H),8.15 - 8.09 (m,1H),7.72 - 7.65 (m,1H),7.61 - 7.52 (m,2H),7.48 - 7.42 (m,1H),7.25 - 7.05 (m,6H),5.51 - 5.42 (m,1H),4.41 (s,2H),3.47 - 3.43 (m,2H),3.19 - 3.09 (m,4H),3.00 - 2.88 (m,1H),2.82 - 2.72 (m,1H),2.69 - 2.62 (m,1H),2.49 - 2.44 (m,4H),2.14 - 2.05 (m, 1H).

[0540] Example 15: Compound 15

[0541]

change

[0542] 1H NMR (400MHz, DMSO-d6)δ 11.15 (br s,1H),8.44 (d,J = 8.4Hz,1H),7.72 - 7.59 (m,2H),7.54 (d,J = 7.6Hz,1H),7.41 (d,J = 6.8Hz,1H),7.23 (br s,5H),7.12 - 7.03 (m,1H),5.45 (d,J = 9.2Hz,1H),4.39 (br s,2H),3.45 (br s,2H),3.13 (br s,4H),2.92 (d,J = 12.0Hz,1H),2.78 - 2.61 (m,2H),2.46 (br s,4H),2.10 (br s,1H).

[0543] Example 16: Compound 17

[0544]

change

[0545] 1 H NMR (400MHz, DMSO-d6)δ 11.14 (br s,1H),8.39 (s,1H),8.12 (s,1H),7.71 - 7.63 (m,1H),7.58 - 7.52 (m,1H),7.47 - 7.41 (m,1H),7.24 (br s,4H),7.17 - 7.12 (m,1H),7.11 - 7.05 (m,1H),5.52 - 5.36 (m,1H),4.38 (br s,2H),3.46 (br s,2H),3.14 (br s,4H),3.02 - 2.87 (m,1H),2.82 - 2.59 (m,2H),2.48 - 2.44 (m,4H),2.10 (br s,1H).

[0546] Example 17: Compound 18

[0547]

change

[0548] 1 H NMR (400MHz, DMSO-d6)δ 11.13 (s,1H),8.35 (d,J = 8.0Hz,1H),8.10 (d,J = 7.2Hz,1H),7.89 - 7.81 (m,1H),7.71 - 7.62 (m,1H),7.58 - 7.51 (m,1H),7.33 (d,J = 7.2Hz,1H),7.20 (t,J = 8.0Hz,1H),7.17 - 7.12 (m,1H),7.12 - 7.02 (m,3H),5.48 - 5.39 (m,1H),4.39 (s,2H),3.54 - 3.43 (m,2H),3.35 - 3.32 (m,4H),3.29 - 3.10 (m,4H),3.07 - 2.87 (m,1H),2.81 - 2.70 (m,1H),2.68 - 2.60 (m,1H),2.16 - 1.97 (m,1H).

[0549] Example 18: Compound 19

[0550]

change

[0551] 1H NMR (400MHz, DMSO-d6)δ 11.13 (s,1H),8.34 - 8.30 (m,1H),8.10 - 8.05 (m,1H),7.85 - 7.77 (m,1H),7.43 - 7.36 (m,1H),7.27 - 7.15 (m,4H),7.13 - 7.07 (m,1H),5.49 - 5.41 (m,1H),4.40 - 4.34 (m,2H),3.54 - 3.50 (m,4H),3.37 (s,2H),3.01 - 2.89 (m,1H),2.81 - 2.69 (m,1H),2.67 - 2.61 (m,1H),2.32 - 2.21 (m,4H),2.13 - 2.04 (m,1H).

[0552] Example 19: Compound 20

[0553]

change

[0554] 1 H NMR (400MHz, DMSO-d6)δ 11.09 - 11.24 (s,1H),8.26 - 8.48 (m,1H),8.03 - 8.13 (m,1H),7.78 - 7.88 (m,1H),7.65 - 7.73 (m,1H),7.52 - 7.59 (m,1H),7.38 - 7.45 (m,1H),7.17 - 7.31 (m,4H),7.02 - 7.15 (m,2H),5.35 - 5.62 (m,1H),4.39 (s,2H),3.45 (s,2H),3.08 - 3.18 (m,4H),2.90 - 2.99 (m,1H),2.74 - 2.81 (m,1H),2.64 - 2.68 (m,1H),2.43 - 2.49 (m,4H),2.04 - 2.15 (m,1H).

[0555] Example 20: Compound 16

[0556] [ka]

[0557] Step 1: Synthesis of intermediate B7-2

[0558] [ka] A pale yellow suspension of intermediate B7-1 (21.0 g, 86.4 mmol), hydroxyamine hydrochloride (6.00 g, 86.4 mmol) and pyridine (70 mL) was stirred at 100 °C for 1 hour, and then p-toluenesulfonyl chloride (32.9 g, 173 mmol) was added and stirred at 80 °C for 2 hours. The reaction mixture was rotary evaporated to give a crude product. Ice water (150 mL) was added to the crude product, and the yellow suspension was filtered. The cake was rotary evaporated to give intermediate B7-2 (35.5 g, yield: 99.7%) as a pale yellow solid.

[0559] 1 H NMR (400MHz,DMSO-d6)δ 9.56 (d,J = 2.4Hz,1H),8.91 (d,J = 2.4Hz,1H),8.88 - 8.82 (m,1H),8.67 (dd,J = 0.8,7.2Hz,1H),8.09 (t,J = 7.6Hz,1H),7.95 (d,J = 8.4Hz,2H),7.53 (d,J = 8.0Hz,2H),2.48 (s,3H).

[0560] Step 2: Synthesis of intermediate B7-3

[0561] [ka] A brown suspension of intermediate B7-2 (15.6 g, 37.83 mmol) and sodium hydroxide (2.7 M, 60.3 mL) in ethanol (64 mL) and water (50 mL) was stirred at 100 °C for 1 hour. The reaction mixture was cooled to 80 °C. Concentrated hydrochloric acid was added until the pH reached 3, and the yellow suspension was filtered. The cake was rotary dried to obtain intermediate B7-3 (8.1 g, crude product) as a yellow solid, which was used directly in the next step.

[0562] LCMS (ESI + ): m / z 215.1 [M+H] + .

[0563] Step 3: Synthesis of intermediate B7-4

[0564] [ka] To a yellow suspension of intermediate B7-3 (8.1 g, crude) in trichloromethane (80 mL) was added liquid bromine (3.06 g, 19.12 mmol, 986 μL) at 0 °C. The yellow suspension was stirred at 20 °C for 16 h. The reaction mixture was evaporated to dryness to give intermediate B7-4 (11.2 g, crude) as a yellow solid, which was used directly in the next step.

[0565] 1 H NMR (400MHz,DMSO-d6)δ 11.22 (br s,1H),8.79 (d,J = 1.2Hz,1H),8.59 (d,J = 1.2Hz,1H),7.88 (d,J = 7.6Hz,1H),7.04 (d,J = 7.6Hz,1H).

[0566] Step 4: Synthesis of intermediate B7-5

[0567] [ka] A yellow suspension of intermediate B7-4 (11.2 g, crude), [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (1.40 g, 1.92 mmol), potassium acetate (5.62 g, 57.3 mmol), and bis(pinacolato)diboron (7.62 g, 30.0 mmol) in dioxane (80 mL) was purged with nitrogen gas three times and stirred at 90 °C for 16 h. The reaction mixture was diluted with dichloromethane (30 mL), loaded onto a short silica gel column, and the filtrate was rotary evaporated to give intermediate B7-5 (13.0 g, crude) as a yellow solid, which was used directly in the next step.

[0568] Step 5: Synthesis of intermediate B7-6

[0569] [ka] A brown suspension of Intermediate 1-1 (5.50 g, 16.00 mmol), Intermediate B7-5 (13.0 g, crude product), [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (1.76 g, 2.40 mmol), and potassium carbonate (6.63 g, 47.99 mmol) in dioxane (50 mL) and water (2.5 mL) was purged with nitrogen gas three times and stirred at 90 °C for 16 h. The reaction mixture was rotary evaporated to give the crude product. The crude product was separated by column chromatography (petroleum ether / ethyl acetate = 3 / 1 to 1 / 1) to give Intermediate B7-6 (1.60 g, yield: 19.2%) as a yellow solid.

[0570] LCMS (ESI + ): m / z 522.3 [M+H] + .

[0571] 1H NMR (400MHz,DMSO-d6)δ11.10 (s,1H),9.12 (d,J = 1.2Hz,1H),8.56 (d,J = 1.2Hz,1H),7.67 (dd,J = 1.6,13.4Hz,1H),7.55 (dd,J = 1.6,8.4Hz,1H),7.49 (d,J = 7.2Hz,1H),7.28 - 7.21 (m,4H),7.14 (d,J = 7.2Hz,1H),7.08 (t,J = 8.8Hz,1H),4.46 (s,2H),3.46 (s,2H),3.18 - 3.09 (m,4H),2.50 - 2.44 (m,4H).

[0572] Step 6: Synthesis of Intermediate B7-7

[0573] [ka] A brown suspension of intermediate B7-6 (660 mg, 1.27 mmol), iron powder (707 mg, 12.7 mmol), and ammonium chloride (677 mg, 12.7 mmol) in tetrahydrofuran (10 mL) and water (3 mL) was stirred at 80 °C for 2 hours. The reaction mixture was extracted with dichloromethane / methanol (10:1, 20 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and rotary evaporated to give the crude product. The crude product was separated by column chromatography (petroleum ether / ethyl acetate = 1 / 1 to 0 / 1) to give intermediate B7-7 (350 mg, yield: 56.3%) as a yellow solid.

[0574] Step 7: Synthesis of Intermediate B7-8

[0575] [ka] A yellow suspension of intermediate B7-7 (240 mg, 488 μmol) and t-butyl nitrite (75.5 mg, 732 μmol, 87 μL) in acetonitrile (10 mL) was stirred at 25 °C for 0.5 h. The reaction mixture was then cooled to 0 °C, and cuprous bromide (70.0 mg, 488 μmol) was added. The reaction mixture was then warmed to 25 °C and stirred for 16 h. The reaction mixture was diluted with dichloromethane / methanol (10:1, 40 mL) and washed with water (30 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and rotary evaporated to obtain the crude product. The crude product was separated by column chromatography (dichloromethane / methanol = 1 / 0 to 20 / 1) to obtain intermediate B7-8 (80 mg, yield: 23.3%) as a yellow solid.

[0576] LCMS (ESI + ): m / z 555.5 [M+H] + .

[0577] Step 8: Synthesis of Compound 16

[0578] [ka] A yellow suspension of 60% sodium hydride (87.0 mg, 2.17 mmol) and intermediate B7-8 (80.0 mg, 144 μmol) in tetrahydrofuran (2 mL) was stirred at 0 °C for 0.5 h. 3-Bromopiperidine-2,6-dione (194 mg, 1.01 mmol) was then added at 0 °C. The yellow suspension was then heated to 60 °C and stirred at 60 °C for 2 h. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with ice water (50 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and rotary evaporated to give the crude product. The crude product was separated by plate chromatography (petroleum ether / ethyl acetate = 1 / 2) to give compound 16 (18.0 mg, yield: 18.3%) as a yellow solid.

[0579] LCMS (ESI + ): m / z 668.0 [M+H] + .

[0580] 1 H NMR (400MHz,DMSO-d6)δ11.15 (s,1H),8.53 (s,1H),8.22 (s,1H),7.67 (d,J = 13.6Hz,1H),7.55 (d,J = 8.4Hz,1H),7.43 (d,J = 7.2Hz,1H),7.23 (s,4H),7.15 (d,J = 7.2Hz,1H),7.08 (t,J = 8.8Hz,1H),5.44 (dd,J = 5.2,12.4Hz,1H),4.37 (s,2H),3.46 (s,2H),3.14 (br s,4H),3.02 - 2.86 (m,1H),2.79 - 2.70 (m,1H),2.68 - 2.62 (m,1H),2.49 - 2.41 (m,4H),2.15 - 2.07 (m,1H).

[0581] Proteolysis experiments of IKZF1 and SALL4 (HiBiT tag bioluminescence detection) The following is a general method for detecting IKZF1 and SALL4 proteolysis induced by molecular glue compounds in a specific cell line. For example, HT-1080 cells were purchased from the American Type Culture Collection (ATCC, catalog number CCL-121) and stably expressed GSPT(Δ1-138) / G575N and HiBiT-tagged IKZF1 or SALL4 proteins by lentiviral transduction. The cells were cultured in DMEM medium supplemented with 10% fetal bovine serum, 1x sodium pyruvate, 1x non-essential amino acids, 1x glutamate, 100 U / ml penicillin, and 100 μg / ml streptomycin. First, increasing concentrations of test compounds were dispensed into empty 384-well plates (Corning, Catalog No. 3764) using a 10-point dilution system using an Echo 650 acoustic dispenser (Beckman Coulter). The concentrations ranged typically from 0.316 nmol to 10 μmol (or 15.81 pmol to 500 nmol), with half-logarithmic dilutions (3.162-fold), and DMSO-treated controls were used. At the time of the experiment, the stable cell lines were seeded into the 384-well plates at an inoculum concentration of 10,000 cells in approximately 35 μL of culture medium per well. The seeded 384-well plates were then incubated in a 37°C, 5% CO2 incubator for 20 hours. Finally, 35 μL / well of Nano-Glo HiBiT Degradation Detection Solution (Promega) was added, and after 30 minutes of incubation at room temperature, bioluminescence readings were performed using an EnVision multifunction microplate reader (PerkinElmer) or a PHERAstar multifunction microplate reader (BMG Labtech). Data were processed using the Collaborative Drug Discovery Vault software package, and the degradation values ​​(percentages of the DMSO sample) of each treated sample were calculated using the DMSO-treated sample as the reference value. Finally, a four-parameter logistic regression model was used to generate degradation curves, and the median degradation concentrations (EC50 and DC50) were calculated. The calculation formula is as follows: y = (A+ ((BA) / (1+ ((C / x)A D)))) however, A = Y min (The lowest IKZF1 or SALL4 reading after treatment of the test sample, calculated by curve fitting) B = Y max (Highest values, i.e., IKZF1 or SALL4 readings in DMSO-treated samples) C = EC 50 half decomposition concentration D = Hill slope x = concentration of compound EC 50 = y = (Y max -Y min ) / 2 hr test sample concentration DC 50 = y = concentration of test sample at the time of reading of IKZF1 or SALL4 in 50% DMSO-treated samples y = IKZF1 or SALL4 readings after treatment of the test sample (normalized to IKZF1 or SALL4 readings in DMSO-treated samples) D max = (1- Y min / Y max ) * 100% D max represents the maximum percentage of IKZF1 or SALL4 protein degradation achievable in measurements with treatment with compound at the highest compound concentration.

[0582] Degradation activity list of IKZF1 and SALL4 Table 1. DCs measured in IKZF1 and SALL4 proteolysis experiments 50 and D max Value (HiBiT tag bioluminescence detection):

[0583] [Table 1]

[0584] Table 2. DCs measured in IKZF1 and SALL4 proteolysis experiments 50 and D max Value (HiBiT tag bioluminescence detection):

[0585] [Table 2] Note: 1) The results in Tables 1 and 2 are from a single experiment. The measurement results for the compounds in Table 1 were not obtained in the same experiment, but the measurement results for the compounds in Table 2 were obtained in the same experiment.

[0586] 2) Pomalidomide and CC-92480 are known compounds having the following structural formulas:

[0587] [ka]

[0588] Comparison of the kinetics of compounds 9-B and 9-A in degrading IKZF1 protein The following is a method for evaluating the kinetics of IKZF1 protein degradation by compounds 9-B and 9-A using HiBiT tag bioluminescence detection experiments. The cell lines and experimental conditions used in the experiments were exactly the same as those described above, except that the incubation time after compound treatment was changed to 1, 2, or 4 hours.

[0589] The experimental results showed that the kinetics of compound 9-B in degrading IKZF1 protein was much better than that of compound 9-A. After 1 hour of treatment with the compound, the D max is about 77%, DC 50 is approximately 0.4 nM, and D of 9-A max is about 68%, DC 50 After 4 hours of treatment with the compounds, the degradation effect of 9-A on IKZF1 protein was significantly improved, but was still inferior to that of 9-B (9-A:D max = 88%,DC 50 = 0.6 nM; 9-B:D max = 92%,DC 50< 0.2 nM), as shown in Figure 1.

[0590] MM.1S cell line proliferation test The following is a method for detecting the cytostatic activity of molecular glue compounds in multiple myeloma cell lines. Taking MM.1S as an example, the MM.1S cell line was purchased from the American Type Culture Collection (ATCC, catalog number CRL-2974). The cells were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum, 1x sodium pyruvate, 1x non-essential amino acids, 1x glutamic acid, 100 U / ml penicillin, and 100 μg / ml streptomycin. First, test compounds were dispensed into blank 384-well plates (Corning, Cat. No. 3764) using an Echo 650 acoustic dispenser (Beckman Coulter) or a D300e digital dispenser (Tecan) at increasing concentrations in 10-point dilutions. The concentrations typically ranged from 0.316 pmol to 10 nmol, with half-logarithmic dilutions (3.162x), and DMSO-treated controls were included. At the time of the experiment, the cell lines were seeded into the 384-well plates at approximately 50 μL of medium per well containing 3000 cells. The seeded 384-well plates were then incubated in a 37°C, 5% CO2 incubator for 120 hours. Finally, 20 μL / well of CellTiter Glo degradation detection solution (Promega) was added, and after 30 minutes of incubation at room temperature, bioluminescence readings were performed using an EnVision multifunction microplate reader (PerkinElmer) or a PHERAstar multifunction microplate reader (BMG Labtech). Data were processed using the Collaborative Drug Discovery Vault software package, and the cellular activity values ​​(percentage of the DMSO sample) of each treated sample were calculated using the DMSO-treated sample as the reference value. Finally, a degradation curve was generated using a four-parameter logistic regression model, and the median inhibitory concentration (EC50) and IC50 were calculated. The calculation formula is as follows: y = (A+ ((BA) / (1+ ((C / x) A D)))) (however, A = Y min (Minimum cell activity reading after treatment of test sample, calculated by curve fitting) B = Y max (At the highest value, i.e., the reading of cell activity in the DMSO-treated sample) C = EC 50 Half inhibitory concentration D = Hill slope x = concentration of compound EC 50 = y = (Y max -Y min ) / 2 hr test sample concentration I C 50 = y = concentration of test sample at the time of cell activity reading in 50% DMSO-treated samples y = Cell activity reading after treatment of the test sample (normalized to cell activity reading in the DMSO-treated sample)

[0591] Table 3. List of MM.1S cytostatic activities

[0592] [Table 3] In Table 3, 1) n is the number of independent test experiments for each compound, and 2) ND is the upper limit of the test concentration of the compound, Y min could not be determined.

[0593] Pharmacokinetic evaluation of compounds in mice Experimental Objective: This study used CD male mice as test animals. The test compounds were administered intravenously or orally to the mice, and the plasma drug concentrations at different time points were quantitatively measured using LC / MS / MS to evaluate the pharmacokinetic characteristics of the test compounds in rats.

[0594] Experimental materials: CD1 mice (male, 20-30 g, 6-8 weeks old, Zhejiang Vital River).

[0595] Experimental procedure: A solution of the test compound was injected intravenously via the tail vein into CD1 mice (ad libitum eating and drinking) or orally administered intragastricly to CD1 mice (ad libitum eating and drinking). For intravenous administration, blood was collected from the dorsal metatarsal vein at 5 min (0.0833 h), 15 min (0.25 h), 30 min (0.5 h), 60 min (1 h), 2 h, 4 h, 6 h, 8 h, and 24 h after administration and placed in an anticoagulant tube containing EDTA-K2. The mixture was thoroughly mixed by vortexing and centrifuged at 4000 g for 5 min at 4°C. For oral intragastric administration, blood was collected from the dorsal metatarsal vein at 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, and 24 h after administration and placed in an anticoagulant tube containing EDTA-K2. The mixture was thoroughly mixed by vortexing and centrifuged at 4000 g for 5 min at 4°C. Blood drug concentrations were measured by LC-MS / MS, and relevant pharmacokinetic parameters were calculated using the non-compartmental linear / log trapezoidal method using Phoenix WinNonlin 6.3 pharmacokinetic software.

[0596] Pharmacokinetic parameters of compound 9 in mice

[0597] [Table 4] Note: NC is not calculated.

[0598] Pharmacokinetic parameters of compound 9-B in mice

[0599] [Table 5]

[0600] The present application also includes any technical solutions among the following numbered items:

[0601] 1. A compound represented by structural formula (I) or a pharmaceutically acceptable salt thereof:

[0602] [ka] (however, R 1 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl groups, heterocyclic groups, aryl groups, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogen atoms, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups, and wherein the cycloalkyl groups, heterocyclic groups, aryl groups, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogen atoms, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0603] R 1’is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0604] R 2 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0605] R 2’ is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0606] R 3is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0607] R 4 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0608] R 5 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups. a is 0, 1 or 2. b is 0, 1 or 2. X 1 appears each time, independently, 14 Or selected from N. X 2 appears each time, independently, 14’ Or selected from N. X 3 appears each time, independently, 14’’ Or selected from N. X 4 appears each time, independently,14’’’ Or selected from N.

[0609] R 14 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0610] R 14’ is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0611] R 14’’ is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0612] R 14’’’is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0613] L, when it occurs each time, is independently O, NR 21 , C.R. 22 , C.R. 23 R 24 , N.R. 25 -CR 26 , C.R. 27 -CR 28 Selected from.

[0614] R 21is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0615] R 22 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0616] L is CR 23 R 24 In the case of R 23 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally substituted with 1, 2, 3 or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH or C1-C6 alkyl groups; R 24is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally substituted with 1, 2, 3 or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups; or R 23 and R 24 are joined together with the carbon atoms to which they are attached to form a monocyclic, bicyclic or tricyclic saturated or unsaturated system having 5-14 ring atoms, wherein 0, 1, 2, 3 or 4 of the ring atoms are heteroatoms selected from N, O and S, and the remainder are carbon atoms, and the ring system is optionally substituted with 1, 2, 3 or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0617] L is NR 25 -CR 26 In the case of R 25is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally substituted with 1, 2, 3 or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH or C1-C6 alkyl groups; R 26 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally substituted with 1, 2, 3 or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups; or R 25 and R 26 together with the attached nitrogen and carbon atoms form a monocyclic, bicyclic or tricyclic saturated or unsaturated system having 5-14 ring atoms, in which 0, 1, 2, 3 or 4 of the other ring atoms other than the nitrogen atom are heteroatoms selected from N, O and S, the remainder being carbon atoms, and the ring system is optionally substituted with 1, 2, 3 or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0618] L is CR 27 -CR 28 In the case of R 27 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally substituted with 1, 2, 3 or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH or C1-C6 alkyl groups; R 28 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally substituted with 1, 2, 3 or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups; or R 27 and R 28 are joined together with the carbon atoms to which they are attached to form a monocyclic, bicyclic or tricyclic saturated or unsaturated system having 5-14 ring atoms, wherein 0, 1, 2, 3 or 4 of the ring atoms are heteroatoms selected from N, O and S, and the remainder are carbon atoms, and the ring system is optionally substituted with 1, 2, 3 or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups. J is NR 31 , C.R. 32 R 33 is. g is 0, 1 or 2. K is NR 34 , C.R. 35 R 36 is. h is 0, 1 or 2.

[0619] R 31 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0620] R 32 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0621] R 33 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0622] R 34is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0623] R 35 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0624] R 36 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl groups, heterocyclic groups, aryl groups, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0625] 2. The compound according to item 1 or a pharmaceutically acceptable salt thereof, wherein the compound of structural formula (I) is a compound of structural formula (II) or a pharmaceutically acceptable salt thereof.

[0626] [ka] (however, T is N or CH.

[0627] P, when occurring each time, is independently selected from the group consisting of: absent, hydrogen, halogen, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C2-C6 alkanoyl, C2-C6 alkyl ester, C1-C6 alkylthio, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), -O-C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl groups, heterocyclic groups, aryl groups, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0628] 3. The compound according to item 1 or a pharmaceutically acceptable salt thereof, wherein the compound of structural formula (I) is a compound of structural formula (II) or a pharmaceutically acceptable salt thereof.

[0629] [ka] (However, the base

[0630] [ka] represents a mono-, bi- or tricyclic saturated or unsaturated ring system having 5-14 ring atoms, U is N, C or O, Y is N, C or O, said ring system further containing 0, 1, 2, 3 or 4 heteroatoms selected from N, O and S, and said ring system is optionally substituted with 1, 2, 3 or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0631] 4. The compound according to item 1 or a pharmaceutically acceptable salt thereof, wherein the compound of structural formula (I) is a compound of structural formula (II) or a pharmaceutically acceptable salt thereof.

[0632] [ka] (however, R 6 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0633] R 7is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0634] R 8 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups.

[0635] R 9 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, nitro, cyano, amino, mercapto, -COOH, or C1-C6 alkyl groups.

[0636] R 10is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0637] R 11 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups. c is 0, 1 or 2. d is 0, 1 or 2. e is 0, 1 or 2. Q is CR 12 R 13 where n is 0, 1, or 2. X 5 , O, CR 15 R 16 , or NR 17 Selected from.

[0638] R 12 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0639] R 13is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0640] R 15 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0641] R 16 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0642] R 17is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups.

[0643] R 18 is, each time it occurs, independently either absent, hydrogen, halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C2-C6 alkanoyl group, C2-C6 alkyl ester, C1-C6 alkylthio group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, hydroxyC1-C6 alkyl group, aminoC1-C6 alkyl group, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl group, -C0-C4 alkyl(C3-C7 cycloalkyl) group, -O-C0-C4 alkyl(C3-C7 cycloalkyl) group, C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C1-C6 alkyl groups. T is N or CH. X 6 is N or C. X 7 is N or C. X 8 is N or C. X 9 is N or C.)

[0644] 5. The compound or pharmaceutically acceptable salt thereof according to any of the preceding items, wherein the compound is a compound of structural formula (II) or a pharmaceutically acceptable salt thereof:

[0645] [ka]

[0646] 6. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (VI) or a pharmaceutically acceptable salt thereof:

[0647] [ka]

[0648] 7. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (VII) or a pharmaceutically acceptable salt thereof:

[0649] [ka]

[0650] 8. The compound or pharmaceutically acceptable salt thereof according to any of the preceding items, wherein the compound is a compound of structural formula (VIII) or a pharmaceutically acceptable salt thereof:

[0651] [ka]

[0652] 9. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (IX) or a pharmaceutically acceptable salt thereof:

[0653] [ka]

[0654] 10. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (X) or a pharmaceutically acceptable salt thereof:

[0655] [ka]

[0656] 11. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XI) or a pharmaceutically acceptable salt thereof:

[0657] [ka]

[0658] 12. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XII) or a pharmaceutically acceptable salt thereof:

[0659] [ka]

[0660] 13. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XIII) or a pharmaceutically acceptable salt thereof:

[0661] [ka]

[0662] 14. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XIV) or a pharmaceutically acceptable salt thereof:

[0663] [ka]

[0664] 15. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XV) or a pharmaceutically acceptable salt thereof:

[0665] [ka]

[0666] 16. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XVI) or a pharmaceutically acceptable salt thereof:

[0667] [ka]

[0668] 17. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XVII) or a pharmaceutically acceptable salt thereof:

[0669] [ka]

[0670] 18. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XVIII) or a pharmaceutically acceptable salt thereof:

[0671] [ka]

[0672] 19. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XIX) or a pharmaceutically acceptable salt thereof:

[0673] [ka]

[0674] 20. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XX) or a pharmaceutically acceptable salt thereof.

[0675] [ka]

[0676] 21. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XXI) or a pharmaceutically acceptable salt thereof:

[0677] [ka]

[0678] 22. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XXII) or a pharmaceutically acceptable salt thereof:

[0679] [ka]

[0680] 23. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XXIII) or a pharmaceutically acceptable salt thereof:

[0681] [ka]

[0682] 24. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XXIV) or a pharmaceutically acceptable salt thereof.

[0683] [ka]

[0684] 25. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XXV) or a pharmaceutically acceptable salt thereof:

[0685] [ka]

[0686] 26. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XXVI) or a pharmaceutically acceptable salt thereof:

[0687] [ka]

[0688] 27. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XXVII) or a pharmaceutically acceptable salt thereof:

[0689] [ka]

[0690] 28. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XXVIII) or a pharmaceutically acceptable salt thereof:

[0691] [ka]

[0692] 29. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XXIX) or a pharmaceutically acceptable salt thereof.

[0693] [ka]

[0694] 30. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XXX) or a pharmaceutically acceptable salt thereof.

[0695] [ka]

[0696] 31. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XXXI) or a pharmaceutically acceptable salt thereof:

[0697] [ka]

[0698] 32. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XXXII) or a pharmaceutically acceptable salt thereof:

[0699] [ka]

[0700] 33. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XXXIII) or a pharmaceutically acceptable salt thereof:

[0701] [ka]

[0702] 34. The compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of structural formula (XXXIV) or a pharmaceutically acceptable salt thereof.

[0703] [ka]

[0704] 35.R 1 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group, heterocyclic group, aryl group, and heteroaryl group are optionally substituted with 1, 2, 3, or 4 halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, or C1-C6 alkyl group.

[0705] 36.R 1 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0706] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0707] 37.R 1 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0708] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0709] 38.R 1 is independently selected from hydrogen, fluorine, a cyano group, a methyl group, and an isopropyl group when it occurs each time, or a pharmaceutically acceptable salt thereof.

[0710] 39.R 1’ each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group, heterocyclic group, aryl group, and heteroaryl group are optionally substituted with 1, 2, 3, or 4 halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, or C1-C6 alkyl group.

[0711] 40.R 1’ each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0712] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0713] 41.R 1’ each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0714] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0715] 42.R 1 is independently selected from hydrogen, fluorine, a cyano group, a methyl group, and an isopropyl group when it occurs each time, or a pharmaceutically acceptable salt thereof.

[0716] 43.R 2 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group, heterocyclic group, aryl group, and heteroaryl group are optionally substituted with 1, 2, 3, or 4 halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, or C1-C6 alkyl group.

[0717] 44.R 2 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0718] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0719] 45.R 2 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0720] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0721] 46.R 2 is independently selected from hydrogen, fluorine, chlorine, bromine, cyano, trifluoromethyl, methoxy, ethoxy, or methyl, each occurrence of which is a compound according to any of the preceding items, or a pharmaceutically acceptable salt thereof.

[0722] 47.R 2’ each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group, heterocyclic group, aryl group, and heteroaryl group are optionally substituted with 1, 2, 3, or 4 halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, or C1-C6 alkyl group.

[0723] 48.R 2’ each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0724] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0725] 49.R 2’ each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0726] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0727] 50.R 2’ is independently selected from hydrogen, fluorine, a cyano group, a methyl group, and an isopropyl group when it occurs each time, or a pharmaceutically acceptable salt thereof.

[0728] 51.R 3 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group, heterocyclic group, aryl group, and heteroaryl group are optionally substituted with 1, 2, 3, or 4 halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, or C1-C6 alkyl group.

[0729] 52.R 3 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0730] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0731] 53.R 3 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0732] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0733] 54.R 3 is independently selected from hydrogen, fluorine, a cyano group, a methyl group, and an isopropyl group when it occurs each time, or a pharmaceutically acceptable salt thereof.

[0734] 55.R 4 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group, heterocyclic group, aryl group, and heteroaryl group are optionally substituted with 1, 2, 3, or 4 halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, or C1-C6 alkyl group.

[0735] 56.R 3 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0736] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0737] 57.R 4 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0738] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0739] 58.R 4 is independently selected from hydrogen, fluorine, a cyano group, a methyl group, and an isopropyl group when it occurs each time, or a pharmaceutically acceptable salt thereof.

[0740] 59.R 5 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group, heterocyclic group, aryl group, and heteroaryl group are optionally substituted with 1, 2, 3, or 4 halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, or C1-C6 alkyl group.

[0741] 60.R 5 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0742] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0743] 61.R 5 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0744] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0745] 62.R 5 is independently selected from hydrogen, fluorine, a cyano group, a methyl group, and an isopropyl group when it occurs each time, or a pharmaceutically acceptable salt thereof.

[0746] 63.R 6 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group, heterocyclic group, aryl group, and heteroaryl group are optionally substituted with 1, 2, 3, or 4 halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, or C1-C6 alkyl group.

[0747] 64.R 6 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0748] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0749] 65.R 6 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0750] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0751] 66.R 6 is independently selected from hydrogen, fluorine, a cyano group, a methyl group, and an isopropyl group when it occurs each time, or a pharmaceutically acceptable salt thereof.

[0752] 67.R 7 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group, heterocyclic group, aryl group, and heteroaryl group are optionally substituted with 1, 2, 3, or 4 halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, or C1-C6 alkyl group.

[0753] 68.R 7 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0754] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0755] 69.R 7 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0756] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0757] 70.R 7 is independently selected from hydrogen, fluorine, a cyano group, a methyl group, and an isopropyl group when it occurs each time, or a pharmaceutically acceptable salt thereof.

[0758] 71.R 8 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group, heterocyclic group, aryl group, and heteroaryl group are optionally substituted with 1, 2, 3, or 4 halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, or C1-C6 alkyl group.

[0759] 72.R 8 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0760] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0761] 73.R 8 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0762] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0763] 74.R 8 is independently selected from hydrogen, fluorine, a cyano group, a methyl group, and an isopropyl group when it occurs each time, or a pharmaceutically acceptable salt thereof.

[0764] 75.R 9 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group, heterocyclic group, aryl group, and heteroaryl group are optionally substituted with 1, 2, 3, or 4 halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, or C1-C6 alkyl group.

[0765] 76.R 9 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0766] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0767] 77.R 9 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0768] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0769] 78.R 9 is independently selected from hydrogen, fluorine, a cyano group, a methyl group, and an isopropyl group when it occurs each time, or a pharmaceutically acceptable salt thereof.

[0770] 79.R 10 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group, heterocyclic group, aryl group, and heteroaryl group are optionally substituted with 1, 2, 3, or 4 halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, or C1-C6 alkyl group.

[0771] 80.R 10 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0772] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0773] 81.R 10 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0774] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0775] 82.R 10 is independently selected from hydrogen, fluorine, a cyano group, a methyl group, and an isopropyl group when it occurs each time, or a pharmaceutically acceptable salt thereof.

[0776] 83.R 11 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group, heterocyclic group, aryl group, and heteroaryl group are optionally substituted with 1, 2, 3, or 4 halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, or C1-C6 alkyl group.

[0777] 84.R 11 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0778] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0779] 85.R 11 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0780] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0781] 86.R 11 is independently selected from hydrogen, fluorine, a cyano group, a methyl group, and an isopropyl group when it occurs each time, or a pharmaceutically acceptable salt thereof.

[0782] 87.R 12 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group, heterocyclic group, aryl group, and heteroaryl group are optionally substituted with 1, 2, 3, or 4 halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, or C1-C6 alkyl group.

[0783] 88.R 12 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0784] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0785] 89.R 12 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0786] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0787] 90.R 12 is independently selected from hydrogen, fluorine, a cyano group, a methyl group, and an isopropyl group when it occurs each time, or a pharmaceutically acceptable salt thereof.

[0788] 91.R 13 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group, heterocyclic group, aryl group, and heteroaryl group are optionally substituted with 1, 2, 3, or 4 halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, or C1-C6 alkyl group.

[0789] 92.R 13 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0790] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0791] 93.R 13 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0792] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0793] 94.R 13 is independently selected from hydrogen, fluorine, a cyano group, a methyl group, and an isopropyl group when it occurs each time, or a pharmaceutically acceptable salt thereof.

[0794] 95.R 14 each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group, heterocyclic group, aryl group, and heteroaryl group are optionally substituted with 1, 2, 3, or 4 halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, or C1-C6 alkyl group.

[0795] 96.R 14 each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0796] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0797] 97.R 14 each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0798] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0799] 98.R 14 is independently selected from hydrogen, fluorine, a cyano group, a methyl group, and an isopropyl group when it occurs each time, or a pharmaceutically acceptable salt thereof.

[0800] 99.R 14’ each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group, heterocyclic group, aryl group, and heteroaryl group are optionally substituted with 1, 2, 3, or 4 halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, or C1-C6 alkyl group.

[0801] 100.R 14’ each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0802] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0803] 101.R 14’ each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0804] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0805] 102.R 14’ is independently selected from hydrogen, fluorine, a cyano group, a methyl group, and an isopropyl group when it occurs each time, or a pharmaceutically acceptable salt thereof.

[0806] 103.R 14’’ each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10 or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group, heterocyclic group, aryl group, and heteroaryl group are optionally substituted with 1, 2, 3, or 4 halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, or C1-C6 alkyl group.

[0807] 104.R 14’’ each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0808] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0809] 106.R 14’’ each time it occurs, independently represents hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy,

[0810] [ka] The compound according to any one of the preceding items, wherein the group is selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group, or a pharmaceutically acceptable salt thereof.

[0811] 106.R 14’’ is independently selected from hydrogen, fluorine, a cyano group, a methyl group, and an isopropyl group when it occurs each time, or a pharmaceutically acceptable salt thereof.

[0812] 107.R 14’’’ each time it occurs, it is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, hydroxy, nitro, cyano, amino, mercapto, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyC1-C6 alkyl, aminoC1-C6 alkyl, (mono- and di-C1-C6 alkylamino)C0-C4 alkyl, -C0-C4 alkyl(C3-C7 cycloalkyl), C3-C 12 Heterocyclic group, C6~C 12 Aryl groups and C5-C 10or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group, heterocyclic group, aryl group, and heteroaryl group are optionally substituted with 1, 2, 3, or 4 halogen, hydroxy group, nitro group, cyano group, amino group, mercapto group, -COOH, or C1-C6 alkyl group.

[0813] 108.R 14’’’ each time it occurs, it independently represents either absent, hydrogen, fluorine, chlorine, cyano, amino, mercapto, -COOH, methyl, ethyl, n-propyl, isopropyl,...

Claims

1. A compound represented by structural formula (I) or a pharmaceutically acceptable salt thereof: 【Chemistry 1】 (however, R １ is hydrogen. R １’ is hydrogen. R ２ is a halogen. R ２’ is hydrogen. R ３ is hydrogen. R ４ is hydrogen. R ５ is hydrogen. a is 2. b is 2. X １ appears each time, independently, １４ Or selected from N. X ２ appears each time, independently, １４’ Or selected from N. X ３ appears each time, independently, １４’’ Or selected from N. X ４ appears each time, independently, １４’’’ Or selected from N. R １４ is independently selected from hydrogen or halogen at each occurrence. R １４’ is independently hydrogen or halogen at each occurrence. R １４’’ is independently selected from hydrogen or halogen at each occurrence. R １４’’’ is independently selected from hydrogen or halogen at each occurrence. L, each occurrence, is independently O, NR ２１ , C.R. ２３ R ２４ , N.R. ２５ -CR ２６ , C.R. ２７ -CR ２８ Selected from. R ２１ each occurrence independently represents hydrogen, halogen, cyano group, C １ ~C ６ Alkyl group, C １ ~C ６ Alkoxy group, C １ ~C ６ Haloalkyl group, C １ ~C ６ Haloalkoxy group, hydroxy C １ ~C ６ Alkyl group, amino C １ ~C ６ Alkyl groups, (mono- and di-C １ ~C ６ alkylamino)C ０ ~C ４ alkyl group, -C ０ ~C ４ Alkyl (C ３ ~C ７ cycloalkyl) group, —O—C ０ ~C ４ Alkyl (C ３ ~C ７ cycloalkyl group), C ３ ~C １２ Heterocyclic group, C ６ ~C １２ Aryl groups and C ５ ~C １０ and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups optionally contain 1, 2, 3, or 4 halogen atoms, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, —COOH, or C １ ~C ６ It is substituted with an alkyl group. L is CR ２３ R ２４ In the case of ２３ is hydrogen, R ２４ each occurrence independently represents hydrogen, halogen, cyano group, C １ ~C ６ Alkyl group, C １ ~C ６ Alkoxy group, C １ ~C ６ Haloalkyl group, C １ ~C ６ Haloalkoxy group, hydroxy C １ ~C ６ Alkyl group, amino C １ ~C ６ Alkyl groups, (mono- and di-C １ ~C ６ alkylamino)C ０ ~C ４ alkyl group, -C ０ ~C ４ Alkyl (C ３ ~C ７ cycloalkyl) group, —O—C ０ ~C ４ Alkyl (C ３ ~C ７ cycloalkyl group), C ３ ~C １２ Heterocyclic group, C ６ ~C １２ Aryl groups and C ５ ~C １０ and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups optionally contain 1, 2, 3, or 4 halogen atoms, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, —COOH, or C １ ~C ６ substituted with an alkyl group, or R ２３ and R ２４ are joined together with the carbon atoms to which they are attached to form a monocyclic, bicyclic or tricyclic saturated or unsaturated system having 5-14 ring atoms, 0, 1, 2, 3 or 4 of which are heteroatoms selected from N, O and S, the remainder being carbon atoms, and the ring system optionally contains 1, 2, 3 or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C １ ~C ６ It is substituted with an alkyl group. L is NR ２５ -CR ２６ in the case of, R ２５ and R ２６ are joined together with the nitrogen atom and carbon atoms to which they are attached to form a monocyclic, bicyclic or tricyclic saturated or unsaturated system having 5-14 ring atoms, wherein 0, 1, 2, 3 or 4 of the other ring atoms other than the nitrogen atom are heteroatoms selected from N, O and S, and the remainder are carbon atoms, and the ring system optionally contains 1, 2, 3 or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C １ ~C ６ It is substituted with an alkyl group. L is CR ２７ -CR ２８ in the case of, R ２７ and R ２８ are joined together with the carbon atoms to which they are attached to form a monocyclic, bicyclic or tricyclic saturated or unsaturated system having 5-14 ring atoms, 0, 1, 2, 3 or 4 of which are heteroatoms selected from N, O and S, the remainder being carbon atoms, and the ring system optionally contains 1, 2, 3 or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C １ ~C ６ It is substituted with an alkyl group. J is for CR ３２ R ３３ is. g is 1 or 2. K is CR ３５ R ３６ is. h is 1 or 2. R ３２ is hydrogen. R ３３ is hydrogen. R ３５ is hydrogen. R ３６ is hydrogen.)

2. 2. The compound of claim 1, wherein the compound of structural formula (I) is a compound of structural formula (II): or a pharmaceutically acceptable salt thereof. 【Chemistry 2】 (however, T is N or CH. P, in each occurrence, is independently hydrogen, halogen, cyano group, C １ ~C ６ Alkyl group, C １ ~C ６ Alkoxy group, C １ ~C ６ Haloalkyl group, C １ ~C ６ Haloalkoxy group, hydroxy C １ ~C ６ Alkyl group, amino C １ ~C ６ Alkyl groups, (mono- and di-C １ ~C ６ alkylamino)C ０ ~C ４ alkyl group, -C ０ ~C ４ Alkyl (C ３ ~C ７ cycloalkyl) group, —O—C ０ ~C ４ Alkyl (C ３ ~C ７ cycloalkyl group), C ３ ~C １２ Heterocyclic group, C ６ ~C １２ Aryl groups and C ５ ~C １０ and heteroaryl groups, wherein the cycloalkyl, heterocyclic, aryl, and heteroaryl groups optionally contain 1, 2, 3, or 4 halogen atoms, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, —COOH, or C １ ~C ６ It is substituted with an alkyl group. R １ , R １’ , R ２ , R ２’ , R ３ , R ４ , R ５ , a, b, X １ , X ２ , X ３ , X ４ , J, g, K, h are as defined in claim 1.

3. 2. The compound of claim 1, wherein the compound of structural formula (I) is a compound of structural formula (III): or a pharmaceutically acceptable salt thereof. 【Transformation 3】 (However, the base 【Chemistry 4】 represents a mono-, bi- or tricyclic saturated or unsaturated system having 5-14 ring atoms, U is N, C or O, Y is N, C or O, said ring system further containing another 0, 1, 2, 3 or 4 heteroatoms selected from N, O, S, and said ring system optionally containing 1, 2, 3 or 4 halogens, hydroxy groups, nitro groups, cyano groups, amino groups, mercapto groups, -COOH, or C １ ~C ６ It is substituted with an alkyl group. R １ , R １’ , R ２ , R ２’ , R ３ , R ４ , R ５ , a, b, X １ , X ２ , X ３ , X ４ , J, g, K, h are as defined in claim 1.

4. 4. The compound of claim 3, wherein the compound is a compound of structural formula (XXIII) or (XXIV), or a pharmaceutically acceptable salt thereof: 【Transformation 5】 (R ２ , X １ , X ３ , J, g, K, h, U, Y are as defined in claim 3.

5. 3. The compound of claim 2, wherein the compound is a compound of structural formula (XXVII) or (XXVIII), or a pharmaceutically acceptable salt thereof: 【Transformation 6】 (R １ , R １’ , R ２ , R ２’ , R ３ , R ４ , R ５ , a, b, X １ , X ２ , X ３ , X ４ , J, g, K, h, T, P are as defined in claim 2.

6. 3. The compound of claim 2, wherein the compound is a compound of structural formula (XXXI) or (XXXII) or a pharmaceutically acceptable salt thereof: 【Transformation 7】 (R ２ , X １ , X ３ , T, P are as defined in claim 2.)

7. 3. The compound of claim 2, wherein the compound is a compound of structural formula (XXXIII) or (XXXIV) or a pharmaceutically acceptable salt thereof: 【Transformation 8】 (R ２ , X １ , X ３ , T, P are as defined in claim 2.)

8. R ２ is fluorine, R １４ is independently selected from hydrogen or fluorine at each occurrence; R １４’ is independently selected from hydrogen or fluorine at each occurrence; R １４’’ is independently selected from hydrogen or fluorine at each occurrence; R １４’’’ is independently selected from hydrogen or fluorine at each occurrence; R ２１ each occurrence independently represents hydrogen, fluorine, chlorine, cyano, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, 【Chemistry 9】 selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group; R ２４ is independently selected from the group consisting of: absent, hydrogen, fluorine, chlorine, cyano, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, 【Chemistry 10】 selected from a trifluoromethyl group, a monofluoromethyl group, a difluoromethyl group, a 2-fluoroethyl group, and a pentafluoroethyl group; X １ is N, CH, or CF, X ２ is N, CH, or CF, X ３ is N, CH, or CF, X ４ is N, CH, or CF; 2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof.

9. P, in each occurrence, is independently hydrogen, fluorine, cyano, methyl, isopropyl, t-butyl, trifluoromethyl, morpholyl, 【Chemistry 11】 Selected from T is N, J is CH ２ in, K is CH ２ That is, 3. The compound according to claim 2 or a pharmaceutically acceptable salt thereof.

10. J is CH ２ in, K is CH ２ in, U is C, N or O, Y is C, N or O; 【Chemistry 12】 is a 5-, 6- or 7-membered monocyclic ring; 4. The compound according to claim 3 or a pharmaceutically acceptable salt thereof.

11. 2. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is the following compound or a pharmaceutically acceptable salt thereof: 【Chemistry 13】

12. 2. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is the following compound or a pharmaceutically acceptable salt thereof: 【Chemistry 14】

13. A pharmaceutical composition comprising the compound according to any one of claims 1 to 12 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

14. 13. Use of a compound according to any one of claims 1 to 12 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating a proliferative disease, comprising: The proliferative disease includes breast cancer, colon cancer, brain cancer, prostate cancer, kidney cancer, pancreatic adenocarcinoma, ovarian cancer, head and neck cancer, melanoma, colorectal cancer, gastric cancer, squamous cell carcinoma, small cell lung cancer, non-small cell lung cancer, testicular cancer, Merkel cell carcinoma, glioblastoma, neurocytoma, cancer of the lymphoid organs and myeloid malignancies.

15. The use described in claim 14, wherein the myeloid malignancies include leukemia, lymphoma and multiple myeloma.

16. The myeloid malignancies are acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute monocytic leukemia (AMOL), hairy cell leukemia (HCL), T-cell prolymphocytic leukemia (T-PLL), large granular lymphocytic leukemia, adult T-cell disease, small lymphocytic lymphoma (SLL), Hodgkin's lymphoma, non-Hodgkin's lymphoma, precursor B-lymphoblastic leukemia, lymphoplasmacytic lymphoma, splenic marginal zone lymphoma, plasma cell neoplasm, extranodal marginal zone B-cell lymphoma, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, mediastinal large cell lymphoma, 15. The use of claim 14, comprising: cutaneous B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt's lymphoma / leukemia, T-cell prolymphocytic leukemia, T-cell large granular lymphocytic leukemia, aggressive NK-cell leukemia, adult T-cell leukemia / lymphoma, extranodal NK / T-cell lymphoma, enteropathic T-cell lymphoma, hepatosplenic T-cell lymphoma, blastic NK-cell lymphoma, mycosis fungoides / Sezary syndrome, primary cutaneous CD30-positive T-lymphoproliferation, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma, anaplastic large cell lymphoma, plasma cell myeloma or Kahler's disease.

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