Ripk1 inhibitors and methods of making and using the same

Abstract

The present disclosure provides a RIPK1 inhibitor compound represented by formula (M-1) or formula (M) or a pharmaceutically acceptable salt thereof, which has good RIPK1 inhibition effect and can be used for preventing and / or treating diseases related to RIPK1 kinase.

Description

[0001] This application claims priority to the following prior patent applications: The prior patent application filed with the China National Intellectual Property Administration on April 30, 2025, with patent application number 202510568868.X and title "RIPK1 inhibitor and its preparation method and use"; The prior patent application filed with the China National Intellectual Property Administration on July 10, 2025, with patent application number 202510953132.4 and title "RIPK1 inhibitor and its preparation method and use"; The prior patent application filed with the China National Intellectual Property Administration on October 30, 2025, with patent application number 202511574417.3 and title "RIPK1 inhibitor and its preparation method and use"; The prior patent application filed with the China National Intellectual Property Administration on March 12, 2026, with patent application number 202610304653.1 and title "RIPK1 inhibitor and its preparation method and use"; The full text of the aforementioned prior applications is incorporated herein by reference. Technical Field

[0002] This invention relates to the pharmaceutical field, specifically to a class of small molecule compounds, which are used as receptor-interacting protein kinase 1 (RIPK1) inhibitors in regulating programmed cell death and related diseases (such as inflammation, autoimmunity, neurodegenerative diseases, etc.). Background Technology

[0003] Programmed necrosis is a type of cell death highly correlated with RIPK1 kinase activity and is widely involved in the development of various diseases, such as sepsis, rheumatoid arthritis, inflammatory bowel disease, Alzheimer's disease, and Parkinson's disease. RIPK1 is a key intracellular signal transduction molecule, and its kinase activity participates in tumor necrosis factor (TNF)-mediated inflammatory responses and cell death signaling pathways.

[0004] In recent years, small molecule drugs that inhibit RIPK1 kinase activity have been considered an important strategy for treating such diseases. Currently available RIPK1 inhibitors have shown significant RIPK1 inhibitory activity in vitro and in some animal models, but they also have several shortcomings: 1) Insufficient metabolic stability: Some compounds are easily degraded in vivo, resulting in short half-lives and failing to achieve ideal pharmacokinetic parameters; 2) Low solubility and bioavailability: Due to relatively rigid molecular structures or strong hydrophobicity, some inhibitors have poor solubility in vivo, making it difficult to maintain effective blood drug concentrations; 3) Poor target selectivity: Some existing compounds also exhibit cross-inhibition of other kinases related to cell death regulation, easily causing non-specific toxic side effects.

[0005] Therefore, developing novel RIPK1 inhibitors with better target binding ability, higher selectivity, and better pharmacokinetic properties remains an important direction for RIPK1 inhibitor research. Summary of the Invention

[0006] To address the aforementioned technical problems, this disclosure provides a compound of formula (M-1) or a pharmaceutically acceptable salt thereof: Formula (M-1) Wherein, R is selected from those that are arbitrarily substituted or arbitrarily replaced by one, two, three or more Rs. Z The following groups are substituted: C 1-20 Alkyl, -OC 1-20 Alkyl, C 3-20 cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, or ; Ring A is selected from the following optionally substituted groups: , , , ; Rings B, C, D, E, and F are independently selected from saturated, partially saturated, aromatic C5-ring hydrocarbons or five-membered heterocycles. Ring G is selected from saturated, partially saturated, aromatic C6-ring hydrocarbon rings or six-membered heterocycles; W1, W4, W5, W6, W7, W 10 W 11 W 12 W 14 W 15 W 16 W 17 W 18 W 19 W 22 W23 W 24 W 25 Same or different, and independently selected from: O, S, S(=O), S(=O)2, N, NR wn1 C, C (=O), CR wc1 CR wc2 R wc3 ; W2, W3, W8, W 13、 W 20、 W 21、 W 26 Same or different, and independently selected from: N, C, CR wc1 ; Fused rings composed of rings B and C contain 1-4 heteroatoms; ring D contains 1-3 heteroatoms; ring E contains 1-3 heteroatoms; fused rings composed of rings F and G contain 1-4 heteroatoms. U1 is selected from: O, S; R1 is selected from: optional substitutions or optional substitutions by one, two, three or more R1s. Z1 The following groups are substituted: C 3-20 cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20 Alkylene-C 3-20 Cycloalkenyl, -C 1-20 Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl), -OC 3-20 cycloalkyl, -OC 3-20 Cycloalkenyl, -O- (3-20 membered heterocyclic groups), -OC 6-20 Aryl, -O- (5-20 heteroaryl), -SC 3-20 cycloalkyl, -SC 3-20 Cycloalkenyl, -S- (3-20 membered heterocyclic groups), -SC 6-20 Aryl, -S-(5-20 heteroaryl), -NH-C 3-20 cycloalkyl, -NH-C 3-20 Cycloalkenyl, -NH- (3-20 membered heterocyclic groups), -NH-C 6-20 Aryl, -NH- (5-20 heteroaryl); R2 is selected from: optional substitutions or optional substitutions by one, two, three or more Rs. Z2 The following groups are substituted: C3-20 cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl; R 31 and R 41 Selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R. Z3 The following groups are substituted: C 1-20 Alkyl, C 3-20 Cycloalkyl, 3-20 membered heterocyclic groups, -OC 1-20 Alkyl, -OC 3-20 Cycloalkyl, -O- (3-20 membered heterocyclic groups), -SC 1-20 Alkyl, -SC 3-20 Cycloalkyl, -S-(3-20 membered heterocyclic groups), -NH-C 1-20 Alkyl, -NH-C 3-20 Cycloalkyl groups, -NH- (3-20 membered heterocyclic groups); Each R wc1 R wc2 R wc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-20 Alkyl, C 3-20 Cycloalkyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20 Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl), -OC 3-20 Cycloalkyl, -O- (3-20 membered heterocyclic groups), -OC 6-20 Aryl, -O- (5-20 heteroaryl), -SC 3-20 Cycloalkyl, -S- (3-20 membered heterocyclic groups), -SC 6-20 Aryl, -S-(5-20 heteroaryl), -NH-C 3-20 Cycloalkyl, -NH- (3-20 membered heterocyclic groups), -NH-C 6-20 Aryl, -NH- (5-20 heteroaryl); Each Rwn1 The same or different, and independently selected from: H, deuterium, and optionally substituted or optionally replaced by one, two, three or more R. Z5 The following groups are substituted: C 1-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl group, C 3-20 cycloalkyl, C 3-20 Cycloalkenyl, C 3-20 Cycloalkynyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 2-20 alkenyl, -C 1-20 Alkylene-C 2-20 alkynyl group, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20 Alkylene-C 3-20 Cycloalkenyl, -C 1-20 Alkylene-C 3-20 Cycloalkynyl, -C 1-20 Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl); R wc1 and R1, or R wc2 and R1, or R wc3 and R1, or R wn1 Together with R1, they form an optional substitution or optional substitution by one, two, three or more Rs. ZZ3 The following groups are substituted: 8-20 membered fused heterocyclic group, 8-20 membered bridged heterocyclic group, 8-20 membered spiroheterocyclic group, C 8-20 Fused ring group, C 8-20 Yuanqiao Ring Base, C 8-20 spirocyclic base; Each R Z R Z1 R Z2 R Z3 R Z4 R Z5 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and optionally substituted or optionally influenced by one, two, three or more Rs. ZZ1 The following groups are substituted: C 1-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl group, C 3-20 cycloalkyl, C3-20 Cycloalkenyl, C 3-20 Cycloalkynyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 2-20 alkenyl, -C 1-20 Alkylene-C 2-20 alkynyl group, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20 Alkylene-C 3-20 Cycloalkenyl, -C 1-20 Alkylene-C 3-20 Cycloalkynyl, -C 1-20 Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl), -OR O1 -SR S1 -NR N1 R N2 -C(O)R C1 -OC(O)R C2 -OC(O)-OR O2 -OC(O)-NR N3 R N4 -N(R) N5 )-C(O)R C3 -N(R) N6 )-C(O)-NR N7 R N8 -S(O)2R S2 -OS(O)2R S3 -OS(O)2-OR O3 -OS(O)2-NR N9 R N10 -N(R) N11 )-S(O)2R S4 -N(R) N12 )-S(O)2-NR N13 R N14 -S(O)R S5 -OS(O)R S6 -OS(O)-OR O4 -OS(O)-NR N15 R N16 -N(R) N17 )-S(O)R S7 -N(R) N18 )-S(O)-NR N19 RN20 -P(=O)R P1 R P2 -P(=O)(OR) O5 )R P2 -P(=O)(OR) O6 (OR) O7 -P(=O)(NR) N21 R N22 )R P3 -P(=O)(NR) N23 R N24 (NR) N25 R N26 -P(=O)(OR) O8 (NR) N27 R N28 ); Or two R atoms connected to the same carbon atom Z1 Together with the carbon atom it is attached to, they form C 3-20 cycloalkyl; Each R O1 R O2 R O3 R O4 R O5 R O6 R O7 R O8 R S1 R S2 R S3 R S4 R S5 R S6 R S7 R C1 R C2 R C3 R P1 R P2 R P3 R N1 R N2 R N3 R N4 R N5 R N6 R N7 R N8 R N9 R N10 R N11 R N12 R N13 R N14 R N15 R N16 R N17 R N18 R N19 R N20R N21 R N22 R N23 R N24 R N25 R N26 R N27 R N28 Whether identical or different, each is independently selected from: H, deuterium, and optionally substituted or optionally replaced by one, two, three or more R. ZZ2 The following groups are substituted: C 1-20 Alkyl, C 3-20 Cycloalkyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20 Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl); Or R N3 With R N4 R N7 With R N8 R N9 With R N10 R N13 With R N14 R N15 With R N16 R N19 With R N20 R N21 With R N22 R N23 With R N24 R N25 With R N26 R N27 With R N28 Together with the N atom it is linked to, it forms a 3-20 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O, S, Si or P; Or R P1 With R P2 Together with the P atom it is linked to, it forms a 3-20 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O, S, Si or P; Or R O5 With R P2 R O6 With R O7 Together with the atoms linked to it, they form a 4-20 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O, S, Si or P; Each R ZZ1 R ZZ2 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and the following optional substituted groups: C 1-20 Alkyl, C 3-20 Cycloalkyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20 Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl), -OC 3-20 Cycloalkyl, -O- (3-20 membered heterocyclic groups), -OC 6-20 Aryl, -O- (5-20 heteroaryl), -SC 3-20 Cycloalkyl, -S- (3-20 membered heterocyclic groups), -SC 6-20 Aryl, -S-(5-20 heteroaryl), -NH-C 3-20 Cycloalkyl, -NH- (3-20 membered heterocyclic groups), -NH-C 6-20 Aryl, -NH- (5-20 heteroaryl); Each R ZZ3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and the following optional substituted groups: C 1-20 Alkyl, C 3-20 Cycloalkyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20 Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl), -OC 3-20 Cycloalkyl, -O- (3-20 membered heterocyclic groups), -OC 6-20 Aryl, -O- (5-20 heteroaryl), -SC 3-20 Cycloalkyl, -S- (3-20 membered heterocyclic groups), -SC 6-20 Aryl, -S-(5-20 heteroaryl), -NH-C 3-20Cycloalkyl, -NH- (3-20 membered heterocyclic groups), -NH-C 6-20 Aryl, -NH- (5-20 heteroaryl).

[0007] According to embodiments of this disclosure, the compound represented by formula (M-1) has the structure shown in formula (M): Formula (M) Wherein, ring A is selected from the following optionally substituted groups: , , ; Rings B, C, D, and E are independently selected from saturated, partially saturated, aromatic C5-ring hydrocarbons or five-membered heterocycles; W1, W4, W5, W6, W7, W 10 W 11 W 12 W 14 W 15 W 16 W 17 Same or different, and independently selected from: O, S, S(=O), S(=O)2, N, NR wn1 C, C (=O), CR wc1 CR wc2 R wc3 ; W2, W3, W8, W 13 Same or different, and independently selected from: N, C, CR wc1 ; The fused ring composed of ring B and ring C contains 1-4 heteroatoms; ring D contains 1-3 heteroatoms; ring E contains 1-3 heteroatoms; U1 is selected from: O, S; R1 is selected from: optional substitutions or optional substitutions by one, two, three or more R1s. Z1 The following groups are substituted: C 3-20 cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20 Alkylene-C 3-20 Cycloalkenyl, -C 1-20 Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl), -OC 3-20 cycloalkyl, -OC 3-20Cycloalkenyl, -O- (3-20 membered heterocyclic groups), -OC 6-20 Aryl, -O- (5-20 heteroaryl), -SC 3-20 cycloalkyl, -SC 3-20 Cycloalkenyl, -S- (3-20 membered heterocyclic groups), -SC 6-20 Aryl, -S-(5-20 heteroaryl), -NH-C 3-20 cycloalkyl, -NH-C 3-20 Cycloalkenyl, -NH- (3-20 membered heterocyclic groups), -NH-C 6-20 Aryl, -NH- (5-20 heteroaryl); R2 is selected from: optional substitutions or optional substitutions by one, two, three or more Rs. Z2 The following groups are substituted: C 3-20 cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl; R 31 and R 41 Selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R. Z3 The following groups are substituted: C 1-20 Alkyl, C 3-20 Cycloalkyl, 3-20 membered heterocyclic groups, -OC 1-20 Alkyl, -OC 3-20 Cycloalkyl, -O- (3-20 membered heterocyclic groups), -SC 1-20 Alkyl, -SC 3-20 Cycloalkyl, -S-(3-20 membered heterocyclic groups), -NH-C 1-20 Alkyl, -NH-C 3-20 Cycloalkyl groups, -NH- (3-20 membered heterocyclic groups); Each R wc1 R wc2 R wc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-20 Alkyl, C 3-20 Cycloalkyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl), -OC 3-20 Cycloalkyl, -O- (3-20 membered heterocyclic groups), -OC 6-20 Aryl, -O- (5-20 heteroaryl), -SC 3-20 Cycloalkyl, -S- (3-20 membered heterocyclic groups), -SC 6-20 Aryl, -S-(5-20 heteroaryl), -NH-C 3-20 Cycloalkyl, -NH- (3-20 membered heterocyclic groups), -NH-C 6-20 Aryl, -NH- (5-20 heteroaryl); Each R wn1 The same or different, and independently selected from: H, deuterium, and optionally substituted or optionally replaced by one, two, three or more R. Z5 The following groups are substituted: C 1-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl group, C 3-20 cycloalkyl, C 3-20 Cycloalkenyl, C 3-20 Cycloalkynyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 2-20 alkenyl, -C 1-20 Alkylene-C 2-20 alkynyl group, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20 Alkylene-C 3-20 Cycloalkenyl, -C 1-20 Alkylene-C 3-20 Cycloalkynyl, -C 1-20 Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl); Each R Z1 R Z2 R Z3 R Z4 R Z5 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and optionally substituted or optionally influenced by one, two, three or more Rs. ZZ1The following groups are substituted: C 1-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl group, C 3-20 cycloalkyl, C 3-20 Cycloalkenyl, C 3-20 Cycloalkynyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 2-20 alkenyl, -C 1-20 Alkylene-C 2-20 alkynyl group, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20 Alkylene-C 3-20 Cycloalkenyl, -C 1-20 Alkylene-C 3-20 Cycloalkynyl, -C 1-20 Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl), -OR O1 -SR S1 -NR N1 R N2 -C(O)R C1 -OC(O)R C2 -OC(O)-OR O2 -OC(O)-NR N3 R N4 -N(R) N5 )-C(O)R C3 -N(R) N6 )-C(O)-NR N7 R N8 -S(O)2R S2 -OS(O)2R S3 -OS(O)2-OR O3 -OS(O)2-NR N9 R N10 -N(R) N11 )-S(O)2R S4 -N(R) N12 )-S(O)2-NR N13 R N14 -S(O)R S5 -OS(O)R S6 -OS(O)-OR O4 -OS(O)-NR N15 R N16 -N(R)N17 )-S(O)R S7 -N(R) N18 )-S(O)-NR N19 R N20 -P(=O)R P1 R P2 -P(=O)(OR) O5 )R P2 -P(=O)(OR) O6 (OR) O7 -P(=O)(NR) N21 R N22 )R P3 -P(=O)(NR) N23 R N24 (NR) N25 R N26 -P(=O)(OR) O8 (NR) N27 R N28 ); Or two R atoms connected to the same carbon atom Z1 Together with the carbon atom it is attached to, they form C 3-20 cycloalkyl; Each R O1 R O2 R O3 R O4 R O5 R O6 R O7 R O8 R S1 R S2 R S3 R S4 R S5 R S6 R S7 R C1 R C2 R C3 R P1 R P2 R P3 R N1 R N2 R N3 R N4 R N5 R N6 R N7 R N8 R N9 R N10 R N11 R N12 R N13 R N14 R N15R N16 R N17 R N18 R N19 R N20 R N21 R N22 R N23 R N24 R N25 R N26 R N27 R N28 Whether identical or different, each is independently selected from: H, deuterium, and optionally substituted or optionally replaced by one, two, three or more R. ZZ2 The following groups are substituted: C 1-20 Alkyl, C 3-20 Cycloalkyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20 Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl); Or R N3 With R N4 R N7 With R N8 R N9 With R N10 R N13 With R N14 R N15 With R N16 R N19 With R N20 R N21 With R N22 R N23 With R N24 R N25 With R N26 R N27 With R N28 Together with the N atom it is linked to, it forms a 3-20 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O, S, Si or P; Or R P1 With R P2 Together with the P atom it is linked to, it forms a 3-20 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O, S, Si or P; Or R O5 With R P2 R O6 With RO7 Together with the atoms linked to it, they form a 4-20 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O, S, Si or P; Each R ZZ1 R ZZ2 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and the following optional substituted groups: C 1-20 Alkyl, C 3-20 Cycloalkyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20 Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl), -OC 3-20 Cycloalkyl, -O- (3-20 membered heterocyclic groups), -OC 6-20 Aryl, -O- (5-20 heteroaryl), -SC 3-20 Cycloalkyl, -S- (3-20 membered heterocyclic groups), -SC 6-20 Aryl, -S-(5-20 heteroaryl), -NH-C 3-20 Cycloalkyl, -NH- (3-20 membered heterocyclic groups), -NH-C 6-20 Aryl, -NH- (5-20 heteroaryl).

[0008] According to the embodiments of this disclosure, in formula (M) or formula (M-1), R wc1 and R1, or R wc2 and R1, or R wc3 and R1, or R wn1 Together with R1, they form an optional substitution or optional substitution by one, two, three or more Rs. ZZ3 The following groups are substituted: 8-20 membered fused heterocyclic group, 8-20 membered bridged heterocyclic group, 8-20 membered spiroheterocyclic group, C 8-20 Fused ring group, C 8-20 Yuanqiao Ring Base, C 8-20 spirocyclic base; Each R ZZ3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and the following optional substituted groups: C 1-20 Alkyl, C 3-20Cycloalkyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20 Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl), -OC 3-20 Cycloalkyl, -O- (3-20 membered heterocyclic groups), -OC 6-20 Aryl, -O- (5-20 heteroaryl), -SC 3-20 Cycloalkyl, -S- (3-20 membered heterocyclic groups), -SC 6-20 Aryl, -S-(5-20 heteroaryl), -NH-C 3-20 Cycloalkyl, -NH- (3-20 membered heterocyclic groups), -NH-C 6-20 Aryl, -NH- (5-20 heteroaryl).

[0009] According to the embodiments of this disclosure, R1 is selected from: optionally replacing or optionally being replaced by one, two, three or more R1s. Z1 The following groups are substituted: C 3-12 cycloalkyl, C 3-12 Cycloalkenyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -C 1-12 Alkylene-C 3-12 cycloalkyl, -C 1-12 Alkylene-C 3-12 Cycloalkenyl, -C 1-12 alkylene-(3-12 membered heterocyclic group), -C 1-12 Alkylene-C 6-12 Aryl, -C 1-12 alkylene-(5-12-membered heteroaryl), -OC 3-12 cycloalkyl, -OC 3-12 Cycloalkenyl, -O-(3-12 membered heterocyclic group), -OC 6-12 Aryl, -O-(5-12 heteroaryl), -SC 3-12 cycloalkyl, -SC 3-12 Cycloalkenyl, -S-(3-12 membered heterocyclic group), -SC 6-12 Aryl, -S-(5-12 heteroaryl), -NH-C 3-12 cycloalkyl, -NH-C 3-12 Cycloalkenyl, -NH- (3-12 membered heterocyclic group), -NH-C 6-12 Aryl, -NH- (5-12 heteroaryl).

[0010] According to the embodiments of this disclosure, R1 is selected from: optionally replacing or optionally being replaced by one, two, three or more R1s. Z1 The following groups are substituted: C 3-10 cycloalkyl, C 3-10 Cycloalkenyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, -C 1-10 Alkylene-C 3-10 cycloalkyl, -C 1-10 Alkylene-C 3-10 Cycloalkenyl, -C 1-10 alkylene-(3-10 membered heterocyclic group), -C 1-10 Alkylene-C 6-10 Aryl, -C 1-10 alkylene-(5-10-membered heteroaryl), -OC 3-10 cycloalkyl, -OC 3-10 Cycloalkenyl, -O- (3-10 membered heterocyclic groups), -OC 6-10 Aryl, -O-(5-10 heteroaryl), -SC 3-10 cycloalkyl, -SC 3-10 Cycloalkenyl, -S- (3-10 membered heterocyclic groups), -SC 6-10 Aryl, -S-(5-10 heteroaryl), -NH-C 3-10 cycloalkyl, -NH-C 3-10 Cycloalkenyl, -NH- (3-10 membered heterocyclic groups), -NH-C 6-10 Aryl, -NH- (5-10 heteroaryl).

[0011] According to the embodiments of this disclosure, R1 is selected from: optionally replacing or optionally being replaced by one, two, three or more R1s. Z1 The following groups are substituted: C 3-6 Monocycloalkyl, C 5-10 Fused cycloalkyl groups, C 5-10 Spirocycloalkyl, C 5-10 Bridged cycloalkyl, C 3-6 Cycloalkenyl, C 5-10 Fused ring cycloalkenyl, C 5-10 Spirocyclic cycloalkenyl, C 5-10 Bridged ring cycloalkenyl, 3-6 membered heterocyclic group, 5-10 membered fused ring heterocyclic group, 5-10 membered spirocyclic heterocyclic group, 5-10 membered bridged ring heterocyclic group, C 6-10 Aryl, 5-6 membered heteroaryl, 5-10 membered fused-ring heteroaryl, -C 1-6 Alkylene-C 3-6 cycloalkyl, -C 1-6 Alkylene-C 5-10 Fused cycloalkyl groups, -C 1-6 Alkylene-C5-10 Spirocycloalkyl, -C 1-6 Alkylene-C 5-10 Bridged cycloalkyl, -C 1-6 Alkylene-C 3-6 Cycloalkenyl, -C 1-6 Alkylene-C 5-10 Fused ring cycloalkenyl, -C 1-6 Alkylene-C 5-10 Spirocyclic cycloalkenyl, -C 1-6 Alkylene-C 5-10 Bridged ring cycloalkenyl, -C 1-6 Alkylene-(3-6 membered heterocyclic group), -C 1-6 alkylene-(5-10 membered fused-ring heterocyclic group), -C 1-6 Alkylene-(5-10 membered spirocyclic heterocyclic group), -C 1-6 Alkylene-(5-10-membered bridged ring heterocyclic group), -C 1-6 Alkylene-C 6-10 Aryl, -C 1-6 alkylene-(5-6-membered heteroaryl), -C 1-6 alkylene-(5-10 membered fused-ring heteroaryl), -OC 3-6 cycloalkyl, -OC 5-10 Fused cycloalkyl groups, -OC 5-10 Spirocycloalkyl, -OC 5-10 Bridged cycloalkyl, -OC 3-6 Cycloalkenyl, -OC 5-10 Fused ring cycloalkenyl, -OC 5-10 Spirocyclic cycloalkenyl, -OC 5-10 Bridged ring cycloalkenyl, -O- (3-6 membered heterocyclic group), -O- (5-10 membered fused ring heterocyclic group), -O- (5-10 membered spirocyclic heterocyclic group), -O- (5-10 membered bridged ring heterocyclic group), -OC 6-10 Aryl, -O-(5-6 membered heteroaryl), -O-(5-10 membered fused-ring heteroaryl), -SC 3-6 cycloalkyl, -SC 5-10 Fused cycloalkyl groups, -SC 5-10 Spirocycloalkyl, -SC 5-10 Bridged cycloalkyl, -SC 3-6 Cycloalkenyl, -SC 5-10 Fused ring cycloalkenyl, -SC 5-10 Spirocyclic cycloalkenyl, -SC 5-10 Bridged ring cycloalkenyl, -S- (3-6 membered heterocyclic group), -S- (5-10 membered fused ring heterocyclic group), -S- (5-10 membered spirocyclic heterocyclic group), -S- (5-10 membered bridged ring heterocyclic group), -SC 6-10Aryl, -S- (5-6 membered heteroaryl), -S- (5-10 membered fused-ring heteroaryl), -NH-C 3-6 cycloalkyl, -NH-C 5-10 Fused ring cycloalkyl, -NH-C 5-10 Spirocycloalkyl, -NH-C 5-10 Bridged cycloalkyl, -NH-C 3-6 Cycloalkenyl, -NH-C 5-10 Fused ring cycloalkenyl, -NH-C 5-10 Spirocyclic cycloalkenyl, -NH-C 5-10 Bridged ring cycloalkenyl, -NH- (3-6 membered heterocyclic group), -NH- (5-10 membered fused ring heterocyclic group), -NH- (5-10 membered spirocyclic heterocyclic group), -NH- (5-10 membered bridged ring heterocyclic group), -NH-C 6-10 Aryl, -NH- (5-6 membered heteroaryl), -NH- (5-10 membered fused-ring heteroaryl).

[0012] According to the embodiments of this disclosure, R1 is selected from: optionally replacing or optionally being replaced by one, two, three or more R1s. Z1 The following groups are substituted: C 3-6 Monocycloalkyl, C 5-10 Fused cycloalkyl groups, C 5-10 Spirocycloalkyl, C 5-10 Bridged cycloalkyl, C 3-6 Cycloalkenyl, C 5-10 Fused ring cycloalkenyl, C 5-10 Spirocyclic cycloalkenyl, C 5-10 Bridged ring cycloalkenyl, 3-6 membered heterocyclic group, 5-10 membered fused ring heterocyclic group, 5-10 membered spirocyclic heterocyclic group, 5-10 membered bridged ring heterocyclic group, C 6-10 Aryl, 5-6 membered heteroaryl, 5-10 membered fused-ring heteroaryl, -C 1-2 Alkylene-C 3-6 cycloalkyl, -C 1-2 Alkylene-C 5-10 Fused cycloalkyl groups, -C 1-2 Alkylene-C 5-10 Spirocycloalkyl, -C 1-2 Alkylene-C 5-10 Bridged cycloalkyl, -C 1-2 Alkylene-C 3-6 Cycloalkenyl, -C 1-2 Alkylene-C 5-10 Fused ring cycloalkenyl, -C 1-2 Alkylene-C 5-10 Spirocyclic cycloalkenyl, -C 1-2 Alkylene-C 5-10 Bridged ring cycloalkenyl, -C 1-2 Alkylene-(3-6 membered heterocyclic group), -C1-2 alkylene-(5-10 membered fused-ring heterocyclic group), -C 1-2 Alkylene-(5-10 membered spirocyclic heterocyclic group), -C 1-2 Alkylene-(5-10-membered bridged ring heterocyclic group), -C 1-2 Alkylene-C 6-10 Aryl, -C 1-2 alkylene-(5-6-membered heteroaryl), -C 1-2 alkylene-(5-10 membered fused-ring heteroaryl), -OC 3-6 cycloalkyl, -OC 5-10 Fused cycloalkyl groups, -OC 5-10 Spirocycloalkyl, -OC 5-10 Bridged cycloalkyl, -OC 3-6 Cycloalkenyl, -OC 5-10 Fused ring cycloalkenyl, -OC 5-10 Spirocyclic cycloalkenyl, -OC 5-10 Bridged ring cycloalkenyl, -O- (3-6 membered heterocyclic group), -O- (5-10 membered fused ring heterocyclic group), -O- (5-10 membered spirocyclic heterocyclic group), -O- (5-10 membered bridged ring heterocyclic group), -OC 6-10 Aryl, -O-(5-6 membered heteroaryl), -O-(5-10 membered fused-ring heteroaryl), -SC 3-6 cycloalkyl, -S-C 5-10 Fused cycloalkyl groups, -S-C 5-10 Spirocycloalkyl, -S-C 5-10 Bridged cycloalkyl, -SC 3-6 Cycloalkenyl, -SC 5-10 Fused ring cycloalkenyl, -SC 5-10 Spirocyclic cycloalkenyl, -SC 5-10 Bridged ring cycloalkenyl, -S- (3-6 membered heterocyclic group), -S- (5-10 membered fused ring heterocyclic group), -S- (5-10 membered spirocyclic heterocyclic group), -S- (5-10 membered bridged ring heterocyclic group), -SC 6-10 Aryl, -S- (5-6 membered heteroaryl), -S- (5-10 membered fused-ring heteroaryl), -NH-C 3-6 cycloalkyl, -NH-C 5-10 Fused ring cycloalkyl, -NH-C 5-10 Spirocycloalkyl, -NH-C 5-10 Bridged cycloalkyl, -NH-C 3-6 Cycloalkenyl, -NH-C 5-10 Fused ring cycloalkenyl, -NH-C 5-10 Spirocyclic cycloalkenyl, -NH-C 5-10Bridged ring cycloalkenyl, -NH- (3-6 membered heterocyclic group), -NH- (5-10 membered fused ring heterocyclic group), -NH- (5-10 membered spirocyclic heterocyclic group), -NH- (5-10 membered bridged ring heterocyclic group), -NH-C 6-10 Aryl, -NH- (5-6 membered heteroaryl), -NH- (5-10 membered fused-ring heteroaryl).

[0013] According to the embodiments of this disclosure, R1 is selected from: optionally replacing or optionally being replaced by one, two, three or more R1s. Z1 The following groups are substituted: C 3-6 Monocycloalkyl, C 5-10 Fused cycloalkyl groups, C 5-10 Spirocycloalkyl, C 5-10 Bridged cycloalkyl, C 3-6 Cycloalkenyl, C 5-10 Fused ring cycloalkenyl, C 5-10 Spirocyclic cycloalkenyl, C 5-10 Bridged ring cycloalkenyl, 3-6 membered heterocyclic group, 5-10 membered fused ring heterocyclic group, 5-10 membered spirocyclic heterocyclic group, 5-10 membered bridged ring heterocyclic group, C 6-10 Aryl, 5-6 membered heteroaryl, 5-10 membered fused-ring heteroaryl, -C 1-2 Alkylene-C 3-6 cycloalkyl, -C 1-2 Alkylene-C 5-10 Fused cycloalkyl groups, -C 1-2 Alkylene-C 5-10 Spirocycloalkyl, -C 1-2 Alkylene-C 5-10 Bridged cycloalkyl, -C 1-2 Alkylene-C 3-6 Cycloalkenyl, -C 1-2 Alkylene-C 5-10 Fused ring cycloalkenyl, -C 1-2 Alkylene-C 5-10 Spirocyclic cycloalkenyl, -C 1-2 Alkylene-C 5-10 Bridged ring cycloalkenyl, -C 1-2 Alkylene-(3-6 membered heterocyclic group), -C 1-2 alkylene-(5-10 membered fused-ring heterocyclic group), -C 1-2 Alkylene-(5-10 membered spirocyclic heterocyclic group), -C 1-2 Alkylene-(5-10-membered bridged ring heterocyclic group), -C 1-2 Alkylene-C 6-10 Aryl, -C 1-2 alkylene-(5-6-membered heteroaryl), -C 1-2 alkylene-(5-10 membered fused-ring heteroaryl), -OC 3-6 cycloalkyl, -OC5-10 Fused cycloalkyl groups, -OC 5-10 Spirocycloalkyl, -OC 5-10 Bridged cycloalkyl, -OC 3-6 Cycloalkenyl, -OC 5-10 Fused ring cycloalkenyl, -OC 5-10 Spirocyclic cycloalkenyl, -OC 5-10 Bridged ring cycloalkenyl, -O- (3-6 membered heterocyclic group), -O- (5-10 membered fused ring heterocyclic group), -O- (5-10 membered spirocyclic heterocyclic group), -O- (5-10 membered bridged ring heterocyclic group), -OC 6-10 Aryl, -O-(5-6 membered heteroaryl), -O-(5-10 membered fused-ring heteroaryl), -NH-C 3-6 cycloalkyl, -NH-C 5-10 Fused ring cycloalkyl, -NH-C 5-10 Spirocycloalkyl, -NH-C 5-10 Bridged cycloalkyl, -NH-C 3-6 Cycloalkenyl, -NH-C 5-10 Fused ring cycloalkenyl, -NH-C 5-10 Spirocyclic cycloalkenyl, -NH-C 5-10 Bridged ring cycloalkenyl, -NH- (3-6 membered heterocyclic group), -NH- (5-10 membered fused ring heterocyclic group), -NH- (5-10 membered spirocyclic heterocyclic group), -NH- (5-10 membered bridged ring heterocyclic group), -NH-C 6-10 Aryl, -NH- (5-6 membered heteroaryl), -NH- (5-10 membered fused-ring heteroaryl).

[0014] According to the embodiments of this disclosure, R1 is selected from: optionally replacing or optionally being replaced by one, two, three or more R1s. Z1 The following groups are substituted: C 3-6 Monocycloalkyl, C 5-10 Fused cycloalkyl groups, C 5-10 Spirocycloalkyl, C 5-10 Bridged cycloalkyl, C 3-6 Cycloalkenyl, C 5-10 Fused ring cycloalkenyl, C 5-10 Spirocyclic cycloalkenyl, C 5-10 Bridged ring cycloalkenyl, 3-6 membered heterocyclic group, 5-10 membered fused ring heterocyclic group, 5-10 membered spirocyclic heterocyclic group, 5-10 membered bridged ring heterocyclic group, phenyl, 5-6 membered heteroaryl, 5-10 membered fused ring heteroaryl, -C 1-2 Alkylene-(3-6 membered heterocyclic group), -C 1-2 alkylene-(5-10 membered fused-ring heterocyclic group), -C 1-2 Alkylene-(5-10 membered spirocyclic heterocyclic group), -C 1-2 Alkylene-(5-10-membered bridged ring heterocyclic group), -C1-2 Alkylene-C 6-10 Aryl, -C 1-2 alkylene-(5-6-membered heteroaryl), -C 1-2 Alkylene-(5-10-membered fused-ring heterocyclic), -O-(3-6-membered heterocyclic), -O-(5-10-membered fused-ring heterocyclic), -O-(5-10-membered spirocyclic heterocyclic), -O-(5-10-membered bridged-ring heterocyclic), -O-phenyl, -O-(5-6-membered heterocyclic), -O-(5-10-membered fused-ring heterocyclic), -NH-(3-6-membered heterocyclic), -NH-(5-10-membered fused-ring heterocyclic), -NH-(5-10-membered spirocyclic heterocyclic), -NH-(5-10-membered bridged-ring heterocyclic), -NH-C 6-10 Aryl, -NH- (5-6 membered heteroaryl), -NH- (5-10 membered fused-ring heteroaryl).

[0015] According to the embodiments of this disclosure, R1 is selected from: optionally replacing or optionally being replaced by one, two, three or more R1s. Z1 The following groups are substituted: C 3-6 Monocycloalkyl, C 5-10 Fused cycloalkyl groups, C 5-10 Spirocycloalkyl, C 5-10 Bridged cycloalkyl, C 3-6 Cycloalkenyl, C 5-10 Fused ring cycloalkenyl, C 5-10 Spirocyclic cycloalkenyl, C 5-10 Bridged ring cycloalkenyl, 3-6 membered heterocyclic group, 5-10 membered fused ring heterocyclic group, 5-10 membered spirocyclic heterocyclic group, 5-10 membered bridged ring heterocyclic group, phenyl, 5-6 membered heteroaryl, 5-10 membered fused ring heteroaryl.

[0016] According to the embodiments of this disclosure, R1 is selected from: optionally replacing or optionally being replaced by one, two, three or more R1s. Z1 The following groups are substituted: -C 1-2 Alkylene-(3-6 membered heterocyclic group), -C 1-2 alkylene-(5-10 membered fused-ring heterocyclic group), -C 1-2 Alkylene-(5-10 membered spirocyclic heterocyclic group), -C 1-2 Alkylene-(5-10-membered bridged ring heterocyclic group), -C 1-2 Alkylene-C 6-10 Aryl, -C 1-2 alkylene-(5-6-membered heteroaryl), -C 1-2 Alkylene-(5-10 membered fused-ring heteroaryl).

[0017] According to the embodiments of this disclosure, R1 is selected from: optionally replacing or optionally being replaced by one, two, three or more R1s. Z1The following groups are substituted: -O-(3-6 membered heterocyclic group), -O-(5-10 membered fused-ring heterocyclic group), -O-(5-10 membered spirocyclic heterocyclic group), -O-(5-10 membered bridged-ring heterocyclic group), -O-phenyl, -O-(5-6 membered heteroaryl), -O-(5-10 membered fused-ring heteroaryl).

[0018] According to the embodiments of this disclosure, R1 is selected from: optionally replacing or optionally being replaced by one, two, three or more R1s. Z1 The following groups are substituted: -NH- (3-6 membered heterocyclic group), -NH- (5-10 membered fused-ring heterocyclic group), -NH- (5-10 membered spirocyclic heterocyclic group), -NH- (5-10 membered bridged-ring heterocyclic group), -NH-phenyl, -NH- (5-6 membered heteroaryl), -NH- (5-10 membered fused-ring heteroaryl).

[0019] According to the embodiments of this disclosure, R1 is selected from: optionally replacing or optionally being replaced by one, two, three or more R1s. Z1 The following groups are substituted: C 3-8 cycloalkyl, C 3-8 Cycloalkenyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, -C 1-6 Alkylene-C 3-8 cycloalkyl, -C 1-6 Alkylene-C 3-8 Cycloalkenyl, -C 1-6 alkylene-(3-10 membered heterocyclic group), -C 1-6 Alkylene-C 6-10 Aryl, -C 1-6 alkylene-(5-10-membered heteroaryl), -OC 3-8 cycloalkyl, -OC 3-8 Cycloalkenyl, -O- (3-10 membered heterocyclic groups), -OC 6-10 Aryl, -O-(5-10 heteroaryl), -SC 3-8 cycloalkyl, -SC 3-8 Cycloalkenyl, -S- (3-10 membered heterocyclic groups), -SC 6-10 Aryl, -S-(5-10 heteroaryl), -NH-C 3-8 cycloalkyl, -NH-C 3-8 Cycloalkenyl, -NH- (3-10 membered heterocyclic groups), -NH-C 6-10 Aryl, -NH- (5-10 heteroaryl).

[0020] According to the embodiments of this disclosure, R1 is selected from: optionally replacing or optionally being replaced by one, two, three or more R1s. Z1 The following groups are substituted: C 3-8Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, -C 1-6 alkylene-(3-10 membered heterocyclic group), -C 1-6 Alkylene-C 6-10 Aryl, -C 1-6 alkylene-(5-10-membered heteroaryl), -O-(3-10-membered heterocyclic), -OC 6-10 Aryl, -O- (5-10 membered heteroaryl), -NH- (3-10 membered heterocyclic), -NH-C 6-10 Aryl, -NH- (5-10 heteroaryl).

[0021] According to the embodiments of this disclosure, R1 is selected from: optionally replacing or optionally being replaced by one, two, three or more R1s. Z1 The following groups are substituted: C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, -C 1-2 alkylene-(3-10 membered heterocyclic group), -C 1-2 Alkylene-C 6-10 Aryl, -C 1-2 alkylene-(5-10-membered heteroaryl), -O-(3-10-membered heterocyclic), -OC 6-10 Aryl, -O- (5-10 membered heteroaryl), -NH- (3-10 membered heterocyclic), -NH-C 6-10 Aryl, -NH- (5-10 heteroaryl).

[0022] According to the embodiments of this disclosure, R1 is selected from: optionally replacing or optionally being replaced by one, two, three or more R1s. Z1 The following groups are substituted: cyclopropyl, phenyl, pyrrolyl, furanyl, pyridyl, pyrimidinyl, benzyl, phenoxy, dihydrobenzofuranyl, indazole, indolyl, indolylmethylene, benzofuranyl, benzofuranylmethyl, indolyloxy, indolylamino, phenylamino, benzofuranyloxy, benzofuranylamino. , , , , .

[0023] According to the embodiments of this disclosure, R1 is selected from: optionally replacing or optionally being replaced by one, two, three or more R1s. Z1 The following groups are substituted: cyclopropyl, phenyl, pyrrolyl, benzyl, phenoxy, dihydrobenzofuran, indazole, indolyl, indolylmethyl, benzofuranylmethyl, indolyloxy, indolylamino. , , .

[0024] According to the embodiments of this disclosure, R1 is selected from: optionally replacing or optionally being replaced by one, two, three or more R1s. Z1 The following groups are substituted: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , .

[0025] According to embodiments of this disclosure, R1 is selected from optionally substituted groups such as cyclopropyl, phenyl, etc. , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , .

[0026] According to the embodiments of this disclosure, R is selected from: optionally replaced or optionally replaced by one, two, three or more R. Z The following groups are substituted: C 1-12 Alkyl, -OC 1-12 Alkyl, C 3-12 cycloalkyl, C 3-12 Cycloalkenyl, 3-12 membered heterocyclic groups, C 6-12 aryl, 5-12 heteroaryl or .

[0027] According to the embodiments of this disclosure, R is selected from: optionally replacing or optionally being replaced by one, two, three or more R. Z The following groups are substituted: C 1-10 Alkyl, -OC 1-10 Alkyl, C 3-10 cycloalkyl, C 3-10 Cycloalkenyl, 3-10 membered heterocyclic groups, C 6-10 aryl, 5-10 quinone heteroaryl or .

[0028] According to the embodiments of this disclosure, R is selected from: optionally replacing or optionally being replaced by one, two, three or more R. Z The following groups are substituted: C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-6 Monocycloalkyl, C 5-10 Fused cycloalkyl groups, C5-10 Spirocycloalkyl, C 5-10 Bridged cycloalkyl, C 3-6 Cycloalkenyl, C 5-10 Fused ring cycloalkenyl, C 5-10 Spirocyclic cycloalkenyl, C 5-10 Bridged ring cycloalkenyl, 3-6 membered heterocyclic group, 5-10 membered fused ring heterocyclic group, 5-10 membered spirocyclic heterocyclic group, 5-10 membered bridged ring heterocyclic group, C 6-10 aryl, 5-6 membered heteroaryl, 5-10 membered fused-ring heteroaryl or .

[0029] According to the embodiments of this disclosure, R is selected from: optionally replacing or optionally being replaced by one, two, three or more R. Z The following groups are substituted: C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-6 Monocycloalkyl, C 5-8 Fused cycloalkyl groups, C 5-8 Spirocycloalkyl, C 5-8 Bridged cycloalkyl, or .

[0030] According to the embodiments of this disclosure, R is selected from: optionally replacing or optionally being replaced by one, two, three or more R. Z The following groups are substituted: methyl, ethyl, propyl, isopropyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetane, azirane, tetrahydropyrrolyl, piperidinyl. , , , , , , or Preferably, R is selected from: optionally substituted or optionally replaced by one, two, three or more R. Z The following groups are substituted: isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, or .

[0031] According to the embodiments of this disclosure, R is selected from: optionally replacing or optionally being replaced by one, two, three or more R. Z The following groups are substituted: , , , , , , , , , , , , , , , , , , , , , , , , , .

[0032] According to embodiments of this disclosure, R is selected from the following optionally substituted groups: , , , , , , , , , , , , , , , , , , , , , , , , , , , , .

[0033] According to the embodiments of this disclosure, R2 is selected from: optionally replacing or optionally being replaced by one, two, three or more Rs. Z2 The following groups are substituted: C 3-12 cycloalkyl, C 3-12 Cycloalkenyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl.

[0034] According to the embodiments of this disclosure, R2 is selected from: optionally replacing or optionally being replaced by one, two, three or more Rs. Z2 The following groups are substituted: C 3-10 cycloalkyl, C 3-10 Cycloalkenyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl.

[0035] According to the embodiments of this disclosure, R2 is selected from: optionally replacing or optionally being replaced by one, two, three or more Rs. Z2 The following groups are substituted: C 3-6 Monocycloalkyl, C 5-10 Fused cycloalkyl groups, C 5-10 Spirocycloalkyl, C 5-10 Bridged cycloalkyl, C 3-6 Cycloalkenyl, C 5-10 Fused ring cycloalkenyl, C 5-10 Spirocyclic cycloalkenyl, C 5-10 Bridged ring cycloalkenyl, 3-6 membered heterocyclic group, 5-10 membered fused ring heterocyclic group, 5-10 membered spirocyclic heterocyclic group, 5-10 membered bridged ring heterocyclic group, C 6-10 Aryl, 5-6 membered heteroaryl, 5-10 membered fused-ring heteroaryl.

[0036] According to the embodiments of this disclosure, R2 is selected from: optionally replacing or optionally being replaced by one, two, three or more Rs. Z2 The following groups are substituted: C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl.

[0037] According to the embodiments of this disclosure, R2 is selected from: optionally replacing or optionally being replaced by one, two, three or more Rs. Z2 The following groups are substituted: cyclopropyl, cyclobutyl, oxetane, azirone, thiohexacyclobutyl, phenyl, cyclopentyl, pyrrolyl, tetrahydropyrrolyl, cyclohexyl, triazolyl, piperidinyl, furanyl, thiazolyl, triazolyl, pyridinyl, pyrimidinyl, , , , , , , , , , , .

[0038] According to the embodiments of this disclosure, R2 is selected from: optionally replacing or optionally being replaced by one, two, three or more Rs. Z2 The following groups are substituted: cyclopropyl, pyridinyl, oxetyl, aziridine, phenyl, cyclopentyl, pyrrolyl, tetrahydropyrrolyl, cyclohexyl, triazolyl, piperidinyl. , , , , , .

[0039] According to the embodiments of this disclosure, R2 is selected from: optionally replacing or optionally being replaced by one, two, three or more Rs. Z2 The following groups are substituted: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , .

[0040] According to the embodiments of this disclosure, R2 is selected from optional replacements or optional replacements by one, two, three or more Rs. Z2 The following groups are substituted: C 1-6 Alkyl, -OC 1-6 Alkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; R Z2 Selected independently from halogens and C 1-6 Alkyl, -OC 1-6 Alkyl, Halogenated C 1-6 Alkyl, -O-halogenated C 1-6 alkyl.

[0041] According to embodiments of this disclosure, R2 is selected from the following optionally substituted groups: C 1-6 Alkyl, -OC 1-6 Alkyl, Halogenated C 1-6 Alkyl, -O-halogenated C 1-6 Alkyl, -NH-C 1-6 Alkyl, -N(C) 1-6 Alkyl)2、-NH-C 3-6 cycloalkyl, -N(C) 1-6 alkyl)-C3-6 Cycloalkyl.

[0042] According to embodiments of this disclosure, R2 is selected from the following optionally substituted groups: methyl, ethyl, propyl, isopropyl, monofluoromethyl, difluoromethyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, methoxy, ethoxy, isopropoxy, etc. , , , , , , .

[0043] According to the implementation scheme of this disclosure, Selected from the following groups that can be substituted: , , , , , , , , , , , , , , , , , , , , , , , .

[0044] According to the implementation scheme of this disclosure, Selected from the following groups that can be substituted: , , , , , , , , .

[0045] According to embodiments of this disclosure, R is selected from the following optionally substituted groups: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , .

[0046] According to embodiments of this disclosure, R is selected from the following optionally substituted groups: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , .

[0047] According to the implementation scheme of this disclosure, R 31 and R 41 Independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z3 The following groups are substituted: C 1-12 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, -OC 1-12 Alkyl, -OC 3-12 Cycloalkyl, -O-(3-12 membered heterocyclic), -SC 1-12 Alkyl, -SC 3-12 Cycloalkyl, -S-(3-12 membered heterocyclic groups), -NH-C 1-12 Alkyl, -NH-C 3-12 Cycloalkyl, -NH- (3-12 membered heterocyclic group).

[0048] According to the implementation scheme of this disclosure, R 31 and R 41 Independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z3 The following groups are substituted: C 1-10 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, -OC 1-10 Alkyl, -OC 3-10Cycloalkyl, -O- (3-10 membered heterocyclic groups), -SC 1-10 Alkyl, -SC 3-10 Cycloalkyl, -S-(3-10 membered heterocyclic groups), -NH-C 1-10 Alkyl, -NH-C 3-10 Cycloalkyl, -NH- (3-10 membered heterocyclic group).

[0049] According to the implementation scheme of this disclosure, R 31 and R 41 Independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z3 The following groups are substituted: C 1-6 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic groups, -OC 1-6 Alkyl, -OC 3-6 Cycloalkyl, -O- (3-6 membered heterocyclic groups), -SC 1-6 Alkyl, -SC 3-6 Cycloalkyl, -S-(3-6 membered heterocyclic groups), -NH-C 1-6 Alkyl, -NH-C 3-6 Cycloalkyl, -NH- (3-6 membered heterocyclic group).

[0050] According to the implementation scheme of this disclosure, R 31 and R 41 Independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z3 The following groups are substituted: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, hydroxymethyl, hydroxyethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, propoxy, methylthio, ethylthio, propylthio, cyclopropoxy, cyclopropylthio, cyclopropylamino, -NHCH3, -NHCH2 CH3, -N(CH3)2, -N(CH2CH3)2, propidinyl, aziridine, oxacyclobutyl, thioheterobutyl, tetrahydrofuranyl, pyrrolyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, homopiperidinyl, aziridineheptyl, oxacycloheptyl, phenyl, naphthyl, furanyl, thiopheneyl, oxazolyl, thiazolyl, imidazoleyl, pyrazolyl, isothiazolyl, isoxazolyl, triazolyl.

[0051] According to the implementation scheme of this disclosure, R 31 Selected from: H, deuterium, halogens, C1-6 Alkyl, -OC 1-6 alkyl.

[0052] According to the implementation scheme of this disclosure, R 31 Selected from: H, F.

[0053] According to the implementation scheme of this disclosure, R 41 Selected from: H, C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-8 cycloalkyl, C 6-10 Aryl.

[0054] According to the implementation scheme of this disclosure, R 41 Selected from: H, methyl, cyclopropyl, phenyl.

[0055] According to the implementation scheme of this disclosure, each R wc1 R wc2 R wc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-12 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -C 1-12 Alkylene-C 3-12 cycloalkyl, -C 1-12 alkylene-(3-12 membered heterocyclic group), -C 1-12 Alkylene-C 6-12 Aryl, -C 1-12 alkylene-(5-12-membered heteroaryl), -OC 3-12 Cycloalkyl, -O-(3-12 membered heterocyclic), -OC 6-12 Aryl, -O-(5-12 heteroaryl), -SC 3-12 Cycloalkyl, -S-(3-12 membered heterocyclic groups), -SC 6-12 Aryl, -S-(5-12 heteroaryl), -NH-C 3-12 Cycloalkyl, -NH- (3-12 membered heterocyclic groups), -NH-C 6-12 Aryl, -NH- (5-12 heteroaryl).

[0056] According to the implementation scheme of this disclosure, each R wc1 R wc2 R wc3The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-10 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, -C 1-10 Alkylene-C 3-10 cycloalkyl, -C 1-10 alkylene-(3-10 membered heterocyclic group), -C 1-10 Alkylene-C 6-10 Aryl, -C 1-10 alkylene-(5-10-membered heteroaryl), -OC 3-10 Cycloalkyl, -O- (3-10 membered heterocyclic groups), -OC 6-10 Aryl, -O-(5-10 heteroaryl), -SC 3-10 Cycloalkyl, -S- (3-10 membered heterocyclic groups), -SC 6-10 Aryl, -S-(5-10 heteroaryl), -NH-C 3-10 Cycloalkyl, -NH- (3-10 membered heterocyclic groups), -NH-C 6-10 Aryl, -NH- (5-10 heteroaryl).

[0057] According to the implementation scheme of this disclosure, each R wc1 R wc2 R wc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -C 1-6 Alkylene-C 3-6 cycloalkyl, -C 1-6 Alkylene-(3-6 membered heterocyclic group), -C 1-6 Alkylene-C 6-10 Aryl, -C 1-6 alkylene-(5-6-membered heteroaryl), -OC 3-6 Cycloalkyl, -O- (3-6 membered heterocyclic groups), -OC 6-10 Aryl, -O-(5-6 quinary heteroaryl), -SC 3-6 Cycloalkyl, -S- (3-6 membered heterocyclic groups), -SC6-10 Aryl, -S-(5-6 membered heteroaryl), -NH-C 3-6 Cycloalkyl, -NH- (3-6 membered heterocyclic groups), -NH-C 6-10 Aryl, -NH- (5-6 membered heteroaryl).

[0058] According to the implementation scheme of this disclosure, each R wc1 R wc2 R wc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -C 1-2 Alkylene-C 3-6 cycloalkyl, -C 1-2 Alkylene-(3-6 membered heterocyclic group), -C 1-2 Alkylene-C 6-10 Aryl, -C 1-2 alkylene-(5-6-membered heteroaryl), -OC 3-6 Cycloalkyl, -O- (3-6 membered heterocyclic groups), -OC 6-10 Aryl, -O-(5-6 quinary heteroaryl), -SC 3-6 Cycloalkyl, -S- (3-6 membered heterocyclic groups), -SC 6-10 Aryl, -S-(5-6 membered heteroaryl), -NH-C 3-6 Cycloalkyl, -NH- (3-6 membered heterocyclic groups), -NH-C 6-10 Aryl, -NH- (5-6 membered heteroaryl).

[0059] According to the implementation scheme of this disclosure, each R wc1 R wc2 R wc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4The following groups are substituted: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, hydroxymethyl, hydroxyethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, propoxy, methylthio, ethylthio, propylthio, cyclopropoxy, cyclopropylthio, cyclopropylamino, -NHCH3, -NHCH2 CH3, -N(CH3)2, -N(CH2CH3)2, propidinyl, aziridine, oxacyclobutyl, thioheterobutyl, tetrahydrofuranyl, pyrrolyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, homopiperidinyl, aziridineheptyl, oxacycloheptyl, phenyl, naphthyl, furanyl, thiopheneyl, oxazolyl, thiazolyl, imidazoleyl, pyrazolyl, isothiazolyl, isoxazolyl, triazolyl.

[0060] According to the implementation scheme of this disclosure, each R wc1 R wc2 R wc3 Same or different, and independently selected from: H, deuterium, halogen, OH, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl.

[0061] According to the implementation scheme of this disclosure, each R wc1 They are selected independently of each other, whether they are the same or different: H, deuterium, halogen, CN, C. 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl.

[0062] According to the implementation scheme of this disclosure, each R wc1 R wc2 R wc3 They are either the same or different, and are independently selected from: H, F, OH or methyl.

[0063] According to the implementation scheme of this disclosure, each R wc1 They are either the same or different, and are selected independently from: H, F, and methyl.

[0064] According to the implementation scheme of this disclosure, each R wn1 The same or different, and independently selected from: H, deuterium, and optionally substituted or optionally replaced by one, two, three or more R. Z5 The following groups are substituted: C 1-12 Alkyl, C 2-12 alkenyl, C 2-12alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -C 1-12 Alkylene-C 2-12 alkenyl, -C 1-12 Alkylene-C 2-12 alkynyl group, -C 1-12 Alkylene-C 3-12 cycloalkyl, -C 1-12 alkylene-(3-12 membered heterocyclic group), -C 1-12 Alkylene-C 6-12 Aryl, -C 1-12 Alkylene-(5-12-membered heteroaryl).

[0065] According to the implementation scheme of this disclosure, each R wn1 The same or different, and independently selected from: H, deuterium, and optionally substituted or optionally replaced by one, two, three or more R. Z5 The following groups are substituted: C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, -C 1-10 Alkylene-C 2-10 alkenyl, -C 1-10 Alkylene-C 2-10 alkynyl group, -C 1-10 Alkylene-C 3-10 cycloalkyl, -C 1-10 alkylene-(3-10 membered heterocyclic group), -C 1-10 Alkylene-C 6-10 Aryl, -C 1-10 Alkylene-(5-10-membered heteroaryl).

[0066] According to the implementation scheme of this disclosure, each R wn1 The same or different, and independently selected from: H, deuterium, and optionally substituted or optionally replaced by one, two, three or more R. Z5 The following groups are substituted: C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -C 1-6 Alkylene-C 2-6 alkenyl, -C 1-6 Alkylene-C 2-6 alkynyl group, -C 1-6 Alkylene-C3-6 cycloalkyl, -C 1-6 Alkylene-(3-6 membered heterocyclic group), -C 1-6 Alkylene-C 6-10 Aryl, -C 1-6 Alkylene-(5-6-membered heteroaryl).

[0067] According to the implementation scheme of this disclosure, each R wn1 The same or different, and independently selected from: H, deuterium, and optionally substituted or optionally replaced by one, two, three or more R. Z5 The following groups are substituted: C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -C 1-2 Alkylene-C 2-6 alkenyl, -C 1-2 Alkylene-C 2-6 alkynyl group, -C 1-2 Alkylene-C 3-6 cycloalkyl, -C 1-2 Alkylene-(3-6 membered heterocyclic group), -C 1-2 Alkylene-C 6-10 Aryl, -C 1-2 Alkylene-(5-6-membered heteroaryl).

[0068] According to the implementation scheme of this disclosure, each R wn1 The same or different, and independently selected from: H, deuterium, and optionally substituted or optionally replaced by one, two, three or more R. Z5 The following groups are substituted: C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl.

[0069] According to the implementation scheme of this disclosure, each R wn1 The same or different, and independently selected from: H, deuterium, and optionally substituted or optionally replaced by one, two, three or more R. Z5The following groups may be substituted: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, hydroxymethyl, hydroxyethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, propidinyl, aziridine, oxadiazinyl, thiohexacyclic, tetrahydrofuranyl, pyrrolylyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, homopiperidinyl, aziridineheptyl, oxadiazeptyl, phenyl, naphthyl, furanyl, thiopheneyl, oxazolyl, thiazolyl, imidazoleyl, pyrazolyl, isothiazolyl, isoxazolyl, triazolyl.

[0070] According to the implementation scheme of this disclosure, each R wn1 Same or different, selected independently from: H, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl.

[0071] According to the implementation scheme of this disclosure, each R wn1 Same or different, selected independently from: H, methyl.

[0072] According to the embodiments of this disclosure, in formula (M) or formula (M-1), R wc1 and R1, or R wc2 and R1, or R wc3 and R1, or R wn1 Together with R1, they form an optional substitution or optional substitution by one, two, three or more Rs. ZZ3 The following groups are substituted: 8-15 membered fused heterocyclic group, 8-15 membered bridged heterocyclic group, 8-15 membered spiroheterocyclic group, C 8-15 Fused ring group, C 8-15 Yuanqiao Ring Base, C 8-15 spirocyclic base; Each R ZZ3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and the following optional substituted groups: C 1-12 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -C 1-12 Alkylene-C 3-12 cycloalkyl, -C 1-12 alkylene-(3-12 membered heterocyclic group), -C 1-12 Alkylene-C 6-12 Aryl, -C 1-12alkylene-(5-12-membered heteroaryl), -OC 3-12 Cycloalkyl, -O-(3-12 membered heterocyclic), -OC 6-12 Aryl, -O-(5-12 heteroaryl), -SC 3-12 Cycloalkyl, -S-(3-12 membered heterocyclic groups), -SC 6-12 Aryl, -S-(5-12 heteroaryl), -NH-C 3-12 Cycloalkyl, -NH- (3-12 membered heterocyclic groups), -NH-C 6-12 Aryl, -NH- (5-12 heteroaryl).

[0073] According to the embodiments of this disclosure, in formula (M) or formula (M-1), R wc1 and R1, or R wc2 and R1, or R wc3 and R1, or R wn1 Together with R1, they form an optional substitution or optional substitution by one, two, three or more Rs. ZZ3 The following groups are substituted: 8-15 membered fused heterocyclic group, 8-15 membered bridged heterocyclic group, 8-15 membered spiroheterocyclic group, C 8-15 Fused ring group, C 8-15 Yuanqiao Ring Base, C 8-15 spirocyclic base; Each R ZZ3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and the following optional substituted groups: C 1-6 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic, phenyl, 5-6 membered heteroaryl, -C 1-3 Alkylene-C 3-6 cycloalkyl, -C 1-3 Alkylene-(3-6 membered heterocyclic group), -C 1-3 alkylene-phenyl, -C 1-3 alkylene-(5-6-membered heteroaryl), -OC 3-6 Cycloalkyl, -O-(3-6 membered heterocyclic), -O-phenyl, -O-(5-6 membered heteroaryl), -SC 3-6 Cycloalkyl, -S-(3-6 membered heterocyclic), -S-phenyl, -S-(5-6 membered heteroaryl), -NH-C 3-6 Cycloalkyl, -NH- (3-6 membered heterocyclic group), -NH-phenyl, -NH- (5-6 membered heteroaryl group).

[0074] According to the embodiments of this disclosure, in formula (M) or formula (M-1), R wc1 and R1, or Rwc2 and R1, or R wc3 and R1, or R wn1 Together with R1, they form an optional substitution or optional substitution by one, two, three or more Rs. ZZ3 The following groups are substituted: , , , , , , , .

[0075] According to the embodiments of this disclosure, in formula (M) or formula (M-1), R wc1 and R1, or R wc2 and R1, or R wc3 and R1, or R wn1 Together with R1, they form the following optionally substituted groups: , , , , , , , , , , , , .

[0076] According to the implementation scheme of this disclosure, each R ZZ3 Same or different, and independently selected from: H, deuterium, halogen, C 1-6 Alkyl, -OC 1-6 Alkyl, Halogenated C 1-6 Alkyl, -O-halogenated C 1-6 alkyl.

[0077] According to the implementation scheme of this disclosure, each R ZZ3 The same or different, and independently selected from: H, deuterium, F, Cl, Br, I, or optionally substituted C. 1-3 Alkyl (e.g., methyl).

[0078] According to the implementation scheme of this disclosure, each R Z The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and optionally substituted or optionally influenced by one, two, three or more Rs. ZZ1 The following groups are substituted: C 1-12 Alkyl, C 2-12 alkenyl, C 2-12alkynyl group, C 3-12 cycloalkyl, C 3-12 Cycloalkenyl, C 3-12 Cycloalkynyl, 3-12 membered heterocyclic group, C 6-12 Aryl, 5-12 heteroaryl, -C 1-12 Alkylene-C 2-12 alkenyl, -C 1-12 Alkylene-C 2-12 alkynyl group, -C 1-12 Alkylene-C 3-12 cycloalkyl, -C 1-12 Alkylene-C 3-12 Cycloalkenyl, -C 1-12 Alkylene-C 3-12 Cycloalkynyl, -C 1-12 alkylene-(3-12 membered heterocyclic group), -C 1-12 Alkylene-C 6-12 Aryl, -C 1-12 alkylene-(5-12-membered heteroaryl), -OR O1 -SR S1 -NR N1 R N2 -C(O)R C1 -OC(O)R C2 -OC(O)-OR O2 -OC(O)-NR N3 R N4 -N(R) N5 )-C(O)R C3 -N(R) N6 )-C(O)-NR N7 R N8 -S(O)2R S2 -OS(O)2R S3 -OS(O)2-OR O3 -OS(O)2-NR N9 R N10 -N(R) N11 )-S(O)2R S4 -N(R) N12 )-S(O)2-NR N13 R N14 -S(O)R S5 -OS(O)R S6 -OS(O)-OR O4 -OS(O)-NR N15 R N16 -N(R) N17 )-S(O)R S7 -N(R) N18)-S(O)-NR N19 R N20 -P(=O)R P1 R P2 -P(=O)(OR) O5 )R P2 -P(=O)(OR) O6 (OR) O7 -P(=O)(NR) N21 R N22 )R P3 -P(=O)(NR) N23 R N24 (NR) N25 R N26 -P(=O)(OR) O8 (NR) N27 R N28 ).

[0079] According to the implementation scheme of this disclosure, each R Z The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and optionally substituted or optionally influenced by one, two, three or more Rs. ZZ1 The following groups are substituted: C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 3-6 Cycloalkenyl, C 3-6 Cycloalkynyl, 3-6 membered heterocyclic, phenyl, 5-6 membered heteroaryl, -C 1-2 Alkylene-C 2-6 alkenyl, -C 1-2 Alkylene-C 2-6 alkynyl group, -C 1-2 Alkylene-C 3-6 cycloalkyl, -C 1-2 Alkylene-C 3-6 Cycloalkenyl, -C 1-2 Alkylene-C 3-6 Cycloalkynyl, -C 1-2 Alkylene-(3-6 membered heterocyclic group), -C 1-2 alkylene-phenyl, -C 1-2 alkylene-(5-6-membered heteroaryl), -OR O1 -SR S1 -NR N1 R N2 -C(O)R C1 -OC(O)R C2 -OC(O)-ORO2 , -O-C(O)-NR N3 R N4 , -N(R N5 )-C(O)R C3 , -N(R N6 )-C(O)-NR N7 R N8 , -S(O)₂R S2 , -O-S(O)₂R S3 , -O-S(O)₂-OR O3 , -O-S(O)₂-NR N9 R N10 , -N(R N11 )-S(O)₂R S4 , -N(R N12 )-S(O)₂-NR N13 R N14 , -S(O)R S5 , -O-S(O)R S6 , -O-S(O)-OR O4 , -O-S(O)-NR N15 R N16 , -N(R N17 )-S(O)R S7 , -N(R N18 )-S(O)-NR N19 R N20 , -P(=O)R P1 R P2 , -P(=O)(OR O5 )R P2 , -P(=O)(OR O6 )(OR O7 ), -P(=O)(NR N21 R N22 )R P3 , -P(=O)(NR N23 R N24 )(NR N25 R N26 ), -P(=O)(OR O8 )(NR N27 R N28 ).

[0080] According to the embodiments of the present disclosure, each R ZThe same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and optionally substituted methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, hydroxymethyl, hydroxyethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, propoxy, methylthio, ethylthio, propylthio, cyclopropoxy, cyclopropylthio, cyclopropylamino, -NHCH3, -NHCH2CH3, -N(CH3)2, -N(CH2CH3)2, -C(O)CH3, -CO2CH3, -CONH2, -CONH CH3, -CON(CH3)2, -S(=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2N(CH3)2, =NH, =NCH3, -N=S(=O)(CH3)2, -S(=O)(=NH)CH3, -S(=O)(=NCH3)CH3, -S(=O)(=N-CN)CH3, -P(=O)(CH3)2, propidinyl, aziridine, oxacyclobutyl, thioheterobutyl, tetrahydrofuranyl, pyrrolyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, aziridine-heptyl, oxacycloheptanyl, phenyl, naphthyl, furanyl, thiopheneyl, oxazolyl, thiazolyl, imidazoleyl, pyrazolyl, isothiazolyl, isoxazolyl, triazolyl.

[0081] According to the implementation scheme of this disclosure, each R Z The same or different, and independently selected from: H, halogen, or optionally substituted groups of the following: C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, Halogenated C 1-6 Alkyl group.

[0082] According to the implementation scheme of this disclosure, each R Z Same or different, and independently selected from: F, Cl, Br, I, or optionally substituted C 1-3 Alkyl (e.g., methyl).

[0083] According to the implementation scheme of this disclosure, each R Z1 R Z2 R Z3 R Z4 R Z5 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and optionally substituted or optionally influenced by one, two, three or more Rs. ZZ1The following groups are substituted: C 1-12 Alkyl, C 2-12 alkenyl, C 2-12 alkynyl group, C 3-12 cycloalkyl, C 3-12 Cycloalkenyl, C 3-12 Cycloalkynyl, 3-12 membered heterocyclic group, C 6-12 Aryl, 5-12 heteroaryl, -C 1-12 Alkylene-C 2-12 alkenyl, -C 1-12 Alkylene-C 2-12 alkynyl group, -C 1-12 Alkylene-C 3-12 cycloalkyl, -C 1-12 Alkylene-C 3-12 Cycloalkenyl, -C 1-12 Alkylene-C 3-12 Cycloalkynyl, -C 1-12 alkylene-(3-12 membered heterocyclic group), -C 1-12 Alkylene-C 6-12 Aryl, -C 1-12 alkylene-(5-12-membered heteroaryl), -OR O1 -SR S1 -NR N1 R N2 -C(O)R C1 -OC(O)R C2 -OC(O)-OR O2 -OC(O)-NR N3 R N4 -N(R) N5 )-C(O)R C3 -N(R) N6 )-C(O)-NR N7 R N8 -S(O)2R S2 -OS(O)2R S3 -OS(O)2-OR O3 -OS(O)2-NR N9 R N10 -N(R) N11 )-S(O)2R S4 -N(R) N12 )-S(O)2-NR N13 R N14 -S(O)R S5 -OS(O)R S6 -OS(O)-OR O4 -OS(O)-NR N15 R N16 -N(R)N17 )-S(O)R S7 -N(R) N18 )-S(O)-NR N19 R N20 -P(=O)R P1 R P2 -P(=O)(OR) O5 )R P2 -P(=O)(OR) O6 (OR) O7 -P(=O)(NR) N21 R N22 )R P3 -P(=O)(NR) N23 R N24 (NR) N25 R N26 -P(=O)(OR) O8 (NR) N27 R N28 ); Or two R atoms connected to the same carbon atom Z1 Together with the carbon atom it is attached to, they form C 3-12 Cycloalkyl.

[0084] According to the implementation scheme of this disclosure, each R Z1 R Z2 R Z3 R Z4 R Z5 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and optionally substituted or optionally influenced by one, two, three or more Rs. ZZ1 The following groups are substituted: C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 3-10 cycloalkyl, C 3-10 Cycloalkenyl, C 3-10 Cycloalkynyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 heteroaryl, -C 1-10 Alkylene-C 2-10 alkenyl, -C 1-10 Alkylene-C 2-10 alkynyl group, -C 1-10 Alkylene-C 3-10 cycloalkyl, -C 1-10 Alkylene-C 3-10 Cycloalkenyl, -C 1-10 Alkylene-C 3-10 Cycloalkynyl, -C1-10 alkylene-(3-10 membered heterocyclyl), -C 1-10 alkylene-C 6-10 aryl, -C 1-10 alkylene-(5-10 membered heteroaryl), -OR O1 , -SR S1 , -NR N1 R N2 , -C(O)R C1 , -O-C(O)R C2 , -O-C(O)-OR O2 , -O-C(O)-NR N3 R N4 , -N(R N5 )-C(O)R C3 , -N(R N6 )-C(O)-NR N7 R N8 , -S(O)2R S2 , -O-S(O)2R S3 , -O-S(O)2-OR O3 , -O-S(O)2-NR N9 R N10 , -N(R N11 )-S(O)2R S4 , -N(R N12 )-S(O)2-NR N13 R N14 , -S(O)R S5 , -O-S(O)R S6 , -O-S(O)-OR O4 , -O-S(O)-NR N15 R N16 , -N(R N17 )-S(O)R S7 , -N(R N18 )-S(O)-NR N19 R N20 , -P(=O)R P1 R P2 , -P(=O)(OR O5 )R P2 , -P(=O)(OR O6 )(OR O7 ), -P(=O)(NR N21 R N22 )R P3 , -P(=O)(NR N23 R N24 )(NR N25 R N26 ), -P(=O)(ORO8 (NR) N27 R N28 ); Or two R atoms connected to the same carbon atom Z1 Together with the carbon atom it is attached to, they form C 3-10 Cycloalkyl.

[0085] According to the implementation scheme of this disclosure, each R Z1 R Z2 R Z3 R Z4 R Z5 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and optionally substituted or optionally influenced by one, two, three or more Rs. ZZ1 The following groups are substituted: C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -C 1-6 Alkylene-C 2-6 alkenyl, -C 1-6 Alkylene-C 2-6 alkynyl group, -C 1-6 Alkylene-C 3-6 cycloalkyl, -C 1-6 Alkylene-(3-6 membered heterocyclic group), -C 1-6 Alkylene-C 6-10 Aryl, -C 1-6 alkylene-(5-6-membered heteroaryl), -OR O1 -SR S1 -NR N1 R N2 -C(O)R C1 -OC(O)R C2 -OC(O)-OR O2 -OC(O)-NR N3 R N4 -N(R) N5 )-C(O)R C3 -N(R) N6 )-C(O)-NR N7 R N8 -S(O)2R S2 -OS(O)2R S3 -OS(O)2-OR O3 -OS(O)2-NR N9 RN10 -N(R) N11 )-S(O)2R S4 -N(R) N12 )-S(O)2-NR N13 R N14 -S(O)R S5 -OS(O)R S6 -OS(O)-OR O4 -OS(O)-NR N15 R N16 -N(R) N17 )-S(O)R S7 -N(R) N18 )-S(O)-NR N19 R N20 -P(=O)R P1 R P2 -P(=O)(OR) O5 )R P2 -P(=O)(OR) O6 (OR) O7 -P(=O)(NR) N21 R N22 )R P3 -P(=O)(NR) N23 R N24 (NR) N25 R N26 -P(=O)(OR) O8 (NR) N27 R N28 ); Or two R atoms connected to the same carbon atom Z1 Together with the carbon atom it is attached to, they form C 3-6 Cycloalkyl.

[0086] According to the implementation scheme of this disclosure, each R Z1 R Z2 R Z3 R Z4 R Z5 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and optionally substituted or optionally influenced by one, two, three or more Rs. ZZ1 The following groups are substituted: C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -C 1-2Alkylene-C 2-6 alkenyl, -C 1-2 Alkylene-C 2-6 alkynyl group, -C 1-2 Alkylene-C 3-6 cycloalkyl, -C 1-2 Alkylene-(3-6 membered heterocyclic group), -C 1-2 Alkylene-C 6-10 Aryl, -C 1-2 alkylene-(5-6-membered heteroaryl), -OR O1 -SR S1 -NR N1 R N2 -C(O)R C1 -OC(O)R C2 -OC(O)-OR O2 -OC(O)-NR N3 R N4 -N(R) N5 )-C(O)R C3 -N(R) N6 )-C(O)-NR N7 R N8 -S(O)2R S2 -OS(O)2R S3 -OS(O)2-OR O3 -OS(O)2-NR N9 R N10 -N(R) N11 )-S(O)2R S4 -N(R) N12 )-S(O)2-NR N13 R N14 -S(O)R S5 -OS(O)R S6 -OS(O)-OR O4 -OS(O)-NR N15 R N16 -N(R) N17 )-S(O)R S7 -N(R) N18 )-S(O)-NR N19 R N20 -P(=O)R P1 R P2 -P(=O)(OR) O5 )R P2 -P(=O)(OR) O6 (OR) O7 -P(=O)(NR) N21 R N22 )RP3 -P(=O)(NR) N23 R N24 (NR) N25 R N26 -P(=O)(OR) O8 (NR) N27 R N28 ); Or two R atoms connected to the same carbon atom Z1 Together with the carbon atom it is attached to, they form C 3-6 Cycloalkyl.

[0087] According to the implementation scheme of this disclosure, each R Z1 R Z2 R Z3 R Z4 R Z5 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and optionally substituted or optionally influenced by one, two, three or more Rs. ZZ1 The following groups may be substituted: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, hydroxymethyl, hydroxyethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, propoxy, methylthio, ethylthio, propylthio, cyclopropoxy, cyclopropylthio, cyclopropylamino, -NHCH3, -NHCH2CH3, -N(CH3)2, -N(CH2CH3)2, -C(O)CH3, -CO2CH3, -CONH2, -CONHCH3, -CON(CH3)2, -S(=O)2CH3, -S(=O)2NH2. -S(=O)2NHCH3, -S(=O)2N(CH3)2, =NH, =NCH3, -N=S(=O)(CH3)2, -S(=O)(=NH)CH3, -S(=O)(=NCH3)CH3, -S(=O)(=N-CN)CH3, -P(=O)(CH3)2, propidinyl, aziridine, oxadiazine, thioheptanyl, tetrahydrofuranyl, pyrrolidinyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, homopiperidinyl, aziridine-heptyl, oxadiazine-heptyl, phenyl, naphthyl, furanyl, thienyl, oxazolyl, thiazolyl, imidazoleyl, pyrazolyl, isothiazolyl, isoxazolyl, triazolyl; Or two R atoms connected to the same carbon atom Z1 Together with the carbon atom it is attached to, it forms a cyclopropyl, cyclobutyl, or cyclopentyl group.

[0088] According to the implementation scheme of this disclosure, each RZ1 The same or different, and independently selected from: halogens, CN, SF5, and optionally substituted with the following groups: methyl, haloC 1-6 Alkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, -P(=O)(C 1-6 Alkyl)2、-S(O)2C 1-6 alkyl; Or two R atoms connected to the same carbon atom Z1 Together with the carbon atom it is attached to, they form C 3-6 Cycloalkyl; preferably, two R atoms attached to the same carbon atom on the alkylene group. Z1 Together with the carbon atom it is attached to, they form C 3-6 Cycloalkyl.

[0089] According to the implementation scheme of this disclosure, each R Z1 The same or different, and independently selected from: F, Cl, CN, CF3, SF5, and optionally substituted with the following groups: methyl, phenyl, , , ; Or two R atoms connected to the same carbon atom Z1 Together with the carbon atom attached thereto, they form a cyclopropyl, cyclobutyl, or cyclopentyl group; preferably, the two R groups attached to the same carbon atom on the alkylene group... Z1 Together with the carbon atom it is attached to, it forms a cyclopropyl, cyclobutyl, or cyclopentyl group.

[0090] According to the implementation scheme of this disclosure, each R Z2 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and optionally substituted or optionally influenced by one, two, three or more Rs. ZZ1 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -C 1-2 Alkylene-C 3-6 cycloalkyl, -C 1-2 Alkylene-(3-6 membered heterocyclic group), -C 1-2 Alkylene-C 6-10 Aryl, -C 1-2 alkylene-(5-6-membered heteroaryl), -OC 1-6 Alkyl, -OC 3-6 Cycloalkyl, -O-3-6-membered heterocyclic groups, -NH-C 1-6 Alkyl, -NH-C 3-6Cycloalkyl, -NH-3-6-membered heterocyclic group, -N(C 1-6 Alkyl)2、-C(O)-C 1-6 Alkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-3-6-membered heterocyclic groups, -C(O)NH2, -C(O)-NH-C 1-6 alkyl.

[0091] According to the implementation scheme of this disclosure, each R Z2 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and optionally substituted or optionally influenced by one, two, three or more Rs. ZZ1 The following groups are substituted: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, hydroxymethyl, hydroxyethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, propoxy, methylthio, ethylthio, propylthio, cyclopropoxy, cyclopropylthio, cyclopropylamino, -NHCH3, -NHCH2CH3, -N(CH3)2, -N(CH2CH3) )2、-C(O)CH3、-CO2CH3、-CONH2、-CONHCH3、-CON(CH3)2、propidinyl、azacyclobutyl、oxacyclobutyl、thiocyclobutyl、tetrahydrofuranyl、pyrrolidinyl、tetrahydropyranyl、piperidinyl、piperazinyl、morpholinyl、thiomorpholinyl、homoperazinyl、homoperidinyl、azacycloheptyl、oxacycloheptyl、phenyl、naphthyl、furanyl、thienyl、oxazolyl、thiazolyl、imidazolyl、pyrazolyl、isothiazolyl、isooxazolyl、triazolyl.

[0092] According to the implementation scheme of this disclosure, each R Z2 Same or different, and independently selected from: halogens, and optionally substituted with the following groups: C 1-6 Alkyl, C 3-8 Cycloalkyl-C(O).

[0093] According to the implementation scheme of this disclosure, each R Z2 Same or different, and independently selected from: F, and optionally substituted with the following groups: methyl, isopropyl, .

[0094] According to the implementation scheme of this disclosure, each R O1 R O2 R O3 R O4 R O5 R O6 R O7 RO8 R S1 R S2 R S3 R S4 R S5 R S6 R S7 R C1 R C2 R C3 R P1 R P2 R P3 R N1 R N2 R N3 R N4 R N5 R N6 R N7 R N8 R N9 R N10 R N11 R N12 R N13 R N14 R N15 R N16 R N17 R N18 R N19 R N20 R N21 R N22 R N23 R N24 R N25 R N26 R N27 R N28 Whether identical or different, each is independently selected from: H, deuterium, and optionally substituted or optionally replaced by one, two, three or more R. ZZ2 The following groups are substituted: C 1-12 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -C 1-12 Alkylene-C 3-12 cycloalkyl, -C 1-12 alkylene-(3-12 membered heterocyclic group), -C 1-12 Alkylene-C 6-12 Aryl, -C 1-12 alkylene-(5-12-membered heteroaryl); Or R N3 With R N4 R N7 With R N8 R N9 With R N10 RN13 With R N14 R N15 With R N16 R N19 With R N20 R N21 With R N22 R N23 With R N24 R N25 With R N26 R N27 With R N28 Together with the N atom it is linked to, it forms a 3-12 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O, S, Si or P; Or R P1 With R P2 Together with the P atom it is linked to, it forms a 3-12 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O, S, Si or P; Or R O5 With R P2 R O6 With R O7 Together with the atoms linked to it, they form a 4-12 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O, S, Si or P.

[0095] According to the implementation scheme of this disclosure, each R O1 R O2 R O3 R O4 R O5 R O6 R O7 R O8 R S1 R S2 R S3 R S4 R S5 R S6 R S7 R C1 R C2 R C3 R P1 R P2 R P3 R N1 R N2 R N3 R N4 R N5 R N6 R N7 R N8 R N9 RN10 R N11 R N12 R N13 R N14 R N15 R N16 R N17 R N18 R N19 R N20 R N21 R N22 R N23 R N24 R N25 R N26 R N27 R N28 Whether identical or different, each is independently selected from: H, deuterium, and optionally substituted or optionally replaced by one, two, three or more R. ZZ2 The following groups are substituted: C 1-10 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, -C 1-10 Alkylene-C 3-10 cycloalkyl, -C 1-10 alkylene-(3-10 membered heterocyclic group), -C 1-10 Alkylene-C 6-10 Aryl, -C 1-10 alkylene-(5-10-membered heteroaryl); Or R N3 With R N4 R N7 With R N8 R N9 With R N10 R N13 With R N14 R N15 With R N16 R N19 With R N20 R N21 With R N22 R N23 With R N24 R N25 With R N26 R N27 With R N28 Together with the N atom it is linked to, it forms a 3-10 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O, S, Si or P; Or R P1 With R P2Together with the P atom it is linked to, it forms a 3-10 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O, S, Si or P; Or R O5 With R P2 R O6 With R O7 Together with the atoms linked to it, they form a 4-10 member heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O, S, Si or P.

[0096] According to the implementation scheme of this disclosure, each R O1 R O2 R O3 R O4 R O5 R O6 R O7 R O8 R S1 R S2 R S3 R S4 R S5 R S6 R S7 R C1 R C2 R C3 R P1 R P2 R P3 R N1 R N2 R N3 R N4 R N5 R N6 R N7 R N8 R N9 R N10 R N11 R N12 R N13 R N14 R N15 R N16 R N17 R N18 R N19 R N20 R N21 R N22 R N23 R N24 R N25 R N26 R N27 R N28Whether identical or different, each is independently selected from: H, deuterium, and optionally substituted or optionally replaced by one, two, three or more R. ZZ2 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -C 1-6 Alkylene-C 3-6 cycloalkyl, -C 1-6 Alkylene-(3-6 membered heterocyclic group), -C 1-6 Alkylene-C 6-10 Aryl, -C 1-6 alkylene-(5-6-membered heteroaryl); Or R N3 With R N4 R N7 With R N8 R N9 With R N10 R N13 With R N14 R N15 With R N16 R N19 With R N20 R N21 With R N22 R N23 With R N24 R N25 With R N26 R N27 With R N28 Together with the N atom it is linked to, it forms a 3-6 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O, S, Si or P; Or R P1 With R P2 Together with the P atom it is linked to, it forms a 3-6 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O, S, Si or P; Or R O5 With R P2 R O6 With R O7 Together with the atoms linked to it, they form a 4-6 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O, S, Si or P.

[0097] According to the implementation scheme of this disclosure, each R O1 R O2 R O3 R O4 R O5 R O6 RO7 R O8 R S1 R S2 R S3 R S4 R S5 R S6 R S7 R C1 R C2 R C3 R P1 R P2 R P3 R N1 R N2 R N3 R N4 R N5 R N6 R N7 R N8 R N9 R N10 R N11 R N12 R N13 R N14 R N15 R N16 R N17 R N18 R N19 R N20 R N21 R N22 R N23 R N24 R N25 R N26 R N27 R N28 Whether identical or different, each is independently selected from: H, deuterium, and optionally substituted or optionally replaced by one, two, three or more R. ZZ2 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -C 1-2 Alkylene-C 3-6 cycloalkyl, -C 1-2 Alkylene-(3-6 membered heterocyclic group), -C 1-2 Alkylene-C 6-10 Aryl, -C 1-2 alkylene-(5-6-membered heteroaryl); Or R N3 With R N4 R N7 With R N8 R N9 With RN10 R N13 With R N14 R N15 With R N16 R N19 With R N20 R N21 With R N22 R N23 With R N24 R N25 With R N26 R N27 With R N28 Together with the N atom it is linked to, it forms a 3-6 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O or S; Or R P1 With R P2 Together with the P atom it is linked to, it forms a 3-6 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O or S; Or R O5 With R P2 R O6 With R O7 Together with the atoms linked to it, they form a 4-6 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O or S.

[0098] According to the implementation scheme of this disclosure, each R O1 R O2 R O3 R O4 R O5 R O6 R O7 R O8 R S1 R S2 R S3 R S4 R S5 R S6 R S7 R C1 R C2 R C3 R P1 R P2 R P3 R N1 R N2 R N3 R N4 R N5 R N6 R N7 R N8 R N9 R N10R N11 R N12 R N13 R N14 R N15 R N16 R N17 R N18 R N19 R N20 R N21 R N22 R N23 R N24 R N25 R N26 R N27 R N28 Whether identical or different, each is independently selected from: H, deuterium, and optionally substituted or optionally replaced by one, two, three or more R. ZZ2 The following groups may be substituted: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, hydroxymethyl, hydroxyethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, propidinyl, aziridine, oxadiazinyl, thiohexacyclic, tetrahydrofuranyl, pyrrolylyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, homopiperidinyl, aziridineheptyl, oxadiazeptyl, phenyl, naphthyl, furanyl, thiopheneyl, oxazolyl, thiazolyl, imidazoleyl, pyrazolyl, isothiazolyl, isoxazolyl, triazolyl.

[0099] According to the implementation scheme of this disclosure, each R ZZ1 R ZZ2 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and the following optional substituted groups: C 1-12 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -C 1-12 Alkylene-C 3-12 cycloalkyl, -C 1-12 alkylene-(3-12 membered heterocyclic group), -C 1-12 Alkylene-C 6-12 Aryl, -C 1-12 alkylene-(5-12-membered heteroaryl), -OC 3-12 Cycloalkyl, -O-(3-12 membered heterocyclic), -OC 6-12 Aryl, -O-(5-12 heteroaryl), -SC 3-12 Cycloalkyl, -S-(3-12 membered heterocyclic groups), -SC6-12 Aryl, -S-(5-12 heteroaryl), -NH-C 3-12 Cycloalkyl, -NH- (3-12 membered heterocyclic groups), -NH-C 6-12 Aryl, -NH- (5-12 heteroaryl).

[0100] According to the implementation scheme of this disclosure, each R ZZ1 R ZZ2 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and the following optional substituted groups: C 1-10 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, -C 1-10 Alkylene-C 3-10 cycloalkyl, -C 1-10 alkylene-(3-10 membered heterocyclic group), -C 1-10 Alkylene-C 6-10 Aryl, -C 1-10 alkylene-(5-10-membered heteroaryl), -OC 3-10 Cycloalkyl, -O- (3-10 membered heterocyclic groups), -OC 6-10 Aryl, -O-(5-10 heteroaryl), -SC 3-10 Cycloalkyl, -S- (3-10 membered heterocyclic groups), -SC 6-10 Aryl, -S-(5-10 heteroaryl), -NH-C 3-10 Cycloalkyl, -NH- (3-10 membered heterocyclic groups), -NH-C 6-10 Aryl, -NH- (5-10 heteroaryl).

[0101] According to the implementation scheme of this disclosure, each R ZZ1 R ZZ2 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and the following optional substituted groups: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -C 1-6 Alkylene-C 3-6 cycloalkyl, -C 1-6 Alkylene-(3-6 membered heterocyclic group), -C 1-6 Alkylene-C 6-10 Aryl, -C 1-6alkylene-(5-6-membered heteroaryl), -OC 3-6 Cycloalkyl, -O- (3-6 membered heterocyclic groups), -OC 6-10 Aryl, -O-(5-6 quinary heteroaryl), -SC 3-6 Cycloalkyl, -S- (3-6 membered heterocyclic groups), -SC 6-10 Aryl, -S-(5-6 membered heteroaryl), -NH-C 3-6 Cycloalkyl, -NH- (3-6 membered heterocyclic groups), -NH-C 6-10 Aryl, -NH- (5-6 membered heteroaryl).

[0102] According to the implementation scheme of this disclosure, each R ZZ1 R ZZ2 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and the following optional substituted groups: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -C 1-2 Alkylene-C 3-6 cycloalkyl, -C 1-2 Alkylene-(3-6 membered heterocyclic group), -C 1-2 Alkylene-C 6-10 Aryl, -C 1-2 alkylene-(5-6-membered heteroaryl), -OC 3-6 Cycloalkyl, -O- (3-6 membered heterocyclic groups), -OC 6-10 Aryl, -O-(5-6 quinary heteroaryl), -SC 3-6 Cycloalkyl, -S- (3-6 membered heterocyclic groups), -SC 6-10 Aryl, -S-(5-6 membered heteroaryl), -NH-C 3-6 Cycloalkyl, -NH- (3-6 membered heterocyclic groups), -NH-C 6-10 Aryl, -NH- (5-6 membered heteroaryl).

[0103] According to the implementation scheme of this disclosure, each R ZZ1 R ZZ2The same or different, and independently selected from: H, deuterium, F, Cl, Br, I, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and optionally substituted with the following groups: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, hydroxymethyl, hydroxyethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, propoxy, methylthio. Ethylthio, propanethio, cyclopropoxy, cyclopropanethio, cyclopropylamino, -NHCH3, -NHCH2CH3, -N(CH3)2, -N(CH2CH3)2, propidinyl, aziridine, oxadiazinyl, thiohexacyclobutyl, tetrahydrofuranyl, pyrrolidinyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, homopiperidinyl, aziridineheptyl, oxadiazinyl, phenyl, naphthyl, furanyl, thiopheneyl, oxazolyl, thiazolyl, imidazoleyl, pyrazolyl, isothiazolyl, isoxazolyl, triazolyl.

[0104] According to the implementation scheme of this disclosure, W1, W4, W5, W6, W7, W 10 W 11 W 12 W 14 W 15 W 16 W 17 W 18 W 19 W 22 W 23 W 24 W 25 Same or different, and independently selected from: O, S, S(=O), S(=O)2, N, NR wn1 C, C (=O), CR wc1 CR wc2 R wc3 ; W2, W3, W8, W 13、 W 20、 W 21、 W 26 Same or different, and independently selected from: N, C, CR wc1 ; Each R wc1 R wc2 R wc3 Same or different, and independently selected from: H, deuterium, halogen, OH, CN, C 1-6 alkyl.

[0105] According to the implementation scheme of this disclosure, W1, W4, W7, W 10 W 11W 12 W 14 W 15 W 16 W 17 Same or different, and independently selected from: O, S, S(=O), S(=O)2, N, NH, N(C) 1-6 Alkyl), C, C(=O), CH, C(C) 1-6 Alkyl), CH2, CH(C) 1-6 Alkyl), C(C) 1-6 Alkyl)2.

[0106] According to the embodiments of this disclosure, W2 and W3 may be the same or different, and are independently selected from: N, NH, N(C) 1-6 Alkyl), C, CH, C(C) 1-6 alkyl).

[0107] According to the implementation scheme of this disclosure, W5, W8, W 13 Same or different, and independently selected from: N, C, CH, C(C) 1-6 alkyl).

[0108] According to the embodiments of this disclosure, W6 is selected from: O, S, NH, N(C) 1-6 Alkyl), CH2, CH(C) 1-6 Alkyl), C(C) 1-6 Alkyl)2.

[0109] According to the implementation scheme of this disclosure, W 18 W 19 W 22 W 23 W 24 W 25 Same or different, and independently selected from: O, S, S(=O), S(=O)2, N, NR wn1 C, C (=O), CR wc1 CR wc2 R wc3 ; W 20、 W 21、 W 26 Same or different, and independently selected from: N, C, CR wc1 ; Each R wc1 R wc2 R wc3 Same or different, and independently selected from: H, deuterium, halogen, OH or C 1-6 alkyl.

[0110] According to the implementation scheme of this disclosure, W 18 W 19Same or different, and independently selected from: CR wc1 or CR wc2 R wc3 ; W 20、 W 21、 W 26 Same or different, and independently selected from: N, C, CR wc1 ; W 22 W 23 W 24 W 25 Same or different, and independently selected from: N, NR wn1 C, C (=O), CR wc1 or CR wc2 R wc3 ; Each R wc1 R wc2 R wc3 Same or different, and independently selected from: H, deuterium, halogen, OH or C 1-6 alkyl.

[0111] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Rings B and C are independently selected from saturated, partially saturated, aromatic C5-ring hydrocarbons or five-membered heterocycles; W1, W4, W5, W6, and W7 may be the same or different, and are independently selected from: O, S, S(=O), S(=O)2, N, and NR. wn1 C, C (=O), CR wc1 CR wc2 R wc3 ; W2, W3, and W8 may be the same or different, and are independently selected from: N, C, CR wc1 ; The fused ring composed of ring B and ring C contains 1-4 heteroatoms; For definitions of other functional groups, please refer to the definitions above.

[0112] According to the implementation scheme of this disclosure, Selected from unsubstituted or arbitrarily assigned to one, two or more R wn1 Or R wc1 The following groups may be substituted: partially saturated 5-membered heterocyclic groups, 5-membered heteroaryl groups; for example, selected from unsubstituted groups or optionally substituted with one, two or more R groups. wn1 Or R wc1 The following groups may be substituted: triazolyl, oxazolyl, thiazolyl, pyrazolyl, dihydropyrazolyl, imidazoleyl, dihydroimidazolyl, isoxazolyl, pyrroleyl; if selected from: , , , , , , , , , , , ;*end and or connect.

[0113] According to the implementation scheme of this disclosure, Selected from unsubstituted or arbitrarily assigned to one, two or more R wn1 Or R wc1 The following groups can be substituted: fused 8-membered heteroaryl groups; for example, selected from: , ;*end and or connect.

[0114] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Rings B and C are independently selected from saturated, partially saturated, aromatic C5-ring hydrocarbons or five-membered heterocycles; W1, W4, W5, W6, and W7 may be the same or different, and are independently selected from: O, S, N, and NR. wn1 C, CR wc1 CR wc2 R wc3 ; W2, W3, and W8 may be the same or different, and are independently selected from: N, C, CR wc1 ; The fused ring composed of ring B and ring C contains 2-4 heteroatoms; For definitions of other functional groups, please refer to the definitions above.

[0115] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring B is selected from a partially saturated C5-membered hydrocarbon ring or a five-membered heterocycle; ring C is independently selected from a partially saturated, aromatic five-membered heterocycle. W1, W4, W5, W6, and W7 may be the same or different, and are independently selected from: O, S, N, and NR. wn1 C, CR wc1 CR wc2 R wc3 ; W2 and W3 may be the same or different, and are independently selected from: N and C; W8 is selected from: N, CR wc1 ; The fused ring composed of ring B and ring C contains 2-4 heteroatoms; For definitions of other functional groups, please refer to the definitions above.

[0116] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring B is selected from a partially saturated C5-ring hydrocarbon ring; ring C is independently selected from a partially saturated, aromatic five-membered heterocycle. W1, W4, and W5 may be the same or different, and each may be independently selected from: O, S, N, NR wn1 C, CR wc1 CR wc2 R wc3 ; W6 and W7 may be the same or different, and are independently selected from: CR wc1 CR wc2 R wc3 ; W2 and W3 may be the same or different, and each is independently selected from: C; W8 is selected from: CR wc1 ; The ring C contains 1-3 heteroatoms; For definitions of other functional groups, please refer to the definitions above.

[0117] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring B is selected from a partially saturated five-membered heterocycle; ring C is independently selected from a partially saturated, aromatic five-membered heterocycle. W1, W4, W5, W6, and W7 may be the same or different, and are independently selected from: O, S, N, and NR. wn1 C, CR wc1 CR wc2 R wc3 ; W2 and W3 may be the same or different, and are independently selected from: N and C; W8 is selected from: N, CR wc1 ; The fused ring composed of ring B and ring C contains 2-4 heteroatoms; For definitions of other functional groups, please refer to the definitions above.

[0118] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring B is selected from a partially saturated C5-membered hydrocarbon ring; ring C is independently selected from an aromatic five-membered heterocycle. W1, W4, and W5 may be the same or different, and each may be independently selected from: O, S, N, NR wn1 C, CR wc1 ; W6 and W7 may be the same or different, and are independently selected from: CR wc1 CR wc2 R wc3 ; W2 and W3 may be the same or different, and each is independently selected from: C; W8 is selected from: CR wc1 ; The ring C contains 1-3 heteroatoms; For definitions of other functional groups, please refer to the definitions above.

[0119] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring B is selected from a partially saturated five-membered heterocycle; ring C is independently selected from an aromatic five-membered heterocycle; W1, W4, and W5 may be the same or different, and each may be independently selected from: O, S, N, NR wn1 C, CR wc1 ; W6 and W7 may be the same or different, and each is independently selected from: O, S, N, NR wn1 C, CR wc1 CR wc2 R wc3 ; W2 and W3 may be the same or different, and are independently selected from: N and C; W8 is selected from: N, CR wc1 ; The fused ring composed of ring B and ring C contains 2-4 heteroatoms; For definitions of other functional groups, please refer to the definitions above.

[0120] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; The bicyclic fused system composed of ring B and ring C is an aromatic system; W1, W4, and W5 may be the same or different, and each may be independently selected from: O, S, N, NR wn1 C, CR wc1 ; W6 and W7 may be the same or different, and each is independently selected from: O, S, N, NR wn1 CR wc1 ; W2 and W3 may be the same or different, and are independently selected from: N and C; W8 is selected from: N, C; The fused ring composed of ring B and ring C contains 2-4 heteroatoms; For definitions of other functional groups, please refer to the definitions above.

[0121] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Rings B and C are independently selected from saturated, partially saturated, aromatic C5-ring hydrocarbons or five-membered heterocycles; W1, W4, W6, and W7 may be the same or different, and are independently selected from: O, S, S(=O), S(=O)2, N, NR wn1 C, C (=O), CR wc1 CR wc2 R wc3 ; W2, W3, W5, and W8 may be the same or different, and are independently selected from: N, C, and CR. wc1 ; The fused ring composed of ring B and ring C contains 1-4 heteroatoms; For definitions of other functional groups, please refer to the definitions above.

[0122] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Rings B and C are independently selected from saturated, partially saturated, aromatic C5-ring hydrocarbons or five-membered heterocycles; W1, W4, W6, and W7 may be the same or different, and are independently selected from: O, S, N, and NR. wn1 C, CR wc1 CR wc2 R wc3 ; W2, W3, W5, and W8 may be the same or different, and are independently selected from: N, C, and CR. wc1 ; The fused ring composed of ring B and ring C contains 2-4 heteroatoms; For definitions of other functional groups, please refer to the definitions above.

[0123] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring B is selected from a partially saturated C5-membered hydrocarbon ring or a five-membered heterocycle; ring C is independently selected from a partially saturated, aromatic five-membered heterocycle. W1, W4, W6, and W7 may be the same or different, and are independently selected from: O, S, N, and NR. wn1 C, CR wc1 CR wc2 R wc3 ; W2 and W3 may be the same or different, and are independently selected from: N and C; W5 is selected from: N, C, CR wc1 ; W8 is selected from: N, CR wc1 ; The fused ring composed of ring B and ring C contains 2-4 heteroatoms; For definitions of other functional groups, please refer to the definitions above.

[0124] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring B is selected from a partially saturated C5-ring hydrocarbon ring; ring C is independently selected from a partially saturated, aromatic five-membered heterocycle. W1 and W4 may be the same or different, and each is independently selected from: O, S, N, NR wn1 C, CR wc1 CR wc2 R wc3 ; W6 and W7 may be the same or different, and are independently selected from: CR wc1 CR wc2 R wc3 ; W2 and W3 may be the same or different, and each is independently selected from: C; W5 is selected from: N, C, CR wc1 ; W8 is selected from: CR wc1 ; The ring C contains 1-3 heteroatoms; For definitions of other functional groups, please refer to the definitions above.

[0125] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring B is selected from a partially saturated five-membered heterocycle; ring C is independently selected from a partially saturated, aromatic five-membered heterocycle. W1, W4, W6, and W7 may be the same or different, and are independently selected from: O, S, N, and NR. wn1 C, CR wc1 CR wc2 R wc3 ; W2 and W3 may be the same or different, and are independently selected from: N and C; W5 is selected from: N, C, CR wc1 ; W8 is selected from: N, CR wc1 ; The fused ring composed of ring B and ring C contains 2-4 heteroatoms; For definitions of other functional groups, please refer to the definitions above.

[0126] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring B is selected from a partially saturated C5-membered hydrocarbon ring; ring C is independently selected from an aromatic five-membered heterocycle. W1 and W4 may be the same or different, and each is independently selected from: O, S, N, NRwn1 C, CR wc1 ; W6 and W7 may be the same or different, and are independently selected from: CR wc1 CR wc2 R wc3 ; W2 and W3 may be the same or different, and each is independently selected from: C; W5 is selected from: N, C; W8 is selected from: CR wc1 ; The ring C contains 1-3 heteroatoms; For definitions of other functional groups, please refer to the definitions above.

[0127] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring B is selected from a partially saturated five-membered heterocycle; ring C is independently selected from an aromatic five-membered heterocycle; W1 and W4 may be the same or different, and each is independently selected from: O, S, N, NR wn1 C, CR wc1 ; W6 and W7 may be the same or different, and each is independently selected from: O, S, N, NR wn1 C, CR wc1 CR wc2 R wc3 ; W2 and W3 may be the same or different, and are independently selected from: N and C; W5 is selected from: N, C; W8 is selected from: N, CR wc1 ; The fused ring composed of ring B and ring C contains 2-4 heteroatoms; For definitions of other functional groups, please refer to the definitions above.

[0128] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; The bicyclic fused system composed of ring B and ring C is an aromatic system; W1 and W4 may be the same or different, and each is independently selected from: O, S, N, NR wn1 CR wc1 ; W6 and W7 may be the same or different, and each is independently selected from: O, S, N, NR wn1 CR wc1 ; W2 and W3 may be the same or different, and are independently selected from: N and C; W5 is selected from: N, C; W8 is selected from: N, C; The fused ring composed of ring B and ring C contains 2-4 heteroatoms; For definitions of other functional groups, please refer to the definitions above.

[0129] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring B is selected from a partially saturated C5-membered hydrocarbon ring or a five-membered heterocycle; ring C is independently selected from a partially saturated, aromatic five-membered heterocycle. W1 and W4 may be the same or different, and each is independently selected from: O, S, N, NR wn1 C, CR wc1 CR wc2 R wc3 ; W2 and W3 may be the same or different, and are independently selected from: N and C; W5 is selected from: N, C, CR wc1 ; W6 is selected from: O, S, NR wn1 CR wc2 R wc3 ; The fused ring composed of ring B and ring C contains 2-4 heteroatoms; R3 is selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more Rs. Z4 The following groups are substituted: C 1-20 Alkyl, C 3-20 Cycloalkyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20 Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl), -OC 3-20 Cycloalkyl, -O- (3-20 membered heterocyclic groups), -OC 6-20 Aryl, -O- (5-20 heteroaryl), -SC 3-20 Cycloalkyl, -S- (3-20 membered heterocyclic groups), -SC 6-20 Aryl, -S-(5-20 heteroaryl), -NH-C 3-20 Cycloalkyl, -NH- (3-20 membered heterocyclic groups), -NH-C 6-20 Aryl, -NH- (5-20 heteroaryl); For definitions of other functional groups, please refer to the definitions above.

[0130] According to embodiments of this disclosure, R3 is selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more Rs. Z4 The following groups are substituted: C 1-12 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -C 1-12 Alkylene-C 3-12 cycloalkyl, -C 1-12 alkylene-(3-12 membered heterocyclic group), -C 1-12 Alkylene-C 6-12 Aryl, -C 1-12 alkylene-(5-12-membered heteroaryl), -OC 1-12 Alkyl, -OC 3-12 Cycloalkyl, -O-(3-12 membered heterocyclic), -OC 6-12 Aryl, -O-(5-12 heteroaryl), -SC 3-12 Cycloalkyl, -S-(3-12 membered heterocyclic groups), -SC 6-12 Aryl, -S-(5-12 heteroaryl), -NH-C 1-12 Alkyl, -NH-C 3-12 Cycloalkyl, -NH- (3-12 membered heterocyclic groups), -NH-C 6-12 Aryl, -NH- (5-12 heteroaryl).

[0131] According to embodiments of this disclosure, R3 is selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more Rs. Z4 The following groups are substituted: C 1-10 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, -C 1-10 Alkylene-C 3-10 cycloalkyl, -C 1-10 alkylene-(3-10 membered heterocyclic group), -C 1-10 Alkylene-C 6-10 Aryl, -C 1-10 alkylene-(5-10-membered heteroaryl), -OC 1-10 Alkyl, -OC 3-10 Cycloalkyl, -O- (3-10 membered heterocyclic groups), -OC 6-10 Aryl, -O-(5-10 heteroaryl), -SC 3-10Cycloalkyl, -S- (3-10 membered heterocyclic groups), -SC 6-10 Aryl, -S-(5-10 heteroaryl), -NH-C 1-10 Alkyl, -NH-C 3-10 Cycloalkyl, -NH- (3-10 membered heterocyclic groups), -NH-C 6-10 Aryl, -NH- (5-10 heteroaryl).

[0132] According to embodiments of this disclosure, R3 is selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more Rs. Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -C 1-6 Alkylene-C 3-6 cycloalkyl, -C 1-6 Alkylene-(3-6 membered heterocyclic group), -C 1-6 Alkylene-C 6-10 Aryl, -C 1-6 alkylene-(5-6-membered heteroaryl), -OC 1-6 Alkyl, -OC 3-6 Cycloalkyl, -O- (3-6 membered heterocyclic groups), -OC 6-10 Aryl, -O-(5-6 quinary heteroaryl), -SC 3-6 Cycloalkyl, -S- (3-6 membered heterocyclic groups), -SC 6-10 Aryl, -S-(5-6 membered heteroaryl), -NH-C 1-6 Alkyl, -NH-C 3-6 Cycloalkyl, -NH- (3-6 membered heterocyclic groups), -NH-C 6-10 Aryl, -NH- (5-6 membered heteroaryl).

[0133] According to embodiments of this disclosure, R3 is selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more Rs. Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -C 1-3 Alkylene-C 3-6 cycloalkyl, -C 1-3 Alkylene-(3-6 membered heterocyclic group), -C 1-3 Alkylene-C6-10 Aryl, -C 1-3 alkylene-(5-6-membered heteroaryl), -OC 1-6 Alkyl, -OC 3-6 Cycloalkyl, -O- (3-6 membered heterocyclic groups), -OC 6-10 Aryl, -O-(5-6 quinary heteroaryl), -SC 3-6 Cycloalkyl, -S- (3-6 membered heterocyclic groups), -SC 6-10 Aryl, -S-(5-6 membered heteroaryl), -NH-C 1-6 Alkyl, -NH-C 3-6 Cycloalkyl, -NH- (3-6 membered heterocyclic groups), -NH-C 6-10 Aryl, -NH- (5-6 membered heteroaryl).

[0134] According to embodiments of this disclosure, R3 is selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more Rs. Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -C 1-3 Alkylene-C 3-6 cycloalkyl, -C 1-3 Alkylene-(3-6 membered heterocyclic group), -C 1-3 Alkylene-C 6-10 Aryl, -C 1-3 alkylene-(5-6-membered heteroaryl), -OC 1-6 Alkyl, -OC 3-6 Cycloalkyl, -O- (3-6 membered heterocyclic groups), -OC 6-10 Aryl, -O-(5-6 quinary heteroaryl), -NH-C 1-6 Alkyl, -NH-C 3-6 Cycloalkyl, -NH- (3-6 membered heterocyclic groups), -NH-C 6-10 Aryl, -NH- (5-6 membered heteroaryl).

[0135] According to embodiments of this disclosure, R3 is selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more Rs. Z4 The following groups are substituted: C 1-6 Alkyl, -OC 1-6 alkyl.

[0136] According to embodiments of this disclosure, R3 is selected from: H, deuterium, halogens, and optionally substituted groups such as C. 1-6 Alkyl, -OC 1-6 alkyl.

[0137] According to the implementation scheme of this disclosure, R3 is selected from: H, F.

[0138] According to embodiments of this disclosure, R3 and R1, together with the atoms they are attached to, form optionally substituted or optionally occupied by one, two, three or more R atoms. ZZ3 The following groups are substituted: 8-15 membered fused heterocyclic groups, C 8-15 Fused ring groups; Each R ZZ3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and the following optional substituted groups: C 1-6 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic, phenyl, 5-6 membered heteroaryl, -C 1-3 Alkylene-C 3-6 cycloalkyl, -C 1-3 Alkylene-(3-6 membered heterocyclic group), -C 1-3 alkylene-phenyl, -C 1-3 alkylene-(5-6-membered heteroaryl), -OC 3-6 Cycloalkyl, -O-(3-6 membered heterocyclic), -O-phenyl, -O-(5-6 membered heteroaryl), -SC 3-6 Cycloalkyl, -S-(3-6 membered heterocyclic), -S-phenyl, -S-(5-6 membered heteroaryl), -NH-C 3-6 Cycloalkyl, -NH- (3-6 membered heterocyclic group), -NH-phenyl, -NH- (5-6 membered heteroaryl group).

[0139] According to the implementation scheme of this disclosure, Selected from optional substitutions or optional substitutions by one, two, three or more Rs ZZ3 The following groups are substituted: , , .

[0140] According to the implementation scheme of this disclosure, Selected from the following groups that can be substituted: , , .

[0141] According to the implementation scheme of this disclosure, Selected from the following groups that can be substituted: , , , , , , , , , , , , , , , , , , ;*end and or connect.

[0142] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring B is selected from a partially saturated C5-ring hydrocarbon ring; ring C is independently selected from a partially saturated, aromatic five-membered heterocycle. W1 and W4 may be the same or different, and each is independently selected from: O, S, N, NR wn1 C, CR wc1 CR wc2 R wc3 ; W2 and W3 may be the same or different, and each is independently selected from: C; W5 is selected from: N, C, CR wc1 ; W6 is selected from: CR wc2 R wc3 ; The ring C contains 1-3 heteroatoms; For definitions of other functional groups, please refer to the definitions above.

[0143] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring B is selected from a partially saturated five-membered heterocycle; ring C is independently selected from a partially saturated, aromatic five-membered heterocycle. W1 and W4 may be the same or different, and each is independently selected from: O, S, N, NR wn1 C, CR wc1 CR wc2 R wc3 ; W2 and W3 may be the same or different, and are independently selected from: N and C; W5 is selected from: N, C, CR wc1 ; W6 is selected from: O, S, NR wn1 CR wc2R wc3 ; The fused ring composed of ring B and ring C contains 2-4 heteroatoms; For definitions of other functional groups, please refer to the definitions above.

[0144] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring B is selected from a partially saturated C5-membered hydrocarbon ring; ring C is independently selected from an aromatic five-membered heterocycle. W1 and W4 may be the same or different, and each is independently selected from: O, S, N, NR wn1 C, CR wc1 ; W2 and W3 may be the same or different, and each is independently selected from: C; W5 is selected from: N, C; W6 is selected from: CR wc2 R wc3 ; The ring C contains 1-3 heteroatoms; For definitions of other functional groups, please refer to the definitions above. According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring B is selected from a partially saturated five-membered heterocycle; ring C is independently selected from an aromatic five-membered heterocycle; W1 and W4 may be the same or different, and each is independently selected from: O, S, N, NR wn1 C, CR wc1 ; W2 and W3 may be the same or different, and are independently selected from: N and C; W5 is selected from: N, C; W6 is selected from: O, S, NR wn1 CR wc2 R wc3 ; The fused ring composed of ring B and ring C contains 2-4 heteroatoms; For definitions of other functional groups, please refer to the definitions above.

[0145] According to the implementation scheme of this disclosure, It consists of the following groups: , , , .

[0146] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: , , , , , , , ; W7 is selected from: O, S, S(=O), S(=O)2, NR wn1 C (=O), CR wc2 R wc3 And W6 is selected from: C (=O), CR wc2 R wc3 ; Or W7 is selected from: C (=O), CR wc2 R wc3 And W6 is selected from: O, S, S(=O), S(=O)2, NR wn1 C (=O), CR wc2 R wc3 ; W8 is selected from: CR wc1 ; Other functional groups are defined as described above. According to embodiments of this disclosure, ring A is selected from the following optionally substituted functional groups: , , , , , , , ; W7 is selected from: O, S, S(=O), S(=O)2, CR wc2 R wc3 And W6 is selected from: CR wc2 R wc3 ; Or W7 is selected from: CR wc2 R wc3 And W6 is selected from: O, S, S(=O), S(=O)2; W8 is selected from: CR wc1 ; For definitions of other functional groups, please refer to the definitions above.

[0147] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: , , , , , , , ; W7 is selected from: O, S, S(=O), S(=O)2, CR wc2 R wc3 , where R wc2 Rwc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; and W6 is selected from: CR wc2 R wc3 , where R wc2 R wc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; Or W7 is selected from: CR wc2 R wc3 , where R wc2 R wc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 Cycloalkyl; and W6 is selected from: O, S, S(=O), S(=O)2; W8 is selected from: CR wc1 , where R wc1Selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R. Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; For definitions of other functional groups, please refer to the definitions above.

[0148] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; W1 is selected from: N, CR wc1 ; W7 is selected from: O, S, S(=O), S(=O)2, NR wn1 C (=O), CR wc2 R wc3 And W6 is selected from: C (=O), CR wc2 R wc3 ; Or W7 is selected from: C (=O), CR wc2 R wc3 And W6 is selected from: O, S, S(=O), S(=O)2, NR wn1 C (=O), CR wc2 R wc3 ; W8 is selected from: CR wc1 ; For definitions of other functional groups, please refer to the definitions above.

[0149] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; W1 is selected from: N, CR wc1 ; W7 is selected from: O, S, S(=O), S(=O)2, CR wc2 R wc3 And W6 is selected from: CR wc2 R wc3 ; Or W7 is selected from: CR wc2 R wc3 And W6 is selected from: O, S, S(=O), S(=O)2; W8 is selected from: CR wc1 ; For definitions of other functional groups, please refer to the definitions above.

[0150] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; W1 is selected from: N, CR wc1 , where R wc1 Selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R. Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; W7 is selected from: O, S, S(=O), S(=O)2, CR wc2 R wc3 , where R wc2 R wc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; and W6 is selected from: CR wc2 R wc3 , where R wc2 R wc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C1-6 Alkyl, -NH-C 3-6 cycloalkyl; Or W7 is selected from: CR wc2 R wc3 , where R wc2 R wc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 Cycloalkyl; and W6 is selected from: O, S, S(=O), S(=O)2; W8 is selected from: CR wc1 , where R wc1 Selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R. Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; For definitions of other functional groups, please refer to the definitions above.

[0151] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; W1 is selected from: CR wc2 R wc3 ; W7 is selected from: O, S, S(=O), S(=O)2, NR wn1 C (=O), CR wc2 R wc3 And W6 is selected from: C (=O), CR wc2 R wc3 ; Or W7 is selected from: C (=O), CR wc2 R wc3And W6 is selected from: O, S, S(=O), S(=O)2, NR wn1 C (=O), CR wc2 R wc3 ; W8 is selected from: CR wc1 ; For definitions of other functional groups, please refer to the definitions above.

[0152] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; W1 is selected from: CR wc2 R wc3 ; W7 is selected from: O, S, S(=O), S(=O)2, CR wc2 R wc3 And W6 is selected from: CR wc2 R wc3 ; Or W7 is selected from: CR wc2 R wc3 And W6 is selected from: O, S, S(=O), S(=O)2; W8 is selected from: CR wc1 ; For definitions of other functional groups, please refer to the definitions above.

[0153] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; W1 is selected from: CR wc2 R wc3 , where R wc2 R wc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; W7 is selected from: O, S, S(=O), S(=O)2, CR wc2 R wc3 , where R wc2 R wc3The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; and W6 is selected from: CR wc2 R wc3 , where R wc2 R wc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; Or W7 is selected from: CR wc2 R wc3 , where R wc2 R wc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 Cycloalkyl; and W6 is selected from: O, S, S(=O), S(=O)2; W8 is selected from: CR wc1 , where R wc1Selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R. Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; For definitions of other functional groups, please refer to the definitions above.

[0154] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; W1 is selected from: C(O) or CR wc1 ; W7 is selected from: CR wc2 R wc3 And W6 is selected from: CR wc2 R wc3 ; W8 is selected from: CR wc1 ; For definitions of other functional groups, please refer to the definitions above.

[0155] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; W1 is selected from: C(O) or CR wc1 Among them, R wc1 Selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R. Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; W7 is selected from: CR wc2 R wc3 ;where R wc2 R wc3The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; W6 is selected from: CR wc2 R wc3 ;where R wc2 R wc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; W8 is selected from: CR wc1 ;where R wc1 Selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R. Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; For definitions of other functional groups, please refer to the definitions above.

[0156] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; W4 is selected from: N, CR wc1 ; W7 is selected from: CR wc1 ; For definitions of other functional groups, please refer to the definitions above.

[0157] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; W4 is selected from: N, CR wc1 , where R wc1 Selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R. Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; W7 is selected from: CR wc1 , where R wc1 Selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R. Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; For definitions of other functional groups, please refer to the definitions above.

[0158] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; W1 is selected from: C(O); W4 is selected from: CR wc1 Or N; W7 is selected from: CR wc2 R wc3 And W6 is selected from: CR wc2 R wc3 ; W8 is selected from: CR wc1 ; For definitions of other functional groups, please refer to the definitions above.

[0159] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; W1 is selected from: C(O); W4 is selected from: CR wc1 Or N; W7 is selected from: CR wc2 R wc3 ;where R wc2 R wc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; W6 is selected from: CR wc2 R wc3 ;where R wc2 R wc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; W8 is selected from: CR wc1 ;where R wc1 Selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R. Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; For definitions of other functional groups, please refer to the definitions above.

[0160] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Among them, W6 is selected from: CR wc2 R wc3 ; W7 is selected from: CR wc2 R wc3 ; W8 is selected from: CR wc1 ; For definitions of other functional groups, please refer to the definitions above.

[0161] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Among them, W6 is selected from: CR wc2 R wc3 ; W7 is selected from: CR wc2 R wc3 ; W8 is selected from: CR wc1 ; Each R wc1 R wc2 R wc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; For definitions of other functional groups, please refer to the definitions above.

[0162] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Among them, W6 is selected from: CR wc2 R wc3 ;where R wc2 R wc3The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; W7 is selected from: CR wc2 R wc3 ;where R wc2 R wc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; W8 is selected from: CR wc2 R wc3 or NR wn1 ;where R wc3 Selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R. Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; R wc2 And R1, or R wn1 R1, together with the atoms to which it is attached, forms an optionally substituted or optionally substituted atom by one, two, three or more R atoms. ZZ3 The following groups are substituted: 8-15 membered fused heterocyclic groups, C8-15 Fused ring groups; Each R ZZ3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and the following optional substituted groups: C 1-6 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic, phenyl, 5-6 membered heteroaryl, -C 1-3 Alkylene-C 3-6 cycloalkyl, -C 1-3 Alkylene-(3-6 membered heterocyclic group), -C 1-3 alkylene-phenyl, -C 1-3 alkylene-(5-6-membered heteroaryl), -OC 3-6 Cycloalkyl, -O-(3-6 membered heterocyclic), -O-phenyl, -O-(5-6 membered heteroaryl), -SC 3-6 Cycloalkyl, -S-(3-6 membered heterocyclic), -S-phenyl, -S-(5-6 membered heteroaryl), -NH-C 3-6 Cycloalkyl, -NH- (3-6 membered heterocyclic group), -NH-phenyl, -NH- (5-6 membered heteroaryl); Preferably, R wc2 And R1, or R wn1 R1, together with the atoms to which it is attached, forms an optionally substituted or optionally substituted atom by one, two, three or more R atoms. ZZ3 The following groups are substituted: , ; For definitions of other functional groups, please refer to the definitions above.

[0163] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Among them, W6 is selected from: CR wc2 R wc3 ;where R wc2 R wc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C3-6 cycloalkyl; W7 is selected from: CR wc2 R wc3 ;where R wc3 Selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R. Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; R wc2 R1 and the atoms to which it is attached form an optionally substituted or optionally substituted atom by one, two, three or more R atoms. ZZ3 The following groups are substituted: 8-15 membered fused heterocyclic groups, C 8-15 Fused ring groups; Preferably, R wc2 R1 and the atoms to which it is attached form an optionally substituted or optionally substituted atom by one, two, three or more R atoms. ZZ3 The following groups are substituted: , , ; W8 is selected from: CR wc1 Or N; where R wc1 Selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R. Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; Each R ZZ3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and the following optional substituted groups: C 1-6 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic, phenyl, 5-6 membered heteroaryl, -C1-3 Alkylene-C 3-6 cycloalkyl, -C 1-3 Alkylene-(3-6 membered heterocyclic group), -C 1-3 alkylene-phenyl, -C 1-3 alkylene-(5-6-membered heteroaryl), -OC 3-6 Cycloalkyl, -O-(3-6 membered heterocyclic), -O-phenyl, -O-(5-6 membered heteroaryl), -SC 3-6 Cycloalkyl, -S-(3-6 membered heterocyclic), -S-phenyl, -S-(5-6 membered heteroaryl), -NH-C 3-6 Cycloalkyl, -NH- (3-6 membered heterocyclic group), -NH-phenyl, -NH- (5-6 membered heteroaryl); For definitions of other functional groups, please refer to the definitions above.

[0164] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: , , , , , , , , , , , , , , , , ; For definitions of other functional groups, please refer to the definitions above.

[0165] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: , , , ; , , , ; , , , ; , , , ; , , , ; , , , ; , , , ; , , , ; , , , ; , , , ; , ; , ; , ; , , , ; , , , ; , , , ; For definitions of other functional groups, please refer to the definitions above.

[0166] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring D is selected from aromatic five-membered heterocycles, and ring D contains 1-3 heteroatoms; W 10 W 11 W 12 Same or different, and independently selected from: O, S, N, NR wn1 C, CR wc1 ; For definitions of other functional groups, please refer to the definitions above.

[0167] According to the implementation scheme of this disclosure, Selected from unsubstituted or arbitrarily assigned to one, two or more R wn1 Or R wc1 The following groups are substituted: 5-membered heteroaryl; for example, selected from unsubstituted or optionally substituted with one, two or more R groups. wn1 Or R wc1 The following groups may be substituted: oxazolyl, thiazolyl, pyrazolyl, dihydropyrazolyl, imidazoleyl, dihydroimidazolyl, isoxazolyl, pyrroleyl; if selected from: , , , , , , ;*end and or connect.

[0168] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring D is selected from aromatic five-membered heterocycles, and ring D contains 1-3 heteroatoms; W 10 Selected from: O, S, N, NR wn1 C, CR wc1 ; W 11 Selected from: N, C, CR wc1 ; W 10 Selected from: O, S, N, NR wn1 C, CR wc1 ; For definitions of other functional groups, please refer to the definitions above.

[0169] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring D is selected from aromatic five-membered heterocycles, and ring D contains 1-3 heteroatoms; W 10 Selected from: O, S, N, NR wn1 C, CR wc1 ; W 11 Selected from: N, C; W 10 Selected from: O, S, N, NR wn1 C, CR wc1 ; For definitions of other functional groups, please refer to the definitions above.

[0170] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: , , , ; For definitions of other functional groups, please refer to the definitions above.

[0171] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: , ; W 10 Selected from: O, S, NR wn1 ; For definitions of other functional groups, please refer to the definitions above.

[0172] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: , ; W 10 Selected from: O, S, NR wn1 , where R wn1 Selected from: H, deuterium, and optionally substituted or optionally replaced by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl; For definitions of other functional groups, please refer to the definitions above.

[0173] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring E is selected from saturated, partially saturated, and aromatic five-membered heterocycles; ring E contains 1-3 heteroatoms; W 14 W 15 W 16 W 17 Same or different, and independently selected from: O, S, S(=O), S(=O)2, N, NR wn1 C, C (=O), CR wc1 CR wc2 R wc3 ; W 13 Same or different, and independently selected from: N, C, CR wc1 ; For definitions of other functional groups, please refer to the definitions above.

[0174] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring E is selected from saturated, partially saturated, and aromatic five-membered heterocycles; ring E contains 1-3 heteroatoms; W 14 W 15 W 16 W 17 Same or different, and independently selected from: O, S, S(=O), S(=O)2, N, NR wn1 C, C (=O), CR wc1 CR wc2 R wc3 ; W 13 Same or different, and independently selected from: N, C, CR wc1 .

[0175] According to the implementation scheme of this disclosure, Selected from unsubstituted or arbitrarily assigned to one, two or more R wn1 Or R wc1 The following groups may be substituted: 5-membered heterocyclic groups, 5-membered heteroaryl groups; for example, selected from unsubstituted groups or optionally substituted with one, two or more R groups. wn1 Or R wc1 The following groups may be substituted: pyrazolyl, dihydropyrazolyl, tetrahydropyrrole, oxazolyl, triazolyl, oxadiazolyl; if selected from: , , , , , , ;*end and or connect.

[0176] According to the implementation scheme of this disclosure, Selected from the following groups that can be substituted: , , , , , , , , , , ;*end and or connect.

[0177] According to the implementation scheme of this disclosure, It is selected from the following groups: U1 is selected from: O, S; R2 is selected from: optional substitutions or optional substitutions by one, two, three or more Rs. Z2 The following groups are substituted: C 3-6 Monocycloalkyl, C 5-10 Fused cycloalkyl groups, C 5-10 Spirocycloalkyl, C 5-10 Bridged cycloalkyl, 3-6 membered heterocyclic, 5-10 membered fused-ring heterocyclic, 5-10 membered spirocyclic heterocyclic, 5-10 membered bridged-ring heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl; Each R Z2 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and optionally substituted or optionally influenced by one, two, three or more Rs. ZZ1 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -C 1-2 Alkylene-C 3-6 cycloalkyl, -C 1-2 Alkylene-(3-6 membered heterocyclic group), -C 1-2 Alkylene-C 6-10 Aryl, -C 1-2 alkylene-(5-6-membered heteroaryl), -OC 1-6 Alkyl, -OC 3-6 Cycloalkyl, -O-3-6-membered heterocyclic groups, -NH-C 1-6 Alkyl, -NH-C 3-6 Cycloalkyl, -NH-3-6-membered heterocyclic group, -N(C 1-6 Alkyl)2、-C(O)-C 1-6 Alkyl, -C(O)-C 3-6 Cycloalkyl, -C(O)-3-6-membered heterocyclic groups, -C(O)NH2, -C(O)-NH-C 1-6 alkyl.

[0178] According to the implementation scheme of this disclosure, Selected from the following groups that can be substituted: ; Ring E is selected from saturated, partially saturated, and aromatic five-membered heterocycles; ring E contains 1-3 heteroatoms; W 13 Selected from: C, CR wc1 Among them, R wc1Selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R. Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; W 14 Selected from: N, NR wn1 CR wc1 CR wc2 R wc3 Among them, R wc1 R wc2 R wc3 R wn1 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; W 15 Selected from: N, NR wn1 CR wc1 CR wc2 R wc3 Among them, R wc1 R wc2 R wc3 R wn1 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; or, R wn1 and R1, or R wc1 and R1, or R wc2 R1, together with the atoms to which it is attached, forms an optionally substituted or optionally substituted atom by one, two, three or more R atoms. ZZ3 The following groups are substituted: 8-15 membered fused heterocyclic groups, C 8-15 Fused cyclic group; preferably, R wn1 and R1, or R wc1 and R1, or R wc2 R1, together with the atoms to which it is attached, forms an optionally substituted or optionally substituted atom by one, two, three or more R atoms. ZZ3 The following groups are substituted: , , , , , ; W 16 Selected from: C, CR wc1 Or N; where R wc1 Selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R. Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; W 17 Selected from: N, NR wn1 CR wc1 CR wc2 R wc3 Among them, R wc1 R wc2 R wc3 R wn1 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; For definitions of other functional groups, please refer to the definitions above.

[0179] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Among them, W 13 Selected from: N; W 17 Selected from: CR wc1 R1 and R wc1 Together with the atoms they are attached, they form optionally substituted or optionally substituted by one, two, three or more R atoms. ZZ3 The following groups are substituted: 8-15 membered fused heterocyclic groups, C 8-15 Fused cyclic group; preferably, R1 and R wc1 Together with the atoms to which they are attached, they form the following optionally substituted groups: , , , , , ; For definitions of other functional groups, please refer to the definitions above.

[0180] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; W 15 Selected from: NR wn1 Among them, R wn1 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-6 Alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl, 5-6 quinone heteroaryl, -OC 1-6 Alkyl, -OC 3-6 cycloalkyl, -NH-C 1-6 Alkyl, -NH-C 3-6 cycloalkyl; or, R wn1 R1 and the atoms to which it is attached form an optionally substituted or optionally substituted atom by one, two, three or more R atoms. ZZ3 The following groups are substituted: 8-15 membered fused heterocyclic groups, C 8-15Fused cyclic group; preferably, R wn1 R1 and the atoms to which it is attached form an optionally substituted or optionally substituted atom by one, two, three or more R atoms. ZZ3 The following groups are substituted: , , , , , ; For other definitions, please refer to the definitions above.

[0181] According to the implementation scheme of this disclosure, It is selected from the following groups: U1 is selected from: O; R2 is selected from: optional substitutions or optional substitutions by one, two, three or more Rs. Z2 The following groups are substituted: , , , , , , , , , , , , , , , , , , , , , , , , , , , , ; Each R Z2 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and optionally substituted or optionally influenced by one, two, three or more Rs. ZZ1The following groups are substituted: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, hydroxymethyl, hydroxyethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, propoxy, methylthio, ethylthio, propylthio, cyclopropoxy, cyclopropylthio, cyclopropylamino, -NHCH3, -NHCH2CH3, -N(CH3)2, -N(CH2CH3) )2、-C(O)CH3、-CO2CH3、-CONH2、-CONHCH3、-CON(CH3)2、propidinyl、azacyclobutyl、oxacyclobutyl、thiocyclobutyl、tetrahydrofuranyl、pyrrolidinyl、tetrahydropyranyl、piperidinyl、piperazinyl、morpholinyl、thiomorpholinyl、homoperazinyl、homoperidinyl、azacycloheptyl、oxacycloheptyl、phenyl、naphthyl、furanyl、thienyl、oxazolyl、thiazolyl、imidazolyl、pyrazolyl、isothiazolyl、isooxazolyl、triazolyl.

[0182] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring F is selected from saturated, partially saturated, aromatic C5-ring hydrocarbon rings or five-membered heterocycles; Ring G is selected from saturated, partially saturated, aromatic C6-ring hydrocarbon rings or six-membered heterocycles; W 18 W 19 W 22 W 23 W 24 W 25 Same or different, and independently selected from: O, S, S(=O), S(=O)2, N, NR wn1 C, C (=O), CR wc1 CR wc2 R wc3 ; W 20、 W 21、 W 26 Same or different, and independently selected from: N, C, CR wc1 ; The fused ring composed of ring F and ring G contains 1-4 heteroatoms; For definitions of other functional groups, please refer to the definitions above.

[0183] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring F is selected from saturated C5-ring hydrocarbon rings or five-membered heterocycles; Ring G is selected from partially saturated, aromatic C6-ring hydrocarbons or six-membered heterocycles; W 18 W19 Same or different, and independently selected from O, S, NR wn1 C (=O) or CR wc2 R wc3 ; W 22 W 23 W 24 W 25 Same or different, and independently selected from: N, NR wn1 C (=O), CR wc1 CR wc2 R wc3 ; W 20、 W 21、 W 26 Same or different, and independently selected from: N, C, CR wc1 ; The fused ring composed of ring F and ring G contains 2-4 heteroatoms; For definitions of other functional groups, please refer to the definitions above.

[0184] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; Ring F is selected from saturated C5-ring hydrocarbon rings or five-membered heterocycles; Ring G is selected from partially saturated, aromatic C6-ring hydrocarbons or six-membered heterocycles; W 18 W 19 Same or different, and independently CR wc2 R wc3 ; W 22 W 23 W 24 W 25 Same or different, and independently selected from: N, NR wn1 C (=O), CR wc1 CR wc2 R wc3 ; W 20、 W 21、 W 26 Same or different, and independently selected from: N, CR wc1 ; The fused ring composed of ring F and ring G contains 2-4 heteroatoms; For definitions of other functional groups, please refer to the definitions above.

[0185] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: ; W 22 Selected from: C(=O), CRwc2 R wc3 ; W 23 Selected from: NR wn1 CR wc2 R wc3 ; W 24 Selected from: N, CR wc1 ; W 25 Selected from: N, CR wc1 ; For definitions of other functional groups, please refer to the definitions above.

[0186] According to embodiments of this disclosure, ring A is selected from the following optionally substituted groups: The definition of R1 is the same as the definition above.

[0187] According to embodiments of this disclosure, the compound represented by formula (M-1) has the following structure: Formula (I'), Among them, rings B, C, R1, R, R3, W1, W2, W3, W4, W5, and W6 each have the definitions described above independently.

[0188] According to embodiments of this disclosure, the compound represented by formula (M-1) has the following structure: , , , , , , , , , , , ; Among them, R, R1, R3, R wc1 They each possess the definitions described above independently.

[0189] According to embodiments of this disclosure, the compound represented by formula (M-1) has the following structure: , , , Among them, rings C, R, R3, and R z1 W1, W2, W4, and W5 are independently defined as described above; m is selected from 0, 1, or 2.

[0190] According to embodiments of this disclosure, the compound represented by formula (M-1) has the following structure: Equation (II'), Among them, ring F, ring G, R1, R, W 18 W 19 W 20 W 21 W 22 W 23、 W 24 W 25 W 26 They each possess the definitions described above independently.

[0191] According to embodiments of this disclosure, the compound represented by formula (M-1) has the following structure: Equation (II'-1), Among them, R and R1 independently have the definitions described above.

[0192] According to embodiments of this disclosure, the compound represented by formula (M-1) has the following structure: , , , ; Among them, rings G, R, and R z1 W 22 W 23 W 24 W 25 Each has the definition described above independently; m is selected from 0, 1, or 2.

[0193] According to embodiments of this disclosure, the compound represented by formula (M-1) or formula (M) has the following structure: Formula (I) Among them, rings B, C, R1, R2, R3, W1, W2, W3, W4, W5, W6, and U1 each have the definitions described above independently.

[0194] According to embodiments of this disclosure, the compound represented by formula (M-1) or formula (M) has the following structure: , , , , , , , , , Among them, R1, R2, R3, and U1 have the definitions described above independently.

[0195] According to embodiments of this disclosure, the compound represented by formula (M-1) or formula (M) has the following structure: , , , Among them, rings C, R2, R3, and R z1 W1, W2, W4, W5, and U1 each have the definitions described above independently; m is selected from 0, 1, or 2.

[0196] According to embodiments of this disclosure, the compound represented by formula (M-1) or formula (M) has the following structure: Equation (II) Among them, rings B, C, R1, R2, W1, W2, W3, W4, W5, W6, W7, W8, and U1 each have the definitions described above independently.

[0197] According to embodiments of this disclosure, the compound represented by formula (M-1) or formula (M) has the following structure: Among them, R1, R2, and U1 have the definitions described above independently of each other.

[0198] According to embodiments of this disclosure, the compound represented by formula (M-1) or formula (M) has the following structure: Equation (III) Among them, rings D, R1, R2, and R 31 W 10 W 11 W 12 U1 and U2 have the definitions described above independently of each other.

[0199] According to embodiments of this disclosure, the compound represented by formula (M-1) or formula (M) has the following structure: , , , , , , , Among them, R1, R2, R 31 R wn1 U1 and U2 have the definitions described above independently of each other.

[0200] According to embodiments of this disclosure, the compound represented by formula (M-1) or formula (M) has the following structure: , , , Among them, rings D, R2, and R 31 R z1 W 10 W 11 W 12 U1 and U2 have the definitions described above independently of each other.

[0201] According to embodiments of this disclosure, the compound represented by formula (M-1) or formula (M) has the following structure: Formula (IV), Among them, rings E, R1, R2, and R 41 W 13 W 14 W 15 W 16 W 17 U1 and U2 have the definitions described above independently of each other.

[0202] According to embodiments of this disclosure, the compound represented by formula (M-1) or formula (M) has the following structure: , , , , , , , Among them, R1, R2, U1, R 41 R wn1 R wc2 They each possess the definitions described above independently.

[0203] According to embodiments of this disclosure, the compound represented by formula (M-1) or formula (M) has the following structure: , , , , , Among them, R1, R 41 R wn1 They each possess the definitions described above independently.

[0204] According to embodiments of this disclosure, the compound represented by formula (M-1) or formula (M) has the following structure: , , , , , , , Among them, rings E and R z1 W 14 W 15 W 17 They each possess the definitions described above independently.

[0205] According to embodiments of this disclosure, the compound represented by formula (M-1) or formula (M) has the following structure: Among them, rings R2, R3, and R z1 They each possess the definitions described above independently.

[0206] According to embodiments of this disclosure, the compound represented by formula (M-1) or formula (M) has the following structure: ; Among them, rings R2, R3, and R z1 They each possess the definitions described above independently.

[0207] According to embodiments of this disclosure, the compound represented by formula (M-1) or formula (M) is selected from the following compounds: Table 1

[0208]

[0209]

[0210]

[0211]

[0212]

[0213]

[0214]

[0215]

[0216]

[0217]

[0218]

[0219] This disclosure also provides a pharmaceutical composition comprising at least one of the compounds represented by formula (M-1) or formula (M) or a pharmaceutically acceptable salt thereof.

[0220] According to embodiments of this disclosure, the pharmaceutical composition further comprises pharmaceutically acceptable excipients, such as carriers or excipients.

[0221] This disclosure also provides a method for preventing and / or treating diseases or conditions associated with RIPK1 kinase, comprising administering at least one of the compounds of formula (M-1) or formula (M) or a pharmaceutically acceptable salt thereof to a patient in need.

[0222] This disclosure also provides the use of at least one of the compounds of formula (M-1) or formula (M) or a pharmaceutically acceptable salt thereof in the prevention and / or treatment of diseases or conditions associated with RIPK1 kinase.

[0223] This disclosure also provides the use of at least one of the compounds of formula (M-1) or formula (M) or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the prevention and / or treatment of diseases or conditions associated with RIPK1 kinase.

[0224] According to the technical solution of this disclosure, the diseases or conditions related to RIPK1 kinase are selected from: inflammation, autoimmune diseases, cancer, infection, central nervous system diseases, metabolic diseases, cardiovascular diseases, respiratory diseases, liver diseases, kidney diseases, eye diseases, lymphatic diseases, psychological disorders, graft-versus-host disease, and abnormal pain.

[0225] According to the technical solution of this disclosure, the diseases or conditions related to RIPK1 kinase are selected from: sepsis, rheumatoid arthritis, inflammatory bowel disease, Parkinson's disease, Lewy body dementia, multiple system atrophy, Parkinson's plus syndrome, tau protein disease, Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, spinal muscular atrophy, primary lateral sclerosis, Huntington's disease, ischemia, stroke, intracranial hemorrhage, cerebral hemorrhage, muscular dystrophy, progressive muscular atrophy, pseudobulbar palsy, progressive bulbar palsy, spinal muscular atrophy, hereditary muscular atrophy, peripheral neuropathy, progressive supranuclear palsy, corticobasal degeneration and demyelinating diseases.

[0226] Terminology Definitions and Explanations The compounds defined or disclosed in this invention include all their stereoisomers, optical isomers, and racemic forms (if such isomers are present). Unless otherwise stated, all chiral (enantiomers and diastereomers) and racemic forms are within the scope of this invention. The compounds of this invention can be isolated in their optically active or racemic forms. The optically active forms can be prepared by resolving the racemic form or by synthesis from optically active raw materials. All methods used to prepare the compounds of this invention and the intermediates prepared therein are considered part of this invention. When preparing enantiomers or diastereomers, they can be isolated by conventional methods, such as chromatography or fractional crystallization.

[0227] The compounds defined or disclosed in this invention may also exist in various geometrical isomers such as C=C double bonds, C=N double bonds, and ring systems, and all the stable isomers described herein are included in this invention. Cis and trans (or E-type and Z-type) geometrical isomers of the compounds of this invention are described and can be separated into mixtures of isomers or separated isomeric forms.

[0228] The compounds defined or disclosed in this invention may exist in various tautomeric forms, wherein hydrogen atoms are transferred to other parts of the molecule and the chemical bonds between atoms in the molecule are rearranged as a result. It should be understood that all tautomeric forms are included in this invention as long as they can exist.

[0229] The compounds defined or disclosed in this invention may exist in free form or as pharmaceutically acceptable salts, and therefore both free form and salts are within the scope of this invention. One form of a compound may be converted into another form as needed. Free bases or acids may be converted into salts; salts may be converted into free compounds or another type of salt.

[0230] The compounds described herein may contain one or more isotopic substitutions. For example, H may be in any isotopic form, including 1 H, 2 H (D or deuterium) and 3 H (T or tritium); C can exist in any isotopic form, including 12 C 13 C and 14 C and O can exist in any isotopic form, including 16 O and 18 O etc.

[0231] When listing a range of values, the intention is to cover every value and subrange within that range. For example, "C1-C 20 The group "" is intended to cover C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 C 11 C 12 C 13 C 14 C15 C 16 C 17 C 18 C 19 C 20 And any range of the above point value combinations.

[0232] The term "alkyl" refers to a saturated straight-chain or branched monovalent hydrocarbon group containing 1 to 20 carbon atoms (C1-C2). 20 In some embodiments, the alkyl group is C1-C. 12 C1-C 10 C1-C8, C1-C6, C1-C5, C1-C4, or C1-C3. Examples of alkyl groups include methyl (Me), ethyl (Et), 1-propyl (n-Pr), 2-propyl (i-Pr), 1-butyl (n-Bu), 2-methyl-1-propyl (-CH2CH(CH3)2), 2-butyl (-CH(CH3)CH2CH3), 2-methyl-2-propyl (-C(CH3)3), 1-pentyl (-CH2CH2CH2CH2CH3), 2-pentyl (-CH(CH3)CH2CH2CH3), 3-pentyl (-CH( CH2CH3)2), 2-methyl-2-butyl (-C(CH3)2CH2CH3), 3-methyl-2-butyl (-CH(CH3)CH(CH3)2), 3-methyl-1-butyl (-CH2CH2CH(CH3)2), 2-methyl-1-butyl (-CH2CH(CH3)CH2CH3), 1-hexyl (-CH2CH2CH2CH2CH2CH3), 2-hexyl (-CH(CH3)CH2CH2CH2CH3), 3 -hexyl(-CH(CH2CH3)(CH2CH2CH3)), 2-methyl-2-pentyl(-C(CH3)2CH2CH2CH3), 3-methyl-2-pentyl(-CH(CH3)CH(CH3)CH2CH3), 4-methyl-2-pentyl(-CH(CH3)CH2CH(CH3)2), 3-methyl-3-pentyl(-C(CH3)(CH2CH3)2), 2-methyl-3-pentyl(-CH(CH2CH3)CH(C H3)2), 2,3-dimethyl-2-butyl (-C(CH3)2CH(CH3)2), 3,3-dimethyl-2-butyl (-CH(CH3)C(CH3)3), 1-heptyl, and 1-octyl. The alkyl group may be optionally substituted independently in each case; in some embodiments, "optionally substituted alkyl" means substituted with 1, 2, 3, 4, or 5 substituents, such as 1-2, 1-3, or 1-4 substituents selected from groups specified herein (see the definition of "optionally substituted").

[0233] The term "alkenyl" refers to a straight-chain or branched monovalent hydrocarbon group having at least one carbon-carbon double bond, containing 2 to 20 carbon atoms (C2-C2). 20 It includes groups having "cis" and "trans" orientations or alternatively "E" and "Z" orientations. In one embodiment, the alkenyl group is C2-C. 12 C2-C 10 C2-C8, C2-C6, or C2-C3. Examples include, but are not limited to, vinyl (-CH=CH2), propenyl (-CH=CHCH3), propenyl (-CH2CH=CH2), 2-methylpropenyl, butenyl, butenyl, butenyl, butenyl, butenyl, 1,3-dienyl, 2-methylbutenyl, hexenyl, hexenyl, hexenyl, hexenyl, hexenyl, hexenyl, hexenyl, hexenyl, and hexenyl-1,3-dienyl. The alkenyl group may be optionally substituted independently in each case; in some embodiments, "optionally substituted alkenyl" means substituted with 1, 2, 3, 4, or 5 substituents, such as 1-2, 1-3, or 1-4 substituents selected from groups specified herein (see the definition of "optionally substituted").

[0234] The term "alkynyl" refers to a straight-chain or branched monovalent hydrocarbon group having at least one carbon-carbon triple bond, containing 2 to 20 carbon atoms (C2-C2). 20 In some implementations, the alkynyl group is C2-C. 12 C2-C 10 C2-C8, C2-C6, or C2-C3. Examples include, but are not limited to, ethynyl (-C≡CH), propynyl (-C≡CCH3), propynyl (propynyl, -CH2C≡CH), butynyl, butynyl, and butynyl-3. The ynyl group may be optionally substituted independently in each case; in some embodiments, "optionally substituted ynyl" means substituted with 1, 2, 3, 4, or 5 substituents, such as 1-2, 1-3, or 1-4 substituents selected from groups specified herein (see the definition of "optionally substituted").

[0235] The term "heteroalkyl" refers to a straight-chain or branched monovalent hydrocarbon group comprising 2 to 20 atoms (2-20-membered), wherein 1 to 5 atoms are heteroatoms selected from O, N, Si, S, and P. The N, Si, S, and P may optionally be oxidized, for example, SO, SO2, PO, PO2; or N may optionally be substituted, as defined by "optionally substituted". In some embodiments, the heteroalkyl group comprises 2 to 12 atoms (2-12-membered), wherein 1 to 3 atoms are heteroatoms selected from O, N, Si, S, and P. In some embodiments, the heteroalkyl group comprises 2 to 6 atoms (2-6-membered), wherein 1 to 2 atoms are heteroatoms selected from O, N, Si, S, and P. Heteratoms may be located at any internal position of the heteroalkyl group, including where the alkyl group is attached to the remainder of the molecule (e.g., -O-CH2-CH3). Exemplary heteroalkyl groups include, but are not limited to: -CH2-CH2-O-CH3, -CH2-CH2-NH-CH3, -CH2-CH2-N(CH3)-CH3, -CH2-S-CH2-CH3, -CH2-CH2, -S(O)2, -S(O)-CH3, -S(O)2-CH2, -CH2-CH2-S(O)2-CH3, -CH=CH-O-CH3, -Si(CH3)3, -CH2-CH=N-OCH3, -CH=CH-N(CH3)-CH3, -O-CH3, and -O-CH2-CH3. At most two or three heteroatoms may be consecutive, for example, -CH2-NH-OCH3 and -CH2-O-Si(CH3)3. In each case, the heteroalkyl group may be optionally substituted independently. In some embodiments, "optionally substituted heteroalkyl" means substituted with 1, 2, 3, 4 or 5 substituents, such as 1-2, 1-3 or 1-4 substituents, selected from groups specified herein (see the definition of "optionally substituted").

[0236] The term "cycloalkyl" refers to any monocyclic, bicyclic, tricyclic, or polycyclic, saturated or partially unsaturated cyclic hydrocarbon group containing 3 to 20 cyclic carbon atoms (C3-C4). 20 The cycloalkyl group can be a monocyclic cycloalkyl, fused cycloalkyl, spirocycloalkyl, or bridged cycloalkyl group; the cycloalkyl ring carbon atom may optionally be substituted with 1, 2, or 3 oxo groups to form a cycloketene structure. In some embodiments, the cycloalkyl group is C3-C6. 14 C3-C 12 C3-C 10 C3-C8, C3-C6 or C5-C 10In some embodiments, the cycloalkyl group may optionally include 1-3 double bonds. The cycloalkyl group may be optionally substituted independently in each case, and in some embodiments, "optionally substituted cycloalkyl group" is a group substituted with 1, 2, 3, 4 or 5 substituents, such as 1-2, 1-3 or 1-4 substituents, selected from groups specified herein (see the definition of "optionally substituted").

[0237] In some implementations, the cycloalkyl group is "C3-C 12 "Monocyclic cycloalkyl", preferably C3-C 10 Monocyclic cycloalkyl or C3-C6 monocyclic cycloalkyl, more preferably C3, C4, C5 or C6 monocyclic cycloalkyl. Examples of monocyclic cycloalkyl include, but are not limited to: cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopent-1-enyl, 1-cyclopent-2-enyl, 1-cyclopent-3-enyl, cyclohexyl, deuterated cyclohexyl, 1-cyclohex-1-enyl, 1-cyclohex-2-enyl, 1-cyclohex-3-enyl, cyclohexadienyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl and cyclododecyl, etc.

[0238] In some implementations, the cycloalkyl group is "C5-C 14 "Spirocycloalkyl", preferably C6-C 12 Spirocycloalkyl or C7-C 10 Spirocycloalkyl, more preferably C6, C7, C8, C9, C 10 C 11 Or C 12 Spirocycloalkyl. Examples of spirocycloalkyl include, but are not limited to: spiro[2.2]pentane, spiro[2.3]hexane, spiro[2.4]heptane, spiro[2.5]octane, spiro[3.3]heptane, spiro[3.4]octane, spiro[3.5]nonane, spiro[3.6]decane, spiro[3.7]undecane, spiro[4.4]nonane, spiro[4.5]decane, spiro[4.6]undecane, spiro[4.7]dodecane, spiro[5.5]undecane, spiro[5.6]dodecane, spiro[5.7]tridecane, spiro[6.6]tridecane, and spiro[6.7]tetradecane.

[0239] In some implementations, the cycloalkyl group is "C5-C 14 "Polycyclic alkyl", preferably C6-C 12 Polycyclic alkyl or C7-C 10 Fused cycloalkyl groups, more preferably C6, C7, C8, C9, ... 10 C 11 Or C 12 Fused cyclic alkyl groups. Examples of fused cyclic alkyl groups include, but are not limited to: , , , , , , , , , , , , , , .

[0240] In some implementations, the cycloalkyl group is "C5-C 14 "Bridged cycloalkyl", preferably C6-C 12 Bridged cycloalkyl or C7-C 10 Bridged cycloalkyl groups, more preferably C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C10 ...1, C16, C18, C19, C10, C11, C19, C10, C11, C19, C1 10 C 11 Or C 12 Bridged cycloalkyl groups. Examples of bridged cycloalkyl groups include, but are not limited to: , , , , , , , , , , , .

[0241] In some embodiments, "cycloalkyl" also includes a ring system fused with one or more aryl groups as defined above, wherein the connection point is on the cycloalkyl ring.

[0242] The term "heterocyclic group" or "heterocyclic alkyl group" means any monocyclic, bicyclic, tricyclic, or polycyclic, saturated or partially unsaturated heterocyclic system comprising 3 to 20 ring atoms (3-20 members), wherein 1 to 5 ring atoms are heteroatoms selected from O, N, Si, S, and P. The heterocyclic group can be a monocyclic heterocyclic group, a fused-ring heterocyclic group, a spirocyclic heterocyclic group, or a bridged-ring heterocyclic group. The ring carbon atoms of the heterocyclic group may optionally be substituted with 1, 2, or 3 oxo groups to form a cyclic ketone, cyclic lactone, or cyclic lactam structure; the N, Si, S, and P may optionally be oxidized, for example, SO, SO2, PO, PO2; or N may optionally be substituted, with the substituent defined as "optionally substituted". In some embodiments, the heterocyclic group comprises 3 to 14 ring atoms (3-14 members), wherein 1 to 3 atoms are heteroatoms selected from O, N, Si, S, and P. In some embodiments, the heterocyclic group comprises 3 to 12 ring atoms (tertiary-12-membered), wherein 1 to 3 of these atoms are heteroatoms selected from O, N, Si, S, and P. In some embodiments, the heterocyclic group comprises 3 to 10 ring atoms (tertiary-10-membered), wherein 1 to 3 of these atoms are heteroatoms selected from O, N, Si, S, and P. In some embodiments, the heterocyclic group comprises 3 to 6 ring atoms (tertiary-6-membered), wherein 1 to 2 of these atoms are heteroatoms selected from O, N, Si, S, and P. In other embodiments, the heterocyclic group is a 5-20-membered, 5-14-membered, 5-12-membered, 5-10-membered, 5-9-membered, 5-8-membered, 5-7-membered, or 5-6-membered heterocyclic group, wherein 1 to 5, 1 to 3, or 1 to 2 of these ring atoms are heteroatoms selected from O, N, Si, S, and P. In other embodiments, the heterocyclic group is a 5-membered, 6-membered, 7-membered, 8-membered, 9-membered, 10-membered, 11-membered, 12-membered, 13-membered, or 14-membered heterocyclic group, wherein one, two, three, four, or five ring atoms are heteroatoms selected from O, N, Si, S, and P. In some embodiments, the heterocyclic group may also optionally include one to three double bonds. The heterocyclic group may be optionally substituted independently in each case; in some embodiments, an "optionally substituted heterocyclic group" is a heterocyclic group substituted with one, two, three, four, or five substituents, such as 1-2, 1-3, or 1-4 substituents, selected from groups specified herein (see the definition of "optionally substituted").

[0243] In some embodiments, "heterocyclic group" or "heterocyclic alkyl group" is "3-12 membered monocyclic heterocyclic group", preferably 3-10 membered monocyclic heterocyclic group or 3-6 membered monocyclic heterocyclic group, more preferably 3 membered, 4 membered, 5 membered or 6 membered monocyclic heterocyclic group, wherein 1, 2, 3 or 4 ring atoms are heteroatoms selected from O, N, Si, S and P. Examples of monocyclic heterocyclic groups include, but are not limited to: oxetane, thiohepane, azirone, oxetane, thiohepane, azirone, pyrrolyl, pyrrolidone (e.g., pyrrolidine-2-one, pyrrolidine-2,5-diketone), dihydropyrrolyl (e.g., 2,5-dihydro-1H-pyrrolyl, 2,3-dihydro-1H-pyrrolyl), pyrrolone (e.g., 1,3-dihydro-2H-pyrrol-2-one, 1,5-dihydro-2H-pyrrol-2-one, 1H-pyrrol-2,5-diketone), dihydrofuranyl (e.g., 2,5-dihydrofuranyl, 2,3-dihydrofuranyl), tetrahydrofuranyl, and dihydrofuranyl. Brønsted, furanone (e.g., dihydrofuran-2(3H)-keto, dihydrofuran-2,5-diketo, furan-2(3H)-keto, furan-2(5H)-keto, furan-2,5-diketo), dihydrothiophene (e.g., 2,3-dihydrothiophene, 2,5-dihydrothiophene), tetrahydrothiophene, imidazoalkyl, imidazolidinone (e.g., imidazolidin-2-keto), dihydroimidazolyl (e.g., 4,5-dihydro-1H-imidazolyl, 2,3-dihydro-1H-imidazolyl, 2,5-dihydro-1H-imidazolyl), imidazolidinone (e.g., 1,3-dihydro-2H-imidazolyl-2-keto), pyrazolyl, dihydropyrazolyl 1,3-Dioxocyclopentyl, 1,3-dioxocyclopentane-2-keto, 1,3-dithiocyclopentyl, oxazolyl, oxazolidine-ketone (e.g., oxazolidine-2-keto), dihydrooxazolyl (e.g., 2,3-dihydrooxazolyl, 4,5-dihydrooxazolyl), isoxazolyl, thiazolyl, isothiazolyl, piperidinyl, piperidinone (e.g., piperidin-2-keto, piperidin-2,6-diketo), tetrahydropyridinyl (e.g., 1,2,3,4-tetrahydropyridinyl, 1,2,3,6-tetrahydropyridinyl), pyridinone (e.g., 3,4-dihydropyridin-2(1H)-keto, 5,6-dihydropyridin-2(1H)-keto, 3, 6-Dihydropyridine-2(1H)-keto, pyridine-2,6-(1H,3H)-diketo, piperazinyl, piperazinone (e.g., piperazin-2-keto), piperazin-diketo, tetrahydropyrazinyl (e.g., 1,2,3,4-tetrahydropyrazinyl), morpholinyl, morpholinone (e.g., morpholin-3-keto, morpholin-2-keto), thiomorpholinyl, 1,1-dioxo-thiomorpholinyl, dihydropyranyl (e.g., 3,4-dihydro-2H-pyranyl, 3,6-dihydro-2H-pyranyl), pyranyl (e.g., 2H-pyranyl, 4H-pyranyl), tetrahydropyranyl, pyranone (e.g., tetrahydro-2H-pyran-2-keto, 3,4-Dihydro-2H-pyran-2-keto, 5,6-Dihydro-2H-pyran-2-keto, 3,6-Dihydro-2H-pyran-2-keto), tetrahydrothiaranyl, hexahydrothiaranyl, dihydropyrimidinyl, tetrahydropyrimidinyl (e.g., 1,2,3,4-tetrahydropyrimidinyl), hexahydropyrimidinyl, pyrimidinoneyl (e.g., tetrahydropyrimidin-2(1H)-keto, 5,6-dihydropyrimidin-4(3H)-keto, 5,6-dihydropyrimidin-4(1H)-keto, pyrimidin-4(3H)-keto, pyrimidin-4(1H)-keto), pyrimidin diketo (e.g., pyrimidin-2,4-diketo), oxazinyl (e.g., 1,3-oxazine). The following groups are listed: alkyl, 1,2-oxazinyl, dihydrooxazinyl (e.g., 3,4-dihydro-2H-1,4-oxazinyl, 3,4-dihydro-2H-1,3-oxazinyl, 3,6-dihydro-2H-1,3-oxazinyl), thiazinyl, thiooxacyclohexyl, dioxinyl (e.g., 1,3-dioxinyl, 1,4-dioxinyl), dioxanoneyl (e.g., 1,4-dioxan-2-one), dithiaalkyl (e.g., 1,3-dithiaalkyl, 1,4-dithiaalkyl), azirheptanyl, oxacycloheptanyl, thioheptanyl, oxacycloheptanyl, diazacycloheptanyl (e.g., 1,4-diazacycloheptanyl), thiocycloheptanyl, etc.

[0244] In some embodiments, the "heterocyclic group" or "heterocyclic alkyl group" is a "5-14 membered spirocyclic heterocyclic group," preferably a 5-12 membered spirocyclic heterocyclic group or a 7-10 membered spirocyclic heterocyclic group, more preferably a 6-, 7-, 8-, 9-, 10-, 11-, or 12-membered spirocyclic heterocyclic group; wherein 1, 2, 3, or 4 ring atoms are heteroatoms selected from O, N, Si, S, and P. Examples of spirocyclic heterocyclic groups include, but are not limited to: , , , , , , , , , , , , , , , , , , , , , , , , , , , , 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , .

[0245] In some embodiments, the "heterocyclic group" or "heterocyclic alkyl group" is a "5-14 membered fused-ring heterocyclic group," preferably a 5-12 membered fused-ring heterocyclic group or a 7-10 membered fused-ring heterocyclic group, more preferably a 6-, 7-, 8-, 9-, 10-, 11-, or 12-membered fused-ring heterocyclic group; wherein 1, 2, 3, or 4 ring atoms are heteroatoms selected from O, N, Si, S, and P. Examples of fused-ring heterocyclic groups include, but are not limited to: , , , , , , , , , 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , .

[0246] In some embodiments, the "heterocyclic group" or "heterocyclic alkyl group" is a "5-14 membered bridged heterocyclic group," preferably a 5-12 membered bridged heterocyclic group or a 7-10 membered bridged heterocyclic group, more preferably a 6-, 7-, 8-, 9-, 10-, 11-, or 12-membered bridged heterocyclic group; wherein 1, 2, 3, or 4 ring atoms are heteroatoms selected from O, N, Si, S, and P. Examples of bridged heterocyclic groups include, but are not limited to: , , , , 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 , , , , , , , , .

[0247] In some embodiments, "heterocyclic" or "heterocyclic alkyl" further includes a ring system fused with one or more aryl or heteroaryl groups as defined above, wherein the connection point is on the heterocyclic alkyl ring. Examples include, but are not limited to: , , , , , , , , , , , .

[0248] In some embodiments, "heterocyclic" or "heterocyclic alkyl" further includes a ring system fused with one or more heterocyclic or heteroaryl groups as defined above, wherein the connection point is on the cycloalkyl ring. Examples include, but are not limited to: , , , , , , , , , , , , , , , , , , , , .

[0249] In some embodiments, "heterocyclic group" or "heterocyclic alkyl group" also includes a ring system in which a cycloalkyl ring as defined above forms a spirocyclic ring with one or more heterocyclic groups, wherein the connection point is on the cycloalkyl ring.

[0250] The term "aryl" refers to any monocyclic, bicyclic, tricyclic, or polycyclic aromatic system containing 6 to 20 ring carbon atoms (C6-C4). 20 It can be a monocyclic aryl or a fused-ring aryl. In some embodiments, the aryl group is C6-C.12 Or C6-C 10 Aryl. In each case, the aryl group may be optionally substituted independently. In some embodiments, an "optionally substituted aryl group" is one, two, three, four, or five substituents, such as 1-2, 1-3, or 1-4 substituents, selected from groups specified herein (see the definition of "optionally substituted"). Examples of aryl groups include, but are not limited to: phenyl, naphthyl (e.g., naphth-1-yl, naphth-2-yl), phenanthryl, anthracene, and fluorenyl (e.g., fluoren-1-yl, fluoren-4-yl, fluoren-9-yl). In some embodiments, "aryl" further includes a ring system fused with one or more saturated, partially saturated cycloalkyl or heterocyclic alkyl groups as defined above, wherein the linking point is on the aryl ring, and optionally, the saturated, partially saturated cycloalkyl or heterocyclic alkyl group fused with the aryl group can be a fused ring, spiro ring, or bridged ring system. Examples of aryl groups include, but are not limited to: , , , , , , , , , , , , , .

[0251] The term "heteroaryl" refers to any monocyclic, bicyclic, tricyclic, or polycyclic heteroaromatic system comprising 5 to 20 ring atoms (5-20 members), wherein 1 to 5 of the ring atoms are heteroatoms selected from O, N, Si, S, and P. In some embodiments, the heteroaryl comprises 5 to 14 ring atoms (5-14 members), wherein 1 to 3 of the ring atoms are heteroatoms selected from O, N, Si, S, and P. In some embodiments, the heteroaryl comprises 5 to 12 ring atoms (5-12 members), wherein 1 to 3 of the ring atoms are heteroatoms selected from O, N, Si, S, and P. In some embodiments, the heteroaryl comprises 5 to 10 ring atoms (5-10 members), wherein 1 to 3 of the ring atoms are heteroatoms selected from O, N, Si, S, and P. In other embodiments, the heteroaryl group is a 5-20, 5-14, 5-12, 5-10, 5-9, 5-8, 5-7, or 5-6 heteroaryl group, wherein 1-5, 1-3, or 1-2 ring atoms are heteroatoms selected from O, N, Si, S, and P. In other embodiments, the heteroaryl group is a 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 heteroaryl group, wherein 1, 2, 3, 4, or 5 ring atoms are heteroatoms selected from O, N, Si, S, and P. The heterocyclic group may be optionally substituted independently in each case; in some embodiments, an "optionally substituted heteroaryl group" is a group substituted with 1, 2, 3, 4, or 5 substituents, such as 1-2, 1-3, or 1-4 substituents selected from groups specified herein (see the definition of "optionally substituted").

[0252] In some embodiments, the heteroaryl group is a "5-6 membered monocyclic heteroaryl group," wherein the 1, 2, 3, or 4 ring atoms are heteroatoms selected from O, N, Si, S, and P. Examples of monocyclic heteroaryl groups include, but are not limited to: pyrrolyl, furanyl, thiophene, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isothiazolyl, isoxazolyl, triazolyl (e.g., 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, 1,3,4-triazole), and oxadiazolyl (e.g., 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl). -oxadiazolyl), thiadiazolyl (e.g., 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl), tetrazolyl, pyranyl, pyridinyl, pyridinyl, pyrazinyl, triazinyl (e.g., 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl), thiadiazinyl, azecinyl, etc.

[0253] In one embodiment, the heteroaryl group is a "5-14 membered fused-ring heteroaryl group", preferably a 5-12 membered fused-ring heteroaryl group or a 7-10 membered fused-ring heteroaryl group, more preferably a 6 membered, 7 membered, 8 membered, 9 membered, 10 membered, 11 membered or 12 membered fused-ring heteroaryl group; wherein 1, 2, 3, 4 or 5 ring atoms are heteroatoms selected from O, N, Si, S and P. Examples of fused-ring heteroaryl groups include, but are not limited to: indolyl, isoyindolyl, benzofuranyl, benzothiophenyl, indazole, benzopyranyl, benzimidazolyl (e.g., 1H-benzo[d]imidazole), benzothiazolyl (e.g., benzo[d]thiazolyl), benzoisothiazolyl (e.g., benzo[d]isothiazolyl), benzooxazolyl (e.g., benzo[d]oxazole), benzoisooxazolyl (e.g., benzo[d]isooxazole), benzooxazinyl, benzotriazolyl (e.g., 1H-benzo[d][1,2,3]triazole), naphthidyl (e.g., 1,5-naphthidine, 1,6-naphthidine, 1,7-naphthidine, 1,8-naphthidine), phthalazinyl, pteridine The compounds include purine, cenolin, quinolin, isoquinolin, quinoxaline, quinazolin, oxazolopyridyl, isoxazolopyridyl, pyrrolopyridyl, furanopyridyl, thiophenolopyridyl, imidazopyridyl, imidazopyrimidyl, pyrazolpyridyl, pyrazolpyrimidyl (e.g., pyrazol[1,5-a]pyrimidine), pyrazoltriazinyl, triazolpyridyl, triazolpyrimidyl, imidazothiazolyl, triazolpyridyl, triazolpyrimidyl, pyridinolpyrimidyl (e.g., pyridinol[3,2-d]pyrimidine, pyridinol[2,3-d]pyrimidine, pyridinol[3,4-d]pyrimidine, pyridinol[4,3-d]pyrimidine, etc.); In some embodiments, "heteroaryl" further includes a ring system fused with one or more saturated, partially saturated cycloalkyl or heterocyclic alkyl groups as defined above, wherein the linking point is on the heteroaryl ring, and optionally, the saturated, partially saturated cycloalkyl or heterocyclic alkyl group fused with the heteroaryl group can be a fused ring, spiro ring, or bridged ring system. Examples of heteroaryl groups include, but are not limited to: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , .

[0254] In some embodiments, "heteroaryl" further includes a ring system fused with one or more saturated, partially saturated heterocyclic alkyl groups as defined above, wherein the linking point is on the aryl ring, and optionally, the saturated, partially saturated heterocyclic alkyl group fused with the aryl group can be a fused ring, spiro ring, or bridged ring system. Examples of heteroaryl groups include, but are not limited to: , , , , , , , , , , , , , , , , , , , .

[0255] The term "fused ring" refers to a saturated, partially saturated (one of which may be an aromatic ring), or aromatic cyclic group formed by two or more cyclic structures sharing two adjacent atoms. A "fused ring" system can be a fused alkyl group, a fused heterocyclic group, a fused aryl group, or a fused heteroaryl group, wherein the ring atoms (e.g., carbon, nitrogen, or sulfur atoms) in the cyclic structure may optionally be oxidized.

[0256] The term "bridged ring" refers to a saturated or partially saturated cyclic group formed by two or more cyclic structures sharing two non-adjacent ring atoms. A "bridged ring" system can be a bridged alkyl group or a bridged heterocyclic group, wherein the ring atoms (e.g., carbon, nitrogen, or sulfur atoms) in the cyclic structure may optionally be oxidized. In a polycyclic bridged ring system, at least one ring may contain one or more double bonds, or be an aromatic ring.

[0257] The term "spirocyclic" refers to a saturated or partially saturated cyclic group formed by two or more cyclic structures sharing a single ring atom. A "spirocyclic" system can be a spiroalkyl group or a spirocyclic heterocyclic group, wherein the ring atom (e.g., a carbon atom, nitrogen atom, or sulfur atom) in the cyclic structure may optionally be oxidized. In a polycyclic spirocyclic system, at least one ring may contain one or more double bonds, or be an aromatic ring.

[0258] Unless otherwise specified, the terms “alkylene,” “alkenylene,” or “alkynylene” mean a divalent group derived from “alkyl,” “alkenyl,” or “alkynyl,” respectively; the terms “heterocyclic” or “cycloalkylene” mean a divalent group derived from “heterocyclic” or “cycloalkyl,” respectively; the term “heteroalkylene” means a divalent group derived from “heteroalkyl,” respectively; and the terms “arylene” and “heteroarylene” mean divalent groups derived from “aryl” and “heteroaryl,” respectively. By way of example only, examples of "alkylene" include, but are not limited to, -CH2-, -CH2CH2-, -CH(CH3)-, -CH2CH2CH2-, -CH(CH2CH3)-, -C(CH3)2-, -CH(CH3)CH2-, -C(CH3)2-CH2CH2CH2-, -C(CH3)2-CH2CH2-, -CH2CH2CH2CH2-, and -CH2CH(CH3)CH2-.

[0259] Unless otherwise specified, “halogen” or “halogenated” alone or as part of another substituent means F, Cl, Br, or I. Furthermore, terms such as “halogenated alkyl” are intended to include monohalogenated and polyhalogenated alkyl groups, wherein one or more halogens replace one or more hydrogen atoms in the alkyl group.

[0260] Additionally, terms such as "haloalkyl" are intended to include both monohaloalkyl and polyhaloalkyl. For example, the term "halo-C1-C6 alkyl" includes, but is not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, 4-chlorobutyl, 3-bromopropyl, and so on.

[0261] Unless otherwise indicated, the term "optionally substituted" means that the group may be unsubstituted or substituted by one or more (e.g., 0, 1, 2, 3, 4, or 5 or more, or any range thereof) of the substituents listed for the group, wherein said substituents may be the same or different. In one embodiment, the optionally substituted group has 1 substituent. In another embodiment, the optionally substituted group has 2 substituents. In another embodiment, the optionally substituted group has 3 substituents. In another embodiment, the optionally substituted group has 4 substituents. In another embodiment, the optionally substituted group has 5 substituents. The optionally substituted group may be selected from the following groups: halogens (F, Cl, Br, I); OH; NH2; CN; NO2; CF3; SF5; SF3; oxo (=O); and optionally substituted groups such as C. 1-6 Alkyl; C 2-6 alkenyl; C 2-6 alkynyl group; C 3-6 cycloalkyl; 3-10 membered heterocyclic group; C 6-10 Aryl; 5-10 heteroaryl; C 2-6 alkenyl-C 1-6 Alkylene-; C 2-6 alkynyl-C 1-6 Alkylene-; C 6-10 Aryl-C 1-6 alkylene-; 5-10 heteroaryl-C 1-6 Alkylene-;-OR';-C(O)R';-CO2R';-OC(O)R';-S(O)R';-S(O)2R';-S(O)(=NH)R';-S(O)(=NR'')R''; NR''R''; -S(O)2NR''R'''; -NR''S(O)R'; -NR''S(O)2R'; -NR'C(O)NR''R'''; -NR'S(O)NR''R'''; -N=S(O)R''R'''; -NR'S(O)2NR''R'''; -P(=O)R''R'''; -(CH2) 1-6 -R';-(CH2) 1-6 -OR';-(CH2) 1-6 -NR''R''';-(CH2) 1-6 -SR';-(CH2) 1-6 -SiR'R''R''';-(CH2) 1-6 -OC(O)R';-(CH2) 1-6 -C(O)R';-(CH2) 1-6-CO2R'; or -(CH2) 1-6 CONR''R'''. Each R', R'', and R''' independently signifies the following group: hydrogen; and optionally substituted groups: C 1-6 Alkyl; C 2-6 alkenyl; C 2-6 alkynyl group; C 3-6 cycloalkyl; 3-6 membered heterocyclic group; C 6-10 Aryl; 5-10 heteroaryl; C 2-6 alkenyl-C 1-6 Alkylene-; C 2-6 alkynyl-C 1-6 Alkylene-; C 6-10 Aryl-C 1-6 alkylene-; 5-10 heteroaryl-C 1-6 Alkylene-; C 1-6 Alkyl acyl; C 2-6 alkenyl acyl; C 2-6 Entyl acyl group; C 3-6 Cycloalkyl acyl; 3-6 membered heterocyclic acyl; C 6-10 Aryl acyl; 5-10 membered heteroaryl acyl; C 1-6 alkylsulfonyl; C 2-6 alkenylsulfonyl; C 2-6 alkynylsulfonyl; C 3-6 Cycloalkylsulfonyl; 3-6 membered heterocyclic sulfonyl; C 6-10 arylsulfonyl; 5-10 membered heteroarylsulfonyl; C 1-6 alkylsulfinyl; C 2-6 alkenylsulfinyl; C 2-6 alkynyl sulfinyl; C 3-6 Cycloalkyl sulfinyl; 3-6 membered heterocyclic sulfinyl; C 6-10 Arylsulfinyl group; 5-10-membered heteroarylsulfinyl group; or R'' and R''' together with the atoms (e.g., N, P, Si) forming a 3-, 4-, 5-, 6-, or 7-membered ring, wherein the ring atoms are optionally substituted with N, O, or S and the ring is optionally substituted with halogen, OH, CN, C. 1-6 Alkyl, C 1-6 Alkoxy or oxo substitution.

[0262] In some embodiments, specific examples of "optionally substituted" substituents are selected from the following groups: F, Cl, Br, I, OH, SH, CN, NO2, N3, SF5, SF3, NH2, oxo(=O), and the following optional substituents: -NHCH3, -N(CH3)2, -C(O)CH3, COOH, -CO2CH3, -CONH2, -CONHCH3, -CON(CH3)2, -CH2OH, =NH, =NCH3, -P(=O)(OH)2, -P(=O)(CH3)2, -S(O)2NH2, -S(O)2NHCH3, -S(O)2N(CH3)2, -S(O)2CH3, -S(O)(=NH)CH3, -S(O)(=NCH3)CH3, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, etc. Butyl, pentyl, isopentyl, neopentyl, trifluoromethyl, difluoromethyl, cyclopropyl, cyclobutyl, cyclopentyl, methoxy, ethoxy, propoxy, methylthio, ethylthio, propylthio, cyclopropoxy, cyclopropylthio, cyclopropylamino, aziridinyl, aziridine, oxacyclobutyl, thioheterobutyl, tetrahydrofuranyl, pyrrolyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, homopiperidinyl, aziridineheptyl Oxyheptanyl, phenyl, naphthyl, furanyl, thiophene, oxazolyl, thiazolyl, imidazole, pyrazolyl, isothiazolyl, isoxazolyl, triazolyl, benzofuranyl, benzothiophene, benzoimidazolyl, benzothiazolyl, benzoisothiazolyl, benzooxazolyl, benzoisooxazolyl, benzooxazinyl, benzotriazolyl, quinolinyl, oxazolopyridyl, isoxazolopyridyl, pyrrolopyridyl, furanolopyridyl, thiophenopyridyl.

[0263] Those skilled in the art will understand that the compounds represented by formula (M) can exist in the form of various pharmaceutically acceptable salts. If these compounds have a basic center, they can form acid addition salts; if these compounds have an acidic center, they can form base addition salts; if these compounds contain both an acidic center (e.g., a carboxyl group) and a basic center (e.g., an amino group), they can also form internal salts.

[0264] The compounds disclosed herein may exist as solvates (such as hydrates), wherein the compounds of this disclosure contain a polar solvent, particularly, for example, water, methanol, or ethanol, as a structural element of the lattice of the compound. The amount of the polar solvent, particularly water, may be stoichiometric or non-stoichiometric. Unless otherwise stated, the compounds of this disclosure should be understood to encompass their solvates.

[0265] As used herein, the term "pharmaceutically acceptable" means a substance (such as a carrier or diluent) that does not affect the biological activity or properties of the compounds of the present invention and is relatively non-toxic, i.e., that the substance can be administered to an individual without causing an adverse biological reaction or interacting adversely with any component contained in the composition.

[0266] Those skilled in the art will understand that the compounds of this disclosure can exist in the form of various pharmaceutically acceptable salts. If these compounds have a basic center, they can form acid addition salts; if these compounds have an acidic center, they can form base addition salts; if these compounds contain both an acidic center (e.g., a carboxyl group) and a basic center (e.g., an amino group), they can also form inner salts.

[0267] Unless otherwise stated, the compounds disclosed herein should be understood to encompass their tautomers. The term "tautomer" refers to a functional group isomer resulting from the rapid movement of an atom between two positions in a molecule. The compounds of this disclosure can exhibit tautomerism. Tautomers can exist in two or more interconvertible forms. Proton-transfer tautomers arise from the migration of covalently bonded hydrogen atoms between two atoms. Tautomers generally exist in equilibrium form, and attempts to isolate a single tautomer usually yield a mixture whose physicochemical properties are consistent with those of the mixture of compounds. The equilibrium position depends on the intramolecular chemical characteristics. For example, in many aliphatic aldehydes and ketones such as acetaldehyde, the keto form is dominant; while in phenols, the enol form is dominant. This disclosure includes all tautomer forms of the compounds.

[0268] Based on their molecular structure, the compounds disclosed herein can be chiral, and therefore may exist in various enantiomeric forms. Thus, these compounds can exist in racemic or optically active forms. The compounds disclosed herein cover isomers of each chiral carbon in the R or S configuration, or mixtures thereof, or racemates. The compounds or intermediates of this disclosure can be isolated as enantiomeric compounds by chemical or physical methods known to those skilled in the art, or used in this form for synthesis. In the case of racemic amines, diastereomers are obtained from the mixture by reaction with an optically active resolving agent. Examples of suitable resolving agents are optically active acids, such as tartaric acid in both R and S forms, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid, suitable N-protected amino acids (e.g., N-benzoylproline or N-benzenesulfonylproline), or various optically active camphorsulfonic acids. Chromatographic enantiomer separation can also be advantageously performed using optically active resolving agents (e.g., dinitrobenzoylphenylglycine immobilized on silica gel, cellulose triacetate, or other carbohydrate derivatives, or chiral derivatized isobutylene ester polymers). Suitable eluents for this purpose are aqueous or alcoholic solvent mixtures, such as hexane / isopropanol / acetonitrile. The corresponding stable isomers can be separated according to known methods, such as extraction, filtration, or column chromatography.

[0269] Unless otherwise stated, the compounds disclosed herein should be understood to encompass their isotopic labels. "Isotope" refers to all isotopes of atoms appearing in the compounds of this invention. Isotopes include those atoms having the same atomic number but different mass numbers. Examples of isotopes suitable for inclusion in the compounds of this invention are hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, and chlorine, respectively, for example, but not limited to, [specific examples]. 2 H, 3 H, 13 C 14 C 15 N、 18 O、 31 P, 32 P, 35 S, 18 F and 36 C1. The isotope-labeled compounds of the present invention can generally be prepared by conventional techniques known to those skilled in the art or by methods similar to those described in the appended examples, using suitable isotope-labeled reagents instead of non-isotope-labeled preparations. Such compounds have a variety of potential uses, for example, as standards and reagents in the determination of biological activity. In the case of stable isotopes, such compounds have the potential to advantageously alter biological, pharmacological, or pharmacokinetic properties.

[0270] The term "prodrug" refers to a compound of this disclosure that can be converted into a biologically active form under physiological conditions or by solvation. The prodrugs of this disclosure are prepared by modifying a functional group in the compound; this modification can be performed conventionally or removed in vivo to yield the parent compound. Prodrugs comprise compounds formed by attaching a hydroxyl or amino group to any group in the compound of this disclosure. When a prodrug of this disclosure is administered to a mammalian individual, the prodrug is cleaved to form a free hydroxyl group and a free amino group.

[0271] The term "patient" refers to any animal, including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, pigs, cattle, sheep, horses, or primates, with humans being the most preferred.

[0272] The term “therapeutic effective amount” refers to the amount of an active compound or drug that researchers, veterinarians, physicians, or other clinicians are searching for in tissues, systems, animals, individuals, or humans to elicit a biological or medical response. It includes one or more of the following: (1) prevention of disease: e.g., prevention of disease, disorder, or condition in individuals susceptible to disease, disorder, or symptom but not yet experiencing or exhibiting the pathology or symptoms of the disease; (2) suppression of disease: e.g., suppression of disease, disorder, or symptom in individuals experiencing or exhibiting the pathology or symptoms of the disease, disorder, or symptom (i.e., prevention of further development of the pathology and / or symptoms); (3) relief of disease: e.g., relief of disease, disorder, or symptom in individuals experiencing or exhibiting the pathology or symptoms of the disease, disorder, or symptom (i.e., reversal of the pathology and / or symptoms).

[0273] Beneficial effects Compared with known RIPK1 inhibitors in the prior art, the compounds provided by this invention have the following advantages: 1) stronger RIPK1 inhibitory activity. In in vitro kinase inhibition experiments, the representative compounds of this invention exhibit a significantly higher half-maximal inhibitory concentration (IC50) for RIPK1. 50 Below 20 nM, some compounds have IC50. 50 1) Lower than 10 nM, showing higher target binding affinity and kinase function inhibition ability; 2) Higher target selectivity: While having high affinity for RIPK1, the compounds of this invention have no significant inhibitory effect on related kinases such as RIPK3 and RIPK2, effectively reducing non-specific target interference and the toxic side effects that may be caused by it; 3) Optimized pharmacokinetic performance: The representative compounds of this invention show good pharmacokinetic parameters in animals, including higher oral bioavailability, prolonged elimination half-life and greater in vivo exposure. Detailed Implementation

[0274] The technical solution of the present invention will be further described in detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explanatory of the present invention, and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are covered within the scope of protection intended by the present invention.

[0275] Example 1 Compound 1-1A: Bicyclo[2.2.2]octane-1-yl((5 S 7 S )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl) methyl ketone, or compound 1-1B: bicyclo[2.2.2]octane-1-yl((5 R 7 R )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl) methyl ketone.

[0276] Compound 1-1C: Bicyclo[2.2.2]octane-1-yl((5 R 7 S )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl) methyl ketone, or compound 1-1D: bicyclo[2.2.2]octane-1-yl((5 S 7 R )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl) methyl ketone.

[0277]

[0278] Synthesis route:

[0279]

[0280]

[0281]

[0282]

[0283] Step-1: Preparation of 3,5-dibromo-1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazole (1-1-A): 0 o Compound 3,5-dibromo-1H-1,2,4-triazole (SM1, 50 g, 1 eq) was dissolved in 500 mL of tetrahydrofuran under nitrogen protection and cooled to 0 °C in an ice-water bath.o Add p-toluenesulfonic acid (5.69 g, 0.15 eq) at C, stir for 5 minutes, then add 3,4-dihydro-2H-pyran (55.62 g, 3 eq), and slowly heat to reflux with stirring. React for 3 hours. After the reaction is complete, characterize by LCMS. After cooling to room temperature, concentrate the residue under reduced pressure, quench with water at room temperature, adjust the pH of the resulting mixture to approximately 9 with saturated sodium carbonate solution, extract three times with ethyl acetate, combine the organic phases, wash with saturated sodium chloride solution, dry the organic phase with anhydrous sodium sulfate, filter, evaporate to dryness, and purify by normal-phase column chromatography to obtain intermediate 1-1-A (56 g, yield: 82%). MS: [M+1] + : 310.

[0284] Step-2: N -Methoxy- N Preparation of methylbicyclo[2.2.2]octane-1-carboxamide (1-1-B): Bicyclo[2.2.2]octane-1-carboxylic acid (2 g, 1 eq) was dissolved in water at room temperature. N,N Add O-(7-azabenzotriazolyl)- to dimethylformamide (DMF, 45 mL). N , N , N' , N' -Tetramethylureaium hexafluorophosphate (HATU, 6.41 g, 1.3 eq). After stirring for 10 minutes, dimethylhydroxylamine hydrochloride (1.64 g, 1.3 eq) and... were added to the above system at room temperature. N,N -Diisopropylethylamine (DIEA, 6.71 g, 4 eq). The reaction was stirred at room temperature for 2 hours. After LCMS characterization, the reaction was quenched with water at room temperature, extracted three times with ethyl acetate, and the organic phases were combined. The mixture was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The resulting product was purified by normal-phase column chromatography to give intermediate 1-1-B (1.3 g, yield: 51%). MS: [M+1] + : 198.

[0285] Step 3: Preparation of tert-butyldimethyl((1-phenylbut-3-en-1-yl)oxy)silane (1-1-C): 4-Phenylacetic-1-buten-4-ol (52 g, 1 eq) was dissolved in dichloromethane (730 mL) at room temperature, followed by the addition of imidazole (47.77 g, 2 eq). The solution was cooled to 0 °C in an ice-water bath under nitrogen protection. oC. Add tert-butyldimethylchlorosilane (68.75 g, 1.3 eq) with stirring, and continue stirring at room temperature for 16 hours. Quench the reaction mixture with saturated sodium bicarbonate aqueous solution at room temperature, extract three times with dichloromethane, combine the organic phases, wash with saturated sodium chloride aqueous solution, dry the organic phase with anhydrous sodium sulfate, filter, evaporate to dryness, and purify by normal phase column chromatography to obtain intermediate 1-1-C (89.5 g, yield: 97%).

[0286] Step 4: Preparation of 3-((tert-butyldimethylsilyl)oxy)-3-phenylpropanal (1-1-D): Compound 1-1-C (88 g, 1 eq) was dissolved in a mixed solvent of tetrahydrofuran (500 mL) and water (500 mL) at room temperature under nitrogen protection for 10... o C, add osmium tetroxide (2.56 g, 0.03 eq), stir and react for 30 minutes, then 10 o Sodium periodate (250.99 g, 3.5 eq) was added in portions at C. After the addition was complete, the system was stirred at room temperature for 2 hours. The reaction mixture was quenched at 10°C with saturated sodium thiosulfate aqueous solution (300 ml), extracted three times with ethyl acetate, and the organic phases were combined, washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by normal phase column chromatography to give intermediate 1-1-D (43.3 g, yield: 49%).

[0287] Step-5: Preparation of 1-(3-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-5-yl)-3-((tert-butyldimethylsilyl)oxy)-3-phenylprop-1-ol (1-1-E): Under nitrogen protection, -78 o To a solution of compound 1-1-A (20 g, 1 eq) in tetrahydrofuran (200 mL), n-butyllithium (28.4 mL, 2.5 M hexane solution, 1.1 eq) was added. After stirring for 10 minutes, the reaction proceeded to -78°C. o A tetrahydrofuran (50 mL) solution of compound 1-1-D (22.11 g, 1.3 eq) was added dropwise to the above reaction solution at temperature C. After the addition was complete, the system was stirred at room temperature for 1 hour. Reaction mixture - 20 o Quenched at C with ammonium chloride aqueous solution, extracted three times with ethyl acetate, the organic phases were combined, washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by normal-phase column chromatography to give intermediate 1-1-E (25 g, yield: 78%). MS: [M+1] + : 496 / 498.

[0288] Step-6: Preparation of trans-2-bromo-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-7-ol (1-1-FA) and cis-2-bromo-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-7-ol (1-1-FB): Under nitrogen protection, 10 o Trifluoroacetic acid (70 mL) was added in portions to a solution of compound 1-1-E (24.4 g, 1 eq) in dichloromethane (80 mL). After the addition was complete, the system was 50 mL thickened. o Stirring continued at C for 3 hours. After the reaction was complete, the reaction system was concentrated under reduced pressure, the pH was adjusted to approximately 9 with saturated sodium carbonate aqueous solution, extracted three times with ethyl acetate, the organic phases were combined, washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by normal phase column chromatography to obtain the peak: trans-2-bromo-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-7-ol (1-1-FA, 3.8 g, yield: 28%), MS: [M+1] + : 280 / 282; yield peak: cis-2-bromo-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-7-ol (1-1-FB, 2.2 g, yield: 16%), MS: [M+1] + : 280 / 282.

[0289] Step-7: Preparation of cis-2-bromo-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazole (1-1-GA) and trans-2-bromo-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazole (1-1-GB): Under nitrogen protection, triethylamine trifluoride (4.37 g, 2 eq) was added to a solution of compound 1-1-FA (3.8 g, 1 eq) in dichloromethane (80 mL) at room temperature, followed by 0... o Sulfonium difluoro(morpholino)tetrafluoroborate (4.94 g, 1.5 eq) was added in batches at C. After the addition was complete, the system was at 0. o Continue stirring at C for 3 hours. After the reaction is complete, 0 o The reaction was quenched with saturated sodium carbonate aqueous solution at C, extracted three times with chloromethane, and the organic phases were combined. The organic phase was washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The resulting product was purified by normal-phase column chromatography to obtain the following peak: cis-2-bromo-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazole (1-1-GA, 1.7 g, yield: 44%), MS: [M+1]. +: 282 / 284; Precipitated peak: trans-2-bromo-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazole (1-1-GB, 1.1 g, yield: 28%), MS: [M+1] + : 282 / 284.

[0290] Step-8: Bicyclo[2.2.2]octane-1-yl((5 S 7 S )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)methyl ketone (1-1A) or bicyclo[2.2.2]octane-1-yl((5 R 7 R Preparation of 7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)methyl ketone (1-1B): Under nitrogen protection, 0 o At step C, isopropyl magnesium chloride (1 mL, 2.3 eq, 2.0 M tetrahydrofuran solution) was added dropwise to a tetrahydrofuran (10 mL) solution of compound 1-1-GA (250 mg, 1 eq) and compound 1-1-B (350 mg, 1.4 eq). After the addition was complete, the system was at 0°C. o Continue stirring at C for 2 hours. Reaction mixture 0 o Quenched at C with ammonium chloride aqueous solution, extracted three times with ethyl acetate, the organic phases were combined, washed with saturated sodium chloride aqueous solution, dried with anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by normal phase column chromatography to obtain racemic cis compound (180 mg, purity: 98%).

[0291] The racemic cis compound was chirally resolved (column type: CHIRALPAK IH, 250 mm * 20 mm, 5 μm; mobile phase A: n-hexane (0.2% formic acid); mobile phase B: methanol: dichloromethane = 1:1; flow rate: 20 mL / min; mobile phase ratio (B%): 30% mobile phase B; wavelength: 254 / 220 nm) to give compound 1-1P1 (tR = 5.62 min) and compound 1-1P2 (tR = 7.74 min).

[0292] Compounds 1-1P1 and 1-1P2 are one of the structures shown in Formula 1-1A or Formula 1-1B. That is, when compound 1-1P1 is the structure of Formula 1-1A, compound 1-1P2 is the structure of Formula 1-1B; when compound 1-1P1 is the structure of Formula 1-1B, compound 1-1P2 is the structure of Formula 1-1A.

[0293] 1-1P1 (tR=5.62 min), MS: [M+1] + : 340.20. 1 H NMR (400 MHz, CDCl3) δ(ppm): 7.46-7.34 (m, 3H), 7.26-7.21 (m, 2H), 6.02-5.92 (m, 1H), 5.50-5.45 (m,1H), 3.64-3.56 (m, 1H), 2.97-2.87 (m, 1H), 2.01-1.98 (m, 6H), 1.70-1,58 (m,7H). 1-1P2 (tR=7.74 min), MS: [M+1) + : 340.15. 1 H NMR (400 MHz, CDCl3) δ(ppm): 7.44-7.37 (m, 3H), 7.26-7.20 (m, 2H), 6.02-5.92 (m, 1H), 5.50-5.46 (m,1H), 3.64-3.58 (m, 1H), 2.97-2.87 (m, 1H), 2.01-1.97 (m, 6H), 1.69-1.60 (m, 7H). Step-9: Bicyclo[2.2.2]octane-1-yl((5 R 7 S )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)methyl ketone (1-1C) or bicyclo[2.2.2]octane-1-yl((5 S 7 R Preparation of 7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)methyl ketone (1-1D): Under nitrogen protection, 0 o At step C, isopropyl magnesium chloride (1 mL, 2.3 eq, 2.0 M tetrahydrofuran solution) was added dropwise to a tetrahydrofuran (10 mL) solution of compound 1-1-GB (250 mg, 1 eq) and compound 1-1-B (350 mg, 1.4 eq). After the addition was complete, the system was at 0°C. o Continue stirring at C for 2 hours. Reaction mixture 0 o Quenched at C with ammonium chloride aqueous solution, extracted three times with ethyl acetate, the organic phases were combined, washed with saturated sodium chloride aqueous solution, dried with anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by normal phase column chromatography to obtain racemic trans compound (150 mg, purity: 95.4%).

[0294] The racemic trans compound was chirally resolved (column type: CHIRALPAK IH, 250 mm * 20 mm, 5 μm; mobile phase A: n-hexane (0.2% formic acid); mobile phase B: methanol: dichloromethane = 1:1; flow rate: 20 mL / min; mobile phase ratio (B%): 40% mobile phase B; wavelength: 254 / 220 nm) to give compound 1-1P3 (tR = 4.52 min) and compound 1-1P4 (tR = 6.76 min).

[0295] Compounds 1-1P3 and 1-1P4 are one of the structures shown in Formula 1-1C or Formula 1-1D. That is, when compound 1-1P3 has the structure of Formula 1-1C, compound 1-1P4 has the structure of Formula 1-1D; when compound 1-1P3 has the structure of Formula 1-1D, compound 1-1P4 has the structure of Formula 1-1C.

[0296] 1-1P3 (tR=4.52 min), MS: [M+1] + : 340.15. 1 H NMR (400 MHz, CDCl3) δ(ppm): 7.42 (d, J = 6.3 Hz, 3H), 7.15 (d, J = 7.6 Hz, 2H), 6.08 (dd, J = 55.8, 6.1Hz, 1H), 5.74-5.72 (m, 1H), 3.47-3.36 (m, 1H), 3.07-2.95 (m, 1H), 2.03-1.97(m, 6H), 1.72-1.61 (m, 7H). 1-1P4 (tR=6.76 min), MS: [M+1) + : 340.15. 1 H NMR (400 MHz, CDCl3) δ(ppm): 7.42 (d, J = 6.5 Hz, 3H), 7.15 (d, J = 6.8 Hz, 2H), 6.08 (dd, J = 55.6, 6.3Hz, 1H), 5.75-5.72 (m, 1H), 3.47-3.36 (m, 1H), 3.07-2.94 (m, 1H), 2.03-2.01(m, 6H), 1.71-1.61 (m, 7H). Example 2 Compound 1-2A: (5 S 7 S )-2-((bicyclo[1.1.1]pentan-1-yl)carbonyl)-7-fluoro-5-phenyl-5,6-dihydropyrrolo[1,2-b][1,2,4]triazole, or compound 1-2B: (5 R 7 R )-2-((bicyclo[1.1.1]pentan-1-yl)carbonyl)-7-fluoro-5-phenyl-5,6-dihydropyrrolo[1,2-b][1,2,4]triazole.

[0297] Compound 1-2C: (5 R 7 S )-2-((bicyclo[1.1.1]pentan-1-yl)carbonyl)-7-fluoro-5-phenyl-5,6-dihydropyrrolo[1,2-b][1,2,4]triazole, or compound 1-2D: (5 S 7 R )-2-((bicyclo[1.1.1]pentan-1-yl)carbonyl)-7-fluoro-5-phenyl-5,6-dihydropyrrolo[1,2-b][1,2,4]triazole.

[0298]

[0299] Synthesis route:

[0300]

[0301]

[0302] Step-1: N -Methoxy- N Preparation of methylbicyclo[1.1.1]pentane-1-carboxamide (1-2-A): Following the procedure in step 2 of Example 1, bicyclo[2.2.2]octane-1-carboxylic acid was replaced with bicyclo[1.1.1]pentane-1-carboxylic acid to prepare compound 1-2A.

[0303] Step-2: (5) S 7 S )-2-((bicyclo[1.1.1]pentan-1-yl)carbonyl)-7-fluoro-5-phenyl-5,6-dihydropyrrolo[1,2-b][1,2,4]triazole (1-2A), or compound (5 R 7 RPreparation of 1-2-((bicyclo[1.1.1]pentan-1-yl)carbonyl)-7-fluoro-5-phenyl-5,6-dihydropyrrolo[1,2-b][1,2,4]triazole (1-2B): Following step 8 in Example 1, 1-1-B was replaced with 1-2-A to prepare 140 mg of the racemic cis compound.

[0304] The racemic cis compound was chirally resolved (column type: CHIRALPAK IH, 250 mm * 20 mm, 5 μm; mobile phase A: n-hexane (0.2% formic acid); mobile phase B: methanol: dichloromethane = 1:1; flow rate: 20 mL / min; mobile phase ratio (B%): 15% mobile phase B; wavelength: 254 / 220 nm) to give compounds 1-2P1 (tR = 8.45 min) and 1-2P2 (tR = 8.45 min).

[0305] Compounds 1-2P1 and 1-2P2 are one of the structures shown in Formula 1-2A or Formula 1-2B. That is, when compound 1-2P1 is the structure of Formula 1-2A, compound 1-2P2 is the structure of Formula 1-2B; when compound 1-2P1 is the structure of Formula 1-2B, compound 1-2P2 is the structure of Formula 1-2A.

[0306] 1-2P1 (tR=8.45 min), MS: [M+1] + : 298.20. 1 H NMR (400 MHz, CDCl3) δ(ppm): 7.44-7.38 (m, 3H), 7.28-7.24 (m, 2H), 6.11-5.95 (m, 1H), 5.53-5.49 (m,1H), 3.67-3.58 (m, 1H), 3.02-2.96 (m, 1H), 2.53 (s, 1H), 2.32 (s, 6H). 1-2P2(tR=11.49 min), MS: [M+1] + : 298.15. 1 H NMR (400 MHz, CDCl3) δ(ppm): 7.44-7.38 (m, 3H), 7.28-7.24 (m, 2H), 6.11-5.95 (m, 1H), 5.53-5.49 (m,1H), 3.67-3.60 (m, 1H), 3.02-2.92 (m, 1H), 2.52 (s, 1H), 2.32 (s, 6H). Step-3: (5)R 7 S )-2-((bicyclo[1.1.1]pentan-1-yl)carbonyl)-7-fluoro-5-phenyl-5,6-dihydropyrrolo[1,2-b][1,2,4]triazole (1-2C), or compound (5 S 7 R Preparation of 1-2-((bicyclo[1.1.1]pentan-1-yl)carbonyl)-7-fluoro-5-phenyl-5,6-dihydropyrrolo[1,2-b][1,2,4]triazole (1-2D): Following step 9 in Example 1, 1-1-B was replaced with 1-2-A to prepare 110 mg of the racemic trans compound.

[0307] The racemic trans compound was chirally resolved (column type: CHIRALPAK IH, 250 mm * 20 mm, 5 μm; mobile phase A: n-hexane (0.2% formic acid); mobile phase B: methanol: dichloromethane = 1:1; flow rate: 20 mL / min; mobile phase ratio (B%): 30% mobile phase B; wavelength: 254 / 220 nm) to give compound 1-2P3 (tR = 3.97 min) and compound 1-2P4 (tR = 6.11 min).

[0308] Compounds 1-2P3 and 1-2P4 are one of the structures shown in Formula 1-2C or Formula 1-2D. That is, when compound 1-2P3 has the structure of Formula 1-2C, compound 1-2P4 has the structure of Formula 1-2D; when compound 1-2P3 has the structure of Formula 1-2D, compound 1-2P4 has the structure of Formula 1-2C.

[0309] 1-2P3 (tR=3.97 min), MS: [M+1) + : 298.15. 1 H NMR (400 MHz, CDCl3) δ(ppm): 7.44-7.40 (m, 3H), 7.28-7.16 (m, 2H), 6.15-5.99 (m, 1H), 5.77-5.72 (m,1H), 3.44-3.36 (m, 1H), 3.09-2.96 (m, 1H), 2.53 (s, 1H), 2.32 (s, 6H). 1-2P4 (tR=6.11 min), MS: [M+1) + : 298.20. 1H NMR (400 MHz, CDCl3) δ(ppm): 7.44-7.41 (m, 3H), 7.28-7.16 (m, 2H), 6.15-6.00 (m, 1H), 5.77-5.73 (m,1H), 3.44-3.36 (m, 1H), 3.07-3.00 (m, 1H), 2.53 (s, 1H), 2.32 (s, 6H). Example 3 Compound 1-3A: (3 S )-1-Cyclopropanoyl-3-phenylpyrrolidine; or compound 1-3B: (3 R )-1-Cyclopropanoyl-3-phenylpyrrolidine.

[0310]

[0311] Synthesis route:

[0312] Step-1: (3) S )-1-Cyclopropanoyl-3-phenylpyrrolidine (1-3A) or compound (3 R Preparation of 1-cyclopropanoyl-3-phenylpyrrolidine (1-3B): Under nitrogen protection, pyridine (1.83 g, 5 eq) and propylphosphonic anhydride (T3P, 5.88 g, 2 eq, 50% ethyl acetate solution) were added to a toluene (10 mL) solution of 3-phenylpyrrolidine (SM1, 680 mg, 1 eq) and cyclopropanoic acid (SM2, 398 mg, 1 eq) at room temperature. After the addition was complete, the system was stirred at room temperature for 16 h. After the reaction was complete, the mixture was quenched with saturated sodium bicarbonate aqueous solution at room temperature, extracted three times with ethyl acetate, and the organic phases were combined, washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The mixture was purified by high performance preparative liquid chromatography to obtain the racemic compound (1-3, 220 mg, purity: 95.4%).

[0313] Racemic compounds (1-3) were chirally resolved (column type: Lux Cellulose-3, 250 mm * 21.2 mm, 5 μm; mobile phase A: n-hexane (0.5% NH3 (2 M methanol solution)); mobile phase B: methanol: ethanol = 1:1; flow rate: 20 mL / min; mobile phase ratio (B%): 5% mobile phase B; wavelength: 254 / 220 nm) to give compounds 1-3P1 (tR = 12.85 min) and 1-3P2 (tR = 16.06 min).

[0314] Compounds 1-3P1 and 1-3P2 are one of the structures shown in Formula 1-3A or Formula 1-3B. That is, when compound 1-3P1 is the structure of Formula 1-3A, compound 1-3P2 is the structure of Formula 1-3B; when compound 1-3P1 is the structure of Formula 1-3B, compound 1-3P2 is the structure of Formula 1-3A.

[0315] 1-3P1(tR=12.85 min), MS: [M+1] + : 216.25. 1 H NMR (400 MHz, DMSO- d 6) δ(ppm): 7.33-7.23 (m, 5H), 4.13-4.09 (m, 1H), 3.85-3.81 (m, 1H), 3.67-3.57 (m,1H), 3.54-3.46 (m, 1H), 3.34-3.17 (m, 1H), 2.50-2.50 (m, 1H), 2.05-1.81 (m,1H), 1.80-1.77 (m, 1H), 0.77-0.69 (m, 4H). 1-3P2(tR=16.06 min), MS: [M+1] + : 216.20. 1 H NMR (400 MHz, DMSO- d 6) δ(ppm): 7.33-7.23 (m, 5H), 4.13-4.09 (m, 1H), 3.86-3.81 (m, 1H), 3.67-3.46 (m,2H), 3.34-3.17 (m, 1H), 2.51-2.50 (m, 1H), 2.05-1.93 (m, 1H), 1.81-1.77 (m,1H), 0.76-0.69 (m, 4H). Example 4 Compound 1-4A: ( S )-Cyclopropyl(3-(1H-indazol-1-yl)pyrrolidine-1-yl)methyl ketone; or compound 1-4B:( R )-Cyclopropyl(3-(1H-indazol-1-yl)pyrrolidine-1-yl)methyl ketone.

[0316]

[0317] Synthesis route:

[0318]

[0319] Step 1: Preparation of 3-(1H-indazole-1-yl)pyrrolidine-1-carboxylic acid tert-butyl ester (1-4-A): Under nitrogen protection, at room temperature, compound 1H-indazole (SM1, 0.82 g, 1 eq), 3-bromopyrrolidine-1-carboxylic acid tert-butyl ester (2.60 g, 1.5 eq), cesium carbonate (6.77 g, 3 eq), and potassium iodide (0.09 g, 0.08 eq) were added to... N,N In 10 mL of dimethylformamide (DMF), heat to 110 °C with stirring. o The reaction was carried out at C for 16 hours. After the reaction was complete, the reaction system was quenched with water, extracted three times with ethyl acetate, and the organic phases were combined. The mixture was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by normal-phase column chromatography to give intermediate 1-4-A (604 mg, yield: 32%). MS: [M+1] + : 288.

[0320] Step 2: Preparation of 1-(pyrrolidone-3-yl)-1H-indazole (1-4-B): Under nitrogen protection, compound 1-4-A (550 mg, 1 eq) was dissolved in 30 mL of ethyl acetate, and 1,4-dioxane-hydrochloric acid solution (4.0 M dioxane solution, 11 mL) was added at room temperature. The mixture was stirred at room temperature for 3 hours. The reaction was characterized by LCMS to indicate completion. The residue was concentrated under reduced pressure to give 1-4-B (380 mg, yield: 89%). The crude product was used directly in the next step without further purification.

[0321] Step 3: Preparation of (3-(1H-indazol-1-yl)pyrrolidine-1-yl)(cyclopropyl)methyl ketone (1-4): Under nitrogen protection, at room temperature, pyridine (1 mL, 5 eq) and propylphosphonic anhydride (T3P, 50% ethyl acetate solution, 1.6 g, 3 eq) were added to a toluene (20 mL) solution of compound 1-4-B (380 mg, 1 eq) and cyclopropylcarboxylic acid (SM2, 146 mg, 1.00 eq). The resulting reaction system was heated to 80°C. o The reaction was stirred for 12 hours. After the reaction was complete, it was quenched with saturated sodium bicarbonate aqueous solution at room temperature, extracted three times with ethyl acetate, the organic phases were combined, washed with saturated sodium chloride aqueous solution, dried with anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by high performance preparative liquid chromatography to obtain racemic compound (1-4, 49 mg, purity: 9.4%).

[0322] Racemic compounds (1-4) were chirally resolved (column type: CHIRAL ART Cellulose-SA, 250 mm * 20 mm, 5 μm; mobile phase A: n-hexane (0.5% NH3 (2 M methanol solution)); mobile phase B: ethanol: dichloromethane = 1:1; flow rate: 20 mL / min; mobile phase ratio (B%): 20% mobile phase B; wavelength: 254 / 220 nm) to give compounds 1-4P1 (tR = 6.56 min) and 1-4P2 (tR = 15.03 min).

[0323] Compounds 1-4P1 and 1-4P2 are one of the structures shown in Formula 1-4A or Formula 1-4B. That is, when compound 1-4P1 is the structure of Formula 1-4A, compound 1-4P2 is the structure of Formula 1-4B; when compound 1-4P1 is the structure of Formula 1-4B, compound 1-4P2 is the structure of Formula 1-4A.

[0324] 1-4P1 (tR=6.56 min), MS: [M+1) + : 256.10. 1 H NMR (400 MHz, DMSO- d 6) δ(ppm): 8.13 (d, J = 8.0 Hz, 1H), 7.80-7.72 (m, 2H), 7.44-7.40 (m, 1H), 7.19-7.15 (m, 1H), 5.64-5.39 (m, 1H), 4.20-4.10 (m, 0.5H), 3.98-3.85 (m, 1H),3.84-3.82 (m, 1H), 3.72-3.65 (m, 1H), 3.57-3.46 (m, 0.5H), 2.51-2.24 (m, 2H),1.83-1.70 (m, 1H), 0.76-0.69 (m, 4H) 1-4P2(tR=15.03 min), MS: [M+1] + : 256.10. 1 H NMR (400 MHz, DMSO- d 6) δ(ppm): 8.12 (d, J=8.0 Hz,1H), 7.80-7.72 (m, 2H), 7.44-7.39 (m, 1H), 7.19-7.15(m, 1H), 5.54-5.40 (m, 1H), 4.21-4.19 (m, 0.5H), 4.09-3.94 (m, 1H), 3.85-3.82(m, 1H), 3.71-3.70 (m, 1H), 3.58-3.48 (m, 0.5H), 2.51-2.47 (m, 2H), 1.89-1.71(m, 1H), 0.76-0.69 (m, 4H). Example 5 Compounds 1-5: (6-benzylbenzo[d]oxazol-2-yl)(cyclopropyl) methyl ketone.

[0325]

[0326] Synthesis route:

[0327] Step-1: 1-Cyclopropyl-2-(dimethyloxo-λ) 6 Preparation of 1-thionyl)ethyl-1-one (1-5-A): Under nitrogen protection, trimethyloxo-λ was added to potassium tert-butoxide (1.0 M tetrahydrofuran solution, 190 mL, 4 eq) solution at room temperature. 6 - Thionium iodide (SM2, 31.58 g, 3 eq), 80 o After stirring at C for 2 hours, the reaction system was cooled to 0°C, and cyclopropionyl chloride (SM1, 5 g, 1 eq) was added dropwise. After naturally returning to room temperature, the mixture was stirred for 3 hours. Upon completion of the reaction, a large amount of solid precipitated. The solid was filtered off, and the mother liquor was evaporated to dryness and purified by column chromatography to obtain compound 1-5-A (6.06 g, yield: 26%). MS: [M+1] + :161.

[0328] Step 2: Preparation of (6-bromobenzo[d]oxazol-2-yl)(cyclopropyl)methyl ketone (1-5-B): Under nitrogen protection, compound 2-amino-5-bromophenol (SM3, 400 mg, 1 eq) and compound 1-5-A (272 mg, 0.8 eq) were dissolved in methanol (8 mL) at room temperature. S8 (102 mg, 1.5 eq) was added at room temperature, and the mixture was heated to 60 °C and stirred for 16 hours. After the reaction was complete, the mixture was quenched with ice-cold brine, extracted three times with ethyl acetate, and the organic phases were combined, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The resulting product was purified by column chromatography to obtain compound 1-5-B (100 mg, yield: 18%). MS: [M+1] + : 266 / 268. Step-3: Preparation of (6-benzylbenzo[d]oxazol-2-yl)(cyclopropyl) methyl ketone (1-5): Compound 1-5-B (100 mg, 1 eq) and benzylboronic acid pinacol ester (SM4, 123 mg, 1.5 eq) were dissolved in tetrahydrofuran (2 mL), followed by the addition of allyl (2-dicyclohexylphosphino-2,4,6-triisopropyl-1,1-biphenyl)palladium chloride (XPhos Pd(crotyl)Cl, 25 mg, 0.1 eq), and potassium phosphate (478 mg, 6 eq) dissolved in 2 mL of water was added dropwise under nitrogen protection. The resulting reaction system was heated to 50°C and stirred for 16 hours. After the reaction was complete, water was added to quench the reaction. The mixture was extracted three times with ethyl acetate, and the organic phases were combined. The organic phases were washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The resulting product was purified by high-performance liquid chromatography (HPLC) to give compounds 1-5 (6.5 mg, yield: 4.2%). MS: [M+1] + : 278.15. 1 H NMR (400 MHz, DMSO- d 6) δ (ppm):7.91-7.89 (m, 1H), 7.78 (s, 1H), 7.32-7.30 (m, 1H), 7.27-7.21 (m, 4H), 7.18-7.16 (m, 1H), 4.13 (s, 2H), 3.18-3.12 (m, 1H), 1.25-1.17 (m, 4H). Example 6 Compound 1-6A: ((5 S 7 S )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)-(( R)-spiro[2.2]pentan-1-yl) methyl ketone, or compound 1-6B: ((5 S 7 S )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)-(( S )-spiro[2.2]pentane-1-yl) methyl ketone, or compound 1-6C: ((5 R 7 R )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)-(( R )-spiro[2.2]pentane-1-yl) methyl ketone, or compound 1-6D: ((5 R 7 R )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)-(( S )-spiro[2.2]pentane-1-yl) methyl ketone.

[0329]

[0330] Synthesis route:

[0331]

[0332]

[0333] Step-1: N -Methoxy- N Preparation of 1-methylspiro[2.2]pentane-1-carboxamide (1-6-A): Following the procedure in step 2 of Example 1, the bicyclic[2.2.2]octane-1-carboxylic acid was replaced with spiro[2.2]pentane-1-carboxylic acid to prepare compound 1-6-A.

[0334] Step-2: ((5) S 7 S )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)-(spiro[2,2]pentan-1-yl)methyl ketone (1-6-BA), or compound ((5 R 7 RPreparation of 1-6-BB (7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)-(spiro[2,2]pentan-1-yl)methyl ketone: Following step 8 in Example 1, 1-1-B was replaced with 1-6-A and reacted with cis-1-1-GA to prepare a mixture of 1-6-BA and 1-6-BB (200 mg, 95% purity).

[0335] A mixture of 1-6-BA and 1-6-BB was chirally resolved (column type: CHIRALPAK IM, 250 mm * 20 mm, 5 μm; mobile phase A: n-hexane; mobile phase B: ethanol: dichloromethane = 1:1; flow rate: 20 mL / min; mobile phase ratio (B%): 30% mobile phase B; wavelength: 254 / 220 nm) to give compound 1-6Y1 (tR = 8.68 min, 90 mg, purity 98%) and compound 1-6Y2 (tR = 12.13 min, 80 mg, purity 98%).

[0336] Compounds 1-6Y1 and 1-6Y2 have one of the structures shown in Formula 1-6-BA or Formula 1-6-BB. That is, when compound 1-6Y1 has the structure of Formula 1-6-BA, compound 1-6Y2 has the structure of Formula 1-6-BB; when compound 1-6Y1 has the structure of Formula 1-6-BB, compound 1-6Y2 has the structure of Formula 1-6-BA.

[0337] 1-6Y1 (tR=8.68 min), MS: [M+1] + : 298.20.

[0338] 1-6Y2 (tR=12.13 min), MS: [M+1] + : 298.10.

[0339] Step-3: ((5) S 7 S )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)-(( R )-spiro[2.2]pentan-1-yl)methyl ketone (1-6A), or compound ((5 S 7 S )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)-(( SPreparation of 1-spiro[2.2]pentan-1-yl)methyl ketone (1-6B): Compound 1-6-BA was chirally resolved (column type: CHIRAL ART Cellulose-SC, 250 mm * 20 mm, 5 μm; mobile phase A: n-hexane; mobile phase B: ethanol: dichloromethane = 1:1; flow rate: 20 mL / min; mobile phase ratio (B%): 30% mobile phase B; wavelength: 254 / 220 nm) to obtain compound 1-6P1 (tR = 8.97 min) and compound 1-6P2 (tR = 11.28 min).

[0340] Compounds 1-6P1 and 1-6P2 have one of the structures shown in Formula 1-6A, Formula 1-6B, Formula 1-6C, or Formula 1-6D. That is, when compound 1-6Y1 has the structure of Formula 1-6-BA, compounds 1-6P1 and 1-6P2 have one of the structures shown in Formula 1-6A or Formula 1-6B. Specifically, when compound 1-6P1 has the structure of Formula 1-6A, compound 1-6P2 has the structure of Formula 1-6B; when compound 1-6P1 has the structure of Formula 1-6B, compound 1-6P2 has the structure of Formula 1-6A. That is, when compound 1-6Y1 has the structure of formula 1-6-BB, compounds 1-6P1 and 1-6P2 have one of the structures shown in formula 1-6C or formula 1-6D. Specifically, when compound 1-6P1 has the structure of formula 1-6C, compound 1-6P2 has the structure of formula 1-6D; when compound 1-6P1 has the structure of formula 1-6D, compound 1-6P2 has the structure of formula 1-6C.

[0341] 1-6P1 (tR=8.97 min), MS: [M+1) + : 298.20. 1 H NMR (400 MHz, CDCl3) δ(ppm): 7.44-7.34 (m, 3H), 7.28-7.26 (m, 2H), 6.11-5.96 (m, 1H), 5.52-5.48 (m,1H), 3.68-3.61 (m, 1H), 3.43-3.41 (m, 1H), 2.99-2.96 (m, 1H), 1.89-1.87(m,1H), 1.63-1.59 (m, 1H), 1.07-1.00 (m, 2H), 0.95-0.86 (m, 2H). 1-6P2(tR=11.28 min), MS: [M+1] + : 298.10. 1H NMR (400 MHz, CDCl3) δ(ppm): 7.42-7.38 (m, 3H), 7.27-7.26 (m, 2H), 6.12-5.96 (m, 1H), 5.52-5.48 (m,1H), 3.68-3.61 (m, 1H), 3.42-3.38 (m, 1H), 3.02-2.95 (m, 1H), 1.87-1.85 (m,1H), 1.64-1.61 (m, 1H), 1.06-1.02 (m, 2H), 0.94-0.86 (m, 2H). Step-4: ((5) R 7 R )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)-(( R )-spiro[2.2]pentane-1-yl)methyl ketone (1-6C), or compound ((5 R 7 R )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)-(( S Preparation of 1-spiro[2.2]pentane-1-yl)methyl ketone (1-6D): Compound 1-6-BB was chirally resolved (column type: CHIRALPAK IH, 250 mm * 20 mm, 5 μm; mobile phase A: n-hexane; mobile phase B: ethanol: dichloromethane = 1:1; flow rate: 20 mL / min; mobile phase ratio (B%): 15% mobile phase B; wavelength: 254 / 220 nm) to obtain compound 1-6P3 (tR = 8.77 min) and compound 1-6P4 (tR = 11.26 min).

[0342] Compounds 1-6P3 and 1-6P4 have one of the structures shown in Formula 1-6A, Formula 1-6B, Formula 1-6C, or Formula 1-6D. That is, when compound 1-6Y2 has the structure of Formula 1-6-BA, compounds 1-6P3 and 1-6P4 have one of the structures shown in Formula 1-6A or Formula 1-6B; that is, when compound 1-6P3 has the structure of Formula 1-6A, compound 1-6P4 has the structure of Formula 1-6B; and when compound 1-6P3 has the structure of Formula 1-6B, compound 1-6P4 has the structure of Formula 1-6A. That is, when compound 1-6Y2 has the structure of formula 1-6-BB, compounds 1-6P3 and 1-6P4 have one of the structures shown in formula 1-6C or formula 1-6D. Specifically, when compound 1-6P3 has the structure of formula 1-6C, compound 1-6P4 has the structure of formula 1-6D; when compound 1-6P3 has the structure of formula 1-6D, compound 1-6P4 has the structure of formula 1-6C.

[0343] 1-6P3 (tR=8.77 min), MS: [M+1) + : 298.10. 1 H NMR (400 MHz, CDCl3) δ(ppm): 7.43-7.38 (m, 3H), 7.28-7.26 (m, 2H), 6.12-5.96 (m, 1H), 5.52-5.49 (m,1H), 3.68-3.60 (m, 1H), 3.43-3.40 (m, 1H), 2.98-2.92 (m, 1H), 1.89-1.87(m,1H), 1.63-1.60 (m, 1H), 1.04-1.00 (m, 2H), 0.97-0.84 (m, 2H). 1-6P4(tR=11.26 min), MS: [M+1] + : 298.15. 1 H NMR (400 MHz, CDCl3) δ(ppm): 7.43-7.39 (m, 3H), 7.28-7.26 (m, 2H), 6.11-5.96 (m, 1H), 5.52-5.48 (m,1H), 3.70-3.60 (m, 1H), 3.42-3.40 (m, 1H), 3.02-2.91 (m, 1H), 1.87-1.85 (m,1H), 1.64-1.61 (m, 1H), 1.07-1.02 (m, 2H), 0.95-0.86 (m, 2H). Example 7 Compound 1-7A: ((5R 7 S )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)-(( R )-spiro[2.2]pentan-1-yl) methyl ketone, or compound 1-7B: ((5 R 7 S )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)-(( S )-spiro[2.2]pentan-1-yl) methyl ketone, or compound 1-7C: ((5 S 7 R )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)-(( R )-spiro[2.2]pentan-1-yl) methyl ketone, or compound 1-7D: ((5 S 7 R )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)-(( S )-spiro[2.2]pentane-1-yl) methyl ketone.

[0344]

[0345] Synthesis route:

[0346]

[0347]

[0348] Step-1: ((5) R 7 S )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)-(spiro[2,2]pentan-1-yl)methyl ketone (1-7-AA), or compound ((5 S, 7 R Preparation of 1-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)-(spiro[2,2]pentan-1-yl)methyl ketone (1-7-AB): Following step 8 in Example 1, 1-1-B was replaced with 1-6-A and reacted with trans-1-1-GB to prepare a mixture of 1-7-AA and 1-7-AB (200 mg, 95% purity).

[0349] A mixture of 1-7-AA and 1-7-AB was chirally resolved (column type: CHIRALPAK IM, 250 mm * 20 mm, 5 μm; mobile phase A: n-hexane; mobile phase B: ethanol: dichloromethane = 1:1; flow rate: 20 mL / min; mobile phase ratio (B%): 30% mobile phase B; wavelength: 254 / 220 nm) to give compound 1-7Y1 (tR = 5.68 min, 90 mg, purity 98%) and compound 1-7Y2 (tR = 7.28 min, 80 mg, purity 98%).

[0350] Compounds 1-7Y1 and 1-7Y2 have one of the structures shown in Formula 1-7-AA or Formula 1-7-AB. That is, when compound 1-7Y1 has the structure of Formula 1-7-AA, compound 1-7Y2 has the structure of Formula 1-7-AB; when compound 1-7Y1 has the structure of Formula 1-7-AB, compound 1-7Y2 has the structure of Formula 1-7-AA.

[0351] 1-7Y1 (tR=5.68 min), MS: [M+1] + : 298.15.

[0352] 1-7Y2 (tR=7.28 min), MS: [M+1] + : 298.10.

[0353] Step-2: ((5) R 7 S )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)-(( R )-spiro[2.2]pentan-1-yl)methyl ketone (1-7A), or compound ((5 R 7 S )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)-(( S Preparation of 1-spiro[2.2]pentane-1-yl)methyl ketone (1-7B): Compound 1-7-AA was chirally resolved (column type: CHIRALPAK IH, 250 mm * 20 mm, 5 μm; mobile phase A: n-hexane; mobile phase B: ethanol: dichloromethane = 1:1; flow rate: 20 mL / min; mobile phase ratio (B%): 15% mobile phase B; wavelength: 254 / 220 nm) to obtain compound 1-7P1 (tR = 7.43 min) and compound 1-7P2 (tR = 8.78 min).

[0354] Compounds 1-7P1 and 1-7P2 have one of the structures shown in Formula 1-7A, Formula 1-7B, Formula 1-7C, or Formula 1-7D. That is, when compound 1-7Y1 has the structure of Formula 1-7-AA, compounds 1-7P1 and 1-7P2 have one of the structures shown in Formula 1-7A or Formula 1-7B. Specifically, when compound 1-7P1 has the structure of Formula 1-7A, compound 1-7P2 has the structure of Formula 1-7B; when compound 1-7P1 has the structure of Formula 1-7B, compound 1-7P2 has the structure of Formula 1-7A. That is, when compound 1-7Y1 has the structure of formula 1-7-AB, compounds 1-7P1 and 1-7P2 have one of the structures shown in formula 1-7C or formula 1-7D. Specifically, when compound 1-7P1 has the structure of formula 1-7C, compound 1-7P2 has the structure of formula 1-7D; when compound 1-7P1 has the structure of formula 1-7D, compound 1-7P2 has the structure of formula 1-7C.

[0355] 1-7P1 (tR=7.43 min), MS: [M+1) + : 298.15. 1 H NMR (400 MHz, CDCl3) δ(ppm): 7.44-7.41 (m, 3H), 7.19-7.16 (m, 2H), 6.17-6.02 (m, 1H), 5.76-5.72 (m,1H), 3.48-3.36 (m, 2H), 3.10-2.96 (m, 1H), 1.91-1.89 (m, 1H), 1.63-1.62 (m,1H), 1.07-1.00 (m, 2H), 0.97-0.85 (m, 2H). 1-7P2 (tR=8.78 min), MS: [M+1) + : 298.15. 1 H NMR (400 MHz, CDCl3) δ(ppm): 7.42-7.39 (m, 3H), 7.16-7.14 (m, 2H), 6.15-6.00 (m, 1H), 5.74-5.70 (m,1H), 3.41-3.38 (m, 2H), 3.07-3.00 (m, 1H), 1.85-1.83 (m, 1H), 1.62-1.59 (m,1H), 1.05-0.98 (m, 2H), 0.92-0.85 (m, 2H). Step-3: ((5) S 7 R)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)-(( R )-spiro[2.2]pentane-1-yl)methyl ketone (1-7C), or compound ((5 S 7 R )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)-(( S Preparation of 1-spiro[2.2]pentane-1-yl)methyl ketone (1-7D): Compound 1-7-AB was chirally resolved (column type: CHIRALPAK IH, 250 mm * 20 mm, 5 μm; mobile phase A: n-hexane; mobile phase B: ethanol: dichloromethane = 1:1; flow rate: 20 mL / min; mobile phase ratio (B%): 30% mobile phase B; wavelength: 254 / 220 nm) to obtain compound 1-7P3 (tR = 5.13 min) and compound 1-7P4 (tR = 6.80 min).

[0356] Compounds 1-7P3 and 1-7P4 have one of the structures shown in Formula 1-7A, Formula 1-7B, Formula 1-7C, or Formula 1-77D. That is, when compound 1-7Y2 has the structure of Formula 1-7-AA, compounds 1-7P3 and 1-7P4 have one of the structures shown in Formula 1-7A or Formula 1-7B. Specifically, when compound 1-7P3 has the structure of Formula 1-7A, compound 1-7P4 has the structure of Formula 1-7B; when compound 1-7P3 has the structure of Formula 1-7B, compound 1-7P4 has the structure of Formula 1-7A. That is, when compound 1-7Y2 has the structure of formula 1-7-AB, compounds 1-7P3 and 1-7P4 have one of the structures shown in formula 1-7C or formula 1-7D. Specifically, when compound 1-7P3 has the structure of formula 1-7C, compound 1-7P4 has the structure of formula 1-7D; when compound 1-7P3 has the structure of formula 1-7D, compound 1-7P4 has the structure of formula 1-7C.

[0357] 1-7P3 (tR=5.13 min), MS: [M+1) + : 298.10. 1H NMR (400 MHz, CDCl3) δ(ppm): 7.43-7.39 (m, 3H), 7.16-7.14 (m, 2H), 6.15-6.00 (m, 1H), 5.74-5.70 (m,1H), 3.41-3.38 (m, 2H), 3.07-2.96 (m, 1H), 1.85-1.83 (m, 1H), 1.66-1.64 (m,1H), 1.05-0.98 (m, 2H), 0.92-0.85 (m, 2H). 1-7P4 (tR=6.80 min), MS: [M+1) + : 298.15. 1 H NMR (400 MHz, CDCl3) δ(ppm): 7.42-7.38 (m, 3H), 7.16-7.14 (m, 2H), 6.15-5.99 (m, 1H), 5.73-5.70 (m,1H), 3.42-3.39 (m, 2H), 3.07-2.96 (m, 1H), 1.89-1.87 (m, 1H), 1.61-1.59 (m,1H), 1.04-0.98 (m, 2H), 0.93-0.85 (m, 2H). Example 8 Compound 1-8A: (bicyclo[2.2.1]heptane-7-yl)((5 S 7 S )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl) methyl ketone, or compound 1-8B: (bicyclo[2.2.1]heptane-7-yl)((5 R 7 R )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl) methyl ketone.

[0358]

[0359] Synthesis route:

[0360] Step-1 and Step-2: (bicyclo[2.2.1]heptane-7-yl)((5 S 7 S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl) methyl ketone (1-8A), or compound (bicyclo[2.2.1]heptane-7-yl)((5 R 7 R Preparation of 7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)methyl ketone (1-8B): Following steps 1 to 2 in Example 2, bicyclic [1.1.1]pentane-1-carboxylic acid was replaced with bicyclic [2.2.1]heptane-7-carboxylic acid to prepare 99 mg of racemic cis compound.

[0361] Racemic cis compounds were chirally resolved (column type: (R,R)-WHELK-O1, 250 mm * 20 mm, 5 μm; mobile phase A: n-hexane (0.5% NH3 (2M methanol solution)); mobile phase B: methanol: dichloromethane = 1:1; flow rate: 20 mL / min; mobile phase ratio (B%): 50% mobile phase B; wavelength: 254 / 220 nm) to give compounds 1-8P1 (tR = 5.76 min) and 1-8P2 (tR = 9.56 min).

[0362] Compounds 1-8P1 and 1-8P2 are one of the structures shown in Formula 1-8A or Formula 1-8B. That is, when compound 1-8P1 is the structure of Formula 1-8A, compound 1-8P2 is the structure of Formula 1-8B; when compound 1-8P1 is the structure of Formula 1-8B, compound 1-8P2 is the structure of Formula 1-8A.

[0363] 1-8P1 (tR=5.76 min), MS: [M+1) + : 326.25. 1 H NMR (400 MHz, CD3OD) δ(ppm): 7.45-7.39 (m, 3H), 7.29-7.26(m, 2H), 6.19-6.03(m, 1H), 5.66-5.62 (m,1H), 3.79-3.73 (m, 1H), 2.81-2.76 (m, 1H), 2.62-2.60 (m, 1H), 2.56-2.54 (m,1H), 1.77-1.70 (m, 4H), 1.31-1.26 (m, 4H) 1-8P2 (tR=9.56 min), MS: [M+1) + : 326.25. 1H NMR (400 MHz, CD3OD) δ(ppm): 7.45-7.39 (m, 3H), 7.29-7.26(m, 2H), 6.19-6.03(m, 1H), 5.66-5.62 (m,1H), 3.81-3.73 (m, 1H), 2.87-2.77 (m, 1H), 2.62-2.56 (m, 2H), 1.90-1.76 (m,4H), 1.31-1.14 (m, 4H). Example 9 Compounds 1-9A: (bicyclo[2.1.1]hexane-5-yl)((5 S 7 S )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl) methyl ketone, or compound 1-9B: (bicyclo[2.1.1]hexane-5-yl)((5 R 7 R )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl) methyl ketone.

[0364]

[0365] Synthesis route:

[0366] Step-1 and Step-2: (bicyclo[2.1.1]hexane-5-yl)((5 S 7 S )-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl) methyl ketone (1-9A), or compound (bicyclo[2.1.1]hexane-5-yl)((5 R 7 R Preparation of 7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl)methyl ketone (1-9B): Following steps 1 to 2 in Example 2, bicyclic [2.2.1]heptane-7-carboxylic acid was replaced with bicyclic [2.1.1]hexane-5-carboxylic acid to prepare 130 mg of racemic cis compound.

[0367] The racemic cis compound was chirally resolved (column type: CHIRALPAK IM, 250 mm * 20 mm, 5 μm; mobile phase A: n-hexane (0.5% NH3 (2M methanol solution)); mobile phase B: methanol: dichloromethane = 1:1; flow rate: 20 mL / min; mobile phase ratio (B%): 20% mobile phase B; wavelength: 254 / 220 nm) to give compound 1-9P1 (tR = 11.56 min) and compound 1-9P2 (tR = 12.89 min).

[0368] Compounds 1-9P1 and 1-9P2 are one of the structures shown in Formula 1-9A or Formula 1-9B. That is, when compound 1-9P1 is the structure of Formula 1-9A, compound 1-9P2 is the structure of Formula 1-9B; when compound 1-9P1 is the structure of Formula 1-9B, compound 1-9P2 is the structure of Formula 1-9A.

[0369] 1-9P1(tR=11.56 min), MS: [M+1] + : 312.10. 1 H NMR (400 MHz, CDCl3) δ(ppm): 7.42-7.40 (m, 3H), 7.29-7.24 (m, 2H), 6.10-5.95 (m, 1H), 5.50-5.48 (m,1H), 3.70-3.59 (m, 1H), 3.11 (s, 1H), 3.02-2.91 (m, 3H), 1.75-1.72 (m, 2H), 1.61-1.56 (m, 2H), 1.28-1.26 (m, 1H), 0.87-0.85 (m, 1H). 1-9P2(tR=12.89 min), MS: [M+1] + : 312.15. 1 H NMR (400 MHz, CDCl3) δ(ppm): 44-7.41 (m, 3H), 7.29-7.24 (m, 2H), 6.11-5.95 (m, 1H), 5.52-5.48 (m,1H), 3.69-3.61 (m, 1H), 3.11-2.91 (m, 4H) 1.77-1.70 (m, 2H), 1.60-1.58 (m,2H), 1.28-1.24 (m, 1H), 0.88-0.86 (m, 1H). Example 10 Compounds 1-10: Cyclopropyl(6-fluoro-4-phenyl-5,6-dihydro-4H-cyclopentadieno[d]thiazolyl) methyl ketone

[0370] Synthesis route:

[0371]

[0372]

[0373] Step 1: Preparation of methyl 2-amino-4-benzylthiazolyl-5-carboxylate (1-10-A): SM1 (10 g, 1 eq), SM2 (7.9 g, 2 eq), and azobisisobutyronitrile (1.7 g, 0.2 eq) were dissolved in 270 mL of methanol. After dissolution, tert-butyl hydroperoxide solution (26.8 g, 4 eq, 70% purity) was added dropwise with stirring at room temperature. After the addition was complete, the system was stirred overnight at room temperature. The reaction mixture was alkalized to pH 8 with saturated sodium bicarbonate aqueous solution. The resulting residue was concentrated by rotary evaporation under reduced pressure. The aqueous phase was extracted with dichloromethane. The combined organic phases were washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The residue was purified by normal-phase column chromatography to obtain intermediate 1-10-A (7 g, yield: 54%). MS: [M+1] + : 249.

[0374] Step-2: 4-Benzyl-2-((triphenyl-λ) 5 Preparation of methyl 1-10-B (phosphine-amino-thiazolyl-5-carboxylate): Triphenylphosphine (11.1 g, 1.5 eq) was dissolved in 70 mL of tetrahydrofuran. The solution was cooled to 0 °C, and diisopropyl azodicarbonate (8.5 g, 1.5 eq) was added dropwise. After the addition was complete, the mixture was stirred at 0 °C for 20 minutes. While maintaining the temperature, a tetrahydrofuran solution of 1-10-A (7 g, 1 eq) was added dropwise, and the reaction was stirred for 4 hours. The reaction mixture was quenched with saturated ammonium chloride aqueous solution, extracted three times with ethyl acetate, and the organic phases were combined, washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by normal-phase column chromatography to obtain intermediate 1-10-B (4 g, yield: 28%). MS: [M+1] + : 509.

[0375] Step-3: 4-(3-ethoxy-3-oxo-1-phenylpropyl)-2-((triphenyl-λ) 5Preparation of methyl 1-10-C (phosphine-amino)thiazole-5-carboxylate: 1-10-B (4 g, 1 eq) was dissolved in 70 mL of tetrahydrofuran. Under nitrogen protection, the mixture was stirred and cooled to -78 °C. While maintaining the temperature, potassium bis(trimethylsilyl)amino (1.0 M in THF) (10 mL, 1.3 eq) was added dropwise. After stirring for 30 min, ethyl bromoacetate (SM3, 1.6 g, 1.2 eq) was added dropwise at -78 °C. After the addition was complete, the system was slowly heated to room temperature and stirred for 2 hours. The reaction mixture was quenched with saturated ammonium chloride aqueous solution, extracted three times with ethyl acetate, and the organic phases were combined, washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by normal-phase column chromatography to obtain intermediate 1-10-C (3.8 g, yield: 82%). MS: [M+1] + : 595.

[0376] Step-4: 5-Carboxylic acid ethyl ester-6-oxo-4-phenyl-2-(triphenyl-λ) 5 Preparation of 1-10-D (-phosphoiminoamino)-5,6-dihydro-4H-cyclopentano[d]thiazole: Under nitrogen protection, a toluene solution of potassium tert-amyloxide (10.2 g, 4 eq, 25% toluene) was added to a 50 mL toluene solution of 1-10-C (3 g, 1 eq) at -15 °C with stirring. After stirring at -15 °C for 30 min, the reaction mixture was quenched at -15 °C by adding acetic acid (1.8 g, 6 eq) in ethyl acetate (300 mL). Then, saturated sodium bicarbonate aqueous solution (150 mL) was added, followed by extraction with ethyl acetate three times. The organic phases were combined, washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by normal-phase column chromatography to obtain intermediate 1-10-D (2.2 g, yield: 78%). MS: [M+1] + : 563.

[0377] Step-5: 4-Phenyl-2-(triphenyl-λ) 5 Preparation of 1-10-E (-phosphoiminoamino)-4,5-dihydro-6H-cyclopentano[d]thiazol-6-one: 1-10-D (2 g, 1 eq) was dissolved in a mixed solvent of dimethyl sulfoxide (15 mL), tetrahydrofuran (10 mL), and water (3 mL). The mixture was heated in an oil bath to 100 °C under nitrogen protection and stirred for 16 hours. After cooling to room temperature, the tetrahydrofuran was evaporated under reduced pressure, and water was added with stirring to precipitate the solid. The solid was filtered, washed with water, and dried to obtain crude intermediate 1-10-E (1.4 g). No further purification was required; it was used directly in the next reaction. MS: [M+1] + : 491.

[0378] Step 6: Preparation of 2-amino-4-phenyl-4,5-dihydro-6H-cyclopentano[d]thiazol-6-one (1-10-F): Under nitrogen protection, 20% sulfuric acid (1.4 g) was added to 30 mL of a 1,4-dioxane solution containing 1-10-E (1.4 g, 1 eq) at room temperature. After the addition was complete, the system was stirred overnight at room temperature. The reaction mixture was alkalized to pH 8 with saturated sodium bicarbonate solution, extracted three times with ethyl acetate, and the organic phases were combined, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and subjected to normal-phase column chromatography to obtain crude intermediate 1-10-F (860 mg) with low purity. No further purification was performed; it was used directly in the next reaction. MS: [M+1] + : 231.

[0379] Step 7: Preparation of 2-bromo-4-phenyl-4,5-dihydro-6H-cyclopentano[d]thiazolyl-6-one (1-10-G): Copper bromide (776 mg, 1 eq) was added to 40 mL of acetonitrile solution of 1-10-F (800 mg, 1 eq) at 0 °C. After nitrogen purging, tert-butyl nitrite (538 mg, 1.5 eq) was added dropwise with stirring. After the addition was complete, the mixture was stirred overnight at room temperature. The reaction mixture was quenched with saturated ammonium chloride aqueous solution at room temperature. The resulting aqueous mixture was extracted three times with ethyl acetate by rotary evaporation under reduced pressure. The organic phases were combined, washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The solution was purified by normal-phase column chromatography to obtain intermediate 1-10-G (610 mg, purity: 95%). MS: [M+1] + : 296 / 294.

[0380] Step-8: Preparation of 2-bromo-4-phenyl-5,6-dihydro-4H-cyclopentano[d]thiazol-6-ol (1-10-H): Sodium borohydride (115.74 mg, 1.5 eq) was added to a solution of 1-10-G (600 mg, 1 eq) in methanol (18 mL) and tetrahydrofuran (4 mL) at 0 °C, and the mixture was slowly heated to room temperature for 4 hours with stirring. The reaction mixture was quenched with saturated sodium bicarbonate solution at room temperature, extracted three times with ethyl acetate, and the organic phases were combined, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by normal-phase column chromatography to give intermediate 1-10-H (550 mg, yield: 83%). MS: [M+1] + : 298 / 296.

[0381] Step-9: Preparation of 2-bromo-6-fluoro-4-phenyl-5,6-dihydro-4H-cyclopentano[d]thiazole (1-10-I): Bis(2-methoxyethyl)aminosulfur trifluoride (747 mg, 2 eq) was added to a solution of 1-10-H (500 mg, 1 eq) in 1,2-dichloroethane (15 mL) at room temperature. After the addition was complete, the system was stirred at 70 °C for 4 hours. The reaction system was cooled to 0 °C and quenched with a saturated ammonium chloride aqueous solution. The resulting mixture was extracted three times with dichloromethane. The combined organic phases were washed with a saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by normal-phase column chromatography to obtain intermediate 1-10-I (100 mg, yield: 20%). MS: [M+1] + 300 / 298. Step-10: Preparation of cyclopropyl(6-fluoro-4-phenyl-5,6-dihydro-4H-cyclopentadieno[d]thiazolyl-2-yl) ketone (1-10): Under nitrogen protection, 1-10-I (70 mg, 1 eq) and SM4 (45.48 mg, 1.5 eq) were dissolved in tetrahydrofuran (4 mL) at -15 °C. Isopropyl magnesium chloride-lithium chloride solution (0.36 mL, 2 eq, 1.3 M in THF) was added dropwise with stirring. After the addition was complete, the reaction system was kept at 0 °C and stirred for 4 hours. The mixture was cooled to -10 °C and quenched with saturated ammonium chloride aqueous solution. The mixture was extracted three times with ethyl acetate, and the organic phases were combined, washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product 1-10 (30 mg, purity: 70%) with low purity was obtained by normal-phase column chromatography. 1-10 (5.5 mg, yield: 8.3%) was obtained by purification via AChiral SFC. MS: [M+1] + : 288.00. 1 H NMR (400 MHz, CDCl3) δ:7.41-7.23 (m, 5H), 6.25-6.08 (m, 1H), 4.42-4.37 (m, 1H), 3.53-3.43 (m, 1H), 3.15-3.10 (m, 1H), 2.76-2.66 (m, 1H), 1.35-1.29 (m, 2H), 1.15-1.11 (m, 2H).

[0382] Example 11 Compound 1-11A: ( R)-2-Cyclobutyl-4-phenyl-2,4,5,6-tetrahydrocyclopentano[c]pyrazole-3-ol, or compound 1-11B: (S)-2-cyclobutyl-4-phenyl-2,4,5,6-tetrahydrocyclopentano[c]pyrazole-3-ol.

[0383]

[0384] Synthesis route:

[0385]

[0386] Step 1: Preparation of methyl 3-oxo-6-phenylhexanoate (1-11-A): Under nitrogen protection, a solution of potassium monomethyl malonate (57.1 g, 1.5 eq) and magnesium dichloride (23.2 g, 1 eq) in tetrahydrofuran (400 mL) was stirred and reacted for 3 hours at 65 °C. Then, a solution of phenylbutyric acid (40 g, 1 eq) and N,N'-carbonyldiimidazole (41.5 g, 1.05 eq) in tetrahydrofuran (400 mL) was stirred and reacted for 1 hour at 40 °C. Afterwards, the reaction system of potassium monomethyl malonate was adjusted to 30 °C, and the reaction system of phenylbutyric acid was added. The resulting mixture was stirred and reacted for 16 hours. The reaction mixture was quenched by adding hydrochloric acid solution (300 mL, 1 M) at 0 °C. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined, washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by normal phase column chromatography to obtain intermediate 1-11-A (46 g, yield: 86%).

[0387] Step 2: Preparation of methyl 2-diazo-3-oxo-6-phenylhexanoate (1-11-B): Under nitrogen protection, at 0°C, triethylamine (42.3 g, 2 eq) was added dropwise to a solution of 1-11-A (46 g, 1 eq) and 4-acetaminobenzenesulfonyl azide (75.3 g, 1.5 eq) in dichloromethane (3680 mL). The reaction system was stirred for 16 hours. The reaction mixture was quenched with an aqueous sodium hydroxide solution (400 mL, 2 M). The organic phase was separated, acidified to pH 5 with an aqueous acetic acid solution (10%), washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by normal-phase column chromatography to obtain intermediate 1-11-B (43 g, yield: 84%).

[0388] Step 3: Preparation of methyl 2-oxo-5-phenylcyclopentane-1-carboxylate (1-11-C): At room temperature, bis[(A,A,A',A'-tetramethyl-1,3-phenylenedipropionic acid)rhodium) (3.99 g, 0.03 eq) and dichloromethane (430 mL) were added to a 2000 mL three-necked flask. The system was cooled to -40 °C, and 1-11-B (43 g, 1 eq) of dichloromethane (430 mL) was slowly added dropwise at a flow rate of 1 mL / min using a syringe pump while stirring. After the addition was complete, the system was allowed to warm to room temperature naturally, and characterization showed that the reaction was complete. The resulting residue was directly concentrated under reduced pressure and purified by normal-phase column chromatography to obtain 1-11-C (30 g, yield: 82%).

[0389] Step-4: ( R )-2-cyclobutyl-4-phenyl-2,4,5,6-tetrahydrocyclopentano[c]pyrazole-3-ol (1-11A), or compound ( S Preparation of 2-cyclobutyl-4-phenyl-2,4,5,6-tetrahydrocyclopentano[c]pyrazole-3-ol (1-11B): Under nitrogen protection, SM3 (899 mg, 2 eq) was added to a methanol (10 mL) solution of compound 1-11-C (800 mg, 1 eq) at room temperature. After stirring the system for 2 hours, a methanol solution of sodium methoxide (3, 5 eq, 30% in MeOH) was added dropwise at room temperature. The resulting system was heated to 70 °C and stirred for 1 hour. After the reaction was completed, the residue was concentrated under reduced pressure and purified by reversed-phase column chromatography to obtain the racemic mixture (240 mg).

[0390] Racemic compounds were chirally resolved (column type: (R, R)-WHELK-O1, 250 mm * 21.2 mm, 5 μm; mobile phase A: n-hexane; mobile phase B: ethanol: dichloromethane = 1:1; flow rate: 20 mL / min; mobile phase ratio (B%): 40% mobile phase B; wavelength: 254 / 220 nm) to give compounds 1-11P1 (tR = 4.23 min) and 1-11P2 (tR = 7.89 min).

[0391] Compounds 1-11P1 and 1-11P2 have one of the structures shown in Formula 1-11A or Formula 1-11B. That is, when compound 1-11P1 has the structure of Formula 1-11A, compound 1-11P2 has the structure of Formula 1-11B; when compound 1-11P1 has the structure of Formula 1-11B, compound 1-11P2 has the structure of Formula 1-11A.

[0392] 1-11P1(tR=4.23 min), MS: [M+1] +: 255.25. 1 H NMR (400 MHz, DMSO- d 6) δ(ppm): 7.27-7.15 (m, 5H), 4.70-4.63 (m, 1H), 4.11-4.08 (m, 1H), 2.81-2.77 (m,1H), 2.63-2.51 (m, 2H), 2.48-2.40 (m, 2H), 2.24-2.19 (m, 2H), 2.07-2.04 (m,1H), 1.72-1.68 (m, 2H). 1-11P2(tR=7.89 min), MS: [M+1] + : 255.25. 1 H NMR (400 MHz, DMSO- d 6) δ(ppm): 7.27-7.17 (m, 5H), 4.72-4.65 (m, 1H), 4.11-4.07 (m, 1H), 2.83-2.76 (m,1H), 2.67-2.50 (m, 2H), 2.48-2.40 (m, 2H), 2.24-2.19 (m, 2H), 2.07-2.04 (m,1H), 1.74-1.68 (m, 2H). Example 12 Compound 1-12A: ( S )-Cyclopropyl(3-hydroxy-4-phenyl-5,6-dihydrocyclopenten[c]pyrazol-2(4H)-yl) ketone, or compound 1-12B: ( R )-Cyclopropyl(3-hydroxy-4-phenyl-5,6-dihydrocyclopentenyl[c]pyrazole-2(4H)-yl) methyl ketone.

[0393]

[0394] Synthesis route:

[0395] Step 1: Preparation of 4-phenyl-2,4,5,6-tetrahydrocyclopenteno[c]pyrazole-3-ol (1-12-A): Hydrazine (176.20 mg, 1.5 eq) was added to a methanol (20 mL) solution of 1-11-C (176.2 mg, 1 eq). The mixture was heated to 50 °C and stirred for 2 hours under nitrogen protection. Then, a methanol solution of sodium methoxide (1.65 g, 30% in MeOH) was added, and the reaction mixture was heated to 70 °C and stirred for 16 hours. After vacuum distillation, the resulting mixture was purified by reversed-phase column chromatography to give compound 1-12-A (280 mg, yield: 38%). MS: [M+1] + 201. Step-2: ( S )-Cyclopropyl(3-hydroxy-4-phenyl-5,6-dihydrocyclopenten[c]pyrazol-2(4H)-yl) methyl ketone (1-12A), or compound ( R Preparation of cyclopropyl(3-hydroxy-4-phenyl-5,6-dihydrocyclopenten[c]pyrazol-2(4H)-yl) ketone (1-12B): 1-12-A (200 mg, 1 eq) and cyclopropionic acid (172 mg, 2 eq) were mixed in 10 mL of toluene, followed by the addition of 1-propylphosphoric anhydride (T3P, 1.27 g, 2 eq) and pyridine (395 mg, 5 eq). The resulting mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with ethyl acetate, backwashed three times with saturated sodium chloride solution, dried over anhydrous sodium chloride, filtered, and evaporated to dryness. The crude product was purified by normal-phase column chromatography to obtain a racemic compound.

[0396] The racemic compounds were chirally resolved (column type: CHIRALPAK IK 250 mm * 20 mm, 5 μm; mobile phase A: n-hexane; mobile phase B: ethanol: dichloromethane = 1:1; flow rate: 20 mL / min; mobile phase ratio (B%): 15% mobile phase B; wavelength: 254 / 220 nm) to give compounds 1-12P1 (tR = 7.77 min) and 1-12P2 (tR = 10.19 min).

[0397] Compounds 1-12P1 and 1-12P2 have one of the structures shown in Formula 1-12A or Formula 1-12B. That is, when compound 1-12P1 has the structure of Formula 1-12A, compound 1-12P2 has the structure of Formula 1-12B; when compound 1-12P1 has the structure of Formula 1-12B, compound 1-12P2 has the structure of Formula 1-12A.

[0398] 1-12P1(tR=7.77 min), MS: [M+1] +: 269.15. 1 H NMR (400 MHz, DMSO- d 6) δ(ppm): 10.92 (s, 1H), 7.31-7.28 (m, 2H), 7.22-7.17 (m, 3H), 4.16-4.14 (m,1H), 3.04-3.00 (m, 2H), 2.99-2.91 (m, 1H), 2.79 (s, 1H), 2.29-2.23 (m, 1H), 1.08-1.01 (m, 4H). 1-12P2(tR=10.19 min), MS: [M+1] + : 269.10. 1 H NMR (400 MHz, DMSO- d 6) δ(ppm): 10.93 (s, 1H), 7.32-7.28 (m, 2H), 7.22-7.17 (m, 3H), 4.17-4.14 (m,1H), 3.04-3.00 (m, 2H), 2.99-2.91 (m, 1H), 2.79 (s, 1H), 2.29-2.24 (m, 1H), 1.08-1.01 (m, 4H). Example 13 Compound 1-13A: ( S )-Cyclopropyl(2,3,5',6'-tetrahydrospiro[indene-1,7'-pyrrolo[1,2-b][1,2,4]triazol]-2'-yl) methyl ketone, or compound 1-13B: ( R )-Cyclopropyl(2,3,5',6'-Tetrahydrospiro[indene-1,7'-pyrrolo[1,2-b][1,2,4]triazole]-2'-yl) methyl ketone.

[0399]

[0400] Synthesis route:

[0401] Step-1: N -Methoxy- N Preparation of 1-methyl-2,3,5',6'-tetrahydrospiro[indene-1,7'-pyrrolo[1,2-b][1,2,4]triazole]-2'-carboxamide (1-13-A): Compound 1-13-A was prepared by replacing dimethylamine hydrochloride with dimethylhydroxyamine hydrochloride in step 2 of Example 12.

[0402] Step-2: Preparation of cyclopropyl(2,3,5',6'-tetrahydrospiro[indene-1,7'-pyrrolo[1,2-b][1,2,4]triazol]-2'-yl) methyl ketone (1-13-B): Under nitrogen protection and stirring at 0°C, cyclopropyl magnesium bromide (1 M in tetrahydrofuran, 0.65 ml, 1.3 eq) was added dropwise to a mixed solution of compound 1-13-A (150 mg, 1 eq) and tetrahydrofuran (10 mL). The ice bath was removed, and the reaction was continued for 1 hour with stirring. The reaction solution was quenched by adding saturated ammonium chloride aqueous solution. The mixture was extracted three times with ethyl acetate, and the organic phases were combined, washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The organic phase was purified by preparative liquid chromatography under high pressure to obtain compound 1-13-B (102 mg, yield: 73.4%).

[0403] Step-3: ( S )-Cyclopropyl(2,3,5',6'-tetrahydrospiro[indene-1,7'-pyrrolo[1,2-b][1,2,4]triazol]-2'-yl)methyl ketone (1-13A), or the compound: ( R Preparation of cyclopropyl(2,3,5',6'-tetrahydrospiro[indene-1,7'-pyrrolo[1,2-b][1,2,4]triazol]-2'-yl) methyl ketone (1-13B): Racemic compound 1-13-B was chirally resolved (column type: (R,R)-WHELK-O1, 250 mm * 30 mm, 5 μm; mobile phase A: CO2; mobile phase B: methanol (containing 0.3% NH3 (7 M in methanol)); flow rate: 90 mL / min; mobile phase ratio (B%): 36% mobile phase B; wavelength: 220 nm) to give compound 1-13P1 (tR=5.28 min) and compound 1-13P2 (tR=7.03 min).

[0404] Compounds 1-13P1 and 1-13P2 have one of the structures shown in Formula 1-13A or Formula 1-13B. That is, when compound 1-13P1 has the structure of Formula 1-13A, compound 1-13P2 has the structure of Formula 1-13B; when compound 1-13P1 has the structure of Formula 1-13B, compound 1-13P2 has the structure of Formula 1-13A.

[0405] 1-13P1(tR=5.28 min), MS: [M+1] + : 280.10. 1 H NMR (400 MHz, DMSO- d6) δ(ppm): 7.34-7.31 (m, 1H), 7.28-7.24 (m, 1H), 7.21-7.17 (m, 1H), 7.13-7.11 (m,1H), 4.50-4.42 (m, 1H), 4.40-4.38 (m, 1H), 3.08-3.04 (m, 2H), 2.99-2.93 (m,2H), 2.90-2.86 (m, 1H), 2.41-2.36 (m, 2H), 1.04-0.99 (m, 4H). 1-13P2(tR=7.03 min), MS: [M+1] + : 280.10. 1 H NMR (400 MHz, DMSO- d 6) δ(ppm): 7.34-7.31 (m, 1H), 7.28-7.24 (m, 1H), 7.20-7.17 (m, 1H), 7.13-7.11 (m,1H), 4.50-4.46 (m, 1H), 4.40-4.38 (m, 1H), 3.08-3.04 (m, 2H), 2.99-2.94 (m,2H), 2.90-2.86 (m, 1H), 2.41-2.36 (m, 2H), 1.04-0.99 (m, 4H). Example 14 Compound 1-14A: 1-Cyclopropyl-3-[( 5S,7S )-7-fluoro-5-phenyl-5H,6H,7H-pyrrolo[1,2-b][1,2,4]triazol-2-yl]-1,2,4-triazole, or compound 1-14B: 1-cyclopropyl-3-[( 5R,7R )-7-fluoro-5-phenyl-5H,6H,7H-pyrrolo[1,2-b][1,2,4]triazol-2-yl]-1,2,4-triazole.

[0406]

[0407] Synthesis route:

[0408] Step 1: Preparation of 3-bromo-1-cyclopropyl-1,2,4-triazole (1-14-A): At room temperature, 3-bromo-1H-1,2,4-triazole (30 g, 1 eq), copper acetate (36.8 g, 1 eq), pyridine (32.1 g, 2 eq), triethylamine (41.1 g, 2 eq), and cyclopropylboronic acid (52.2 g, 3 eq) were added sequentially. The mixture was dissolved in 1,2-dichloroethane (500 mL). The reaction system was purged with oxygen and heated to 80°C. o The reaction mixture was stirred overnight at C. After the reaction was characterized by LCMS, the reaction mixture was quenched with water at room temperature, extracted three times with dichloromethane, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by high-performance liquid chromatography to give compound 1-14-A (2.57 g, yield: 6.7%).

[0409] Step 2: Preparation of 1-cyclopropyl-3-(trimethyltinyl)-1,2,4-triazole (1-14-B): Under nitrogen protection, at room temperature, compound 1-14-A (400 mg, 1 eq), hexamethyldistin (900 mg, 1.3 eq), and tetrakis(triphenylphosphine)palladium (123 mg, 0.05 eq) were dissolved sequentially in 8 mL of toluene, and the mixture was heated to 110°C with stirring. o The reaction was carried out for 16 hours, quenched with water, and extracted three times with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain crude product 1-14-B (600 mg, purity: 40%). The crude product was not further purified and was used directly in the next reaction.

[0410] Step-3: 1-Cyclopropyl-3-[( 5S,7S )-7-fluoro-5-phenyl-5H,6H,7H-pyrrolo[1,2-b][1,2,4]triazol-2-yl]-1,2,4-triazole (1-14A), or compound 1-cyclopropyl-3-[( 5R,7R Preparation of 1-7-fluoro-5-phenyl-5H,6H,7H-pyrrolo[1,2-b][1,2,4]triazol-2-yl]-1,2,4-triazole (1-14B). Under nitrogen protection, at room temperature, crude compound 1-14-B (600 mg), 1-1-GA (120 mg, 1 eq), and tetrakis(triphenylphosphine)palladium (73.7 mg, 0.05 eq) were dissolved in 8 mL of toluene, and the mixture was heated to 110 °C with stirring. oThe reaction was carried out at C for 16 hours. The reaction was quenched with water, extracted three times with ethyl acetate, and the organic phases were combined, washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by normal-phase column chromatography to obtain the racemic compound. The racemic compound was chirally resolved (column type: CHIRALARTAmylose-SA, 250 mm * 20 mm, 5 μm; mobile phase A: n-hexane; mobile phase B: ethanol:dichloromethane = 1: 1; flow rate: 20 mL / min; mobile phase ratio (B%): 30% mobile phase B; wavelength: 254 / 220 nm) to give compound 1-14P1 (tR = 8.24 min) and compound 1-14P2 (tR = 10.7 min).

[0411] Compounds 1-14P1 and 1-14P2 have one of the structures shown in Formula 1-14A or Formula 1-14B. That is, when compound 1-14P1 has the structure of Formula 1-14A, compound 1-14P2 has the structure of Formula 1-14B; when compound 1-14P1 has the structure of Formula 1-14B, compound 1-14P2 has the structure of Formula 1-14A.

[0412] 1-14P1(tR=8.24 min), MS: [M+1] + : 311.10. 1 H NMR (400 MHz, CDCl3) δ(ppm): 8.30 (s, 1H), 7.41-7.33 (m, 3H), 7.30-7.28 (m, 2H), 6.12-5.97 (m, 1H), 5.53-5.48 (m, 1H),, 3.72-3.58 (m, 2H), 3.01-2.91(m, 1H), 1.29 -1.21 (m, 2H), 1.15-1.13(m, 2H). 1-14P2(tR=10.7 min), MS: [M+1] + : 311.10. 1 H NMR (400 MHz, CDCl3) δ(ppm): 8.30 (s, 1H), 7.41-7.33 (m, 3H), 7.30-7.28 (m, 2H), 6.13-5.97 (m, 1H),5.53-5.48 (m, 1H), 3.74-3.58 (m, 2H), 3.00-2.90(m, 1H), 1.29-1.23 (m, 2H), 1.16-1.12(m, 2H). Example 15 Compound 1-15A: (4 S )-2-cyclopropanecarbonyl-4-phenyl-4H,5H,6H-cyclopentano[d][1,2,3]triazole, or compound 1-15B: (4 R )-2-cyclopropanecarbonyl-4-phenyl-4H,5H,6H-cyclopentano[d][1,2,3]triazole.

[0413]

[0414] Synthesis route:

[0415] Step-1: Preparation of 1-azido-4-nitrobenzene (1-15-A): Nitrogen protection, 30 o At C, a 220 mL aqueous solution of 4-nitrobenzenediazamonium tetrafluoroborate (SM1, 20 g, 1 eq) and hydroxylamine hydrochloride (5.87 g, 1 eq) was stirred and reacted for 16 hours. The reaction mixture was directly extracted three times with dichloromethane, and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain crude compound 1-15-A (14 g). The crude product was not further purified and was used directly in the next reaction.

[0416] Step-2: Preparation of 1-((4-methoxyphenyl)methyl)-4-phenyl-4H,5H,6H-cyclopentano[d][1,2,3]triazole (1-15-B): Compound 1-15-A (13 g, 1 eq), 2-phenylcyclopentan-1-one (SM2, 13.3 g, 1.05 eq), 4-methoxybenzylamine (14.13 g, 1.3 eq), 4A molecular sieve (13 g), and acetic acid (4.6 mL) were added to 140 mL of toluene. After nitrogen purging, the mixture was heated to 120°C with stirring. o The reaction was carried out at C for 4 hours. The reaction was characterized by LCMS after completion. The reaction mixture was diluted with ethyl acetate, backwashed three times with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by normal phase column chromatography to give compound 1-15-B (15 g, yield: 62.7%).

[0417] Step-3: Preparation of 4-phenyl-2H,4H,5H,6H-cyclopentano[d][1,2,3]triazole (1-15-C): Compound 1-15-B (14.4 g, 1 eq) and aluminum trichloride (18.86 g, 3 eq) were added to 170 mL of toluene solution, purged with hydrogen, and heated to 80°C under hydrogen atmosphere. oThe reaction was stirred at C for 4 hours. The reaction was characterized as complete by LCMS. The reaction system was then cooled to 0°C with stirring. o The reaction was quenched by pouring the solution into a saturated sodium bicarbonate solution at C, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by normal-phase column chromatography to give compound 1-15-C (8 g, purity: 85%).

[0418] Step-4: (4) S )-2-cyclopropanecarbonyl-4-phenyl-4H,5H,6H-cyclopentano[d][1,2,3]triazole (1-15A), or compound (4 R Preparation of 2-cyclopropanecarbonyl-4-phenyl-4H,5H,6H-cyclopentano[d][1,2,3]triazole (1-15B): Compound 1-15-C (2 g, 1 eq), cyclopropionic acid (1.21 g, 1.3 eq), N,N -Diisopropylethylamine (4.19 g, 3 eq) and 1H-benzotriazol-1-yloxytripyrrolidinyl hexafluorophosphate (8.41 g, 1.5 eq) were added to 55 mL of... N,N- In dimethylformamide, after nitrogen purging, the reaction system was stirred at room temperature for 24 hours. The reaction was characterized by LCMS to indicate completion. The reaction mixture was diluted with ethyl acetate, backwashed three times with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by normal-phase column chromatography to obtain 1.5 g of the racemic compound. 300 mg of the racemic compound was purified by high-performance liquid chromatography (HPLC) to obtain a racemic compound (130 mg) with a purity greater than 95%. 130 mg of racemic compound was chirally resolved (column type: (R, R)-WHELK-O1, 250 mm * 21.2 mm, 5 μm; mobile phase A: n-hexane (0.5% NH3 (2 M methanol solution)); mobile phase B: ethanol: dichloromethane = 1:1; flow rate: 20 mL / min; mobile phase ratio (B%): 80% mobile phase B; wavelength: 254 / 220 nm) to give compounds 1-15P1 (tR = 4.29 min) and 1-15P2 (tR = 7.58 min).

[0419] Compounds 1-15P1 and 1-15P2 have one of the structures shown in Formula 1-15A or Formula 1-15B. That is, when compound 1-15P1 has the structure of Formula 1-15A, compound 1-15P2 has the structure of Formula 1-15B; when compound 1-15P1 has the structure of Formula 1-15B, compound 1-15P2 has the structure of Formula 1-15A.

[0420] 1-15P1(tR=4.29 min), MS: [M+1] + : 254.15. 1 H NMR (400 MHz, DMSO- d 6) δ(ppm): 7.38-7.34 (m, 2H), 7.30-7.26 (m, 3H), 4.46-4.42 (m, 1H), 3.15-3.07 (m,2H), 3.05-3.00 (m, 1H), 2.98-2.89 (m, 1H), 2.65-2.57 (m, 1H), 1.41-1.37 (m, 2H), 1.20-1.16 (m, 2H). 1-15P2(tR=7.58 min), MS: [M+1] + : 254.10. 1 H NMR (400 MHz, DMSO- d 6) δ(ppm): 7.38-7.34 (m, 2H), 7.32-7.23(m, 3H), 4.47-4.43 (m, 1H), 3.18-3.08 (m,2H), 3.07-3.00 (m, 1H), 2.98-2.90 (m, 1H), 2.65-2.55 (m, 1H), 1.43-1.36 (m, 2H), 1.21-1.15 (m, 2H). Example 16 Compound 1-16A: (6 S )-6-(2-chlorophenyl)-1-cyclopropanecarbonyl-4H,5H,6H-cyclopentano[c]pyrazole, or compound 1-16B: (6 R )-6-(2-chlorophenyl)-1-cyclopropanecarbonyl-4H,5H,6H-cyclopentano[c]pyrazole; Compound 1-16C: (6 S )-6-(2-chlorophenyl)-2-cyclopropanecarbonyl-4H,5H,6H-cyclopentano[c]pyrazole, or compound 1-16D: (6 R )-6-(2-chlorophenyl)-2-cyclopropanecarbonyl-4H,5H,6H-cyclopentano[c]pyrazole

[0421] Synthesis route:

[0422]

[0423] Step 1: Preparation of 2-(2-chlorophenyl)cyclopentan-1-one (1-16-A): Compound SM1 (10 g, 1.00 eq), cyclopentanone (3.53 g, 1.00 eq), 2,4,4-trimethylpentane-2-amine hydrochloride (1.74 g, 0.25 eq), tetrahydropyrrole (745.7 mg, 0.25 eq), tris(o-tolyl)phosphine (638.2 mg, 0.05 eq), sodium acetate (2.75 g, 0.8 eq), and palladium acetate (188.3 mg, 0.02 eq) were added to 90 mL of 1,4-dioxane. After nitrogen purging, the mixture was heated to 110 °C with stirring and reacted for 16 hours. The reaction was characterized by LCMS to indicate completion. After cooling to room temperature, the reaction mixture was concentrated by rotary evaporation under reduced pressure. The reaction mixture was diluted with ethyl acetate, backwashed three times with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by normal phase column chromatography to give compound 1-16-A (1 g, yield: 13%).

[0424] Step-2: Preparation of (5Z)-2-(2-chlorophenyl)-5-[(dimethylamino)methylene]cyclopentan-1-one (1-16-B): Under nitrogen protection, compound 1-16-A (1 g, 1 eq) and N,N -Dimethylformamide dimethyl acetal (3.06 g, 5 eq) N,N A 22 mL solution of dimethylformamide was heated to 110 °C and stirred for 16 hours. The reaction was characterized by LCMS after completion. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate, backwashed three times with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by normal-phase column chromatography to give compound 1-16-B (0.6 g, yield: 48%).

[0425] Step 3: Preparation of 6-(2-chlorophenyl)-2H,4H,5H,6H-cyclopentano[c]pyrazole (1-16-C): Under nitrogen protection, a solution of compound 1-16-B (0.55 g, 1 eq) and hydrazine hydrate (0.6 g) in ethanol (10 mL) was heated to 80 °C and stirred for 6 hours. The reaction was characterized by LCMS after completion. The reaction system was concentrated by rotary evaporation under reduced pressure, and the crude product was purified by normal-phase column chromatography to obtain compound 1-16-C (0.6 g, purity: 80%).

[0426] Step 4: Preparation of 6-(2-chlorophenyl)-1-cyclopropanecarbonyl-4H,5H,6H-cyclopentano[c]pyrazole (1-16-D) and 6-(2-chlorophenyl)-2-cyclopropanecarbonyl-4H,5H,6H-cyclopentano[c]pyrazole (1-16-E): Under nitrogen protection at room temperature, cyclopropylformic acid (153.54 mg, 1.3 eq) and 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (782.45 mg, 1.5 eq) were mixed... N,N - Dimethylformamide (6 mL) solution was stirred and reacted for 20 minutes. Compound 1-16-C (300 mg, 1 eq) and... N,N -Diisopropylethylamine (531.93 mg, 3 eq). After addition, the system was stirred at room temperature for 16 hours. The reaction mixture was diluted with ethyl acetate, backwashed three times with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was separated by high-performance liquid chromatography to obtain compound 1-16-D (25 mg) and compound 1-16-E (20 mg). Compounds 1-16-D and 1-16-E were distinguished by NOESY.

[0427] Step-5: (6) S )-6-(2-chlorophenyl)-1-cyclopropanecarbonyl-4H,5H,6H-cyclopentano[c]pyrazole (1-16A), or compound (6 R )-6-(2-chlorophenyl)-1-cyclopropanecarbonyl-4H,5H,6H-cyclopentano[c]pyrazole (1-16B); (6 S )-6-(2-chlorophenyl)-2-cyclopropanecarbonyl-4H,5H,6H-cyclopentano[c]pyrazole (1-16C), or compound (6 R Preparation of 6-(2-chlorophenyl)-2-cyclopropanecarbonyl-4H,5H,6H-cyclopentano[c]pyrazole (1-16D): Racemic compound 1-16-D was chirally resolved (column type: (R, R)-WHELK-O1, 250 mm * 21.2 mm, 5 μm; mobile phase A: n-hexane (0.5% NH3 (2 M methanol solution)); mobile phase B: ethanol: dichloromethane = 1:1; flow rate: 20 mL / min; mobile phase ratio (B%): 25% mobile phase B; wavelength: 254 / 220 nm) to give compounds 1-16P1 (tR = 4.96 min) and 1-16P2 (tR = 7.40 min).

[0428] Compounds 1-16P1 and 1-16P2 have one of the structures shown in Formula 1-16A or Formula 1-16B. That is, when compound 1-16P1 has the structure of Formula 1-16A, compound 1-16P2 has the structure of Formula 1-16B; when compound 1-16P1 has the structure of Formula 1-16B, compound 1-16P2 has the structure of Formula 1-16A.

[0429] 1-16P1(tR=4.96 min), MS: [M+1] + : 287.05. 1 H NMR (400 MHz, DMSO- d 6) δ(ppm): 8.10 (s, 1H), 7.51-7.48 (m, 1H), 7.32-7.28 (m, 2H), 7.21-7.18 (m, 1H), 4.69-4.66 (m, 1H), 2.98-2.92 (m, 2H), 2.77-2.74 (m, 2H), 2.31-2.21 (m, 1H), 1.09-1.05 (m, 4H). 1-16P2(tR=7.40 min), MS: [M+1] + : 287.05. 1 H NMR (400 MHz, DMSO- d 6) δ(ppm): 8.09 (s, 1H), 7.51-7.48 (m, 1H), 7.33-7.28 (m, 2H), 7.23-7.18 (m, 1H), 4.69-4.65 (m, 1H), 3.00-2.90 (m, 2H), 2.78-2.72 (m, 2H), 2.29-2.23 (m, 1H), 1.11-1.04 (m, 4H). Racemic compound 1-16-E was chirally resolved (column type: (R, R)-WHELK-O1, 250 mm * 21.2 mm, 5 μm; mobile phase A: n-hexane (0.5% NH3 (2 M methanol solution)); mobile phase B: ethanol: dichloromethane = 1:1; flow rate: 20 mL / min; mobile phase ratio (B%): 25% mobile phase B; wavelength: 254 / 220 nm) to give compounds 1-16P3 (tR = 4.71 min) and 1-16P4 (tR = 6.45 min).

[0430] Compounds 1-16P3 and 1-16P4 have one of the structures shown in Formula 1-16C or Formula 1-16D. That is, when compound 1-16P3 has the structure of Formula 1-16C, compound 1-16P4 has the structure of Formula 1-16D; when compound 1-16P3 has the structure of Formula 1-16D, compound 1-16P4 has the structure of Formula 1-16C.

[0431] 1-16P3 (tR=4.71min), MS: [M+1) + : 287.05. 1 H NMR (400 MHz, DMSO- d 6) δ(ppm): 7.79 (s, 1H), 7.46-7.44 (m, 1H), 7.24-7.17 (m, 2H), 6.56-6.54 (m, 1H), 4.85-4.82 (m, 1H), 3.16-3.11 (m, 1H), 3.02-2.98 (m, 1H), 2.65-2.60 (m, 2H), 2.26-2.18 (m, 1H), 1.10-1.03 (m, 2H), 0.96-0.92 (m, 1H), 0.90-0.83 (m, 1H). 1-16P4 (tR=6.45min), MS: [M+1] + : 287.10. 1 H NMR (400 MHz, DMSO- d 6) δ(ppm): 7.80 (s, 1H), 7.46-7.44 (m, 1H), 7.24-7.18 (m, 2H), 6.56-6.54 (m, 1H), 4.85-4.82 (m, 1H), 3.16-3.08 (m, 1H), 3.04-2.97 (m, 1H), 2.69-2.57 (m, 2H), 2.26-2.18 (m, 1H), 1.13-1.01 (m, 2H), 0.99-0.92 (m, 1H), 0.90-0.83 (m, 1H). Example 17 Compound 1-17A: ( S )-Cyclopropyl(4-phenyl-5,6-dihydrocyclopentano[c]pyrazol-2(4H)-yl) ketone, or compound 1-17B: ( R )-Cyclopropyl(4-phenyl-5,6-dihydrocyclopentano[c]pyrazol-2(4H)-yl) methyl ketone;

[0432] Synthesis route:

[0433] Step 1: Preparation of 2-(cyclopropanecarbonyl)-4-phenyl-2,4,5,6-tetrahydrocyclopentano[c]pyrazole-3-yl trifluoromethanesulfonate (1-17-A): Racemic compound 1-10 (980 mg, 1 eq) was dissolved in 50 mL of dichloromethane, purged with nitrogen, and cooled to 0 °C. Pyridine (0.87 g, 3 eq) and trifluoromethanesulfonic anhydride (1.55 g, 1.5 eq) were added, and the mixture was stirred for 2 hours. The reaction mixture was quenched with water at 0 °C, and then extracted three times with dichloromethane. The organic phases were combined, backwashed three times with 0.1 M hydrochloric acid solution, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude compound 1-17-A (1.4 g, purity: 81%) was obtained. The crude compound was not further purified and was used directly in the next step of the reaction.

[0434] Step-2: Preparation of cyclopropyl(4-phenyl-5,6-dihydrocyclopentano[c]pyrazole-2(4H)-yl) methyl ketone (1-17-B): Under nitrogen protection, wet palladium on carbon (250 mg, 10%) was added to an ethyl acetate solution of compound 1-17-A (250 mg, 1 eq). After hydrogen purging, the reaction was maintained under hydrogen atmosphere and reacted at room temperature for 16 hours. The mixture was filtered, the filter cake was washed three times with ethyl acetate, and evaporated to dryness. The crude product was purified by preparative thin-layer chromatography to obtain the racemic compound 1-17-B (15 mg). Step-3: ( S )-Cyclopropyl(4-phenyl-5,6-dihydrocyclopentano[c]pyrazole-2(4H)-yl) methyl ketone (1-17A), or the compound, R Preparation of cyclopropyl(4-phenyl-5,6-dihydrocyclopentano[c]pyrazol-2(4H)-yl) methyl ketone (1-17B): Racemic compound 1-17-B was chirally resolved (column type: CHIRALPAK IJ, 250 mm * 20 mm, 5 μm; mobile phase A: n-hexane (0.5% NH3 (2 M methanol solution)); mobile phase B: ethanol; flow rate: 20 mL / min; mobile phase ratio (B%): 2% mobile phase B; wavelength: 254 / 220 nm) to obtain compound 1-17P1 (tR = 8.91 min) and compound 1-17P2 (tR = 11.23 min).

[0435] Compounds 1-17P1 and 1-17P2 have one of the structures shown in Formula 1-17A or Formula 1-17B. That is, when compound 1-17P1 has the structure of Formula 1-17A, compound 1-17P2 has the structure of Formula 1-17B; when compound 1-17P1 has the structure of Formula 1-17B, compound 1-17P2 has the structure of Formula 1-17A.

[0436] 1-17P1(tR=8.91 min), MS: [M+1] + : 253.15. 1 H NMR (400 MHz, DMSO- d 6) δ(ppm): 8.01 (s, 1H), 7.34-7.30 (m, 2H), 7.27-7.23 (m, 3H), 4.34-4.32 (m, 1H), 3.05-3.01 (m, 1H), 2.92-2.81 (m, 3H), 2.33-2.22 (m, 1H), 1.18-1.13 (m, 4H). 1-17P2(tR=11.23 min), MS: [M+1] + : 253.20. 1 H NMR (400 MHz, DMSO- d 6) δ(ppm): 8.01 (s, 1H), 7.32-7.31 (m, 2H), 7.27-7.23 (m, 3H), 4.34-4.32 (m, 1H), 3.07-3.01 (m, 1H), 2.89-2.81 (m, 3H), 2.33-2.22 (m, 1H), 1.14-1.07 (m, 4H). Example 18 Compound 1-18A: Cyclopropyl ((4 S 6 S )-4-fluoro-6-phenyl-5,6-dihydro-4H-cyclopentano[d]thiazolyl) methyl ketone, or compound 1-18B: cyclopropyl((4 R 6 R )-4-fluoro-6-phenyl-5,6-dihydro-4H-cyclopenta[d]thiazolyl) methyl ketone.

[0437] Compound 1-18C: Cyclopropyl ((4 R 6 S )-4-fluoro-6-phenyl-5,6-dihydro-4H-cyclopentano[d]thiazolyl) methyl ketone, or compound 1-18D: cyclopropyl((4 S6 R )-4-fluoro-6-phenyl-5,6-dihydro-4H-cyclopenta[d]thiazolyl) methyl ketone.

[0438]

[0439] Synthesis route:

[0440]

[0441]

[0442] Step 1: Preparation of ethyl 3-bromo-2-oxo-4-phenylbutyrate (1-18-A): Compound SM1 (50.1 g, 1 eq) was added to a three-necked flask at room temperature and dissolved in chloroform (810 mL) and ethyl acetate (1600 mL). Copper bromide (161.4 g, 2.98 eq) was added to the system with stirring at room temperature. The mixture was heated to 100 °C and stirred for 6 hours. The mixture was filtered, the filter cake was washed with ethyl acetate, and the filtrate was concentrated under reduced pressure. The residue was purified by normal-phase column chromatography to give compound 1-18-A (44.5 g, yield: 66.1%).

[0443] Step 2: Preparation of ethyl 2-amino-5-benzylthiazol-4-carboxylate (1-18-B): Compound 1-18-A (22 g, 1 eq) was dissolved in 220 mL of ethanol, and thiourea (14.7 g, 2.5 eq) was added with stirring. The mixture was heated to 110 °C and stirred for 2.5 hours. The reaction was characterized by LCMS to indicate completion. After cooling to room temperature, the reaction system was concentrated under reduced pressure. The resulting residue was slurryed with ethyl acetate, filtered, and the filter cake was washed three times with ethyl acetate. The mother liquors were combined, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by normal-phase column chromatography to obtain compound 1-18-B (16.3 g, yield: 80.2%).

[0444] Step 3: Preparation of ethyl 5-benzyl-2-bromothiazol-4-carboxylate (1-18-C): Compound 1-18-B (10 g, 1 eq) was dissolved in 100 mL of acetonitrile. Copper bromide (10.2 g, 1.2 eq) was added with stirring. Under nitrogen protection, the reaction system was cooled to below 0 °C, and tert-butyl nitrite (3.2 mL) was added dropwise. The resulting mixture was slowly heated to room temperature and stirred for 16 hours. After LCMS characterization, the reaction was quenched with saturated ammonium chloride aqueous solution and water. The mixture was extracted three times with ethyl acetate, and the organic phases were combined. The organic phase was washed once with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by normal-phase column chromatography to obtain compound 1-18-C (8.2 g, yield: 66.7%).

[0445] Step-4: Preparation of ethyl 2-bromo-5-(3-ethoxy-3-oxo-1-phenylpropyl)thiazolium-4-carboxylate (1-18-D): Compound 1-18-C (8.2 g, 1 eq) was dissolved in 320 mL of tetrahydrofuran. Under nitrogen protection, the reaction system was cooled to -78 °C and stirred dropwise with bis(trimethylsilylaminolithium) (1.0 M in tetrahydrofuran, 30 mL). After stirring at -78 °C for 30 minutes, ethyl bromoacetate (4.62 g, 1.1 eq) was added dropwise. After the reaction system was allowed to return to room temperature, stirring was continued for another 30 minutes. The reaction was characterized by LCMS to be complete. The reaction system was quenched by adding a saturated ammonium chloride aqueous solution, extracted three times with ethyl acetate, the organic phases were combined, washed once with a saturated sodium chloride aqueous solution, dried with anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by normal phase column chromatography to give compound 1-18-D (7.5 g, yield: 70.4%).

[0446] Step 5: Preparation of ethyl 2-bromo-4-oxo-6-phenyl-5,6-dihydro-4H-cyclopentano[d]thiazolium-5-carboxylate (1-18-E): Compound 1-18-D (4 g, 1 eq) was dissolved in 48 mL of toluene. Under nitrogen protection and stirring, the reaction system was cooled to -10 °C and potassium tert-amyloxide (8.5 mL, 2 eq) was added. The temperature was maintained and the mixture was stirred for 30 minutes. The reaction was characterized by LCMS to indicate completion. The reaction was quenched by adding acetic acid (3 mL) at -10 °C, and the pH was adjusted to 7-8 with saturated sodium bicarbonate aqueous solution. The mixture was extracted three times with ethyl acetate, and the organic phases were combined and washed once with saturated sodium chloride aqueous solution. The organic phase was dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by normal phase column chromatography to obtain compound 1-18-E (2.15 g, yield: 57.7%).

[0447] Step 6: Preparation of 2-bromo-6-phenyl-5,6-dihydro-4H-cyclopentano[d]thiazol-4-one (1-18-F): Compound 1-18-E (2.15 g, 1 eq) was dissolved in a mixture of 25 mL dimethyl sulfoxide and 5 mL water. The mixture was heated to 100 °C and reacted for 16 hours under nitrogen protection and stirring. The reaction was characterized by LCMS until complete. The reaction system was quenched with water, and the mixture was extracted three times with ethyl acetate. The combined organic phases were washed once with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by normal-phase column chromatography to give compound 1-18-F (1.45 g, yield: 83.4%).

[0448] Step 7: Preparation of 2-bromo-6-phenyl-5,6-dihydro-4H-cyclopentano[d]thiazol-4-ol (1-18-G): Compound 1-18-F (1.45 g, 1 eq) was dissolved in 16 mL of methanol. Under nitrogen protection and stirring, sodium borohydride (0.18 g, 1 eq) was added in portions at 0 °C. The reaction was maintained at this temperature for 1 hour, and the reaction was characterized by LCMS to indicate completion. The reaction system was quenched in a saturated sodium bicarbonate aqueous solution. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed once with a saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by normal-phase column chromatography to obtain compound 1-18-G (1.32 g, yield: 91.1%).

[0449] Step-8: Preparation of cyclopropyl(4-hydroxy-6-phenyl-5,6-dihydro-4H-cyclopentano[d]thiazolyl) methyl ketone (1-18-H): Compound 1-18-G (700 mg, 1 eq) and N -Methoxy- N 1-Methylcyclopropaneformamide (427.4 mg, 1.4 eq) was dissolved in 7 mL of tetrahydrofuran. Under nitrogen protection and stirring, isopropyl magnesium chloride (2.0 M in tetrahydrofuran, 2.6 mL, 2.3 eq) was added dropwise at 0 °C. The reaction was maintained at this temperature for 2 hours, and the reaction was characterized by LCMS to indicate completion. The reaction system was quenched in a saturated aqueous ammonium chloride solution. The mixture was extracted three times with ethyl acetate, and the combined organic phases were washed once with a saturated aqueous sodium chloride solution. The organic phase was dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by normal-phase column chromatography to give compound 1-18-H (580 mg, yield: 86.1%).

[0450] Step-9: Preparation of cyclopropyl ((cis)-4-fluoro-6-phenyl-5,6-dihydro-4H-cyclopentano[d]thiazol-2-yl) methyl ketone (1-18-IA) and cyclopropyl ((trans)-4-fluoro-6-phenyl-5,6-dihydro-4H-cyclopentano[d]thiazol-2-yl) methyl ketone (1-18-IB): Compound 1-18-H (300 mg, 1 eq) and triethylamine trihydrofluoride (339 mg, 2 eq) were dissolved in 3 mL of dichloromethane. Under nitrogen protection and stirring, the mixture was cooled to 0 °C and (diethylamino)difluorosulfonium tetrafluoroborate (361 mg, 1.5 eq) was added dropwise. The reaction was maintained at this temperature for 2 hours, and the reaction was characterized by LCMS to indicate completion. The reaction system was quenched in a saturated sodium bicarbonate aqueous solution. The mixture was extracted three times with a large amount of ethyl acetate. The organic phases were combined and washed once with a saturated sodium chloride aqueous solution. The organic phase was dried with anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by preparative chromatographic plate to obtain cis compound 1-18-IA (44 mg) and trans compound 1-18-IB (116 mg).

[0451] Step-10: Cyclopropyl((4) S 6 S )-4-fluoro-6-phenyl-5,6-dihydro-4H-cyclopentano[d]thiazolyl) methyl ketone (1-18A), or the compound cyclopropyl((4 R 6 R Preparation of 4-fluoro-6-phenyl-5,6-dihydro-4H-cyclopentano[d]thiazol-2-yl)methyl ketone (1-18B): cis compound 1-18-IA was chirally resolved (column type: CHIRALPAK IM, 250 mm * 20 mm, 5 μm; mobile phase A: n-hexane (0.2% formic acid); mobile phase B: ethanol: dichloromethane; flow rate: 20 mL / min; mobile phase ratio (B%): 10% mobile phase B; wavelength: 254 / 220 nm) to obtain compound 1-18P1 (tR = 5.53 min) and compound 1-18P2 (tR = 8.51 min).

[0452] Compounds 1-18P1 and 1-18P2 have one of the structures shown in Formula 1-18A or Formula 1-18B. That is, when compound 1-18P1 has the structure of Formula 1-18A, compound 1-18P2 has the structure of Formula 1-18B; when compound 1-18P1 has the structure of Formula 1-18B, compound 1-18P2 has the structure of Formula 1-18A.

[0453] 1-18P1(tR=5.53 min), MS: [M+1] + : 288.10. 1H NMR (400 MHz, CDCl3) δ(ppm): 7.36-7.33 (m, 4H), 7.18-7.16 (m, 1H), 5.52-5.40 (m, 1H), 4.81-4.78 (m,1H), 3.50-3.18 (m, 1H), 2.97-2.95 (m, 1H), 2.84-2.78 (m, 1H), 1.35-1.28 (m,2H), 1.20-1.17 (m, 2H) 1-18P2(tR=8.51 min), MS: [M+1] + : 288.10. 1 H NMR (400 MHz, CDCl3) δ(ppm): 7.35-7.30 (m, 3H), 7.27-7.25 (m, 2H), 6.15-5.98 (m, 1H), 4.53-4.47 (m,1H), 3.52-3.42 (m, 1H), 3.27-3.23 (m, 1H), 2.74-2.63 (m, 1H), 1.35-1.32 (m,2H), 1.21-1.17 (m, 2H). Step-11: Cyclopropyl((4) R 6 S )-4-fluoro-6-phenyl-5,6-dihydro-4H-cyclopentano[d]thiazolyl) methyl ketone (1-18C), or the compound cyclopropyl((4 S 6 R Preparation of 4-fluoro-6-phenyl-5,6-dihydro-4H-cyclopentano[d]thiazolyl)methyl ketone (1-18D): The trans compound 1-18-IB was chirally resolved (column type: CHIRALPAK IM, 250 mm * 20 mm, 5 μm; mobile phase A: n-hexane (0.2% formic acid); mobile phase B: ethanol: dichloromethane; flow rate: 20 mL / min; mobile phase ratio (B%): 10% mobile phase B; wavelength: 254 / 220 nm) to obtain compound 1-18P3 (tR = 6.79 min) and compound 1-18P4 (...

Claims

1. The compound represented by formula (M-1) or a pharmaceutically acceptable salt thereof: Formula (M-1) in, R is selected from any alternative substitution or is arbitrarily replaced by one, two, three or more Rs. Z The following groups are substituted: C 1-20 Alkyl, -OC 1-20 Alkyl, C 3-20 cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, or ; Ring A is selected from the following optionally substituted groups: 、 、 、 ； Rings B, C, D, E, and F are independently selected from saturated, partially saturated, aromatic C5-ring hydrocarbons or five-membered heterocycles. Ring G is selected from saturated, partially saturated, aromatic C6-ring hydrocarbon rings or six-membered heterocycles; W1, W4, W5, W6, W7, W 10 W 11 W 12 W 14 W 15 W 16 W 17 W 18 W 19 W 22 W 23 W 24 W 25 Same or different, and independently selected from: O, S, S(=O), S(=O)2, N, NR wn1 C, C (=O), CR wc1 CR wc2 R wc3 ; W2, W3, W8, W 13、 W 20、 W 21、 W 26 Same or different, and independently selected from: N, C, CR wc1 ; Fused rings composed of rings B and C contain 1-4 heteroatoms; ring D contains 1-3 heteroatoms; ring E contains 1-3 heteroatoms; fused rings composed of rings F and G contain 1-4 heteroatoms. U1 is selected from: O, S; R1 is selected from: optional substitutions or optional substitutions by one, two, three or more R1s. Z1 The following groups are substituted: C 3-20 cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20 Alkylene-C 3-20 Cycloalkenyl, -C 1-20 Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl), -OC 3-20 cycloalkyl, -OC 3-20 Cycloalkenyl, -O- (3-20 membered heterocyclic groups), -OC 6-20 Aryl, -O- (5-20 heteroaryl), -SC 3-20 cycloalkyl, -SC 3-20 Cycloalkenyl, -S- (3-20 membered heterocyclic groups), -SC 6-20 Aryl, -S-(5-20 heteroaryl), -NH-C 3-20 cycloalkyl, -NH-C 3-20 Cycloalkenyl, -NH- (3-20 membered heterocyclic groups), -NH-C 6-20 Aryl, -NH- (5-20 heteroaryl); R2 is selected from: optional substitutions or optional substitutions by one, two, three or more Rs. Z2 The following groups are substituted: C 3-20 cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl; R 31 and R 41 Selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R. Z3 The following groups are substituted: C 1-20 Alkyl, C 3-20 Cycloalkyl, 3-20 membered heterocyclic groups, -OC 1-20 Alkyl, -OC 3-20 Cycloalkyl, -O- (3-20 membered heterocyclic groups), -SC 1-20 Alkyl, -SC 3-20 Cycloalkyl, -S-(3-20 membered heterocyclic groups), -NH-C 1-20 Alkyl, -NH-C 3-20 Cycloalkyl groups, -NH- (3-20 membered heterocyclic groups); Each R wc1 R wc2 R wc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-20 Alkyl, C 3-20 Cycloalkyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20 Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl), -OC 3-20 Cycloalkyl, -O- (3-20 membered heterocyclic groups), -OC 6-20 Aryl, -O- (5-20 heteroaryl), -SC 3-20 Cycloalkyl, -S- (3-20 membered heterocyclic groups), -SC 6-20 Aryl, -S-(5-20 heteroaryl), -NH-C 3-20 Cycloalkyl, -NH- (3-20 membered heterocyclic groups), -NH-C 6-20 Aryl, -NH- (5-20 heteroaryl); Each R wn1 The same or different, and independently selected from: H, deuterium, and optionally substituted or optionally replaced by one, two, three or more R. Z5 The following groups are substituted: C 1-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl group, C 3-20 cycloalkyl, C 3-20 Cycloalkenyl, C 3-20 Cycloalkynyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 2-20 alkenyl, -C 1-20 Alkylene-C 2-20 alkynyl group, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20 Alkylene-C 3-20 Cycloalkenyl, -C 1-20 Alkylene-C 3-20 Cycloalkynyl, -C 1-20 Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl); R wc1 and R1, or R wc2 and R1, or R wc3 and R1, or R wn1 Together with R1, they form an optional substitution or optional substitution by one, two, three or more Rs. ZZ3 The following groups are substituted: 8-20 membered fused heterocyclic group, 8-20 membered bridged heterocyclic group, 8-20 membered spiroheterocyclic group, C 8-20 Fused ring group, C 8-20 Yuanqiao Ring Base, C 8-20 spirocyclic base; Each R Z R Z1 R Z2 R Z3 R Z4 R Z5 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and optionally substituted or optionally influenced by one, two, three or more Rs. ZZ1 The following groups are substituted: C 1-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl group, C 3-20 cycloalkyl, C 3-20 Cycloalkenyl, C 3-20 Cycloalkynyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 2-20 alkenyl, -C 1-20 Alkylene-C 2-20 alkynyl group, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20 Alkylene-C 3-20 Cycloalkenyl, -C 1-20 Alkylene-C 3-20 Cycloalkynyl, -C 1-20 Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl), -OR O1 -SR S1 -NR N1 R N2 -C(O)R C1 -OC(O)R C2 -OC(O)-OR O2 -OC(O)-NR N3 R N4 -N(R) N5 )-C(O)R C3 -N(R) N6 )-C(O)-NR N7 R N8 -S(O)2R S2 -OS(O)2R S3 -OS(O)2-OR O3 -OS(O)2-NR N9 R N10 -N(R) N11 )-S(O)2R S4 、-N(R N12 )-S(O)2-NR N13 R N14 、-S(O)R S5 、-O-S(O)R S6 、-O-S(O)-OR O4 、-O-S(O)-NR N15 R N16 、-N(R N17 )-S(O)R S7 、-N(R N18 )-S(O)-NR N19 R N20 、-P(=O)R P1 R P2 、-P(=O)(OR O5 )R P2 、-P(=O)(OR O6 )(OR O7 )、-P(=O)(NR N21 R N22 )R P3 、-P(=O)(NR N23 R N24 )(NR N25 R N26 )、-P(=O)(OR O8 )(NR N27 R N28 ); Or two R atoms connected to the same carbon atom Z1 Together with the carbon atom it is attached to, they form C 3-20 cycloalkyl; Each R O1 R O2 R O3 R O4 R O5 R O6 R O7 R O8 R S1 R S2 R S3 R S4 R S5 R S6 R S7 R C1 R C2 R C3 R P1 R P2 R P3 R N1 R N2 R N3 R N4 R N5 R N6 R N7 R N8 R N9 R N10 R N11 R N12 R N13 R N14 R N15 R N16 R N17 R N18 R N19 R N20 R N21 R N22 R N23 R N24 R N25 R N26 R N27 R N28 Whether identical or different, each is independently selected from: H, deuterium, and optionally substituted or optionally replaced by one, two, three or more R. ZZ2 The following groups are substituted: C 1-20 Alkyl, C 3-20 Cycloalkyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20 Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl); Or R N3 With R N4 R N7 With R N8 R N9 With R N10 R N13 With R N14 R N15 With R N16 R N19 With R N20 R N21 With R N22 R N23 With R N24 R N25 With R N26 R N27 With R N28 Together with the N atom it is linked to, it forms a 3-20 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O, S, Si or P; Or R P1 With R P2 Together with the P atom it is linked to, it forms a 3-20 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O, S, Si or P; Or R O5 With R P2 R O6 With R O7 Together with the atoms linked to it, they form a 4-20 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O, S, Si or P; Each R ZZ1 R ZZ2 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and the following optional substituted groups: C 1-20 Alkyl, C 3-20 Cycloalkyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20 Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl), -OC 3-20 Cycloalkyl, -O- (3-20 membered heterocyclic groups), -OC 6-20 Aryl, -O- (5-20 heteroaryl), -SC 3-20 Cycloalkyl, -S- (3-20 membered heterocyclic groups), -SC 6-20 Aryl, -S-(5-20 heteroaryl), -NH-C 3-20 Cycloalkyl, -NH- (3-20 membered heterocyclic groups), -NH-C 6-20 Aryl, -NH- (5-20 heteroaryl); Each R ZZ3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and the following optional substituted groups: C 1-20 Alkyl, C 3-20 Cycloalkyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20 Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl), -OC 3-20 Cycloalkyl, -O- (3-20 membered heterocyclic groups), -OC 6-20 Aryl, -O- (5-20 heteroaryl), -SC 3-20 Cycloalkyl, -S- (3-20 membered heterocyclic groups), -SC 6-20 Aryl, -S-(5-20 heteroaryl), -NH-C 3-20 Cycloalkyl, -NH- (3-20 membered heterocyclic groups), -NH-C 6-20 Aryl, -NH- (5-20 heteroaryl).

2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, characterized in that, R1 is selected from: optional substitutions or optional substitutions by one, two, three or more R1s. Z1 The following groups are substituted: C 3-12 cycloalkyl, C 3-12 Cycloalkenyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -C 1-12 Alkylene-C 3-12 cycloalkyl, -C 1-12 Alkylene-C 3-12 Cycloalkenyl, -C 1-12 alkylene-(3-12 membered heterocyclic group), -C 1-12 Alkylene-C 6-12 Aryl, -C 1-12 alkylene-(5-12-membered heteroaryl), -OC 3-12 cycloalkyl, -OC 3-12 Cycloalkenyl, -O-(3-12 membered heterocyclic group), -OC 6-12 Aryl, -O-(5-12 heteroaryl), -SC 3-12 cycloalkyl, -SC 3-12 Cycloalkenyl, -S-(3-12 membered heterocyclic group), -SC 6-12 Aryl, -S-(5-12 heteroaryl), -NH-C 3-12 cycloalkyl, -NH-C 3-12 Cycloalkenyl, -NH- (3-12 membered heterocyclic group), -NH-C 6-12 Aryl, -NH- (5-12 heteroaryl); Preferably, R1 is selected from: optionally substituted or optionally replaced by one, two, three or more R1s. Z1 The following groups are substituted: C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, -C 1-6 alkylene-(3-10 membered heterocyclic group), -C 1-6 Alkylene-C 6-10 Aryl, -C 1-6 alkylene-(5-10-membered heteroaryl), -O-(3-10-membered heterocyclic), -OC 6-10 Aryl, -O- (5-10 membered heteroaryl), -NH- (3-10 membered heterocyclic), -NH-C 6-10 Aryl, -NH- (5-10 heteroaryl); Preferably, R1 is selected from: optionally substituted or optionally replaced by one, two, three or more R1s. Z1 The following groups are substituted: cyclopropyl, phenyl, pyrrolyl, furanyl, pyridyl, pyrimidinyl, benzyl, phenoxy, dihydrobenzofuranyl, indazole, indolyl, indolylmethylene, benzofuranyl, benzofuranylmethyl, indolyloxy, indolylamino, phenylamino, benzofuranyloxy, benzofuranylamino. , , , , ; Preferably, R1 is selected from: cyclopropyl, phenyl, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 。 3. The compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, characterized in that, R is selected from: optional substitutions or optional substitutions by one, two, three or more Rs. Z The following groups are substituted: C 1-12 Alkyl, -OC 1-12 Alkyl, C 3-12 cycloalkyl, C 3-12 Cycloalkenyl, 3-12 membered heterocyclic groups, C 6-12 aryl, 5-12 heteroaryl or ; Preferably, R is selected from: optionally substituted or optionally replaced by one, two, three or more R. Z The following groups are substituted: methyl, ethyl, propyl, isopropyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetane, azirane, tetrahydropyrrolyl, piperidinyl. , , , , , , or ; R2 is selected from: optional substitutions or optional substitutions by one, two, three or more Rs. Z2 The following groups are substituted: C 3-12 cycloalkyl, C 3-12 Cycloalkenyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl; Preferably, R2 is selected from: optionally substituted or optionally replaced by one, two, three or more Rs. Z2 The following groups are substituted: C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl; Preferably, R2 is selected from: optionally substituted or optionally replaced by one, two, three or more Rs. Z2 The following groups are substituted: cyclopropyl, cyclobutyl, oxetane, azirone, thiohexacyclobutyl, phenyl, cyclopentyl, pyrrolyl, tetrahydropyrrolyl, cyclohexyl, triazolyl, piperidinyl, furanyl, thiazolyl, triazolyl, pyridinyl, pyrimidinyl, , , , , , , , , , , ; Preferably, R is selected from the following optionally substituted groups: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , 、 、 、 、 。 4. The compound according to any one of claims 1-3, or a pharmaceutically acceptable salt thereof, characterized in that, R 31 and R 41 Selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R. Z3 The following groups are substituted: C 1-12 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, -OC 1-12 Alkyl, -OC 3-12 Cycloalkyl, -O-(3-12 membered heterocyclic), -SC 1-12 Alkyl, -SC 3-12 Cycloalkyl, -S-(3-12 membered heterocyclic groups), -NH-C 1-12 Alkyl, -NH-C 3-12 Cycloalkyl groups, -NH- (3-12 membered heterocyclic groups); Preferably, R 31 and R 41 Selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R. Z3 The following groups are substituted: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, hydroxymethyl, hydroxyethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, propoxy, methylthio, ethylthio, propylthio, cyclopropoxy, cyclopropylthio, cyclopropylamino, -NHCH3, -NHCH2 CH3, -N(CH3)2, -N(CH2CH3)2, propidinyl, aziridine, oxoheterobutyl, thioheterobutyl, tetrahydrofuranyl, pyrrolyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, homopiperidinyl, aziridine-heptyl, oxoheterobutyl, phenyl, naphthyl, furanyl, thiophenyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isothiazolyl, isoxazolyl, triazolyl; Preferably, R 31 Selected from: H, deuterium, halogens, C 1-6 Alkyl, -OC 1-6 alkyl; Preferably, R 31 Selected from: H, F; Preferably, R 41 Selected from: H, C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-8 cycloalkyl, C 6-10 Aryl; Preferably, R 41 Selected from: H, methyl, cyclopropyl, phenyl; Each R wc1 R wc2 R wc3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more R Z4 The following groups are substituted: C 1-12 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -C 1-12 Alkylene-C 3-12 cycloalkyl, -C 1-12 alkylene-(3-12 membered heterocyclic group), -C 1-12 Alkylene-C 6-12 Aryl, -C 1-12 alkylene-(5-12-membered heteroaryl), -OC 3-12 Cycloalkyl, -O-(3-12 membered heterocyclic), -OC 6-12 Aryl, -O-(5-12 heteroaryl), -SC 3-12 Cycloalkyl, -S-(3-12 membered heterocyclic groups), -SC 6-12 Aryl, -S-(5-12 heteroaryl), -NH-C 3-12 Cycloalkyl, -NH- (3-12 membered heterocyclic groups), -NH-C 6-12 Aryl, -NH- (5-12 heteroaryl); Preferably, each R wc1 R wc2 R wc3 The same or different elements are selected independently from: H, deuterium, halogen, OH, CN, C. 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl; Preferably, each R wc1 R wc2 R wc3 They are either the same or different, and are independently selected from: H, F, OH, or methyl; Each R wn1 The same or different, and independently selected from: H, deuterium, and optionally substituted or optionally replaced by one, two, three or more R. Z5 The following groups are substituted: C 1-12 Alkyl, C 2-12 alkenyl, C 2-12 alkynyl group, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -C 1-12 Alkylene-C 2-12 alkenyl, -C 1-12 Alkylene-C 2-12 alkynyl group, -C 1-12 Alkylene-C 3-12 cycloalkyl, -C 1-12 alkylene-(3-12 membered heterocyclic group), -C 1-12 Alkylene-C 6-12 Aryl, -C 1-12 alkylene-(5-12-membered heteroaryl); Preferably, each R wn1 Same or different, selected independently from: H, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl; Preferably, each R wn1 They are either the same or different, and are independently selected from: H, methyl; Each R Z R Z1 R Z2 R Z3 R Z4 R Z5 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and optionally substituted or optionally influenced by one, two, three or more Rs. ZZ1 The following groups are substituted: C 1-12 Alkyl, C 2-12 alkenyl, C 2-12 alkynyl group, C 3-12 cycloalkyl, C 3-12 Cycloalkenyl, C 3-12 Cycloalkynyl, 3-12 membered heterocyclic group, C 6-12 Aryl, 5-12 heteroaryl, -C 1-12 Alkylene-C 2-12 alkenyl, -C 1-12 Alkylene-C 2-12 alkynyl group, -C 1-12 Alkylene-C 3-12 cycloalkyl, -C 1-12 Alkylene-C 3-12 Cycloalkenyl, -C 1-12 Alkylene-C 3-12 Cycloalkynyl, -C 1-12 alkylene-(3-12 membered heterocyclic group), -C 1-12 Alkylene-C 6-12 Aryl, -C 1-12 alkylene-(5-12-membered heteroaryl); -OR O1 -SR S1 -NR N1 R N2 ;-C(O)R C1 -OC(O)R C2 -OC(O)-OR O2 -OC(O)-NR N3 R N4 -N(R) N5 )-C(O)R C3 -N(R) N6 )-C(O)-NR N7 R N8 ;-S(O)2R S2 -OS(O)2R S3 -OS(O)2-OR O3 -OS(O)2-NR N9 R N10 -N(R) N11 )-S(O)2R S4 、-N(R N12 )-S(O)2-NR N13 R N14 ;-S(O)R S5 、-O-S(O)R S6 、-O-S(O)-OR O4 、-O-S(O)-NR N15 R N16 、-N(R N17 )-S(O)R S7 、-N(R N18 )-S(O)-NR N19 R N20 ;-P(=O)R P1 R P2 、-P(=O)(OR O5 )R P2 、-P(=O)(OR O6 )(OR O7 )、-P(=O)(NR N21 R N22 )R P3 、-P(=O)(NR N23 R N24 )(NR N25 R N26 )、-P(=O)(OR O8 )(NR N27 R N28 ); Or two R atoms connected to the same carbon atom Z1 Together with the carbon atom it is attached to, they form C 3-12 cycloalkyl; Preferably, each R Z The same or different, and independently selected from: H, halogen, or optionally substituted groups of the following: C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, Halogenated C 1-6 Alkoxy; Preferably, each R Z Same or different, and independently selected from: F, Cl, Br, I, or optionally substituted C 1-3 Alkyl groups (e.g., methyl groups); Preferably, each R Z1 Same or different, and independently selected from: halogen, CN, SF5, methyl, halogenated C 1-6 Alkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, -P(=O)(C 1-6 Alkyl)2、-S(O)2C 1-6 Alkyl group; or two R atoms attached to the same carbon atom Z1 Together with the carbon atom it is attached to, they form C 3-6 Cycloalkyl; preferably, two R atoms attached to the same carbon atom on the alkylene group. Z1 Together with the carbon atom it is attached to, they form C 3-6 cycloalkyl; Preferably, each R Z1 Same or different, and independently selected from: F, Cl, CN, CF3, SF5, methyl, phenyl, , , ; or two R atoms connected to the same carbon atom Z1 Together with the carbon atom attached thereto, they form a cyclopropyl, cyclobutyl, or cyclopentyl group; preferably, the two R groups attached to the same carbon atom on the alkylene group... Z1 Together with the carbon atom attached to it, it forms a cyclopropyl, cyclobutyl, or cyclopentyl group; Preferably, each R Z2 Same or different, and independently selected from: halogen, C 1-6 Alkyl, C 3-8 Cycloalkyl-C(O); Preferably, each R Z2 Same or different, and independently selected from: F, methyl, isopropyl, .

5. The compound according to any one of claims 1-4, or a pharmaceutically acceptable salt thereof, characterized in that, Each R O1 R O2 R O3 R O4 R O5 R O6 R O7 R O8 R S1 R S2 R S3 R S4 R S5 R S6 R S7 R C1 R C2 R C3 R P1 R P2 R P3 R N1 R N2 R N3 R N4 R N5 R N6 R N7 R N8 R N9 R N10 R N11 R N12 R N13 R N14 R N15 R N16 R N17 R N18 R N19 R N20 R N21 R N22 R N23 R N24 R N25 R N26 R N27 R N28 Whether identical or different, each is independently selected from: H, deuterium, and optionally substituted or optionally replaced by one, two, three or more R. ZZ2 The following groups are substituted: C 1-12 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -C 1-12 Alkylene-C 3-12 cycloalkyl, -C 1-12 alkylene-(3-12 membered heterocyclic group), -C 1-12 Alkylene-C 6-12 Aryl, -C 1-12 alkylene-(5-12-membered heteroaryl); Or R N3 With R N4 R N7 With R N8 R N9 With R N10 R N13 With R N14 R N15 With R N16 R N19 With R N20 R N21 With R N22 R N23 With R N24 R N25 With R N26 R N27 With R N28 Together with the N atom it is linked to, it forms a 3-12 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O, S, Si or P; Or R P1 With R P2 Together with the P atom it is linked to, it forms a 3-12 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O, S, Si or P; Or R O5 With R P2 R O6 With R O7 Together with the atoms linked to it, they form a 4-12 membered heterocyclic group, wherein the heterocyclic group optionally contains one, two or more heteroatoms selected from N, O, S, Si or P; Each R ZZ1 R ZZ2 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and the following optional substituted groups: C 1-12 Alkyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-12 Aryl, 5-12 heteroaryl, -C 1-12 Alkylene-C 3-12 cycloalkyl, -C 1-12 alkylene-(3-12 membered heterocyclic group), -C 1-12 Alkylene-C 6-12 Aryl, -C 1-12 alkylene-(5-12-membered heteroaryl), -OC 3-12 Cycloalkyl, -O-(3-12 membered heterocyclic), -OC 6-12 Aryl, -O-(5-12 heteroaryl), -SC 3-12 Cycloalkyl, -S-(3-12 membered heterocyclic groups), -SC 6-12 Aryl, -S-(5-12 heteroaryl), -NH-C 3-12 Cycloalkyl, -NH- (3-12 membered heterocyclic groups), -NH-C 6-12 Aryl, -NH- (5-12 heteroaryl); W1, W4, W5, W6, W7, W 10 W 11 W 12 W 14 W 15 W 16 W 17 W 18 W 19 W 22 W 23 W 24 W 25 Same or different, and independently selected from: O, S, S(=O), S(=O)2, N, NR wn1 C, C (=O), CR wc1 CR wc2 R wc3 ; Preferably, each R wc1 R wc2 R wc3 Same or different, and independently selected from: H, deuterium, halogen, OH or C 1-6 alkyl; Preferably, W1, W4, W7, W 10 W 11 W 12 W 14 W 15 W 16 W 17 Same or different, and independently selected from: O, S, S(=O), S(=O)2, N, NH, N(C) 1-6 Alkyl), C, C(=O), CH, C(C) 1-6 Alkyl), CH2, CH(C) 1-6 Alkyl), C(C) 1-6 Alkyl)2; Preferably, W2 and W3 may be the same or different, and are independently selected from: N, NH, N(C) 1-6 Alkyl), C, CH, C(C) 1-6 alkyl); Preferably, W5, W8, W 13 Same or different, and independently selected from: N, C, CH, C(C) 1-6 alkyl); Preferably, W6 is selected from: O, S, NH, N(C) 1-6 Alkyl), CH2, CH(C) 1-6 Alkyl), C(C) 1-6 Alkyl)2.

6. The compound according to any one of claims 1-5, or a pharmaceutically acceptable salt thereof, characterized in that, R wc1 and R1, or R wc2 and R1, or R wc3 and R1, or R wn1 Together with R1, they form an optional substitution or optional substitution by one, two, three or more Rs. ZZ3 The following groups are substituted: 8-15 membered fused heterocyclic group, 8-15 membered bridged heterocyclic group, 8-15 membered spiroheterocyclic group, C 8-15 Fused ring group, C 8-15 Yuanqiao Ring Base, C 8-15 spirocyclic base; Each R ZZ3 The same or different, and independently selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, oxo (=O), thio (=S), -COOH, and the following optional substituted groups: C 1-6 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocyclic, phenyl, 5-6 membered heteroaryl, -C 1-3 Alkylene-C 3-6 cycloalkyl, -C 1-3 Alkylene-(3-6 membered heterocyclic group), -C 1-3 alkylene-phenyl, -C 1-3 alkylene-(5-6-membered heteroaryl), -OC 3-6 Cycloalkyl, -O-(3-6 membered heterocyclic), -O-phenyl, -O-(5-6 membered heteroaryl), -SC 3-6 Cycloalkyl, -S-(3-6 membered heterocyclic), -S-phenyl, -S-(5-6 membered heteroaryl), -NH-C 3-6 Cycloalkyl, -NH- (3-6 membered heterocyclic group), -NH-phenyl, -NH- (5-6 membered heteroaryl); Preferably, R wc1 and R1, or R wc2 and R1, or R wc3 and R1, or R wn1 Together with R1, they form an optional substitution or optional substitution by one, two, three or more Rs. ZZ3 The following groups are substituted: , , , , , , , ; Preferably, R wc1 and R1, or R wc2 and R1, or R wc3 and R1, or R wn1 Together with R1, they form the following optionally substituted groups: , , , , , , , , , , , , ; Preferably, each R ZZ3 Same or different, and independently selected from: H, deuterium, halogen, C 1-6 Alkyl, -OC 1-6 Alkyl, Halogenated C 1-6 Alkyl, -O-halogenated C 1-6 alkyl; Preferably, each R ZZ3 The same or different, and independently selected from: H, deuterium, F, Cl, Br, I, or optionally substituted C. 1-3 Alkyl (e.g., methyl).

7. The compound according to any one of claims 1-5, or a pharmaceutically acceptable salt thereof, characterized in that, The compound represented by formula (M-1) has the following structure: Equation (I'), Among them, rings B, C, R1, R, W1, W2, W3, W4, W5, and W6 independently have the definitions described in any one of claims 1-5; R3 is selected from: H, deuterium, halogen, OH, SH, NH2, CN, SF5, SF3, NO2, -COOH, and optionally substituted or optionally substituted by one, two, three or more Rs. Z4 The following groups are substituted: C 1-20 Alkyl, C 3-20 Cycloalkyl, 3-20 membered heterocyclic groups, C 6-20 Aryl, 5-20 heteroaryl, -C 1-20 Alkylene-C 3-20 cycloalkyl, -C 1-20 Alkylene-(3-20 membered heterocyclic group), -C 1-20 Alkylene-C 6-20 Aryl, -C 1-20 alkylene-(5-20-membered heteroaryl), -OC 3-20 Cycloalkyl, -O- (3-20 membered heterocyclic groups), -OC 6-20 Aryl, -O- (5-20 heteroaryl), -SC 3-20 Cycloalkyl, -S- (3-20 membered heterocyclic groups), -SC 6-20 Aryl, -S-(5-20 heteroaryl), -NH-C 3-20 Cycloalkyl, -NH- (3-20 membered heterocyclic groups), -NH-C 6-20 Aryl, -NH- (5-20 heteroaryl); Preferably, the compound represented by formula (M-1) has the following structure: 、 、 、 、 、 、 、 、 、 、 、 ； Among them, R, R1, R3, R wc1 Each of them independently possesses the definition described in any one of claims 1-5; Preferably, the compound represented by formula (M-1) has the following structure: 、 、 、 Among them, rings C, R, R3, and R z1 W1, W2, W4, and W5 independently have the definition described in any one of claims 1-5; m is selected from 0, 1, or 2; Preferably, the compound shown in formula (M-1) has the following structure: Equation (I), Among them, ring B, ring C, R1, R2, R3, W1, W2, W3, W4, W5, W6, and U1 independently have the definition described in any one of claims 1-5; Preferably, the compound represented by formula (M-1) has the following structure: 、 、 、 、 、 、 、 、 ； Wherein, R1, R2, R3, and U1 independently have the definitions described in any one of claims 1-5; Preferably, the compound represented by formula (M-1) has the following structure: ， Among them, rings C, R2, R3, and R z1 W1, W2, W4, W5, and U1 each have the definition of any one of claims 1-5 independently; m is selected from 0, 1, or 2; Preferably, the compound represented by formula (M-1) has the following structure: Equation (II), Among them, rings B, C, R1, R2, W1, W2, W3, W4, W5, W6, W7, W8, and U1 each have the definitions described above independently; Preferably, the compound represented by formula (M-1) has the following structure: ， Wherein, R1, R2, and U1 independently have the definitions described in any one of claims 1-5; Preferably, the compound represented by formula (M-1) has the following structure: Formula (III) Among them, rings D, R1, R2, and R 31 W 10 W 11 W 12 U1 and U1 are each independently defined as described in any one of claims 1-5; Preferably, the compound represented by formula (M-1) has the following structure: ， Among them, R1, R2, R 31 R wn1 U1 and U1 are each independently defined as described in any one of claims 1-5; Preferably, the compound represented by formula (M-1) has the following structure: ， Among them, rings D, R2, and R 31 R z1 W 10 W 11 W 12 U1 and U1 are each independently defined as described in any one of claims 1-5; Preferably, the compound represented by formula (M-1) has the following structure: Formula (IV), Among them, rings E, R1, R2, and R 41 W 13 W 14 W 15 W 16 W 17 U1 and U1 are independently defined as described in any one of claims 1-5; Preferably, the compound represented by formula (M-1) has the following structure: 、 、 、 、 、 ， , Among them, R1, R2, U1, R 41 R wn1 R wc2 Each of them independently possesses the definition described in any one of claims 1-5; Preferably, the compound represented by formula (M-1) has the following structure: Among them, rings R2, R3, and R z1 Each of them independently possesses the definition described in any one of claims 1-7; Preferably, the compound represented by formula (M-1) has the following structure: ； Among them, rings R2, R3, and R z1 Each of them independently has the definition as described in any one of claims 1-7.

8. The compound according to any one of claims 1-7, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the following compounds:

9. A pharmaceutical composition comprising at least one of a compound of formula (M-1) according to any one of claims 1-8 or a pharmaceutically acceptable salt thereof.

10. Use of at least one of the compounds of formula (M-1) according to any one of claims 1-8 or a pharmaceutically acceptable salt thereof in the preparation of a medicament, wherein the medicament is for the prevention and / or treatment of diseases or conditions associated with RIPK1 kinase; Preferably, the diseases or conditions associated with RIPK1 kinase are selected from: inflammation, autoimmune diseases, cancer, infection, central nervous system diseases, metabolic diseases, cardiovascular diseases, respiratory diseases, liver diseases, kidney diseases, eye diseases, lymphatic diseases, psychological disorders, graft-versus-host disease, and abnormal pain. Preferably, the diseases or conditions associated with RIPK1 kinase are selected from: sepsis, rheumatoid arthritis, inflammatory bowel disease, Parkinson's disease, Lewy body dementia, multiple system atrophy, Parkinson's plus syndrome, tau proteinosis, Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, spinal muscular atrophy, primary lateral sclerosis, Huntington's disease, ischemia, stroke, intracranial hemorrhage, cerebral hemorrhage, muscular dystrophy, progressive muscular atrophy, pseudobulbar palsy, progressive bulbar palsy, spinal muscular atrophy, hereditary muscular atrophy, peripheral neuropathy, progressive supranuclear palsy, corticobasal degeneration, and demyelinating diseases.

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