Kras modulators

By providing KRAS inhibitor compounds with specific structures, the problem of targeting the KRAS protein in existing technologies has been solved, enabling effective treatment of KRAS-related cancers.

CN122180689APending Publication Date: 2026-06-09ALTEROME THERAPEUTICS INC
View PDF 2 Cites 0 Cited by

Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
ALTEROME THERAPEUTICS INC
Filing Date
2024-09-18
Publication Date
2026-06-09

Smart Images

  • Figure CN122180689A_ABST
    Figure CN122180689A_ABST
Patent Text Reader

Abstract

Provided herein are inhibitors of KRAS, pharmaceutical compositions comprising the inhibitory compounds, and methods of using the KRAS inhibitory compounds to treat diseases or disorders.
Need to check novelty before this filing date? Find Prior Art

Claims

1. A compound having the structure of formula (I) or a pharmaceutically acceptable salt or solvate thereof: （I） in: X 1 It is N or C-CN; X 2 It is N, CH, CF, C-CH3, C-Cl, C- (optionally substituted C1-C6 alkyl), C- (optionally substituted C2-C6 alkenyl) or C- (optionally substituted C3-C6 carbocyclic); X 3 It is N, CH, CF, C-Cl, C-CN, or C-CF3; Ar is an optionally substituted monocyclic or bicyclic aryl group, or an optionally substituted monocyclic or bicyclic heteroaryl ring system; R 1 It is LG; where L is an optionally substituted C1-C4 alkylene group. ; Furthermore, G is optionally a substituted 5- to 10-membered heterocyclic group; -N(R 2 )R 3 The following heterocyclic substituents are optionally substituted and selected from the group consisting of: (a) optionally substituted azabicyclo[3.1.0]hexane; (b) Optionally substituted azabicyclo[4.1.0]heptane; (c) Optionally substituted oxazadicyclo[4.1.0]heptane; (d) Optionally substituted azabicyclo[5.1.0]octane; (e) Optionally substituted oxazabicyclo[5.1.0]octane; (f) Optionally substituted azabicyclo[6.1.0]nonane; (g) Optionally substituted oxazabicyclo[6.1.0]nonane; (h) optionally substituted azabicyclo[5.1.0]oct-5-en-2-yl; (i) optionally substituted azabicyclo[5.1.0]oct-4-en-2-yl; (j) Optionally substituted azabicyclo[6.1.0]non-6-en-2-yl; (k) optionally substituted azabicyclo[6.1.0]non-5-en-2-yl; (l) optionally substituted azabicyclo[6.1.0]non-4-en-2-yl; (m) optionally substituted 3-oxa-2,6-diazabicyclo[5.1.0]oct-1-en-6-yl; (n) optionally substituted 2-oxa-3,6-diazabicyclo[5.1.0]oct-3-en-6-yl; (o) Optionally substituted 4-oxa-2,5-diazabicyclo[5.1.0]oct-5-en-2-yl; (p) Optionally substituted 3-oxa-2,7-diazabicyclo[6.1.0]non-1-en-7-yl; (q) Optionally substituted 2-oxa-3,7-diazabicyclo[6.1.0]non-3-en-7-yl; (r) optionally substituted 5-oxa-2,6-diazabicyclo[6.1.0]non-6-en-2-yl; (s) optionally substituted 6-oxa-2,5-diazabicyclo[6.1.0]non-4-en-2-yl; and (t) optionally substituted 4-oxa-2,5-diazabicyclo[6.1.0]non-5-en-2-yl; and R 4 It is selected from H, -OH, -CN, halogen, optionally substituted C1-C4 alkoxy, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 cycloalkyl or C1-C6 cycloalkylalkyl.

2. A compound having the structure of formula (Ia) or a pharmaceutically acceptable salt or solvate thereof: (It) in: X 1 It is N or C-CN; X 2 It is N, CH, CF, C-CH3, or C-Cl; X 3 It is N, CH, CF, C-Cl, C-CN, or C-CF3; Ar is an optionally substituted monocyclic or bicyclic aryl group, or an optionally substituted monocyclic or bicyclic heteroaryl ring system; R 1 It is LG; where L is an optionally substituted C1-C4 alkylene group. ; Furthermore, G is optionally a substituted 5- to 10-membered heterocyclic group; -N(R 2 )R 3 The following heterocyclic substituents are optionally substituted and selected from the group consisting of: (a) optionally substituted azabicyclo[3.1.0]hexane; (b) Optionally substituted azabicyclo[4.1.0]heptane; (c) Optionally substituted oxazadicyclo[4.1.0]heptane; (d) Optionally substituted azabicyclo[5.1.0]octane; (e) Optionally substituted oxazabicyclo[5.1.0]octane; (f) Optionally substituted azabicyclo[6.1.0]nonane; (g) Optionally substituted oxazabicyclo[6.1.0]nonane; (h) optionally substituted azabicyclo[5.1.0]oct-5-en-2-yl; (i) optionally substituted azabicyclo[5.1.0]oct-4-en-2-yl; (j) Optionally substituted azabicyclo[6.1.0]non-6-en-2-yl; (k) optionally substituted azabicyclo[6.1.0]non-5-en-2-yl; (l) optionally substituted azabicyclo[6.1.0]non-4-en-2-yl; (m) optionally substituted 3-oxa-2,6-diazabicyclo[5.1.0]oct-1-en-6-yl; (n) optionally substituted 2-oxa-3,6-diazabicyclo[5.1.0]oct-3-en-6-yl; (o) Optionally substituted 4-oxa-2,5-diazabicyclo[5.1.0]oct-5-en-2-yl; (p) Optionally substituted 3-oxa-2,7-diazabicyclo[6.1.0]non-1-en-7-yl; (q) Optionally substituted 2-oxa-3,7-diazabicyclo[6.1.0]non-3-en-7-yl; (r) optionally substituted 5-oxa-2,6-diazabicyclo[6.1.0]non-6-en-2-yl; (s) optionally substituted 6-oxa-2,5-diazabicyclo[6.1.0]non-4-en-2-yl; and (t) optionally substituted 4-oxa-2,5-diazabicyclo[6.1.0]non-5-en-2-yl; and R 4 It is selected from H, optionally substituted C1-C4 alkoxy, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 cycloalkyl, C1-C6 cycloalkylalkyl, cyano, or halogen.

3. A compound having the structure of formula (Ib) or a pharmaceutically acceptable salt or solvate thereof: (One) in: X 1 It is N or C-CN; X 2 It is N, CH, CF, C-CH3, or C-Cl; X 3 It is N, CH, CF, C-Cl, or C-CF3; Ar is an optionally substituted monocyclic or bicyclic aryl group, or an optionally substituted monocyclic or bicyclic heteroaryl ring system; R 1 It is LG; where L is an optionally substituted C1-C4 alkylene group. ; Furthermore, G is optionally a substituted 5- to 10-membered heterocyclic group; -N(R 2 )R 3 The following heterocyclic substituents are optionally substituted and selected from the group consisting of: (a) optionally substituted azabicyclo[3.1.0]hexane; (b) Optionally substituted azabicyclo[4.1.0]heptane; (c) Optionally substituted oxazadicyclo[4.1.0]heptane; (d) Optionally substituted azabicyclo[5.1.0]octane; (e) Optionally substituted oxazabicyclo[5.1.0]octane; (f) Optionally substituted azabicyclo[6.1.0]nonane; (g) Optionally substituted oxazabicyclo[6.1.0]nonane; (h) optionally substituted azabicyclo[5.1.0]oct-5-en-2-yl; (i) optionally substituted azabicyclo[5.1.0]oct-4-en-2-yl; (j) Optionally substituted azabicyclo[6.1.0]non-6-en-2-yl; (k) optionally substituted azabicyclo[6.1.0]non-5-en-2-yl; (l) optionally substituted azabicyclo[6.1.0]non-4-en-2-yl; (m) optionally substituted 3-oxa-2,6-diazabicyclo[5.1.0]oct-1-en-6-yl; (n) optionally substituted 2-oxa-3,6-diazabicyclo[5.1.0]oct-3-en-6-yl; (o) Optionally substituted 4-oxa-2,5-diazabicyclo[5.1.0]oct-5-en-2-yl; (p) Optionally substituted 3-oxa-2,7-diazabicyclo[6.1.0]non-1-en-7-yl; (q) Optionally substituted 2-oxa-3,7-diazabicyclo[6.1.0]non-3-en-7-yl; (r) optionally substituted 5-oxa-2,6-diazabicyclo[6.1.0]non-6-en-2-yl; (s) optionally substituted 6-oxa-2,5-diazabicyclo[6.1.0]non-4-en-2-yl; and (t) optionally substituted 4-oxa-2,5-diazabicyclo[6.1.0]non-5-en-2-yl; and R 4 It is selected from H, optionally substituted C1-C4 alkoxy, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 cycloalkyl, C1-C6 cycloalkylalkyl, cyano, or halogen.

4. A compound having the structure of formula (Ic) or a pharmaceutically acceptable salt or solvate thereof: (Ic) in: X 1 It is N or C-CN; X 2 It is N, CH, CF or C-Cl; X 3 It is N, CH, CF, C-Cl, or C-CF3; Ar is an optionally substituted monocyclic or bicyclic aryl group, or an optionally substituted monocyclic or bicyclic heteroaryl ring system; R 1 It is LG; where L is an optionally substituted C1-C4 alkylene group. ; Furthermore, G is optionally a substituted 5- to 10-membered heterocyclic group; -N(R 2 )R 3 The following heterocyclic substituents are optionally substituted and selected from the group consisting of: (a) optionally substituted azabicyclo[3.1.0]hexane; (b) Optionally substituted azabicyclo[4.1.0]heptane; (c) Optionally substituted oxazadicyclo[4.1.0]heptane; (d) Optionally substituted azabicyclo[5.1.0]octane; (e) Optionally substituted oxazabicyclo[5.1.0]octane; (f) Optionally substituted azabicyclo[6.1.0]nonane; (g) Optionally substituted oxazabicyclo[6.1.0]nonane; (h) optionally substituted azabicyclo[5.1.0]oct-5-en-2-yl; (i) optionally substituted azabicyclo[5.1.0]oct-4-en-2-yl; (j) Optionally substituted azabicyclo[6.1.0]non-6-en-2-yl; (k) optionally substituted azabicyclo[6.1.0]non-5-en-2-yl; (l) optionally substituted azabicyclo[6.1.0]non-4-en-2-yl; (m) optionally substituted 3-oxa-2,6-diazabicyclo[5.1.0]oct-1-en-6-yl; (n) optionally substituted 2-oxa-3,6-diazabicyclo[5.1.0]oct-3-en-6-yl; (o) Optionally substituted 4-oxa-2,5-diazabicyclo[5.1.0]oct-5-en-2-yl; (p) Optionally substituted 3-oxa-2,7-diazabicyclo[6.1.0]non-1-en-7-yl; (q) Optionally substituted 2-oxa-3,7-diazabicyclo[6.1.0]non-3-en-7-yl; (r) optionally substituted 5-oxa-2,6-diazabicyclo[6.1.0]non-6-en-2-yl; (s) optionally substituted 6-oxa-2,5-diazabicyclo[6.1.0]non-4-en-2-yl; and (t) optionally substituted 4-oxa-2,5-diazabicyclo[6.1.0]non-5-en-2-yl; and R 4 Selected from H or optionally substituted C1-C4 alkoxy groups.

5. A compound having the structure of formula (Id) or a pharmaceutically acceptable salt or solvate thereof: (Id) in: X 1 It is N or C-CN; X 2 It is N, CH, CF or C-Cl; X 3 It is N, CH, CF or C-Cl; Ar is an optionally substituted monocyclic or bicyclic aryl group, or an optionally substituted monocyclic or bicyclic heteroaryl ring system; R 1 It is LG; where L is an optionally substituted C1-C4 alkylene group. ; Furthermore, G is optionally a substituted 5- to 10-membered heterocyclic group; -N(R 2 )R 3 Forming a heterocyclic group selected from the following optionally substituted groups: (a) Optionally substituted azabicyclo[4.1.0]heptane; (b) Optionally substituted oxazadicyclo[4.1.0]heptane; (c) Optionally substituted azabicyclo[5.1.0]octane; (d) Optionally substituted oxazadicyclo[5.1.0]octane; (e) Optionally substituted azabicyclo[6.1.0]nonane; (f) Optionally substituted oxazabicyclo[6.1.0]nonane; or (g) optionally substituted azabicyclo[5.1.0]oct-5-en-2-yl; and R 4 Selected from H or optionally substituted C1-C4 alkoxy groups.

6. The compound of any one of claims 1 to 5, or a pharmaceutically acceptable salt or solvate thereof, wherein X 1 It is N.

7. The compound of any one of claims 1 to 5, or a pharmaceutically acceptable salt or solvate thereof, wherein X 1 It is C-CN.

8. The compound of any one of claims 1 to 7, or a pharmaceutically acceptable salt or solvate thereof, wherein X 2 It is N.

9. The compound of any one of claims 1 to 7, or a pharmaceutically acceptable salt or solvate thereof, wherein X 2 It is CH, CF, or C-Cl.

10. The compound of any one of claims 1 to 7, or a pharmaceutically acceptable salt or solvate thereof, wherein X 2 It is C-CH3.

11. The compound of any one of claims 1 to 7, or a pharmaceutically acceptable salt or solvate thereof, wherein X 2 It is C-(optionally substituted C1-C6 alkyl).

12. The compound of any one of claims 1 to 7, or a pharmaceutically acceptable salt or solvate thereof, wherein X 2 It is a C-(C2-C6 optionally substituted alkenyl group).

13. The compound of any one of claims 1 to 7, or a pharmaceutically acceptable salt or solvate thereof, wherein X 2 It is C- (optionally substituted C3-C6 carbocyclic group).

14. The compound of any one of claims 1 to 13, or a pharmaceutically acceptable salt or solvate thereof, wherein X 3 It is N.

15. The compound of any one of claims 1 to 13, or a pharmaceutically acceptable salt or solvate thereof, wherein X 3 It is CH, CF, or C-Cl.

16. The compound of any one of claims 1 to 13, or a pharmaceutically acceptable salt or solvate thereof, wherein X 3 It's CF.

17. The compound of any one of claims 1 to 13, or a pharmaceutically acceptable salt or solvate thereof, wherein X 3 It is C-CF3.

18. The compound of any one of claims 1 to 17 or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is a monocyclic, optionally substituted aryl group.

19. The compound of claim 18 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted monocyclic aryl group is an optionally substituted phenyl group.

20. The compound of claim 19 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted phenyl group is substituted at the meta position with an -OH group.

21. The compound of claim 19 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted phenyl group is .

22. The compound of claim 19 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted phenyl group is selected from: 。 23. The compound of claim 19 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted phenyl group is substituted at the meta position with an -NH2 group.

24. The compound of claim 19 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted phenyl group is selected from: .

25. The compound of claim 19 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted phenyl group is selected from: 。 26. The compound of claim 19 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted phenyl group is a 2,3,5-trisubstituted phenyl group.

27. The compound of claim 26 or a pharmaceutically acceptable salt or solvate thereof, wherein the 2,3,5-trisubstituted phenyl group is 3-hydroxylated.

28. The compound of any one of claims 1 to 17 or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is a bicyclic aryl group optionally substituted.

29. The compound of claim 28 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted aryl group of the bicyclic ring is an optionally substituted naphthyl group.

30. The compound of claim 29 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted naphthyl group is an optionally substituted 1-naphthyl group.

31. The compound of claim 30 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted 1-naphthyl group is further substituted at the 8-position.

32. The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 33. The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 34. The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 35. The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 36. The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 37. The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 38. The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 39. The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 40. The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 41. The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 42. The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 43. The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 44. The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 45. The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 46. ​​The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 47. The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 48. The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 49. The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 50. The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 51. The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 52. The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 53. The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 54. The compound of any one of claims 28 to 30, or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 55. The compound of claim 28 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted aryl group of the bicyclic ring is described by formula (a): （a） in: R 12 It is hydrogen, deuterium, or F; R 13 It is hydrogen, deuterium, -OH, -NH2, Cl, -CN, -OCONHMe, -NHCO2Me; R 14 It is hydrogen, deuterium, F, Cl, or Br; R 15 It is hydrogen, deuterium, F, Cl, or Br; R 16 It is hydrogen, deuterium, F, Cl, Br, -CN or -CH3; R 17 It is hydrogen, deuterium, F, Cl, or -CN; and R 18 It is hydrogen, deuterium, -CH3, -CH2CH3, -CD2CD 3、 -CH=CH2, -C≡CH, -OCHF2, -OCF3, -CH2F, -CHF2, -CF3, -CN, Cl, F, -OCH3, -OCD3, -OCH2F or -OCD2F.

56. The compound of any one of claims 1 to 17 or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is a monocyclic, optionally substituted heteroaryl group.

57. The compound of claim 56 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted monocyclic heteroaryl group is optionally substituted 2-pyridyl.

58. The compound of claim 57 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted 2-pyridyl group is .

59. The compound of claim 57 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted 2-pyridyl group is 。 60. The compound of claim 57 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted monocyclic heteroaryl group is optionally substituted 4-pyridyl.

61. The compound of claim 60 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted 4-pyridyl group is 。 62. The compound of claim 60 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted 4-pyridyl group is 。 63. The compound of any one of claims 1 to 17 or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is a bicyclic, optionally substituted heteroaryl group.

64. The compound of claim 63 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted bicyclic heteroaryl group is selected from: 。 65. The compound of claim 63 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted bicyclic heteroaryl group is selected from: 。 66. The compound of claim 63 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted bicyclic heteroaryl group is selected from: 。 67. The compound of claim 63 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted bicyclic heteroaryl group is selected from: 。 68. The compound of claim 63 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted heteroaryl group of the bicyclic ring is 。 69. The compound of claim 63 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted bicyclic heteroaryl group is selected from: 。 70. The compound of claim 63 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted bicyclic heteroaryl group is described by formula (b1): （b1） in: R 13 It is hydrogen, deuterium, -OH, -NH2, Cl, -CN, -OCONHMe, -NHCO2Me; R 14 It is hydrogen, deuterium, F, Cl, or Br; R 15 It is hydrogen, deuterium, F, Cl, or Br; R 16 It is hydrogen, deuterium, F, Cl, Br, -CN or -CH3; R 17 It is hydrogen, deuterium, F, Cl, or -CN; and R 18 It is hydrogen, deuterium, -CH3, -CH2CH3, -CD2CD 3、 -CH=CH2, -C≡CH, -OCHF2, -OCF3, -CH2F, -CHF2, -CF3, -CN, Cl, F, -OCH3, -OCD3, -OCH2F or -OCD2F.

71. The compound of claim 63 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted bicyclic heteroaryl group is described by formula (b2): （b2） in: R 12 It is hydrogen, deuterium, or F; R 14 It is hydrogen, deuterium, F, Cl, or Br; R 15 It is hydrogen, deuterium, F, Cl, or Br; R 16 It is hydrogen, deuterium, F, Cl, Br, -CN or -CH3; R 17 It is hydrogen, deuterium, F, Cl, or -CN; and R 18 It is hydrogen, deuterium, -CH3, -CH2CH3, -CD2CD 3、 -CH=CH2, -C≡CH, -OCHF2, -OCF3, -CH2F, -CHF2, -CF3, -CN, Cl, F, -OCH3, -OCD3, -OCH2F or -OCD2F.

72. The compound of claim 63 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted bicyclic heteroaryl group is described by formula (b3): （b3） in: R 12 It is hydrogen, deuterium, or F; R 13 It is hydrogen, deuterium, -OH, -NH2, Cl, -CN, -OCONHMe, -NHCO2Me; R 15 It is hydrogen, deuterium, F, Cl, or Br; R 16 It is hydrogen, deuterium, F, Cl, Br, -CN or -CH3; R 17 It is hydrogen, deuterium, F, Cl, or -CN; and R 18 It is hydrogen, deuterium, -CH3, -CH2CH3, -CD2CD 3、 -CH=CH2, -C≡CH, -OCHF2, -OCF3, -CH2F, -CHF2, -CF3, -CN, Cl, F, -OCH3, -OCD3, -OCH2F or -OCD2F.

73. The compound of claim 63 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted bicyclic heteroaryl group is described by formula (b4): （b4） in: R 12 It is hydrogen, deuterium, or F; R 13 It is hydrogen, deuterium, -OH, -NH2, Cl, -CN, -OCONHMe, -NHCO2Me; R 14 It is hydrogen, deuterium, F, Cl, or Br; R 16 It is hydrogen, deuterium, F, Cl, Br, -CN or -CH3; R 17 It is hydrogen, deuterium, F, Cl, or -CN; and R 18 It is hydrogen, deuterium, -CH3, -CH2CH3, -CD2CD 3、 -CH=CH2, -C≡CH, -OCHF2, -OCF3, -CH2F, -CHF2, -CF3, -CN, Cl, F, -OCH3, -OCD3, -OCH2F or -OCD2F.

74. The compound of claim 63 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted bicyclic heteroaryl group is described by formula (b5): （b5） in: R 12 It is hydrogen, deuterium, or F; R 13 It is hydrogen, deuterium, -OH, -NH2, Cl, -CN, -OCONHMe, -NHCO2Me; R 14 It is hydrogen, deuterium, F, Cl, or Br; R 15 It is hydrogen, deuterium, F, Cl, or Br; R 17 It is hydrogen, deuterium, F, Cl, or -CN; and R 18 It is hydrogen, deuterium, -CH3, -CH2CH3, -CD2CD 3、 -CH=CH2, -C≡CH, -OCHF2, -OCF3, -CH2F, -CHF2, -CF3, -CN, Cl, F, -OCH3, -OCD3, -OCH2F or -OCD2F.

75. The compound of claim 63 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted bicyclic heteroaryl group is described by formula (b6): （b6） in: R 12 It is hydrogen, deuterium, or F; R 13 It is hydrogen, deuterium, -OH, -NH2, Cl, -CN, -OCONHMe, -NHCO2Me; R 14 It is hydrogen, deuterium, F, Cl, or Br; R 15 It is hydrogen, deuterium, F, Cl, or Br; R 16 It is hydrogen, deuterium, F, Cl, Br, -CN, or -CH3; and R 18 It is hydrogen, deuterium, -CH3, -CH2CH3, -CD2CD 3、 -CH=CH2, -C≡CH, -OCHF2, -OCF3, -CH2F, -CHF2, -CF3, -CN, Cl, F, -OCH3, -OCD3, -OCH2F or -OCD2F.

76. The compound of claim 63 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted bicyclic heteroaryl group is described by formula (b7): （b7） in: R 12 It is hydrogen, deuterium, or F; R 13 It is hydrogen, deuterium, -OH, -NH2, Cl, -CN, -OCONHMe, -NHCO2Me; R 16 It is hydrogen, deuterium, F, Cl, Br, -CN or -CH3; R 17 It is hydrogen, deuterium, F, Cl, or -CN; and R 18 It is hydrogen, deuterium, -CH3, -CH2CH3, -CD2CD 3、 -CH=CH2, -C≡CH, -OCHF2, -OCF3, -CH2F, -CHF2, -CF3, -CN, Cl, F, -OCH3, -OCD3, -OCH2F or -OCD2F.

77. The compound of claim 63 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted bicyclic heteroaryl group is described by formula (b8): （b8） in: R 13 It is hydrogen, deuterium, -OH, -NH2, Cl, -CN, -OCONHMe, -NHCO2Me; R 15 It is hydrogen, deuterium, F, Cl, or Br; R 16 It is hydrogen, deuterium, F, Cl, Br, -CN or -CH3; R 17 It is hydrogen, deuterium, F, Cl, or -CN; and R 18 It is hydrogen, deuterium, -CH3, -CH2CH3, -CD2CD 3、 -CH=CH2, -C≡CH, -OCHF2, -OCF3, -CH2F, -CHF2, -CF3, -CN, Cl, F, -OCH3, -OCD3, -OCH2F or -OCD2F.

78. The compound of any one of claims 1 to 77 or a pharmaceutically acceptable salt or solvate thereof, wherein L is optionally a substituted C1-C4 alkylene group.

79. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein L is .

80. The compound of claim 78 or a pharmaceutically acceptable salt or solvate thereof, wherein L is .

81. The compound of any one of claims 1 to 78 or a pharmaceutically acceptable salt or solvate thereof, wherein L is optionally a substituted C1 alkylene group.

82. The compound of any one of claims 1 to 81, or a pharmaceutically acceptable salt or solvate thereof, wherein G is optionally a substituted 5- to 10-membered heterocyclic group.

83. The compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt or solvate thereof, wherein G is selected from: 。 84. The compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt or solvate thereof, wherein G is selected from: 。 85. The compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt or solvate thereof, wherein G is selected from: 。 86. The compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt or solvate thereof, wherein G is described by formula (c): （c） in, Each R 20 -R 30 It is independently selected from hydrogen or deuterium.

87. The compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt or solvate thereof, wherein G is described by formula (d): （d） in, R 31 Selected from hydrogen, F, Cl, -CN, -OH or optionally substituted C1-C4 alkyl groups; R 32 It is hydrogen, deuterium, or optionally substituted C1-C4 alkyl; and R 33 It is a C1-C4 alkyl group consisting of hydrogen, deuterium, F, or optionally substituted compounds.

88. The compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt or solvate thereof, wherein G is selected from: 。 89. The compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt or solvate thereof, wherein G is selected from: 。 90. The compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt or solvate thereof, wherein G is selected from: 。 91. The compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt or solvate thereof, wherein G is selected from: 。 92. The compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 93. The compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 94. The compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 95. The compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 96. The compound of any one of claims 1 to 82, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 97. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1为 yes 。 98. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 99. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 100. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 101. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 102. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: , 。 103. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 104. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 105. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 106. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 107. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 108. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 109. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 110. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 111. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 112. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 113. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 114. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 115. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 116. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 117. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 118. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 119. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 120. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 121. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 122. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 123. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 124. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: 。 125. The compound of any one of claims 1 to 77, or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 Selected from: , , , , 。 126. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R) 2 )R 3 Forming a heterocyclic group selected from the following optionally substituted groups: (a) Optionally substituted 2-azabicyclo[4.1.0]hept-2-yl; (b) Optionally substituted 2-oxa-5-azabicyclo[4.1.0]hept-5-yl; (c) Optionally substituted 2-azabicyclo[5.1.0]oct-2-yl; (d) Optionally substituted 2-oxa-6-azabicyclo[5.1.0]oct-6-yl (e) Optionally substituted 5-oxa-2-azabicyclo[5.1.0]oct-2-yl; (f) Optionally substituted 2-azabicyclo[6.1.0]non-2-yl; (g) Optionally substituted 2-oxa-7-azabicyclo[6.1.0]non-7-yl; (h) Optionally substituted 6-oxa-2-azabicyclo[6.1.0]non-2-yl; (i) Optionally substituted 5-oxa-2-azabicyclo[6.1.0]non-2-yl (j) Optionally substituted 2-azabicyclo[5.1.0]oct-5-en-2-yl; (k) Optionally substituted 2-azabicyclo[5.1.0]oct-4-en-2-yl; (l) Optionally substituted 2-azabicyclo[3.1.0]hex-2-yl; (m) Optionally substituted 2-azabicyclo[6.1.0]non-4-en-2-yl; (n) optionally substituted 2-azabicyclo[6.1.0]non-5-en-2-yl; or (o) Optionally substituted 2-azabicyclo[6.1.0]non-6-en-2-yl.

127. The compound of claim 126 or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R) 2 )R 3 Forming an optionally substituted 2-azabicyclic [4.1.0]hept-2-yl.

128. The compound of claim 126 or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R 2 )R 3 Formation of optionally substituted 2-oxa-5-azabicyclo[4.1.0]hept-5-yl.

129. The compound of claim 126 or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R) 2 )R 3 Forming optionally substituted 2-azabicyclo[5.1.0]oct-2-yl.

130. The compound of claim 129, wherein the optionally substituted 2-azabicyclo[5.1.0]oct-2-yl is substituted with an oxo group.

131. The compound of claim 126 or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R) 2 )R 3 Formation of optionally substituted 2-oxa-6-azabicyclo[5.1.0]oct-6-yl.

132. The compound of claim 126 or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R) 2 )R 3 Forming optionally substituted 5-oxa-2-azabicyclo[5.1.0]oct-2-yl.

133. The compound of claim 126 or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R) 2 )R 3 Formation of optionally substituted 2-azabicyclic [6.1.0]non-2-yl.

134. The compound of claim 126 or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R) 2 )R 3 Formation of optionally substituted 2-oxa-7-azabicyclo[6.1.0]non-7-yl.

135. The compound of claim 126 or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R) 2 )R 3 Forming optionally substituted 6-oxa-2-azabicyclo[6.1.0]non-2-yl.

136. The compound of claim 126 or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R) 2 )R 3 Forming optionally substituted 5-oxa-2-azabicyclo[6.1.0]non-2-yl.

137. The compound of claim 126 or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R) 2 )R 3 Forming optionally substituted 2-azabicyclo[5.1.0]oct-5-en-2-yl.

138. The compound of claim 126 or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R) 2 )R 3 Forming optionally substituted 2-azabicyclo[5.1.0]oct-4-en-2-yl.

139. The compound of claim 126 or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R) 2 )R 3 Forming an optionally substituted 2-azabicyclic [3.1.0]hex-2-yl.

140. The compound of claim 126 or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R) 2 )R 3 Formation of optionally substituted 2-azabicyclo[6.1.0]non-4-en-2-yl.

141. The compound of claim 126 or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R) 2 )R 3 Formation of optionally substituted 2-azabicyclo[6.1.0]non-5-en-2-yl.

142. The compound of claim 126 or a pharmaceutically acceptable salt or solvate thereof, Where -N(R) 2 )R 3 Formation of optionally substituted 2-azabicyclo[6.1.0]non-6-en-2-yl.

143. The compound of claim 126 or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted heterocyclic group is optionally substituted with a group selected from the group consisting of halogen, cyano, and hydroxyl.

144. The compound of claim 143, wherein the group is chlorine.

145. The compound of claim 143, wherein the group is fluorine.

146. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted azabicyclo[5.1.0]octane heterocyclic group has a structure selected from: 。 147. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted azabicyclo[5.1.0]octane heterocyclic group has a structure selected from: , where Z is a halogen or cyano group.

148. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted azabicyclo[5.1.0]octane heterocyclic group has a structure selected from: 。 149. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted azabicyclo[5.1.0]octane heterocyclic group has a structure selected from: Z is selected from the group consisting of: halogen, cyano, and hydroxyl.

150. The compound of claim 149, wherein the halogen is fluorine or chlorine.

151. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted azabicyclo[5.1.0]octane heterocyclic group has a structure selected from: Z is selected from the group consisting of: halogen, cyano, and hydroxyl.

152. The compound of claim 151, wherein the halogen is fluorine or chlorine.

153. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvation thereof, wherein the optionally substituted oxazabicyclo[4.1.0]heptane heterocyclic group has a structure selected from: Z is selected from the group consisting of: halogen, cyano, and hydroxyl.

154. The compound of claim 153, wherein the halogen is fluorine or chlorine.

155. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted azabicyclo[4.1.0]heptane heterocyclic group has a structure selected from: Z is selected from the group consisting of: halogen, cyano, and hydroxyl.

156. The compound of claim 155, wherein the halogen is fluorine or chlorine.

157. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted azabicyclo[3.1.0]hexane heterocyclic group has a structure selected from: Z is selected from the group consisting of: halogen, cyano, and hydroxyl.

158. The compound of claim 157, wherein the halogen is fluorine or chlorine.

159. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted azabicyclo[5.1.0]octane heterocyclic group has a structure selected from: 。 160. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted oxazabicyclo[5.1.0]octane heterocyclic group has a structure selected from: 。 161. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted oxazabicyclo[5.1.0]octane heterocyclic group is: 。 162. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted oxazabicyclo[5.1.0]octane heterocyclic group has a structure selected from: 。 163. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted oxazabicyclo[5.1.0]octane heterocyclic group has a structure selected from: Z is selected from the group consisting of: halogen, cyano, and hydroxyl.

164. The compound of claim 163, wherein the halogen is fluorine or chlorine.

165. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted oxazabicyclo[5.1.0]octane heterocyclic group has a structure selected from: 。 166. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted oxazabicyclo[5.1.0]octane heterocyclic group has a structure selected from: 。 167. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted oxazabicyclo[5.1.0]octane heterocyclic group has a structure selected from: Z is selected from the group consisting of: halogen, cyano, and hydroxyl.

168. The compound of claim 167, wherein the halogen is fluorine or chlorine.

169. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted oxazabicyclo[5.1.0]octane heterocyclic group has a structure selected from: 。 170. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted oxazabicyclo[5.1.0]octane heterocyclic group has a structure selected from: 。 171. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvation thereof, wherein the optionally substituted oxazabicyclo[6.1.0]nonane heterocyclic group has a structure selected from: Z is selected from the group consisting of: halogen, cyano, and hydroxyl.

172. The compound of claim 171, wherein the halogen is fluorine or chlorine.

173. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted azabicyclo[6.1.0]nonane heterocyclic group has a structure selected from: Z is selected from the group consisting of: halogen, cyano, and hydroxyl.

174. The compound of claim 173, wherein the halogen is fluorine or chlorine.

175. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R) 2 )R 3 Form an optionally substituted azabicyclic [4.1.0]heptane heterocyclic group.

176. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R) 2 )R 3 Form an optionally substituted oxazine bicyclic [4.1.0]heptane heterocyclic group.

177. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R) 2 )R 3 Form an optionally substituted azabicyclic [6.1.0]nonane heterocyclic group.

178. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R) 2 )R 3 Form an optionally substituted oxazonibicyclo[6.1.0]nonane heterocyclic group.

179. The compound of any one of claims 1 to 125, or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R) 2 )R 3 Forming groups selected from the following: Optionally substituted 3-oxa-2,6-diazabicyclo[5.1.0]oct-1-en-6-yl; Optionally substituted 2-oxa-3,6-diazabicyclo[5.1.0]oct-3-en-6-yl; Optionally substituted 4-oxa-2,5-diazabicyclo[5.1.0]oct-5-en-2-yl; Optionally substituted 3-oxa-2,7-diazabicyclo[6.1.0]non-1-en-7-yl; Optionally substituted 2-oxa-3,7-diazabicyclo[6.1.0]non-3-en-7-yl; Optionally substituted 5-oxa-2,6-diazabicyclo[6.1.0]non-6-en-2-yl; Optionally substituted 6-oxa-2,5-diazabicyclo[6.1.0]non-4-en-2-yl; and Optionally substituted 4-oxa-2,5-diazabicyclo[6.1.0]non-5-en-2-yl.

180. The compound of claim 179 or a pharmaceutically acceptable salt or solvate thereof, wherein the group is optionally halogenated.

181. The compound of claim 179 or 180, or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R) 2 )R 3 Forming groups selected from the following: 。 182. The compound of any one of claims 179 to 181, or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R 2 )R 3 Forming groups selected from the following: Z is selected from the group consisting of: halogen, cyano, and hydroxyl.

183. The compound of any one of claims 1 to 182, or a pharmaceutically acceptable salt or solvate thereof, wherein R 4 It is H.

184. The compound of any one of claims 1 to 182, or a pharmaceutically acceptable salt or solvate thereof, wherein R 4 It is optionally a substituted C1-C4 alkoxy group.

185. The compound of any one of claims 1 to 182, or a pharmaceutically acceptable salt or solvate thereof, wherein R 4 It is -OCH3.

186. The compound of any one of claims 1 to 182, or a pharmaceutically acceptable salt or solvate thereof, wherein R 4 It is an optional substituted C1-C6 alkyl group.

187. The compound of any one of claims 1 to 182, or a pharmaceutically acceptable salt or solvate thereof, wherein R 4 Selected from optionally substituted C1-C6 cycloalkyl or C1-C6 cycloalkylalkyl groups.

188. The compound of any one of claims 1 to 182, or a pharmaceutically acceptable salt or solvate thereof, wherein R 4 It is a cyano group.

189. The compound of any one of claims 1 to 182, or a pharmaceutically acceptable salt or solvate thereof, wherein R 4 It is halogen.

190. The compound of any one of claims 1 to 182, or a pharmaceutically acceptable salt or solvate thereof, wherein R 4 It is selected from H, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 cycloalkyl, C1-C6 cycloalkylalkyl, cyano or halogen.

191. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein R 4 It is H, and R 1 yes .

192. The compound of claim 191 or a pharmaceutically acceptable salt or solvate thereof, wherein X 1 and X 3 It is N, and X 2 It's CF.

193. The compound of claim 191 or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 194. The compound of claim 191 or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 195. The compound of claim 191 or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 196. The compound of claim 191 or a pharmaceutically acceptable salt or solvate thereof, wherein Ar is selected from: 。 197. The compound of any one of claims 191 to 196, or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R 2 )R 3 Forming groups selected from the following: 。 198. The compound of any one of claims 191 to 196, or a pharmaceutically acceptable salt or solvate thereof, wherein -N(R) 2 )R 3 Forming groups selected from the following: Z is selected from the group consisting of: halogen, cyano, and hydroxyl.

199. The compound of claim 198, wherein the halogen is fluorine or chlorine.

200. The compound of any one of claims 191 to 196, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted oxazabicyclo[5.1.0]octane heterocyclic group has a structure selected from: 。 201. The compound of any one of claims 191 to 196, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted oxazabicyclo[5.1.0]octane heterocyclic group has a structure selected from: 。 202. The compound of any one of claims 191 to 196, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted oxazabicyclo[5.1.0]octane heterocyclic group has a structure selected from: 。 203. The compound of any one of claims 191 to 196, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted oxazabicyclo[5.1.0]octane heterocyclic group has a structure selected from: 。 204. A compound or a pharmaceutically acceptable salt or solvation thereof, said compound or a pharmaceutically acceptable salt or solvation thereof as described in Table 1.

205. A compound or a pharmaceutically acceptable salt or solvation thereof, as described in any one of Figures 1 to 26.

206. A pharmaceutical composition comprising a compound as claimed in any one of claims 1 to 205, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

207. A method for preparing a pharmaceutical composition, the method comprising mixing a compound as described in any one of claims 1 to 205, or a pharmaceutically acceptable salt or solvate thereof, with a pharmaceutically acceptable carrier.

208. The compound of any one of claims 1 to 205, or a pharmaceutically acceptable salt or solvate thereof, for use in a method of treating a human or animal body.

209. The compound of any one of claims 1 to 205, or a pharmaceutically acceptable salt or solvate thereof, for use in a method of treating cancer.

210. Use of the compound of any one of claims 1 to 205 or a pharmaceutically acceptable salt or solvation thereof in the manufacture of a medicament for treating cancer.

211. A method of treating cancer in a patient in need, the method comprising administering to the patient a compound as described in any one of claims 1 to 205 or a pharmaceutically acceptable salt or solvate thereof.

212. A method of treating cancer in a patient in need, the method comprising administering a pharmaceutical composition to the patient, the pharmaceutical composition comprising a compound as described in any one of claims 1 to 205 or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable excipient.

213. A method for inhibiting KRAS, the method comprising contacting the enzyme with a compound as described in any one of claims 1 to 205, wherein the KRAS is contacted in an in vitro environment.

214. A method for inhibiting KRAS, the method comprising contacting the enzyme with a compound as described in any one of claims 1 to 205, wherein KRAS is contacted in an in vivo environment.

215. A compound having the structure of formula (A), or a salt or stereoisomer thereof: Equation (A-1) in, XY is -CH=CH-; or X is CH2 or O; and Y is CH2 or O; the condition is that X and Y are not both O. R a It is halogen; R a’ It is hydrogen or halogen; and R b It is a hydrogen or amine protecting group.

216. The compound of claim 215 or a salt thereof, wherein the compound of formula (A) is a compound of formula (A-1): Equation (A-2).

217. The compound of claim 215 or a salt thereof, wherein the compound of formula (A) is a compound of formula (A-2): Formula (A-3).

218. The compound or its salt or stereoisomer as claimed in any one of claims 215 to 217, wherein: X is CH2 and Y is CH2.

219. The compound or its salt or stereoisomer as claimed in any one of claims 215 to 217, wherein: X is CH2 and Y is O.

220. The compound or its salt or stereoisomer as claimed in any one of claims 215 to 217, wherein: X is O and Y is CH2.

221. A compound having the structure of formula (A-4) or a salt or stereoisomer thereof: Equation (A-4) in: R a It is halogen; R a’ It is hydrogen or halogen; and R b It is a hydrogen or amine protecting group.

222. The compound or its salt or stereoisomer as claimed in any one of claims 215 to 221, wherein: R a It is Cl or F.

223. The compound or its salt or stereoisomer as claimed in any one of claims 215 to 221, wherein: R a It is Cl.

224. The compound or its salt or stereoisomer as claimed in any one of claims 215 to 221, wherein: R a It is F.

225. The compound or its salt or stereoisomer as claimed in any one of claims 215 to 221, wherein: R a’ It is Br.

226. The compound or its salt or stereoisomer as claimed in any one of claims 215 to 221, wherein: R a’ It is H.

227. The compound or its salt or stereoisomer as claimed in any one of claims 215 to 221, wherein R b It is hydrogen, benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc), acetyl (Ac), benzoyl (Bz), benzyl (Bn), 2-(trimethylsilyl)ethoxycarbonyl (Teoc), trifluoroacetamide, 2,2,2-trichloroethoxycarbonyl (Troc), or allyl (All).

228. The compound or its salt or stereoisomer as claimed in any one of claims 215 to 221, wherein: R b It is hydrogen.

229. The compound or a salt thereof as claimed in any one of claims 215 to 221, wherein: R b It is benzyloxycarbonyl (Cbz).

230. A compound having the structure of formula (B1) or (B2), or a salt or stereoisomer thereof: Equation (B1) Equation (B2) in: XY is -CH=CH-; or X is CH2 or O; and Y is CH2 or O; the condition is that X and Y are not both O. R a It is halogen; R b It is F or CH3; R c It is a halogen, -SMe, -S(O)Me, -S(O)2Me, -OSO2CF3, or -OSO2C6H7CH3; and R d It is a halogen, -B(OH)2, -BKF3, , , , , , , -Sn (alkyl)3 or -Zn (halide).

231. The compound of claim 230 or a salt thereof, wherein the compound of formula (B1) is a compound of formula (B3): Formula (B3).

232. The compound of claim 230 or a salt thereof, wherein the compound of formula (B1) is a compound of formula (B4): Formula (B4).

233. The compound or a salt thereof as claimed in any one of claims 230 to 232, wherein: X is CH2 and Y is CH2.

234. The compound or a salt thereof as claimed in any one of claims 230 to 232, wherein: X is CH2 and Y is O.

235. The compound or a salt thereof as claimed in any one of claims 230 to 232, wherein: X is O and Y is CH2.

236. The compound of claim 230 or a salt thereof, wherein the compound of formula (B1) is a compound of formula (B5): Formula (B5).

237. The compound or a salt thereof as claimed in claims 230 to 236, wherein the compound of formula (B1) is a compound of formula (B6): Formula (B6).

238. The compound or a salt thereof as claimed in any one of claims 230 to 237, wherein: R a It is Cl or F.

239. The compound or a salt thereof as claimed in any one of claims 230 to 237, wherein: R a It is Cl.

240. The compound or a salt thereof as claimed in any one of claims 230 to 237, wherein: R a It is F.

241. The compound or a salt thereof as claimed in any one of claims 230 to 237, wherein: R c It is halogen.

242. The compound or a salt thereof as claimed in any one of claims 230 to 237, wherein: R c It is Cl.

243. The compound or a salt thereof as claimed in any one of claims 230 to 237, wherein: R d It is halogen.

244. The compound or a salt thereof as claimed in any one of claims 230 to 237, wherein: R d It is Cl.

245. The compound or a salt thereof as claimed in any one of claims 230 to 237, wherein: R b It is F.

246. The compound or a salt thereof as claimed in any one of claims 230 to 237, wherein: R b It is CH3.

247. A compound having the structure of formula (C1) or (C2), or a salt or stereoisomer thereof: Equation (C1) Equation (C2) in: XY is -CH=CH-; or X is CH2 or O; Y is CH2 or O; the condition is that X and Y are not both O. R a It is halogen; R b It is F or CH3; L is -O-; G is ,in: R 3 and R 4 Independently selected from H, D, halogen, -CN, optionally substituted C1-C4 alkoxy, optionally substituted C1-C4 alkyl; or R 3 and R 4 The connection forms an optionally substituted subunit; or R 3 and R 4 The linkage forms an optionally substituted C3-C6 carbocyclic group; or R 4 and R 5 Linking forms a bond; or R 4 and R 5 The linkage forms optionally substituted C3-C6 carbon cyclogroups; R 5 and R 6 Independently selected from H, D, halogen, -CN, -OH, optionally substituted C1-C4 alkoxy, optionally substituted C1-C4 alkyl; or R 5 and R 6 The connection forms an optionally substituted subunit; or R 5 and R 6 The linkage forms an oxy group; or R 5 and R 6 The linkage forms optionally substituted C3-C6 carbon cyclogroups; R 7 and R 8 Independently selected from H, D, and optionally substituted C1-C4 alkyl groups; or R 7 and R 8 The linkage forms optionally substituted C3-C6 carbon cyclogroups; R 9 and R 10 Independently selected from H, D, and optionally substituted C1-C4 alkyl groups; or R 9 and R 10 The linkage forms optionally substituted C3-C6 carbon cyclogroups; R 11 and R 12 Independently selected from H, D, halogen, optionally substituted C1-C4 alkyl, optionally substituted C1-C4 alkoxy; or R 11 and R 12 The connection forms an optionally substituted subunit; or R 11 and R 12 The linkage forms optionally substituted C3-C6 carbon cyclogroups; R 13 Or R 14 Independently selected from H, D, halogen, or optionally substituted C1-C4 alkyl; or R 12 and R 13 The connection forms a bond; R 15 It is H or D; and R d It is a halogen, -B(OH)2, -BKF3, , , , , , , -Sn (alkyl)3 or -Zn (halide).

248. The compound of claim 247 or a salt thereof, wherein the compound of formula (C1) is a compound of formula (C3): Formula (C3).

249. The compound of claim 247 or a salt thereof, wherein the compound of formula (C1) is a compound of formula (C4): Formula (C4).

250. The compound or its salt or stereoisomer as claimed in any one of claims 247 to 249, wherein: X is CH2 and Y is CH2.

251. The compound or its salt or stereoisomer as claimed in any one of claims 247 to 249, wherein: X is CH2 and Y is O.

252. The compound or its salt or stereoisomer as claimed in any one of claims 247 to 249, wherein: X is O and Y is CH2.

253. The compound of claim 247 or a salt thereof, wherein the compound of formula (C2) is a compound of formula (C5): Formula (C5).

254. The compound of claim 247 or a salt thereof, wherein the compound of formula (C2) is a compound of formula (C6): Formula (C6).

255. The compound or its salt or stereoisomer as claimed in any one of claims 247 to 254, wherein: R a It is Cl or F.

256. The compound or its salt or stereoisomer as claimed in any one of claims 247 to 254, wherein: R a It is Cl.

257. The compound or its salt or stereoisomer as claimed in any one of claims 247 to 254, wherein: R a It is F.

258. The compound or its salt or stereoisomer as claimed in any one of claims 247 to 254, wherein: R b It is F.

259. The compound or its salt or stereoisomer as claimed in any one of claims 247 to 254, wherein: R b It is CH3.

260. The compound or its salt or stereoisomer as claimed in any one of claims 247 to 254, wherein: R d It is halogen.

261. The compound or its salt or stereoisomer as claimed in any one of claims 247 to 254, wherein: R d It is Cl.

262. The compound or its salt or stereoisomer as claimed in any one of claims 247 to 254, wherein: G is , , , , , , , , , , , , , , .

263. The compound or its salt or stereoisomer as claimed in any one of claims 247 to 254, wherein: G is .

264. The compound or its salt or stereoisomer as claimed in any one of claims 247 to 254, wherein: G is .

265. The compound or its salt or stereoisomer as claimed in any one of claims 247 to 254, wherein: G is or .

266. The compound or its salt or stereoisomer as claimed in any one of claims 247 to 254, wherein: G is or .

267. The compound or its salt or stereoisomer as claimed in any one of claims 247 to 254, wherein: G is , or .

268. The compound or its salt or stereoisomer as claimed in any one of claims 247 to 254, wherein: G is or .

269. The compound or its salt or stereoisomer as claimed in any one of claims 247 to 254, wherein: G is or .

270. The compound or its salt or stereoisomer as claimed in any one of claims 247 to 254, wherein: G is , or .

271. A compound having the structure of formula (D1) or (D2) or a salt thereof: Equation (D1) Equation (D2) in: XY is -CH=CH-; or X is CH2 or O; Y is CH2 or O; the condition is that X and Y are not both O; and R b It is an amine protecting group.

272. The compound or a salt thereof as claimed in claim 271, wherein: X is CH2 and Y is CH2.

273. The compound or a salt thereof as claimed in claim 271, wherein: X is CH2 and Y is O.

274. The compound or a salt thereof as claimed in claim 271, wherein: X is O and Y is CH2.

275. The compound or a salt thereof as claimed in any one of claims 271 to 274, wherein R b It is benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc), acetyl (Ac), benzoyl (Bz), benzyl (Bn), 2-(trimethylsilyl)ethoxycarbonyl (Teoc), trifluoroacetamide, 2,2,2-trichloroethoxycarbonyl (Troc), or allyl (All).

276. The compound or a salt thereof as claimed in claim 275, wherein R b It is benzyloxycarbonyl (Cbz).