Prodrugs of xanthene, prodrugs of trospium chloride, and methods of use thereof

By developing analogues of fenofibrate and troxyl chloride and their prodrugs, the shortcomings of existing drugs in the treatment of schizophrenia and neuropsychiatric disorders have been addressed, improving therapeutic efficacy and drug bioavailability.

CN122070276APending Publication Date: 2026-05-19TERRAN BIOSCIENCES INC
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
TERRAN BIOSCIENCES INC
Filing Date
2024-04-24
Publication Date
2026-05-19

AI Technical Summary

Technical Problem

Existing medications for treating schizophrenia and other neuropsychiatric disorders are still insufficient, and new treatments are needed to improve treatment outcomes.

Method used

Develop analogues and prodrugs of sennamidrine and troxyl chloride, and use compounds with specific structures for the treatment of neuropsychiatric disorders, including analogues of sennamidrine such as compounds having formula (XI) and analogues of troxyl chloride such as compounds having formula (TI), for the preparation of pharmaceutical compositions and administration for the treatment of neuropsychiatric disorders.

Benefits of technology

It improves the treatment efficacy for neuropsychiatric disorders and enhances the bioavailability and therapeutic potential of drugs.

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Abstract

Disclosed herein are xanthene and trospium chloride prodrugs and analogs, and methods for making and using these prodrugs and analogs in the treatment of, for example, neuropsychiatric disorders.
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Claims

1. A compound having formula (1), in: X - It is absent or an anion; R 1 yes: (ii) in: Each R 5 and R 6 Independently, they are hydrogen, deuterium, and C. 1-24 Alkyl, -C 1-24 Haloalkyl, C 2-30 alkenyl, -OC(O)-C1-C 24 Alkyl group, -OC(O)-C2-C 30 alkenyl, -C(O)-C1-C 24 Alkyl, -C(O)-C 1-24 Haloalkyl, -C(O)-C2-C 30 alkenyl, -C(O)-C 2-24 alkynyl group, -(C 1-24 alkylene)-Si(R iij )2-C 1-24 Alkyl, -Si(R) iij )2-C 1-24 Alkyl, -(C 2-30 (alkenyl)-Si(R) iij )2-C 1-24 Alkyl, -(C 2-24 (alkenyl)-Si(R) iij )2-C 2-24 alkenyl, -Si(R) iij )2-C 2-24 alkenyl, -(C1-C 24 alkylene)-Si(R iij )2-C 2-24 alkenyl, -(C 1-24 alkylene)-S(O)-C 1-24 Alkyl, -(C 1-24 alkylene)-S(O)2-C 1-24 Alkyl, -(C 1-24 alkylene)-S(O)-C 1-24 Alkylene, -(C 1-24 alkylene)-S(O)2-C 1-24 Alkylene, -(C 1-24 (alkylene)-(O-CH2CH2) 1-50 -OR iv -C(O)-(C 1-24 (alkylene)-(O-CH2CH2) 1-50 -OR iv C 6-10 Aryl, 5- to 10-membered heteroaryl, 4- to 10-membered heterocyclic, C 3-8 cycloalkyl, -C 1-6 Alkylene-(C 6-10 Aryl), C 1-6 alkylene-(5 to 10-membered heteroaryl), -C 1-6 Alkylene-(C 3-8 cycloalkyl), -C 1-6 alkylene-(4 to 10-membered heterocyclic groups), -C(O)-(C 6-10 aryl), -C(O)-(5 to 10 heteroaryl), -C(O)-(C 3-8 Cycloalkyl), or -C(O)- (4 to 10-membered heterocyclic group), wherein the alkyl, alkenyl, alkylene, alkenylene, cycloalkyl, heterocyclic, heteroaryl, or aryl group is unsubstituted or optionally substituted, or R 5 and R 6 Combining to form oxygen groups, C 3-8 Cycloalkyl or 3 to 10-membered heterocyclic groups, wherein the cycloalkyl or heterocyclic group is unsubstituted or optionally substituted; Each R iij C is independent 1-6 Alkyl, or two R iij Together with the atoms to which they are attached, they form 3-8 membered rings. Each R iv Independently, they are H, deuterium, and C. 1-22 Alkyl or C 2-24 alkenyl; R 4 yes: (ii-a)-C(O)-C 1-24 Alkyl, -C(O)-C 1-24 Haloalkyl, -C(O)-C 2-30 alkenyl, -C(O)-C 2-24 alkynyl group, -C(O)-(C 1-24 (alkylene)-C 6-14 Aryl, -C(O)-(C 2-24 (alkenyl)-C 6-14 Aryl, -C(O)-(C 2-24 (ethynyl)-C 6-10 Aryl, -C(O)-(C 1-24 alkylene)-C(O)-OC 1-24 Alkyl, -C(O)-(C 1-24 alkylene)-C(O)-OC 2-24 alkenyl, -C(O)-(C 2-24 (alkenyl)-C(O)-OC 1-24 Alkyl, -C(O)-C(O)-OC 1-24 Alkyl groups, -C(O)-C(O)-OH, -C(O)-C(O)- (cholesterol or dihydrocholesterol), -C(O)-C(O)- (bile acids), -C(O)-(C 2-24 (-Imyynyl)-C(O)-OC 1-24 Alkyl, -C(O)-(C 2-24 -C(O)-OH, -C(O)-(C) 1-24 alkylene)-C(O)-(cholesterol or dihydrocholesterol), -C(O)-(C 1-24 alkylene)-C(O)-(bile acids), -C(O)-(C 2-24 -C(O)- (cholesterol or dihydrocholesterol), -C(O)- (C 2-24 -C(O)-(bile acids), -C(O)-(C 1-24 alkylene)-OC(O)-(cholesterol or dihydrocholesterol), -C(O)-(C 1-24 alkylene)-OC(O)-(bile acids), -C(O)-(C 2-24 -C(O)- (cholesterol or dihydrocholesterol), -C(O)- (C 2-24 -C(O)-(bile acid), -C(O)-(C 1-24 alkylene)-C(O)OH, -C(O)-(C 2-24 (-Alkenyl)-C(O)OH, -C(O)-C 6-14 Aryl, -C(O)-C 3-15 Cycloalkyl, -C(O)- (3 to 10-membered heterocyclic), -C(O)- (5 to 10-membered heteroaryl), -C(O)- (C 1-24 alkylene)-(3 to 10-membered cycloalkyl), -C(O)-(C 1-24 alkylene)-(C 6-14 aryl), -C(O)-(C 1-22 alkylene)-(3 to 10-membered heterocycles), -C(O)-(C 1-24 alkylene)-(5 to 10-membered heteroaryl), -C(O)-(C 2-24 -(3 to 10-membered cycloalkyl), -C(O)-(C 2-24 (-(C)-)-(alkenyl)-(C) 6-14 aryl), -C(O)-(C 2-24 -(3 to 10-membered heterocycles), -C(O)-(C 2-24 -(5 to 10-membered heteroaryl), -C(O)-(C 1-24 alkylene)-(cholesterol or dihydrocholesterol), -C(O)-(C 1-24 alkylene)-(bile acids), -C(O)-(C 1-24 alkylene)-O-(C 6-14 aryl), -C(O)-(C 1-24 alkylene)-O-(3 to 10-membered heterocycles), -C(O)-(C 1-24 alkylene)-O-(5 to 10-membered heteroaryl), -C(O)-(C 1-24 -O- (bile acids), -C(O)- (cholesterol or dihydrocholesterol), -C(O)- (bile acids), - (bile acids), or -C(O)- (C 1-24 (alkylene)-(O-CH2CH2) 1-50 -OR iia' Wherein the alkyl, alkenyl, ynylene, alkylene, alkenylene, ynylene, cycloalkyl, heterocyclic, heteroaryl, or aryl group is unsubstituted or optionally substituted. R iia’ It is H, deuterium, and C. 1-24 Alkyl or C 2-24 Alkenyl, wherein the alkyl or alkenyl group is unsubstituted or optionally substituted; (ii-b)-C(O)-OC 1-24 Alkyl, -C(O)-OC 1-24 Haloalkyl, -C(O)-OC 2-30 alkenyl, -C(O)-OC 2-24 alkynyl group, -C(O)-O-(C 1-24 (alkylene)-C 6-14 Aryl, -C(O)-O-(C 2-24 (alkenyl)-C 6-14 Aryl, -C(O)-O-(C 1-24 alkylene)-C(O)-OC 1-24 Alkyl, -C(O)-O-(C 2-24 (alkenyl)-C(O)-OC 1-24 Alkyl, -C(O)-O-(C 1-24 alkylene)-C(O)OH, -C(O)-O-(C 2-24 (-Alkenyl)-C(O)OH, -C(O)-OC 6-14 Aryl, -C(O)-OC 3-15 Cycloalkyl, -C(O)-O- (3 to 10-membered heterocyclic), -C(O)-O- (5 to 10-membered heteroaryl), -C(O)-O- (C 1-24 alkylene)-(3 to 10-membered cycloalkyl), -C(O)-O-(C 1-24 alkylene)-(C 6-14 Aryl), -C(O)-O-(C 1-24 alkylene)-(3 to 10-membered heterocycles), -C(O)-O-(C 1-24 alkylene)-(5 to 10-membered heteroaryl), -C(O)-O-(C 2-24 -(3 to 10-membered cycloalkyl), -C(O)-O-(C 2-24 (-(C)-)-(alkenyl)-(C) 6-14 Aryl), -C(O)-O-(C 2-24 (-(3 to 10-membered heterocycles)-(-C(O)-O-(C)-(- ... 2-24 -(5 to 10-membered heteroaryl), -C(O)-O-(C 1-24 alkylene)-(cholesterol or dihydrocholesterol), -C(O)-O-(C 2-24 alkylene)-(bile acids), -C(O)-(C 1-24 alkylene)-O-(C 6-14 aryl), -C(O)-(C 1-24 alkylene)-O-(3 to 10-membered heterocycles), -C(O)-(C 1-24 alkylene)-O-(5 to 10-membered heteroaryl), -C(O)-(C 1-24 alkylene)-(cholesterol or dihydrocholesterol), -C(O)-(C 1-24 alkylene)-O-(bile acids), C(O)-(C 1-24 alkylene)-C(O)-(cholesterol or dihydrocholesterol), -C(O)-(C 1-24 -C(O)-(bile acids), -C(O)-(cholesterol or dihydrocholesterol), -C(O)-(bile acids), -(bile acids), or -C(O)-O-(C 1-24 (alkylene)-(O-CH2CH2) 1-50 -OR iib' In which the alkyl, alkenyl, ynylene, alkylene, alkenylene, ynylene, cycloalkyl, heterocyclic, heteroaryl, or aryl group is unsubstituted or optionally substituted, and R iib’ It is H, deuterium, and C. 1-22 Alkyl or C 2-24 Alkenyl, wherein the alkyl or alkenyl group is unsubstituted or optionally substituted; (ii-c)-Si(R Si )3, Each R Si C is independent 1-24 Alkyl, C 2-30 alkenyl, C 6-10 Aryl, -OC 1-24 Alkyl, -OC 2-30 Alkenyl or -OH, wherein the alkyl, alkenyl, or aryl group is unsubstituted or optionally substituted; R 2 It is CH3, CH2D, CHD2, or CD3; and R 3 C is optionally substituted with one or more fluorine and / or deuterium. 1-6 alkyl.

2. A compound having the formula (1-F), in: X - It is absent or an anion; Each R 1 and R 2 Independently, it is as defined for equation (1); and Each R 1Fa R 1Fb R 1Fc R 2Fa R 2Fb R 3Fa R 3Fb R 4Fa R 4Fb R 5Fa R 5Fb R 6Fa R 6Fb R 7F R 8Fa R 8Fb R 9Fa and R 9Fb It can be H, D, or F independently.

3. The compound of claim 1, wherein, The compound has the formula (1-ii-ai), in: X - It is absent or an anion; R 2 It is CH3, CH2D, CHD2, or CD3; R 3 C is optionally substituted with one or more fluorine and / or deuterium. 1-6 alkyl; Each R 5 and R 6 Independently, it is as defined for equation (1); Each R 4’ CH3 that is independently absent, or that contains H, deuterium, fluorine, or optionally substituted with one or more deuterium atoms; and L is -C 1-24 Alkylene, -C 1-24 Halogenated alkylene, -C 2-30 alkenyl or -C 2-24 Alynyl group, wherein the alkylene group, alkenyl group, or alynyl group is unsubstituted or optionally substituted.

4. The compound as claimed in any one of the preceding claims, wherein, An R 4’ It does not exist.

5. The compound as claimed in any one of the preceding claims, wherein, Two Rs 4’ It does not exist.

6. The compound as claimed in any one of the preceding claims, wherein, At least one R 4’ It's H.

7. The compound as claimed in any one of the preceding claims, wherein, At least one R 4’ It is either deuterium or fluorine.

8. The compound as claimed in any one of the preceding claims, wherein, At least one R 4’ It is CH3.

9. The compound as claimed in any one of the preceding claims, wherein, Each R 4’ It's H.

10. The compound as claimed in any one of the preceding claims, wherein, Each R 4’ It is either deuterium or fluorine.

11. The compound as claimed in any one of the preceding claims, wherein, Each R 4’ It is CH3.

12. The compound as claimed in any one of the preceding claims, wherein, L is unsubstituted or optionally substituted -C 1-24 Alkylene.

13. The compound as claimed in any one of the preceding claims, wherein, L is unsubstituted or optionally substituted -C 1-24 Alkyl halides.

14. The compound as claimed in any of the preceding claims, wherein, L is unsubstituted or optionally substituted -C 2-30 Alkenyl group.

15. The compound as claimed in any one of the preceding claims, wherein, L is unsubstituted or optionally substituted -C 2-24 Alynyl group.

16. The compound as claimed in any one of the preceding claims, wherein, L is -C 1-24 Alkylene.

17. The compound as claimed in any of the preceding claims, wherein, L is -C 1-24 Alkyl halides.

18. The compound as claimed in any one of the preceding claims, wherein, L is -C 2-30 Alkenyl group.

19. The compound as claimed in any one of the preceding claims, wherein, L is -C 2-24 Alynyl group.

20. The compound as claimed in any one of the preceding claims, wherein, L is unsubstituted or optionally substituted -C 1-18 Alkylene.

21. The compound as claimed in any one of the preceding claims, wherein, L is unsubstituted or optionally substituted -C 1-18 Alkyl halides.

22. The compound as claimed in any one of the preceding claims, wherein, L is unsubstituted or optionally substituted -C 2-18 Alkenyl group.

23. The compound as claimed in any one of the preceding claims, wherein, L is unsubstituted or optionally substituted -C 2-18 Alynyl group.

24. The compound as claimed in any of the preceding claims, wherein, L is -C 1-18 Alkylene.

25. The compound as claimed in any one of the preceding claims, wherein, L is -C 1-18 Alkyl halides.

26. The compound as claimed in any one of the preceding claims, wherein, L is -C 2-18 Alkenyl group.

27. The compound as claimed in any one of the preceding claims, wherein, L is -C 2-18 Alynyl group.

28. The compound as claimed in any of the preceding claims, wherein, L stands for methylene.

29. The compound as claimed in any one of the preceding claims, wherein, L is methylene and each R 4’ It's H.

30. The compound as claimed in any one of the preceding claims, wherein, L is C 1-6 Alkylene.

31. The compound as claimed in any one of the preceding claims, wherein, L is C without substitution. 1-6 Alkylene.

32. The compound as claimed in any one of the preceding claims, wherein, L is a straight chain C 1-6 Alkylene.

33. The compound as claimed in any of the preceding claims, wherein, L is an unsubstituted linear C. 1-6 Alkylene.

34. The compound as claimed in any of the preceding claims, wherein, L is C 1-10 Alkylene.

35. The compound as claimed in any one of the preceding claims, wherein, L is C without substitution. 1-10 Alkylene.

36. The compound as claimed in any one of the preceding claims, wherein, L is a straight chain C 1-10 Alkylene.

37. The compound as claimed in any of the preceding claims, wherein, L is an unsubstituted linear C. 1-10 Alkylene.

38. The compound as claimed in any of the preceding claims, wherein, L is C 1-6 Alkenyl group.

39. The compound as claimed in any one of the preceding claims, wherein, L is C without substitution. 1-6 Alkenyl group.

40. The compound as claimed in any one of the preceding claims, wherein, L is a straight chain C 1-6 Alkenyl group.

41. The compound as claimed in any one of the preceding claims, wherein, L is an unsubstituted linear C. 1-6 Alkenyl group.

42. The compound as claimed in any one of the preceding claims, wherein, L is C 1-10 Alkenyl group.

43. The compound as claimed in any one of the preceding claims, wherein, L is C without substitution. 1-10 Alkenyl group.

44. The compound as claimed in any of the preceding claims, wherein, L is a straight chain C 1-10 Alkenyl group.

45. The compound as claimed in any one of the preceding claims, wherein, L is an unsubstituted linear C. 1-10 Alkenyl group.

46. ​​The compound of claim 1, wherein, The compound has the formula (1-ii-a-ii), in: X - It is absent or an anion; R 2 It is CH3, CH2D, CHD2, or CD3; R 3 C is optionally substituted with one or more fluorine and / or deuterium. 1-6 alkyl; Each R 5 and R 6 Independently, it is as defined for equation (1); and n is between 0 and 20.

47. The compound as claimed in any of the preceding claims, wherein, n is between 0 and 15.

48. The compound as claimed in any of the preceding claims, wherein, n is between 0 and 10.

49. The compound as claimed in any of the preceding claims, wherein, n is between 1 and 15.

50. The compound as claimed in any one of the preceding claims, wherein, n is between 1 and 10.

51. The compound of claim 1, wherein, The compound has the formula (1-ii-a-iii). in: X - It is absent or an anion; R 2 It is CH3, CH2D, CHD2, or CD3; R 3 C is optionally substituted with one or more fluorine and / or deuterium. 1-6 alkyl; Each R 5 and R 6 Independently, it is as defined for equation (1); L is a key, C 1-24 alkylene, or -C 1-24 Alkylene-O-*, where * indicates attachment to ring A; and Ring A is: (i)C 6-14 Aryl, (ii) 3- to 10-membered heterocyclic rings (iii)C 3-15 cycloalkyl, (iv) 5 to 10 aryl compounds, or (v) Cholesterol, dihydrocholesterol, or bile acids; The aryl, heterocyclic, cycloalkyl, heteroaryl, cholesterol, dihydrocholesterol, or bile acid is either unsubstituted or optionally substituted.

52. The compound as claimed in any one of the preceding claims, wherein, L is a key, C 1-24 alkylene, or -C 1-24 Alkylene-O-*, where -* indicates attachment to ring A; and Ring A is: (i)C 6-14 aryl, wherein the aryl group is optionally substituted with one or more mono- or di-C 1-6 Alkylamino, 4- to 10-membered heterocycles, or C 1-6 Alkyl substitution, (ii) 4- to 10-membered heterocycles, wherein the heterocycle is optionally composed of one or more mono- or di-C 1-6 Alkylamino, 4- to 10-membered heterocycles, or C 1-6 Alkyl substitution, (iii) Optionally, it can be controlled by one or more Cs 1-8 Alkyl-substituted C 3-15 cycloalkyl, or (iv) Optionally, it may be subject to one or more oxo groups or C 1-6 Alkyl-substituted 5- or 6-membered heteroaryl groups.

53. The compound as claimed in any one of the preceding claims, wherein, Ring A is m is between 0 and 6; and R A’ It is -C(O)- (optionally substituted C) 6-10 aryl), -C(O)- (optionally substituted 5- to 10-membered heteroaryl), -C(O)- (optionally substituted 3- to 10-membered heterocyclic), -C(O)- (optionally substituted C3-C 15 cycloalkyl), -(optionally substituted C 6-10 aryl), -(optionally substituted 5- to 10-membered heteroaryl), -(optionally substituted 3- to 10-membered heterocyclic), -C(optionally substituted C3-C) 15 cycloalkyl), halogen, cyano, hydroxyl, C 1-6 alkoxy, monoalkylamino, dialkylamino, or C 1-6 alkyl.

54. The compound as claimed in any one of the preceding claims, wherein, Ring A is a 4- to 10-membered heterocycle, wherein the heterocycle is optionally composed of one or more mono- or di-C 1-6 Alkylamino, 4- to 10-membered heterocycles, or C 1-6 Alkyl substitution.

55. The compound as claimed in any one of the preceding claims, wherein, Ring A is a 4- to 10-membered heterocyclic ring.

56. The compound as claimed in any one of the preceding claims, wherein, Ring A is a 4- to 10-membered heterocycle containing at least one oxygen atom.

57. The compound as claimed in any one of the preceding claims, wherein, Ring A is a 4-membered heterocycle containing at least one oxygen atom.

58. The compound as claimed in any one of the preceding claims, wherein, Ring A is a 2-oxocyclic butyl group.

59. The compound as claimed in any one of the preceding claims, wherein, Ring A is a 3-oxocyclic butyl group.

60. The compound as claimed in any one of the preceding claims, wherein, Ring A is a 5-membered heterocycle containing at least one oxygen atom.

61. The compound as claimed in any one of the preceding claims, wherein, Ring A is 2-tetrahydrofuranyl.

62. The compound as claimed in any one of the preceding claims, wherein, Ring A is 3-tetrahydrofuranyl.

63. The compound as claimed in any one of the preceding claims, wherein, Ring A is a 6-membered heterocycle containing at least one oxygen atom.

64. The compound as claimed in any of the preceding claims, wherein, Ring A is 2-tetrahydropyranyl.

65. The compound as claimed in any one of the preceding claims, wherein, Ring A is 3-tetrahydropyranyl.

66. The compound as claimed in any one of the preceding claims, wherein, Ring A is 4-tetrahydropyranyl.

67. The compound as claimed in any of the preceding claims, wherein, Cyclic A contains bile acids.

68. The compound as claimed in any one of the preceding claims, wherein, Cyclic A is bile acid.

69. The compound as claimed in any one of the preceding claims, wherein, Ring A is glycocholic acid.

70. The compound as claimed in any one of the preceding claims, wherein, Ring A is taurine.

71. The compound as claimed in any of the preceding claims, wherein, Ring A is deoxycholic acid.

72. The compound as claimed in any of the preceding claims, wherein, Ring A is chenodeoxycholic acid.

73. The compound as claimed in any of the preceding claims, wherein, Ring A is glycine chenodeoxycholic acid.

74. The compound as claimed in any of the preceding claims, wherein, Ring A is taurine chenodeoxycholic acid.

75. The compound as claimed in any one of the preceding claims, wherein, Ring A is lithocholic acid.

76. The compound as claimed in any of the preceding claims, wherein, L stands for bond.

77. The compound of claim 1, wherein, This compound has the formula (1-ii-a-iv). in: X - It is absent or an anion; R 2 It is CH3, CH2D, CHD2, or CD3; R 3 C is optionally substituted with one or more fluorine and / or deuterium. 1-6 alkyl; Each R 5 and R 6 Independently, it is as defined for equation (1); L is a key, C 1-24 Alkylene, C 2-24 alkenyl, or C 2-24 etyne group; and R 4” It is H, or C 1-24 Alkyl groups, or together with the attached oxygen atom, are cholesterol, dihydrocholesterol, bile acids. Among them, alkylene, alkenylene, alkynyl, cholesterol, dihydrocholesterol, bile acids, and C 1-24 Alkyl groups are either unsubstituted or optionally substituted.

78. The compound as claimed in any of the preceding claims, wherein, R 4” It's H.

79. The compound as claimed in any of the preceding claims, wherein, (R 4” -O-) is a sterol.

80. The compound as claimed in any one of the preceding claims, wherein, (R 4” -O-) represents cholesterol, dihydrocholesterol, or bile acids.

81. The compound as claimed in any one of the preceding claims, wherein, (R 4” -O-) is cholesterol.

82. The compound as claimed in any one of the preceding claims, wherein, (R 4” -O-) are bile acids.

83. The compound as claimed in any one of the preceding claims, wherein, (R 4” -O-) is dihydrocholesterol.

84. The compound as claimed in any of the preceding claims, wherein, R 4” It is C 1-24 Alkyl group, wherein the alkyl group is optionally substituted.

85. The compound of claim 1, wherein, The compound has the formula (1-ii-bi). in: X - It is absent or an anion; R 2 It is CH3, CH2D, CHD2, or CD3; R 3 C is optionally substituted with one or more fluorine and / or deuterium. 1-6 alkyl; Each R 5 and R 6 Independently, it is as defined for equation (1); L is a key, C 1-24 Halogenated alkylene, C 1-24 alkylene, or C 2-30 imidene group, C 2-24 The alkylene group, wherein the alkylene group, alkenylene group, or alkynylene group is unsubstituted or optionally substituted; and Each R 4’ CH3 that is not present independently, or that is optionally replaced by one or more deuterium atoms.

86. The compound as claimed in any of the preceding claims, wherein: L is a key, C 1-20 alkylene, or C 2-20 The alkylene group, wherein the alkylene group and the alkenylene group are unsubstituted or optionally substituted; and Each R 4’ It is either H or CH3.

87. The compound as claimed in any of the preceding claims, wherein: L is a key, C 1-20 alkylene, or C 2-20 The alkenyl group, wherein the alkylene group and the alkenyl group are unsubstituted or optionally substituted.

88. The compound as claimed in any of the preceding claims, wherein, L is an optional substitute for C. 1-20 Alkylene.

89. The compound as claimed in any of the preceding claims, wherein, L is an optional substitute for C. 2-20 Alkenyl group.

90. The compound as claimed in any one of the preceding claims, wherein, L is an optional substitute for C. 1-20 Alkylene, wherein the alkylene is branched.

91. The compound as claimed in any one of the preceding claims, wherein, L is an optional substitute for C. 2-20 An alkenyl group, wherein the alkenyl group is branched.

92. The compound as claimed in any one of the preceding claims, wherein, L is an optional substitute for C. 1-20 Alkylene, wherein the alkylene is straight-chain.

93. The compound as claimed in any of the preceding claims, wherein, L is an optional substitute for C. 2-20 An alkenyl group, wherein the alkenyl group is a straight chain.

94. The compound as claimed in any of the preceding claims, wherein, L stands for bond.

95. The compound of claim 1, wherein, The compound has the formula (1-ii-b-ii). in: X - It is absent or an anion; R 2 It is CH3, CH2D, CHD2, or CD3; R 3 C is optionally substituted with one or more fluorine and / or deuterium. 1-6 alkyl; Each R 5 and R 6 Independently, as defined for equation (1), and n is between 0 and 20.

96. The compound as claimed in any one of the preceding claims, wherein, n is between 0 and 15.

97. The compound as claimed in any of the preceding claims, wherein, n is between 0 and 10.

98. The compound as claimed in any of the preceding claims, wherein, n is between 1 and 15.

99. The compound as claimed in any one of the preceding claims, wherein, n is between 1 and 10.

100. The compound of claim 1, wherein, The compound has the formula (1-ii-b-iii). in: X - It is absent or an anion; R 2 It is CH3, CH2D, CHD2, or CD3; R 3 C is optionally substituted with one or more fluorine and / or deuterium. 1-6 alkyl; R 5 and R 6 Independently, it is as defined for equation (1); L is a key, C 1-24 alkylene, or -C 1-24 Alkylene-O-* The -* indicates attachment to ring A; and Ring A is: (i)C 6-14 Aryl, (ii) 3- to 10-membered heterocyclic rings (iii)C 3-15 cycloalkyl; (iv) 5 to 10-membered heteroaryl groups; (v) Cholesterol, dihydrocholesterol, or bile acids; The aryl, heterocyclic, cycloalkyl, heteroaryl, cholesterol, dihydrocholesterol, or bile acid is either unsubstituted or optionally substituted.

101. The compound as claimed in any one of the preceding claims, wherein, Ring A is: (i)C 6-14 aryl, wherein the aryl group is optionally substituted with one or more mono- or di-C 1-6 Alkylamino, 4- to 10-membered heterocycles, or C 1-6 Alkyl substitution, (ii) 4- to 10-membered heterocycles, wherein the heterocycle is optionally composed of one or more mono- or di-C 1-6 Alkylamino, 4- to 10-membered heterocycles, or C 1-6 Alkyl substitution, (iii) Optionally, it can be controlled by one or more Cs 1-8 Alkyl-substituted C 3-15 cycloalkyl, or (iv) Optionally, it may be subject to one or more oxo groups or C 1-6 Alkyl-substituted 5- or 6-membered heteroaryl groups.

102. The compound as claimed in any one of the preceding claims, wherein, Ring A is a 4- to 10-membered heterocycle, wherein the heterocycle is optionally composed of one or more mono- or di-C 1-6 Alkylamino, 4- to 10-membered heterocycles, or C 1-6 Alkyl substitution.

103. The compound as claimed in any one of the preceding claims, wherein, Ring A is a 4- to 10-membered heterocyclic ring.

104. The compound as claimed in any of the preceding claims, wherein, Ring A is a 4- to 10-membered heterocycle containing at least one oxygen atom.

105. The compound as claimed in any one of the preceding claims, wherein, Ring A is a 4-membered heterocycle containing at least one oxygen atom.

106. The compound as claimed in any one of the preceding claims, wherein, Ring A is a 2-oxocyclic butyl group.

107. The compound as claimed in any of the preceding claims, wherein, Ring A is a 3-oxocyclic butyl group.

108. The compound as claimed in any one of the preceding claims, wherein, Ring A is a 5-membered heterocycle containing at least one oxygen atom.

109. The compound as claimed in any of the preceding claims, wherein, Ring A is 2-tetrahydrofuranyl.

110. The compound as claimed in any one of the preceding claims, wherein, Ring A is 3-tetrahydrofuranyl.

111. The compound as claimed in any of the preceding claims, wherein, Ring A is a 6-membered heterocycle containing at least one oxygen atom.

112. The compound as claimed in any one of the preceding claims, wherein, Ring A is 2-tetrahydropyranyl.

113. The compound as claimed in any one of the preceding claims, wherein, Ring A is 3-tetrahydropyranyl.

114. The compound as claimed in any of the preceding claims, wherein, Ring A is 4-tetrahydropyranyl.

115. The compound of claim 1, wherein, The compound has the formula (1-ii-c). in X - It is absent or an anion; R 2 It is CH3, CH2D, CHD2, or CD3; R 3 C is optionally substituted with one or more fluorine and / or deuterium. 1-6 alkyl; Each R 5 and R 6 Independently, it is as defined for equation (1); and Each R Si C is independent 1-20 Alkyl, C 6-10 Aryl, -OC 1-20 Alkyl groups or -OH groups The alkyl, aryl, or -O-alkyl group is either unsubstituted or optionally substituted.

116. The compound as claimed in any one of the preceding claims, wherein, Each R Si C is independent 1-20 Alkyl, C 6-10 Aryl, -OC 1-20 Alkyl, -OC 6-10 Aryl or -OH.

117. The compound as claimed in any of the preceding claims, wherein, R Si It is C 1-20 Alkyl or C 6-10 Aryl.

118. The compound as claimed in any one of the preceding claims, wherein, At least one R Si It is C 1-20 alkyl.

119. The compound as claimed in any of the preceding claims, wherein, At least one R Si It is C 6-10 Aryl.

120. The compound as claimed in any one of the preceding claims, wherein, At least one R Si Yes - OC 1-20 Alkyl, -OC 6-10 Aryl or -OH.

121. The compound as claimed in any one of the preceding claims, wherein, At least one R Si Yes - OC 1-20 alkyl.

122. The compound as claimed in any one of the preceding claims, wherein, At least one R Si Yes - OC 6-10 Aryl.

123. The compound as claimed in any one of the preceding claims, wherein, At least one R Si It is -OH.

124. The compound as claimed in any of the preceding claims, wherein, R 2 It is CH3 or CD3.

125. The compound as claimed in any one of the preceding claims, wherein, R 2 It is CH3.

126. The compound as claimed in any one of the preceding claims, wherein, R 2 It's CD3.

127. The compound as claimed in any of the preceding claims, wherein, R 3 It is a C6 alkyl group that may be optionally substituted with one or more deuterium and / or fluorine.

128. The compound as claimed in any of the preceding claims, wherein, R 3 It is a C6 alkyl group that may be optionally substituted with one or more deuterium atoms.

129. The compound as claimed in any one of the preceding claims, wherein, R 3 It is a C6 alkyl group that may optionally be substituted with one or more fluorine molecules.

130. The compound as claimed in any one of the preceding claims, wherein, R 3 It is a C6 alkyl group, wherein the C6 alkyl group is a straight-chain alkyl group.

131. The compound as claimed in any of the preceding claims, wherein, R 3 It is a C6 alkyl group, wherein the C6 alkyl group is a branched alkyl group.

132. The compound as claimed in any one of the preceding claims, wherein, R 3 It is an unsubstituted C6 alkyl group.

133. The compound as claimed in any one of the preceding claims, wherein, R 3 It is an unsubstituted C6 alkyl group, wherein the C6 alkyl group is a straight-chain alkyl group.

134. The compound as claimed in any of the preceding claims, wherein, R 3 It is an unsubstituted C6 alkyl group, wherein the C6 alkyl group is a branched alkyl group.

135. The compound as claimed in any one of the preceding claims, wherein, Each R 5 and R 6 Independently, it is hydrogen and C 1-18 Alkyl, C 2-30 alkenyl, C 3-8 cycloalkyl, 3 to 10-membered heterocyclic, 3 to 10-membered heteroaryl, or C 6-10 Aryl, wherein the C 1-18 Alkyl or C 2-30 Alkene can be optionally C 6-10 Aryl, C 3-8 Cycloalkyl, 3- to 10-membered heterocyclic, or 3- to 10-membered heteroaryl substitutions, and the C 6-10 The aryl group may be optionally coated with OH or C. 1-6 Alkoxy substitution, or R 5 and R 6 Combining to form oxygen groups, C 3-8 Cycloalkyl or 3 to 10-membered heterocyclic groups.

136. The compound as claimed in any one of the preceding claims, wherein, R 5 Or R 6 At least one of them is hydrogen.

137. The compound as claimed in any of the preceding claims, wherein, R 5 It is hydrogen.

138. The compound as claimed in any of the preceding claims, wherein, R 5 It is C 1-18 alkyl.

139. The compound as claimed in any of the preceding claims, wherein, R 5 It is C 1-10 alkyl.

140. The compound as claimed in any of the preceding claims, wherein, R 5 It is a straight-chain alkyl group.

141. The compound as claimed in any one of the preceding claims, wherein, R 5 It is a branched alkyl group.

142. The compound as claimed in any one of the preceding claims, wherein, R 5 It is an unsubstituted alkyl group.

143. The compound as claimed in any of the preceding claims, wherein, R 5 It is unreplaced C 1-10 Alkyl, wherein the C 1-10 Alkyl groups are straight-chain alkyl groups.

144. The compound as claimed in any of the preceding claims, wherein, R 5 It is unreplaced C 1-10 Alkyl, wherein the C 1-10 Alkyl groups are branched alkyl groups.

145. The compound as claimed in any of the preceding claims, wherein, R 5 It is C 2-30 Alkenyl group.

146. The compound as claimed in any one of the preceding claims, wherein, R 5 It is C 2-25 Alkenyl group.

147. The compound as claimed in any of the preceding claims, wherein, R 5 It is a straight-chain alkenyl group.

148. The compound as claimed in any of the preceding claims, wherein, R 5 It is a branched alkenyl group.

149. The compound as claimed in any of the preceding claims, wherein, R 5 It is an unsubstituted alkenyl group.

150. The compound as claimed in any one of the preceding claims, wherein, R 5 It is unreplaced C 2-25 alkenyl, wherein the C 2-25 The alkenyl group is a straight-chain alkenyl group.

151. The compound as claimed in any one of the preceding claims, wherein, R 5 It is unreplaced C 2-25 alkenyl, wherein the C 2-25 The alkenyl group is a branched alkenyl group.

152. The compound as claimed in any one of the preceding claims, wherein, R 5 It is C 6-10 Aryl.

153. The compound as claimed in any one of the preceding claims, wherein, R 5 It is phenyl.

154. The compound as claimed in any of the preceding claims, wherein, R 5 It is C 3-8 Cycloalkyl.

155. The compound as claimed in any one of the preceding claims, wherein, R 5 It is a 3- to 10-membered heterocyclic group.

156. The compound as claimed in any one of the preceding claims, wherein, R 6 It is hydrogen.

157. The compound as claimed in any one of the preceding claims, wherein, R 6 It is C 1-18 alkyl.

158. The compound as claimed in any one of the preceding claims, wherein, R 6 It is C 1-10 alkyl.

159. The compound as claimed in any one of the preceding claims, wherein, R 6 It is a straight-chain alkyl group.

160. The compound as claimed in any one of the preceding claims, wherein, R 6 It is a branched alkyl group.

161. The compound as claimed in any one of the preceding claims, wherein, R 6 It is an unsubstituted alkyl group.

162. The compound as claimed in any one of the preceding claims, wherein, R 6 It is unreplaced C 1-10 Alkyl, wherein the C 1-10 Alkyl groups are straight-chain alkyl groups.

163. The compound as claimed in any one of the preceding claims, wherein, R 6 It is unreplaced C 1-10 Alkyl, wherein the C 1-10 Alkyl groups are branched alkyl groups.

164. The compound as claimed in any of the preceding claims, wherein, R 6 It is C 2-30 Alkenyl group.

165. The compound as claimed in any of the preceding claims, wherein, R 6 It is C 2-25 Alkenyl group.

166. The compound as claimed in any of the preceding claims, wherein, R 6 It is a straight-chain alkenyl group.

167. The compound as claimed in any of the preceding claims, wherein, R 6 It is a branched alkenyl group.

168. The compound as claimed in any of the preceding claims, wherein, R 6 It is an unsubstituted alkenyl group.

169. The compound as claimed in any of the preceding claims, wherein, R 6 It is unreplaced C 2-25 alkenyl, wherein the C 2-25 The alkenyl group is a straight-chain alkenyl group.

170. The compound as claimed in any of the preceding claims, wherein, R 6 It is unreplaced C 2-25 alkenyl, wherein the C 2-25 The alkenyl group is a branched alkenyl group.

171. The compound as claimed in any of the preceding claims, wherein, R 6 It is C 6-10 Aryl.

172. The compound as claimed in any one of the preceding claims, wherein, R 6 It is phenyl.

173. The compound as claimed in any one of the preceding claims, wherein, R 6 It is C 3-8 Cycloalkyl.

174. The compound as claimed in any of the preceding claims, wherein, R 6 It is a 3- to 10-membered heterocyclic group.

175. The compound as claimed in any one of the preceding claims, wherein, R 5 and R 6 They combine to form oxy groups.

176. The compound as claimed in any of the preceding claims, wherein, R 5 and R 6 Combining to form C 3-8 Cycloalkyl.

177. The compound as claimed in any of the preceding claims, wherein, X - It is a pharmaceutically acceptable anion.

178. The compound as claimed in any of the preceding claims, wherein, X - It is acetate.

179. The compound as claimed in any of the preceding claims, wherein, This compound is the one listed in Table 1.

180. A compound listed in Table 1.

181. A method for preparing a compound as described in any of the preceding claims.

182. A pharmaceutically acceptable salt of one of the compounds in Table 1.

183. A pharmaceutical composition comprising a compound as described in any one of the preceding claims and a pharmaceutically acceptable excipient.

184. A pharmaceutical composition comprising a compound having formula (1) and a pharmaceutically acceptable excipient.

185. A pharmaceutical composition comprising a compound having formula (1-F) and a pharmaceutically acceptable excipient.

186. A pharmaceutical composition comprising a compound described in this disclosure and a pharmaceutically acceptable excipient.

187. A method for treating a neuropsychiatric disease according to any one of the claims of this disclosure.

188. A method for treating neuropsychiatric disorders, comprising administering an effective amount of the compound as described in any of the preceding claims.

189. A method for treating neuropsychiatric disorders, comprising administering an effective amount of the pharmaceutical composition as described in any of the preceding claims.

190. A method for treating a neuropsychiatric disorder in a subject in need, the method comprising administering to the subject a compound having formula (1).

191. A method for treating a neuropsychiatric disorder in a subject in need, the method comprising administering to the subject a compound having the formula (1-F).

192. A method for treating a neuropsychiatric disorder in a subject in need, the method comprising administering to the subject the compounds listed in Table 1.

193. The method as described in any of the preceding claims, wherein, The neuropsychiatric disorder is migraine, headache (e.g., cluster headache), post-traumatic stress disorder (PTSD), anxiety, depression, neurodegenerative disorders, Alzheimer's disease, Parkinson's disease, mental disorders, treatment-resistant depression, suicidal ideation, major depressive disorder, bipolar disorder, schizophrenia, stroke, traumatic brain injury, or addiction (e.g., substance use disorder).

194. Use of the compound as claimed in any of the preceding claims in the preparation of a medicament for treating a neuropsychiatric disorder in a subject in need.

195. Use of the compound as claimed in any of the preceding claims in a method for treating a neuropsychiatric disorder in a subject in need.

196. The compound as claimed in any of the preceding claims, in a method of treating a neuropsychiatric disorder in a subject in need.

197. The method as described in any of the preceding claims, wherein, The neuropsychiatric disorder is schizophrenia.

198. The method as described in any of the preceding claims, wherein, This neuropsychiatric disorder is a psychotic form of Alzheimer's disease.