Tricyclic fused imidazole compounds as cd38 modulators and uses thereof

Abstract

The present disclosure provides compounds and salts for the treatment of disease.

Description

(19) State Intellectual Property Office (12) Invention Patent Application (10) Application Publication Number (43) Application Publication Date (21) Application Number 202480043019.6 (22) Application Date 2024.04.24 (30) Priority Data 63 / 498,182 2023.04.25 US 63 / 578,614 2023.08.24 US 63 / 627,213 2024.01.31 US (85) PCT International Application Entering National Phase Date 2025.12.25 (86) PCT International Application Application Data PCT / US2024 / 026107 2024.04.24 (87) PCT International Application Publication Data WO2024 / 226685 EN 2024.10.31 (71) Applicant: Iovia Pharmaceuticals, Inc. Address: California, USA (72) Inventors: John Chinkard, Anthony Kyle Bauer (74) Patent Agency: Beijing Anxin Fangda Intellectual Property Agency Co., Ltd. 11262 Patent Attorneys: Liang Feifei, Wu Jingjing (51) Int.Cl. C07D 498 / 04 (2006.01) C07D 487 / 04 (2006.01) C07D 519 / 00 (2006.01) A61P 5 / 00 (2006.01) A61P 7 / 00 (2006.01) A61K 31 / 553 (2006.01) A61P 11 / 00 (2006.01) A61P 17 / 00 (2006.01) A61P 25 / 00 (2006.01) A61P 27 / 00(2006.01) C07D 498 / 14(2006.01) C07D 498 / 18(2006.01) A61K 31 / 4985(2006.01) (54) Invention Title: Tricyclic Fused Imidazole Compound as CD38 Modifier and Its Use Thereof (57) Abstract: This disclosure provides compounds and salts for the treatment of diseases. Claims: 45 pages Description: 240 pages CN 121568943 A 2026.02.24 CN 1 21 56 89 43 A 1. A compound of formula (I): , or a pharmaceutically acceptable salt or solvation thereof; wherein Z is selected from and,Where t represents the connection point between Z and the imidazole ring; X is selected from O and S; Y is selected from -N(R10)2, -OR 10 and -SR10; A is selected from N and CR18; D is selected from N and CR19; R4 is selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C1-6 cyanoalkyl, C1-6 alkoxyalkyl, C1-6 alkyl-N(R20)2, C3-5 cycloalkyl and 3 to 6 membered heterocyclic rings; R5 is selected from hydrogen and C1-6 alkyl; R6 is selected from hydrogen, C1-6 alkyl, halogen, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C1-6 cyanoalkyl, C1-6 alkoxyalkyl, C1-6 alkyl-N(R20)2, C4-6 cycloalkyl and 3 to 6 membered heterocyclic alkyl. R7 is selected from C3-C12 carbon rings and 5- to 15-membered heterocycles, each optionally substituted by one or more R8s; each R8 is independently selected from halogens, -N(R20)2, -OR20, -SR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), -NR20S(O)2R20, -C(O)N(R20)2, -C(=NR20)N(R20)2, -C(O)NR20OR20, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R 20) C(O)OR20, -C(O)R20, -C(O)OR20, -OC(O)R20, -OC(O)N(R20)2, -NO2, =O, =N(R20), =NO(R20), -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-C12 carbon ring and 5 to 12 membered heterocycles, wherein the C3-C12 carbon ring and the 5 to 12 membered heterocycles are each optionally selected from one or more halogens, -OH, -CN, -NO2, -NH2, oxo groups, Substituents of C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, and C1-C6 alkoxyalkyl; R9 is selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R20)2, C3-6 carbon ring, and 4- to 6-membered heterocycles.The C3-6 carbon ring and the 4- to 6-membered heterocycle are each optionally substituted by one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R20)2, C2-10 alkenyl, and C2-10 alkynyl; each R10 is independently selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, and C1-C6 alkyl-N(R20)2; Claims 1 / 45 page 2 CN 121568943 A R17 is selected from hydrogen, halogens, -N(R20)2, -OR20, -SR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), -NR20S(O)2R20, -C(O)N(R20)2, -C(=NR20)N(R20)2, -C(O)NR20OR20, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R20)C(O)OR20, -C(O)R20, -C(O)OR20, -OC(O)R20, -OC(O)N(R20)2, -NO2, - CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-12 carbon ring and 5 to 12 membered heterocycles; R18 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, -O-C1-10 alkyl, C1-C6 alkyl and C1-C6 haloalkyl; R19 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, -O-C1-10 alkyl, C1-C6 Alkyl and C1-C6 haloalkyl; and R20, each time appearing, is independently selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-12 carbon ring, and 3 to 12-membered heterocycles, each optionally substituted by one or more substituents independently selected from: halogen, -OH, -CN, -NO2, -NH2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 ynyl, C3-12 carbon ring, and 3 to 12-membered heterocycles. 2. The compound or salt according to claim 1,3. The compound or salt according to claim 1, wherein formula (I) is represented by formula (IA): , or a pharmaceutically acceptable salt or solvate thereof. 4. The compound or salt according to any one of claims 1-3, wherein R18 and R19 are each independently selected from hydrogen and halogen. 5. The compound or salt according to any one of claims 1-4, wherein R4 is selected from hydrogen and C1-6 alkyl. 6. The compound or salt according to any one of claims 1-5, wherein R4 is hydrogen. 7. The compound or salt according to any one of claims 1-6, wherein R6 is hydrogen. 8. The compound or salt according to any one of claims 1-7, wherein R5 is selected from hydrogen and methyl. 9. The compound or salt according to any one of claims 1-7, wherein R5 is hydrogen. 10. The compound or salt according to any one of claims 1, 2, or 4-9, wherein R9 is selected from hydrogen and C1-6 alkyl. 11. The compound or salt according to any one of claims 1, 2, or 4-10, wherein R9 is selected from hydrogen and methyl. Claims 2 / 45 Page 3 CN 121568943 A 12. A compound or salt according to any one of claims 1, 2, or 4-11, wherein R9 is hydrogen. 13. A compound or salt according to any one of claims 1 or 3-9, wherein each R10 is independently selected from hydrogen, C1-6 alkyl, and C1-C6 alkoxyalkyl. 14. A compound or salt according to claim 13, wherein R10 occurring at least once is hydrogen. 15. A compound or salt according to claim 1, wherein formula (I) is represented by formula (IC): Formula (IC), or a pharmaceutically acceptable salt or solvate thereof. 16. A compound or salt according to claim 1, wherein formula (I) is represented by formula (ID): Formula (ID), or a pharmaceutically acceptable salt or solvate thereof. 17. A compound or salt according to claim 15, wherein R9 is selected from hydrogen and methyl. 18. A compound or salt according to claim 16, wherein R10 is selected from hydrogen, methyl, and C1-C6 alkoxyalkyl. 19. The compound or salt according to any one of claims 1-18, wherein R7 is selected from C6-C8 carbon rings and 5- to 6-membered heterocycles, each optionally substituted with one or more R8s. 20. The compound or salt according to any one of claims 1-19, wherein R7 is selected from C6-C8 carbon rings, optionally substituted with one or more R8s. 21. The compound or salt according to claim 20, wherein R7 is selected from C6 carbon rings, optionally substituted with one or more R8s. 22. The compound or salt according to any one of claims 1-21, wherein R7 is...Optionally substituted with one or more R8s. 23. The compound or salt according to any one of claims 1-22, wherein each R8 is independently selected from halogens, C1-6 haloalkyls, -OR20, -N(R20)2, -NR20S(O)2R20, -C(O)N(R20)2, and 5- to 6-membered heterocycles, wherein the 5- to 6-membered heterocycles are optionally substituted with one or more substituents selected from halogens, -OH, -CN, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, and -O-C1-10 alkyl. 24. The compound or salt according to claim 23, wherein R7 is selected from, , , and . 25. The compound or salt according to any one of claims 1-21, wherein R7 is, which is optionally substituted with one or more R8s. 26. The compound or salt according to any one of claims 1-21 or 25, wherein each R8 is independently selected from halogens and -S(O)2 (R 2O). 27. The compound or salt according to claim 26, wherein R7 is selected from […]. 28. The compound or salt according to any one of claims 1-18, wherein R7 is selected from C9 carbon rings, optionally substituted with one or more R8s. 29. The compound or salt according to claim 28, wherein R7 is […]. 30. The compound or salt according to any one of claims 1-18, wherein R7 is selected from 5- to 10-membered heterocycles, each optionally substituted with one or more R8s. 31. The compound or salt according to claim 30, wherein R7 is selected from […]. [Claims 4 / 45 page 5 CN 121568943 A], […]. […]. 32. The compound or salt according to any one of claims 30-31, wherein each R8 is independently selected from halogens, -OR2O, -S(O)2(R2O), -C(O)OR2O, =O, C1-6 alkyl, and C1-6 haloalkyl. 33. The compound or salt according to any one of claims 30-32, wherein R7 is selected from... 34. The compound or salt according to any one of claims 1-19, wherein R7 is selected from 5- to 6-membered saturated heterocycles, each optionally substituted by one or more R8s. 35. The compound or salt according to claim 34...Each R8 is independently selected from -S(O)2(R 20), -S(O)2N(R 20)2, -S(O)N(R 20)2, -S(O)R 20 (=NR20), and =O. 36. The compound or salt according to claim 35, wherein each R8 is independently selected from -S(O)2(R 20) and =O. 37. The compound or salt according to any one of claims 34-36, wherein R7 is selected from [missing information - likely a specific compound or salt]. 38. The compound or salt according to any one of claims 1-19, wherein R7 is selected from optionally substituted 5- to 6-membered heteroaryl groups. 39. The compound or salt according to claim 38, wherein R7 is selected from optionally substituted 6-membered heteroaryl groups. 40. The compound or salt according to claim 39, wherein R7 is selected from optionally substituted pyridine. Claims 5 / 45, page 6, CN 121568943 A 41. The compound or salt according to any one of claims 38-40, wherein each R8 is selected from halogens, -N(R20)2, -OR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20 (=NR20), -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, and C1-6 alkyl. 42. The compound or salt according to claim 41, wherein each R8 is selected from halogens, -OR20, -CN, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, and C1-6 alkyl. 43. The compound or salt according to any one of claims 3, 8-4, 2, wherein R7 is selected from [the group consisting of]. 44. The compound or salt according to any one of claims 1-19, wherein R7 is selected from a 6-membered heterocycle, optionally substituted with one or more R8 atoms. 45. The compound or salt according to claim 44, wherein the 6-membered heterocycle has a nitrogen atom. 46. The compound or salt according to any one of claims 1-19, wherein R7 is selected from a 6-membered heteroaryl group, optionally substituted with one or more R8 atoms. 47. The compound or salt according to claim 46, wherein the 6-membered heteroaryl group has a nitrogen atom. 48. The compound or salt according to any one of claims 44-47,Each R8 is independently selected from halogens, -OR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20 (=NR20), -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, and C1-6 alkyl. 49. The compound or salt according to any one of claims 44-48, wherein each R8 is independently selected from halogens, -S(O)2(R20), =O, C1-6 alkyl, and C1-6 haloalkyl. 50. The compound or salt according to any one of claims 44 to 49, wherein R7 is selected from, (Claims 6 / 45, page 7, CN 121568943 A) and... 51. The compound or salt according to any one of claims 1-18, wherein R7 is selected from 9- to 10-membered heterocycles, each optionally substituted with one or more R8s. 52. The compound or salt according to claim 51, wherein the 9- to 10-membered heterocycle is a bicyclic ring. 53. The compound or salt according to claim 51 or 52, wherein R7 is selected from , , , , , , , , , , , and, each optionally substituted with one or more R8s. 54. The compound or salt according to any one of claims 51-53, wherein each R8 is independently selected from halogens, -OR2O, -S(O)2(R2O), -C(O)OR2O, =O, C1-6 alkyl, and C1-6 haloalkyl. 55. The compound or salt according to any one of claims 51-53, wherein each R8 is independently selected from =O, -S(O)2 (C1-6 alkyl), -CF3, -CH3, -C(O)OC1-6 alkyl, -OMe, and. 56. The compound or salt according to any one of claims 51-55, wherein R7 is selected from [the group consisting of halogens]. 57. The compound or salt according to any one of claims 1-19, wherein R7 is selected from phenyl, optionally substituted with one or more R8 groups. 58. The compound or salt according to claim 57, wherein each R8 is selected from halogens, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, and C1-6 alkyl. 59. The compound or salt according to claim 57 or 58, wherein R7 is selected from phenyl, optionally substituted with one or more substituents selected from halogens and C1-6 hydroxyalkyl. Claims 7 / 45 page 8 CN 121568943 A 60. The compound or salt according to any one of claims 57-59,R7 is selected from , , , and . 61. A compound of formula (II): , or a pharmaceutically acceptable salt or solvate thereof; wherein Z is selected from, wherein t represents the junction between Z and; Y is selected from -O-, -NR9-, -S- and -SO2-; each R50 is independently selected from hydrogen, halogen and C1-C6 alkyl; or combined to form; each R51 is independently selected from hydrogen, halogen and C1-C6 alkyl; k is selected from 1 and 2; A is selected from N and CR18; selected from optionally substituted imidazoles, wherein the imidazole is optionally substituted by one or more R14s; D is selected from N and CR19; R5 is selected from hydrogen and C1-6 alkyl; R7 is selected from hydrogen; and C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-C14 carbocyclic and 5 to 15-membered heterocycles, each optionally substituted by one or more R8s; each R8 is independently selected from halogen, -N(R20)2, -OR 20. ‑SR20, ‑S(O)2(R 20), ‑S(O)2N(R 20)2, ‑S(O)N (R20)2, ‑S(O)R 20(=NR20), ‑NR20S(O)2R 20, ‑C(O)N(R20)2, ‑C(=NR 20)N(R20)2, ‑C(O)NR 20OR20,‑N (R20)C(O)R20,‑N(R20)C(O)N(R20)2,‑N(R 20)C(O)OR20,‑C(O)R20,‑C(O)OR20,‑OC(O)R20,‑OC(O) N(R20)2,‑NO2, =O, =N(R 20), =NO(R20), -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-C12 carbon ring and 4 to 12 membered heterocycles, wherein the C1-6 alkyl is optionally substituted with one or more R8*, and wherein the C3-C12 carbon ring and 4 to 12 membered heterocycles are each optionally substituted with one or more substituents selected from halogen, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl and C1-C6 alkoxyalkyl; Each R8* is independently selected from 4 to 12-membered heterocyclic rings.The 4- to 12-membered heterocycles are optionally substituted by one or more substituents selected from halogens, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, and C1-C6 alkoxyalkyl; R9 is selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R20)2, C3-6 carbon rings, and 4- to 6-membered heterocycles.The C3-6 carbon ring and the 4- to 6-membered heterocycle are each optionally substituted by one or more substituents independently selected from halogens, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R20)2, C2-10 alkenyl, and C2-10 alkynyl; each R14 is independently selected from halogens, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbon rings, and 3- to 12-membered heterocycles; R17 is selected from hydrogen, halogens, -N(R20)2, -OR20, -SR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), -NR20S(O)2R20, -C(O)N(R20)2, -C(=NR20)N(R20)2, -C(O)NR20OR20, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R20)C(O)OR20, -C(O)R20, -C(O)OR20, -OC(O)R20, -OC(O)N(R20)2, -NO2, - CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-12 carbon ring and 5 to 12 membered heterocycles; R18 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, -O-C1-10 alkyl, C1-C6 alkyl and C1-C6 haloalkyl; R19 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, -O-C1-10 alkyl, C1-C6 Alkyl and C1-C6 haloalkyl; and R20 is independently selected each time it appears from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-12 carbon ring and 3 to 12 membered heterocycles.Each of them is optionally substituted by one or more substituents independently selected from: halogen, -OH, -CN, -NO2, -NH2, -S(O)2 (C1-6 alkyl), C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbide ring, and 3 to 12 membered heterocycles. 62. The compound or salt according to claim 61, wherein Z is . 63. The compound or salt according to claim 61 or 62, wherein Z is . 64. The compound or salt according to claim 61, wherein formula (II) is represented by formula (IIA): [Claims 9 / 45 page 10 CN 121568943 A], or a pharmaceutically acceptable salt or solvation thereof. 65. The compound or salt according to claim 61, wherein formula (II) is represented by formula (IIB): [Claims 9 / 45 page 10 CN 121568943 A], or a pharmaceutically acceptable salt or solvation thereof. 66. The compound or salt of claim 61, wherein formula (II) is represented by formula (IIC): , or a pharmaceutically acceptable salt or solvation thereof. 67. The compound or salt of any one of claims 61 to 66, wherein A is selected from N, CF, and CH. 68. The compound or salt of claim 67, wherein A is CH. 69. The compound or salt of claim 67, wherein A is N. 70. The compound or salt of any one of claims 61 to 69, wherein D is selected from N, CF, and CH. 71. The compound or salt of claim 70, wherein D is CH. 72. The compound or salt of claim 70, wherein D is N. 73. The compound or salt of any one of claims 61 to 64, wherein formula (II) is represented by formula (IID): , or a pharmaceutically acceptable salt or solvation thereof. Claims 10 / 45 pages 11 CN 121568943 A 74. The compound or salt according to any one of claims 61 to 63 or 65, wherein formula (II) is represented by formula (IIIE): , or a pharmaceutically acceptable salt or solvation thereof. 75. The compound or salt according to any one of claims 61 to 63 or 66, wherein formula (II) is represented by formula (IIF): , or a pharmaceutically acceptable salt or solvation thereof. 76. The compound or salt according to claim 61, wherein formula (II) is represented by formula (IIF): , or a pharmaceutically acceptable salt or solvation thereof. 77. The compound or salt according to any one of claims 61 to 76, wherein R5 is selected from hydrogen and methyl. 78. The compound or salt according to any one of claims 61 to 77, wherein R5 is hydrogen. 79. The compound or salt according to any one of claims 61 to 78, wherein R7 is selected from C6-C8 carbon rings and 5- to 6-membered heterocycles,Each of them is optionally substituted with one or more R8. 80. The compound or salt according to any one of claims 61 to 79, wherein R7 is selected from C6-C8 carbon rings and is optionally substituted with one or more R8. 81. The compound or salt according to any one of claims 61 to 78, wherein R7 is selected from C4-C7 carbon rings and is optionally substituted with one or more R8. 82. The compound or salt according to any one of claims 61 to 81, wherein R7 is selected from […], […], and […], and is optionally substituted with one or more R8. 83. The compound or salt according to any one of claims 61 to 82, wherein each R8 is independently selected from halogens, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, -OR20, -N(R20)2, -NR20S(O)2R20, -N(R20)C(O)R20, -C(O)N(R20)2, -S(O)2(R20) and 4- to 6-membered heterocycles, wherein the 4- to 6-membered heterocycle is optionally substituted by one or more substituents selected from halogens, -OH, -CN, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl and -O-C1-10 alkyl; and wherein the C1-6 alkyl of R8 is optionally substituted by a 4- to 6-membered heterocycle, wherein the 4- to 6-membered heterocycle is optionally substituted by one or more substituents selected from halogens. 84. The compound or salt according to any one of claims 61 to 83, wherein each R8 is independently selected from F, methyl, ethyl, etc. 85. The compound or salt according to any one of claims 61 to 84, wherein R7 is selected from CN 121568943 A (page 12 / 45 of claims) 86. The compound or salt according to any one of claims 61 to 81, wherein R7 is selected from optionally substituted phenyl groups, which are optionally substituted by one or more R8 groups. 87. The compound or salt according to any one of claims 61 to 81 or 86, wherein each R8 is independently selected from halogen, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl. 88. The compound or salt according to claim 86 or 87, wherein R7 is selected from phenyl groups optionally substituted with one or more substituents selected from halogens and C1-6 hydroxyalkyl groups. 89. The compound or salt according to claim 88, wherein R7 is selected from [missing information - likely a specific group or group]. 90. The compound or salt according to any one of claims 61 to 81,Wherein R7 is, optionally substituted by one or more R8s. 91. The compound or salt according to any one of claims 61 to 81 or 90, wherein each R8 is independently selected from halogens and -S(O)2(R2O). 92. The compound or salt according to claim 90 or 91, wherein R7 is selected from and . 93. The compound or salt according to any one of claims 61 to 78, wherein R7 is selected from C9 carbon rings, optionally substituted by one or more R8s. Claims 14 / 45 pages 15 CN 121568943 A 94. The compound or salt according to claim 93, wherein R7 is . 95. The compound or salt according to any one of claims 61 to 78, wherein R7 is selected from 5- to 10-membered heterocycles, each optionally substituted by one or more R8s. 96. The compound or salt according to claim 95, wherein R7 is selected from , , , , , , , , , , , , , , , , , , , and, each of which is optionally substituted by one or more R8s. 97. The compound or salt according to any one of claims 61 to 78, 95 or 96, wherein each R8 is independently selected from halogens, -OR20, -N(R20)2, -S(O)2(R20), -C(O)OR20, =O, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl and 4 to 6-membered heterocycles, wherein the 4 to 6-membered heterocycles are optionally substituted by one or more substituents selected from halogens and -C1-3 haloalkyls. 98. The compound or salt according to any one of claims 61 to 78 or 95 to 97, wherein each R8 is independently selected from , ... 102. The compound or salt according to claim 101, wherein each R8 is independently selected from -S(O)2(R 2O) and =O. 103. The compound or salt according to any one of claims 61 to 79 or 100 to 102.R7 is selected from [aspects], [aspects], and [aspects]. 104. The compound or salt according to any one of claims 61 to 79, wherein R7 is selected from optionally substituted 5- to 6-membered heteroaryl groups. 105. The compound or salt according to claim 104, wherein R7 is selected from optionally substituted 6-membered heteroaryl groups, which are optionally substituted with one or more R8 groups. Claims 16 / 45 pages 17 CN 121568943 A 106. The compound or salt according to claim 105, wherein R7 is selected from optionally substituted pyridine, which are optionally substituted with one or more R8 groups. 107. The compound or salt according to any one of claims 61 to 79 or 104 to 106, wherein each R8 is independently selected from halogens, -N(R20)2, -OR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20 (=NR20), -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, and C1-6 alkyl. 108. The compound or salt according to claim 107, wherein each R8 is selected from halogens, -OR20, -CN, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, and C1-6 alkyl. 109. The compound or salt according to any one of claims 61 to 79 or 104 to 108, wherein R7 is selected from [the group consisting of]. 110. The compound or salt according to any one of claims 61 to 79, wherein R7 is selected from a 6-membered heterocycle, optionally substituted with one or more R8 atoms. 111. The compound or salt according to claim 110, wherein the 6-membered heterocycle has a nitrogen atom. 112. The compound or salt according to any one of claims 61 to 79, wherein R7 is selected from a 6-membered heteroaryl group, optionally substituted with one or more R8 atoms. 113. The compound or salt according to claim 112, wherein the 6-membered heteroaryl group has a nitrogen atom. 114. The compound or salt according to any one of claims 61 to 79 or 110 to 113, wherein each R8 is independently selected from halogens, -OR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20 (=NR20), -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, and C1-6 alkyl. 115. The compound or salt according to any one of claims 61 to 79 or 110 to 114,Each R8 is independently selected from halogens, -S(O)2(R 2O), =O, C1-6 alkyl, and C1-6 haloalkyl. 116. The compound or salt according to any one of claims 61 to 79 or 110 to 114, wherein R7 is selected from [missing information - likely a specific type of compound]. 117. The compound or salt according to any one of claims 61 to 78, wherein R7 is selected from 9- to 10-membered heterocycles, each of which is optionally substituted with one or more R8s. 118. The compound or salt according to claim 117, wherein the 9- to 10-membered heterocycle is a bicyclic ring. 119. The compound or salt according to claim 117 or 118, wherein R7 is selected from [missing information - likely a specific type of compound], ... 120. The compound or salt according to any one of claims 61 to 78 or 117 to 119, wherein each R8 is independently selected from halogens, -OR2O, -S(O)2(R2O), -C(O)OR2O, =O, C1-6 alkyl, and C1-6 haloalkyl. 121. The compound or salt according to any one of claims 61 to 78 or 117 to 120, wherein each R8 is independently selected from =O, -S(O)2(C1-6 alkyl), -CF3, -CH3, -C(O)OC1-6 alkyl, -OMe, and. 122. The compound or salt according to any one of claims 61 to 78 or 117 to 121, wherein R7 is selected from , ... 123. The compound or salt according to any one of claims 61 to 72 or 77 to 122, wherein R17 is selected from hydrogen, halogen, -OR20, C1-6 alkyl, C1-6 haloalkyl, and saturated C3-6 carbide rings. 124. The compound or salt according to any one of claims 61 to 82, wherein R7 is [missing information]. 125. The compound or salt according to any one of claims 61 to 82 or 124, wherein R7 is selected from [missing information] (page 18 / 45 of claims, CN 121568943 A). 126. The compound or salt according to any one of claims 61 to 82 or 125, wherein R7 is [missing information]. 127. The compound or salt according to any one of claims 61 to 82 or 125, wherein R7 is selected from [missing information] and [missing information]. 128. The compound or salt according to any one of claims 61 to 82 or 125, [missing information].Wherein R7 is. 129. The compound or salt according to any one of claims 61 to 82, 124 or 125, wherein R7 is. 130. The compound or salt according to any one of claims 61 to 82, wherein R7 is substituted by at least one R8 selected from C1-6 alkyl, C1-6 hydroxyalkyl and C1-6 haloalkyl. Claims 19 / 45 pages 20 CN 121568943 A 131. The compound or salt according to any one of claims 61 to 82 or 130, wherein R7 is selected from, , , , , , , , and. 132. The compound or salt according to any one of claims 61 to 82, wherein R7 is substituted by at least one R8 selected from -S(O)2(R2O). 133. The compound or salt according to any one of claims 61 to 82 or 132, wherein R7 is. 134. The compound or salt according to any one of claims 61 to 82, wherein R7 is substituted by at least one R8 selected from -N(R2O)2. 135. The compound or salt according to any one of claims 61 to 82 or 134, wherein R7 is selected from [missing information - likely a specific compound or salt]. 136. The compound or salt according to claim 1, selected from: [missing information - likely a specific compound or salt]; ...Selected from: Claims 22 / 45, page 23, CN 121568943 A; Claims 23 / 45, page 24, CN 121568943 A; Claims 24 / 45, page 25, CN 121568943 A; Claims 25 / 45, page 26, CN 121568943 A; Claims 26 / 45, page 27, CN 121568943 A; Claims 27 / 45, page 28, CN 121568943 A; Claims 28 / 45, page 29, CN 121568943 A; Claims 29 / 45, page 30, CN 121568943 A; Claims 30 / 45, page 31, CN 121568943 A; Claims 31 / 45, page 32, CN 121568943 A; Claims 32 / 45, page 33, CN 121568943 A Claims 33 / 45 Page 34 CN 121568943 A Claims 34 / 45 Page 35 CN 121568943 A Claims 35 / 45 Page 36 CN 121568943 A Claims 36 / 45 Page 37 CN 121568943 A Claims 37 / 45 Page 38 CN 121568943 A Claims 38 / 45 Page 39 CN 121568943 A Claims 39 / 45 Page 40 CN 121568943 A Claims 40 / 45 Page 41 CN 121568943 A Claims 41 / 45 Page 42 CN 121568943 A Claims 42 / 45 Page 43 CN 121568943 A Claims 43 / 45, page 44, CN 121568943 A; or a pharmaceutically acceptable salt or solvate thereof. 138. A pharmaceutical composition comprising: a compound or salt according to any one of claims 1 to 137 and at least one pharmaceutically acceptable excipient. 139. Use of the compound or salt according to any one of claims 1 to 137 or the pharmaceutical composition according to claim 138 for treating a disease or condition. 140. A method of treating a disease or condition.The method comprises administering to a subject in need a therapeutically effective amount of the compound or salt of any one of claims 1 to 137 or the pharmaceutical composition of claim 138. 141. The method of claim 140, wherein the subject would benefit from the inhibition of CD38. 142. The method of claim 140 or 141, wherein the method results in the inhibition of CD38 in the subject. 143. The method according to any one of claims 140 to 142, wherein the disease or condition is selected from: neurodegenerative diseases, type 1 diabetes, insulin resistance, Leber hereditary amaurosis, Parkinson's disease, amyotrophic lateral sclerosis, chronic lymphocytic leukemia, periodontitis, psoriasis, UV skin damage, radiation protection, diabetic neuropathy, hyperpigmentation, pellagra, hereditary niacin deficiency, diabetes, Huntington's disease, bipolar disorder, schizophrenia, postmenopausal osteoporosis, optic neuropathy, neurocognitive impairment, multiple sclerosis, Alzheimer's disease, fatty degeneration, NASH, hearing loss, dyslipidemia, end-stage renal disease, metabolic syndrome, obesity, sarcopenic obesity, gout, irritable bowel syndrome, colitis, COPD, asthma, cystic fibrosis, pancreatitis, idiopathic pulmonary fibrosis, organ reperfusion injury. Stroke, muscular dystrophy, cardiac hypertrophy, CHF, leishmaniasis, tuberculosis, Hansen's disease, hypoxic pulmonary vasoconstriction, hypertension, clear cell renal cell carcinoma, small pulmonary cell carcinoma, exercise intolerance, epilepsy, sleep disorders, ataxia-telangiectasia, rheumatoid arthritis, lupus, alcohol intolerance, hyperphosphatemia, acute lung injury, and ARDS. 144. The method of any one of claims 140 to 143, wherein the disease or condition is a neurodegenerative disease. 145. The method of any one of claims 140 to 143, wherein the disease or condition is muscular dystrophy. 146. The method of any one of claims 140 to 143, wherein the disease or condition is a metabolic disorder. 147. The method of any one of claims 140 to 143, wherein the disease or condition is fibrosis. 148. The method of any one of claims 140 to 143, wherein the disease or condition is Duchenne muscular dystrophy. 149. The method according to any one of claims 140 to 143, wherein the disease or condition is systemic sclerosis. 150. The method according to any one of claims 140 to 143, wherein the disease or condition is selected from encephalopathy, vascular disease, liver disease, muscle disease, pancreatic disease, adipose tissue disease, and inflammation-related diseases. 151. A method for regulating CD38 in a subject.This includes administering to the subject a compound or salt according to any one of claims 1 to 137 (pages 44 / 45, CN 121568943 A) or a pharmaceutical composition according to claim 138. 152. The method according to claim 151, further comprising treating the subject with a disease or condition selected from: neurodegenerative diseases, type 1 diabetes, insulin resistance, Leber hereditary amaurosis, Parkinson's disease, amyotrophic lateral sclerosis, chronic lymphocytic leukemia, periodontitis, psoriasis, UV-induced skin damage, radiation protection, diabetic neuropathy, hyperpigmentation, pellagra, hereditary niacin deficiency, diabetes, Huntington's disease, bipolar disorder, schizophrenia, postmenopausal osteoporosis, optic neuropathy, neurocognitive impairment, multiple sclerosis, Alzheimer's disease, fatty degeneration. Sexual dysfunction, NASH, hearing loss, dyslipidemia, end-stage renal disease, metabolic syndrome, obesity, sarcopenic obesity, gout, irritable bowel syndrome, colitis, COPD, asthma, cystic fibrosis, pancreatitis, idiopathic pulmonary fibrosis, organ reperfusion injury, stroke, muscular dystrophy, cardiac hypertrophy, CHF, leishmaniasis, tuberculosis, Hansen's disease, hypoxic pulmonary vasoconstriction, hypertension, clear cell renal cell carcinoma, small pulmonary cell carcinoma, exercise intolerance, epilepsy, sleep disorders, ataxia-telangiectasia, rheumatoid arthritis, lupus, alcohol intolerance, hyperphosphatemia, acute lung injury, and ARDS. Claims 45 / 45 Page 46 CN 121568943 A Tricyclic Fused Imidazole Compounds as CD38 Regulators and Their Uses Cross-Reference

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 498,182, filed April 25, 2023; U.S. Provisional Patent Application No. 63 / 578,614, filed August 24, 2023; and U.S. Provisional Patent Application No. 63 / 627,213, filed January 31, 2024, the entire contents of each of which are incorporated herein by reference. Background Art

[0002] Nicotinamide adenine dinucleotide (NAD+) is a biochemical substance found in all cells and was first characterized more than 100 years ago for its role in redox enzyme reactions. Since then, NAD+ and its associated pyridine nucleotides NADH, NADP+, and NADPH have been considered major redox carriers in all organisms. These pyridine dinucleotides regulate cytoplasmic and mitochondrial redox states and are key players in monitoring cellular metabolic status. This is because NAD+ and NADH act as cofactors for hydride acceptance and supply to metabolic enzymes involved in glycolysis, the TCA cycle, and the respiratory chain.This leads to the redistribution of the reducing equivalents generated during these catabolic processes to the de novo synthesis of new biomolecules. (Houtkooper et al. Endo Reviews (2010) 31:194-223; Koch-Nolte et al. Science Signaling (2009) 2: mr1; Houtkooper and Auwerx J. Cell Biol (2012) 199:205-209; Berger et al. Trends in Bioch Sci (2004) 29:111-18).

[0003] In addition to its long-established role as a cofactor for oxidoreductases, recent studies have shown that NAD+ is also a substrate for a variety of enzymes, consumed in the process of supplying its ADP-ribose to acceptor molecules. The enzymes that are major consumers of NAD+ are ADP-ribosyltransferases (i.e., the PARP and ART enzyme families), sirtuins (Sirt1-7), and ADP-ribosylcyclases / hydrolases (CD38 / CD157). These enzymes are involved in regulating pathways of Ca++ signaling, gene transcription, DNA repair, cell survival, energy metabolism, and oxidative stress. Therefore, NAD+ and its phosphorylated relatives NADP and NAADP (both derived from NAD+) also act as signaling molecules. NAD+ is also a key component of the circadian rhythm, with its daily fluctuations linking cellular metabolism to chromatin remodeling and gene transcription.

[0004] It is well known that exercise and calorie restriction increase NAD+ levels, while aging and obesity decrease cellular NAD+ levels. Restoring NAD+ levels in disease states that deplete significant amounts of NAD+ may have medical benefits when cells struggle to maintain their energy state during periods of stress. (Tevy et al. Trends in Endo and Metab (2013) 24:229-237; Pugh et al. Aging Cell (2013) 12:672-681; Massudi et al. PLoS ONE (2012) 7:e42357; Xu and Sauve (2010) Mech of Ageing and Development 131:287-298). Cellular NAD+ is produced via de novo tryptophan synthesis or via salvage synthesis of precursors such as nicotinic acid / niacin and nicotinamide (both of which are derived from dietary sources).

[0005] A third method of regulating cellular NAD+ levels is to block NAD+ consumption by inhibiting enzymes that consume NAD+. Differentiation cluster 38 (CD38) is one such NAD+ consumer. CD38 is also known as ADP-ribosylcyclase.It is a type II membrane-anchored enzyme. It can efficiently catalyze the breakdown of NAD+ into nicotinamide and ADPR, and hydrolyze NAADP into ADPRP. CD38 can also act as a cyclase to convert NAD+ into cADPR, although its efficiency as a cyclase is 1 / 100 of that as a hydrolase.

[0006] CD38 was first characterized as a surface antigen on immune cells and is widely distributed in most tissues in the body. It is present on the plasma membrane as well as on the membranes of intracellular organelles such as the nucleus and mitochondria. As predicted from its function as an NAD+ glycosyl hydrolase, as described in the specification 1 / 240 page 47 CN 121568943 A, the NAD+ level in CD38 KO mice is higher than that in wild-type controls. Similarly, CD38 enzyme activity inhibitors can also regulate NAD+ tissue levels and can be used to treat various diseases with CD38 overexpression or decreased or desynchronized cellular NAD+ levels. Compounds that inhibit CD38 and thereby increase NAD+ levels can be used to treat diseases or conditions that have been shown to benefit from NAD+, including mitochondrial-related diseases or conditions.

[0007] There is a need for new compounds and treatments for diseases or conditions related to CD38.

[0008] In one aspect, this disclosure provides a compound represented by the structure of formula I: , or a pharmaceutically acceptable salt or solvate thereof; wherein Z is selected from and , wherein t represents the connection point between Z and the imidazole ring; X is selected from O and S; Y is selected from -N(R10)2, -OR 10 and -SR10; A is selected from N and CR18; D is selected from N and CR19; R4 is selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C1-6 cyanoalkyl, C1-6 alkoxyalkyl, C1-6 alkyl-N(R20)2, C3-5 cycloalkyl and 3 to 6 membered heterocycles; R5 is selected from hydrogen and C1-6 alkyl; R6 is selected from hydrogen, C1-6 alkyl, halogen, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C1-6 cyanoalkyl, C1-6 alkoxyalkyl, C1-6 alkyl-N(R20)2, C4-6 cycloalkyl, and 3- to 6-membered heterocyclic alkyl; R7 is selected from C3-C12 carbon rings and 5- to 15-membered heterocycles.Each of these components is optionally replaced by one or more R8s; each R8 is independently selected from halogens, -N(R20)2, -OR20, -SR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), -NR20S(O)2R20, -C(O)N(R20)2, -C(=NR20)N(R20)2, -C(O)NR20OR20, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R20)C(O)OR20, -C(O)R20, -C(O)OR20, -OC(O)R20, -OC(O) N(R20)2, -NO2, =O, =N(R20), =NO(R20), -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-C12 carbon ring and 5 to 12-membered heterocycles, wherein the C3-C12 carbon ring and the 5 to 12-membered heterocycles are each optionally substituted by one or more substituents selected from halogen, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl and C1-C6 alkoxyalkyl; R9 is selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R20)2, C3-6 carbon rings, and 4- to 6-membered heterocycles.The C3-6 carbon ring and the 4- to 6-membered heterocycles are each optionally substituted by one or more substituents independently selected from halogens, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R20)2, C2-10 alkenyl, and C2-10 alkynyl; each R10 is independently selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, and C1-C6 alkyl-N(R20)2; R17 is selected from hydrogen, halogens, -N(R20)2, and -OR. 20. ‑SR20, ‑S(O) 2(R 20), ‑S(O) 2N(R 20) 2, ‑S(O)N (R20)2, ‑S(O)R 20(=NR20), ‑NR20S(O)2R 20, ‑C(O)N(R20)2, ‑C(=NR 20)N(R20)2, ‑C(O)NR 20OR20, ‑N (R20)C(O)R20, ‑N(R20)C(O)N(R20)2, ‑N(R 20)C(O)OR20, ‑C(O)R20, ‑C(O)OR20, ‑OC(O)R20, ‑OC(O) N(R20)2, -NO2, -CN, C1-6 alkyl, -N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-12 carbon ring and 5 to 12-membered heterocycles; R18 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, -O-C1-10 alkyl, C1-C6 alkyl and C1-C6 haloalkyl; R19 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, -O-C1-10 alkyl, C1-C6 alkyl and C1-C6 haloalkyl; and R20, each time appearing, is independently selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-12 carbon ring and 3 to 12-membered heterocycles, each optionally substituted by one or more substituents independently selected from: halogen, -OH, -CN, -NO2, -NH2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 ynyl, C3-12 carbon ring and 3 to 12-membered heterocycles.

[0009] In one aspect, this disclosure provides compounds represented by the structure of formula (II): ,Or a pharmaceutically acceptable salt or solvate thereof; wherein Z is selected from, where t represents the junction between Z and; Y is selected from -O-, -NR9-, -S- and -SO2-; each R50 is independently selected from hydrogen, halogen, C1-C6 alkyl; or combined to form; each R51 is independently selected from hydrogen, halogen and C1-C6 alkyl; k is selected from 1 and 2; A is selected from N and CR18; A is selected from optionally substituted imidazoles, wherein the imidazole is optionally substituted by one or more R14s; D is selected from N and CR19; R5 is selected from hydrogen and C1-6 alkyl; R7 is selected from hydrogen; and C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-C14 carbocyclic and 5 to 15-membered heterocycles, each optionally substituted by one or more R8s; each R8 is independently selected from halogen, -N(R20)2, -OR 20. ‑SR20, ‑S(O)2(R 20), ‑S(O)2N(R 20)2, ‑S(O)N (R20)2, ‑S(O)R 20(=NR20), ‑NR20S(O)2R 20, ‑C(O)N(R20)2, ‑C(=NR 20)N(R20)2, ‑C(O)NR 20OR20,‑N (R20)C(O)R20,‑N(R20)C(O)N(R20)2,‑N(R 20)C(O)OR20,‑C(O)R20,‑C(O)OR20,‑OC(O)R20,‑OC(O) N(R20)2,‑NO2, =O, =N(R 20), =NO(R20), -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-C12 carbon ring and 4 to 12-membered heterocycles, wherein the C1-6 alkyl is optionally substituted by one or more R8*, and wherein the C3-C12 carbon ring and the 4 to 12-membered heterocycles are each optionally substituted by one or more substituents selected from halogens, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl and C1-C6 alkoxyalkyl; each R8* is independently selected from 4 to 12-membered heterocycles.The 4- to 12-membered heterocycles are optionally substituted by one or more substituents selected from halogens, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, and C1-C6 alkoxyalkyl; R9 is selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R20)2, C3-6 carbon rings, and 4- to 6-membered heterocycles.Each of the C3-6 carbon rings and the 4- to 6-membered heterocycles is optionally substituted by one or more substituents independently selected from halogens, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R20)2, C2-10 alkenyl, and C2-10 alkynyl; each R14 is independently selected from halogens, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbon rings, and 3- to 12-membered heterocycles; R17 is selected from hydrogen, halogens, -N(R20)2, -OR20, -SR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), -NR20S(O)2R20, -C(O)N(R20)2, -C(=NR20)N(R20)2, -C(O)NR20OR20, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R20)C(O)OR20, -C(O)R20, -C(O)OR20, -OC(O)R20, -OC(O) N(R20)2, -NO2, -CN, C1-6 alkyl, -N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-12 carbon ring and 5 to 12 membered heterocycles; R18 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, -O-C1-10 alkyl, C1-C6 alkyl and C1-C6 haloalkyl; R19 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, -O-C1-10 alkyl, C1-C6 alkyl and C1-C6 haloalkyl; and R20 is independently selected each time it appears from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-12 carbon ring and 3 to 12 membered heterocycles.Each of them is optionally substituted by one or more substituents independently selected from the following: halogen, -OH, -CN, -NO2, -NH2, -S(O)2 (C1-6 alkyl), C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbide ring, and 3 to 12 membered heterocycles.

[0010] In some embodiments, this disclosure provides a pharmaceutical composition comprising a compound or salt of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF) or formula (IIG), and a pharmaceutically acceptable excipient.

[0011] In some embodiments, this disclosure provides a method of treating a disease or condition, comprising administering to a subject in need a compound or salt of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), or (IIF), or a pharmaceutical composition comprising a compound or salt of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), or (IIF), and a pharmaceutically acceptable excipient. In some cases, the subject will benefit from CD38 inhibition. In some cases, the disease is a neurodegenerative disease. In some cases, the disease or condition is muscular dystrophy. In some cases, the disease or condition is a metabolic disorder. In some cases, the disease or condition is fibrosis. In some cases, the disease or condition is Duchenne muscular dystrophy. In some cases, the disease or condition is systemic sclerosis. In other cases, the disease or condition is selected from brain diseases, vascular diseases, liver diseases, muscle diseases, pancreatic diseases, adipose tissue diseases, and inflammation-related diseases. In some cases,Diseases or conditions selected from: neurodegenerative diseases, type 1 diabetes, insulin resistance, Leber's hereditary amaurosis, Parkinson's disease, amyotrophic lateral sclerosis, chronic lymphocytic leukemia, periodontal disease, psoriasis, UV skin damage, radiation protection, diabetic neuropathy, hyperpigmentation, pellagra, hereditary niacin deficiency, diabetes, Huntington's disease, bipolar disorder, schizophrenia, postmenopausal osteoporosis, optic neuropathy, neurocognitive impairment, multiple sclerosis, Alzheimer's disease, fatty degeneration, NASH, hearing loss, dyslipidemia, end-stage renal disease, metabolic syndrome, obesity, sarcopenic obesity, gout, irritable bowel syndrome, colitis, COPD, asthma, cystic fibrosis, pancreatitis, idiopathic pulmonary fibrosis. Organ reperfusion injury, stroke, muscular dystrophy, cardiac hypertrophy, CHF, leishmaniasis, tuberculosis, Hansen's disease, hypoxic pulmonary vasoconstriction, hypertension, clear cell renal cell carcinoma, small lung cell carcinoma, exercise intolerance, epilepsy, sleep disorders, ataxia-telangiectasia, rheumatoid arthritis, lupus, alcohol intolerance, hyperphosphatemia, acute lung injury, and ARDS.

[0012] In some embodiments, this disclosure provides a method of inhibiting CD38, comprising administering a compound or salt of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG). In some cases, the method includes inhibiting CD38 by administering a pharmaceutical composition comprising a compound or salt of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG) and a pharmaceutically acceptable excipient.

[0013] All publications, patents, and patent applications mentioned in this specification are incorporated herein by reference to the extent that each individual publication, patent, or patent application has been specifically and individually indicated to be incorporated herein by reference. If any publication or patent or patent application incorporated herein by reference conflicts with the disclosure contained in this specification, then this specification is intended to substitute for and / or give preference to any such conflicting material. Detailed Description

[0014] Although preferred embodiments of the invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Without departing from the invention,Numerous changes, variations, and substitutions will now be apparent to those skilled in the art. It should be understood that various alternatives to the embodiments of the invention described herein can be used to practice the invention. The following claims are intended to define the scope of the invention, and methods and structures within the scope of these claims, as well as their equivalents, are covered by the claims. Definitions

[0015] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the description of the field to which this invention pertains, page 5 / 240, 51 CN 121568943 A. All patents and publications mentioned herein are incorporated herein by reference.

[0016] Unless the context clearly specifies otherwise, as used in the description and claims, the singular forms “a / an” and “the” include a plurality of indicators.

[0017] The term “Cx-y” when used in conjunction with chemical portions such as alkyl, alkenyl, or alkynyl is intended to include groups containing x to y carbons in the chain. For example, the term "C1-6 alkyl" refers to a saturated hydrocarbon group containing 1 to 6 carbons, including straight-chain alkyl and branched-chain alkyl. The term –Cx-y alkylene – refers to a substituted or unsubstituted alkylene chain having x to y carbons in the alkylene chain. For example, –C1-6 alkylene – can be selected from methylene, ethylene, propylene, butylene, pentylene, and hexylene, any of which may optionally be substituted.

[0018] As used herein, "alkyl" means a straight-chain or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, without unsaturated groups, and preferably having one to fifteen carbon atoms (i.e., C1-C15 alkyl). In some embodiments, the alkyl comprises one to thirteen carbon atoms (i.e., C1-C13 alkyl). In some embodiments, the alkyl comprises one to eight carbon atoms (i.e., C1-C8 alkyl). In other embodiments, the alkyl comprises one to five carbon atoms (i.e., C1-C5 alkyl). In other embodiments, the alkyl group comprises one to four carbon atoms (i.e., C1-C4 alkyl). In other embodiments, the alkyl group comprises one to three carbon atoms (i.e., C1-C3 alkyl). In other embodiments, the alkyl group comprises one to two carbon atoms (i.e., C1-C2 alkyl). In other embodiments, the alkyl group comprises one carbon atom (i.e., C1 alkyl). In other embodiments, the alkyl group comprises five to fifteen carbon atoms (i.e., C5-C15 alkyl). In other embodiments, the alkyl group comprises five to eight carbon atoms (i.e., C5-C8 alkyl). In other embodiments, the alkyl group comprises two to five carbon atoms (i.e., C2-C5 alkyl). In other embodiments, the alkyl group comprises three to five carbon atoms (i.e., C3-C5 alkyl). In some embodiments,The alkyl group is selected from methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl (isopropyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (isobutyl), 1,1-dimethylethyl (tert-butyl), and 1-pentyl (n-pentyl). The alkyl group is attached to the rest of the molecule by a single bond.

[0019] As used herein, "alkenyl" refers to a straight-chain or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, containing at least one carbon-carbon double bond, and preferably having two to twelve carbon atoms (i.e., C2-C12 alkenyl). In some embodiments, the alkenyl group contains two to eight carbon atoms (i.e., C2-C8 alkenyl). In some embodiments, the alkenyl group contains two to six carbon atoms (i.e., C2-C6 alkenyl). In other embodiments, the alkenyl group contains two to four carbon atoms (i.e., C2-C4 alkenyl). Alkenyl groups are connected to the rest of the molecule via single bonds, such as ethenyl, propenyl, butenyl, pentenyl, pent-1,4-dienyl, etc.

[0020] As used herein, "alkynyl" refers to a straight-chain or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond and preferably having two to twelve carbon atoms (i.e., C2-C12 alkynyl). In some embodiments, the alkynyl group contains two to eight carbon atoms (i.e., C2-C8 alkynyl). In other embodiments, the alkynyl group contains two to six carbon atoms (i.e., C2-C6 alkynyl). In other embodiments, the alkynyl group contains two to four carbon atoms (i.e., C2-C4 alkynyl). Alynyl groups are connected to the rest of the molecule via single bonds, such as ethynyl, propynyl, butynyl, pentynyl, hexynyl, etc.

[0021] The terms “Cx-y alkenyl” and “Cx-y ynyl” refer to unsaturated aliphatic groups that are similar to the alkyl groups described above in length and possible substitutions, but each contains at least one double or triple bond. The term –Cx-y alkenyl – refers to an alkenyl chain, substituted or unsubstituted, having x to y carbons in the alkenyl chain. For example, –C2-6 alkenyl – can be selected from vinylene, propenylene, butenylene, pentenylene, and hexenylene, any of which may optionally be substituted. The alkenyl chain may have one or more double bonds in the alkenyl chain. The term –Cx-y ynyl – refers to an ynylene chain, substituted or unsubstituted, having x to y carbons in the ynylene chain. For example, –C2-6 ynylene – can be selected from ynylene, propynylene, butynylene, pentylyne, and hexynylene, any of which may be optionally substituted. The ynylene chain may have one or more triple bonds in the ynylene chain.

[0022] “Alkylene” means that the rest of the molecule is attached to the group, consisting only of carbon and hydrogen, and does not contain unsaturation.And preferably, it is a straight-chain divalent hydrocarbon chain having one to twelve carbon atoms, such as methylene, ethylene, propylene, butylene, etc. The alkylene chain is connected to the rest of the molecule by a single bond and to the group by a single bond. The connection point between the alkylene chain and the rest of the molecule and the group is achieved by a terminal carbon. The alkylene chain may optionally be substituted by one or more substituents such as those described herein.

[0023] "Alkenyl" refers to a straight-chain divalent hydrocarbon chain consisting only of carbon and hydrogen, containing at least one carbon-carbon double bond, and preferably having two to twelve carbon atoms, with the rest of the molecule connected to the group by a single bond. The alkenyl chain is connected to the rest of the molecule by a single bond and to the group by a single bond. The connection point between the alkenyl chain and the rest of the molecule and the group is achieved by a terminal carbon. The alkenyl chain may optionally be substituted by one or more substituents such as those described herein.

[0024] “Alynyl” refers to a straight-chain divalent hydrocarbon chain consisting only of carbon and hydrogen, containing at least one carbon-carbon triple bond, and preferably having two to twelve carbon atoms, to which the remainder of the molecule is attached. The alynyl chain is attached to the remainder of the molecule by a single bond and to the group by a single bond. The connection between the alynyl chain and the remainder of the molecule and to the group is achieved by a terminal carbon, respectively. The alynyl chain may optionally be substituted by one or more substituents such as those described herein.

[0025] “Halogen” or “halogen” as used herein refers to a halogen substituent, such as a bromine, chlorine, fluorine, or iodine substituent.

[0026] “Halogenated alkyl” as used herein refers to an alkyl group as defined above substituted with one or more halogen groups, such as trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, etc. Examples of halogen-substituted alkanes (“haloalkanes”) include halomethanes (e.g., chloromethane, bromomethane, fluoromethane, iodomethane), dihalomethanes and trihalomethanes (e.g., chloroform, tribromomethane, trifluoromethane, triiodomethane), 1-haloethanes, 2-haloethanes, 1,2-dihaloethanes, and any other suitable combination of alkanes (or substituted alkanes) and halogens. When the alkyl group is substituted with more than one halogen group, each halogen can be chosen independently, for example, 1-chloro,2-bromoethane.

[0027] “Aminoalkyl” means an alkyl group as defined above substituted with one or more amino groups, such as propane-2-amine, butane-1,2-diamine, pentane-1,2,4-triamine, etc.

[0028] “Hydroxyalkyl” means an alkyl group as defined above substituted with one or more hydroxyl groups, such as propane-1-ol, butane-1,4-diol, pentane-1,2,4-triol, etc.

[0029] "Alkoxyalkyl" refers to an alkyl group as defined above that is substituted with one or more alkoxy groups.Examples include methoxymethane, 1,3-dimethoxybutane, 1-methoxypropane, 2-ethoxypentane, etc.

[0030] As used herein, "cyanoalkyl" refers to an alkyl group as defined above substituted with one or more cyano groups, such as acetonitrile, 2-ethyl-3-methylbutadiene, butyronitrile, etc.

[0031] As used herein, the term "carbocyclic ring" refers to a saturated, unsaturated, or aromatic ring, wherein each atom of the ring is carbon. Carbocyclic rings may include 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 6- to 12-membered bridged rings. Each ring of a bicyclic carbocyclic ring may be selected from saturated, unsaturated, and aromatic rings. In some embodiments, the carbocyclic ring is aryl. In some embodiments, the carbocyclic ring is cycloalkyl. In some embodiments, the carbocyclic ring is cycloalkenyl. In an exemplary embodiment, an aromatic ring such as a phenyl group may be fused to a saturated or unsaturated ring such as cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated, and aromatic bicyclic rings is included in the definition of a carbocyclic ring when valence permits. Exemplary carbocyclic rings include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. Bicyclic carbocyclic rings may be fused, bridged, or spirocyclic systems. The carbocyclic ring may optionally be substituted with one or more substituents such as those described herein. Specification 7 / 240 pages 53 CN 121568943 A

[0032] The term “unsaturated carbocyclic ring” refers to a carbocyclic ring having at least one degree of unsaturation and does not include aromatic carbocyclic rings. Examples of unsaturated carbocyclic rings include cyclohexadiene, cyclohexene, and cyclopentene.

[0033] The term “cycloalkyl” as used herein refers to a saturated carbocyclic ring. Exemplary cycloalkyl rings include cyclopropyl, cyclohexyl, and norbornene. The carbocyclic ring may optionally be substituted with one or more substituents such as those described herein.

[0034] The term “Cx-y carbocyclic ring” refers to a ring comprising groups containing x to y carbons. For example, “C3-6 carbon ring” refers to a saturated, unsaturated, or aromatic ring containing 3 to 6 carbon atoms. For example, a C3-6 carbon ring can be selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl, any of which may be optionally substituted.

[0035] As used herein, “aryl” refers to a group derived from an aromatic monocyclic or aromatic polycyclic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. An aromatic monocyclic or aromatic polycyclic hydrocarbon ring system contains only hydrogen and carbon and five to eighteen carbon atoms, wherein at least one ring in the ring system is an aromatic ring, i.e., it contains a cyclic, delocalized (4n+2) π electron system conforming to Hückel's theory. Ring systems from which aryl groups are derived include, but are not limited to, groups such as benzene, fluorene, indene, indene, tetrahydronaphthalene, and naphthalene.

[0036] As used herein, the term “heterocyclic” refers to a saturated, unsaturated, or aromatic ring containing one or more heteroatoms. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Where valence is permissibleHeterocycles can be attached to the rest of the molecule by any atom in the heterocycle, such as a carbon or nitrogen atom. Heterocycles include 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 6- to 12-membered bridged rings. Bicyclic heterocycles include any combination of saturated, unsaturated, and aromatic bicyclic rings, when valence permits. In one exemplary embodiment, an aromatic ring (e.g., a pyridyl group) may be fused with a saturated or unsaturated ring (e.g., cyclohexane, cyclopentane, morpholine, piperidine, or cyclohexene). Bicyclic heterocycles include combinations of ring sizes, such as 4-5 fused ring systems, 5-5 fused ring systems, 5-6 fused ring systems, 6-6 fused ring systems, 5-7 fused ring systems, 6-7 fused ring systems, 5-8 fused ring systems, and 6-8 fused ring systems. Bicyclic heterocycles can be fused, bridged, or spirocyclic systems. Spirocyclic systems may be referred to as "spiroheterocycles" or "spirocyclic heterocycles". In some cases, a spiroheterocyclic, spirocyclic, or spirocyclic ring has at least two molecular rings having only one common atom. A spirocyclic, spirocyclic, or spirocyclic ring contains one or more heteroatoms.

[0037] A “heteroaryl” or “aromatic heterocycle” refers to a group derived from a heteroaromatic ring group containing one to eleven carbon atoms and at least one heteroatom, wherein each heteroatom may be selected from N, O, and S. As used herein, a heteroaromatic ring may be selected from monocyclic or bicyclic rings and fused or bridged ring systems, wherein at least one ring in the ring system is aromatic, i.e., it contains a cyclic, delocalized (4n+2) electron system conforming to Hückel's theory. One or more heteroatoms in a heteroaryl group may optionally be oxidized. If one or more nitrogen atoms are present, they may optionally be quaternized. Where valence permits, a heteroaryl group may be attached to the remainder of the molecule by any atom of the heteroaryl group, such as a carbon or nitrogen atom of the heteroaryl group. Examples of heteroaryl groups include, but are not limited to, pyridine, pyrimidine, oxazole, furan, thiophene, benzothiazole, and imidazopyridine.

[0038] “X-membered heteroaryl” refers to the number of intracyclic atoms in the ring, i.e., X. For example, a 5-membered heteroaryl ring or a 5-membered aromatic heterocycle contains 5 intracyclic atoms, such as triazole, oxazole, thiophene, etc.

[0039] The term “unsaturated heterocycle” refers to a heterocycle having at least one degree of unsaturation and does not include aromatic heterocycles. Examples of unsaturated heterocycles include dihydropyrrole, dihydrofuran, oxazoline, pyrazoline, and dihydropyridine. The heterocycle may optionally be substituted by one or more substituents such as those described herein.

[0040] The term “substituted” refers to a substituent that partially has hydrogen on one or more carbons or substituted heteroatoms, such as NH or NH2, of the substituted compound. It should be understood that "substitution" or "being substituted" includes implicit conditions, namely that the substitution meets the permissible valence of the substituted atom and the substituent, and that the substitution produces a stable compound, i.e., a compound that does not spontaneously undergo transformations such as rearrangement, cyclization, or elimination. In some embodiments, being substituted refers to a substituent that partially replaces two hydrogen atoms on the same carbon atom.Such as replacing two hydrogen atoms on a single carbon atom with an oxo group, imino group, or thio group. As used herein, the term "substituted" is considered to include all permissible substituents of an organic compound. In a broad sense, permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of organic compounds. For a suitable organic compound, permissible substituents may be one or more, and may be the same or different.

[0041] In some embodiments, the substituents may include any substituents described herein, such as: halogen, hydroxyl, oxo (=O), thio (=S), cyano (-CN), nitro (-NO2), imino (=N-H), oxime (=N-OH), hydrazine (=N-NH2), -Rb-ORa, -Rb-OC(O)-Ra, -Rb-OC(O)-ORa, -Rb-OC(O)-N(Ra)2, -Rb-N(Ra)2, -Rb-C(O)Ra, -Rb-C(O)ORa, -Rb-C(O)N(Ra)2, -Rb-O-Rc-C(O)N(Ra)2, -Rb-N(Ra)C(O)ORa, -Rb-N(Ra)C(O)Ra, -Rb-N(Ra)S(O)tRa (where t is 1 or 2), -Rb-S(O)tRa (where t is 1 or 2), -Rb-S(O)tORa (where t is 1 or 2) and -Rb-S(O)tN(Ra)2 (where t is 1 or 2); and alkyl, alkenyl, alkynyl, aryl, aralkyl, aryl-alkenyl, arylynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl and heteroarylalkyl,Any of these may optionally be substituted by: alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thio (=S), cyano (-CN), nitro (-NO2), imino (=N-H), oxime (=N-OH), hydrazine (=N-NH2), -Rb-ORa, -Rb-OC(O)-Ra, -Rb-OC(O)-ORa, -Rb-OC(O)-N(Ra)2, -Rb-N(Ra)2, -Rb-C(O)Ra, -Rb-C(O)ORa, -Rb-C(O)N(Ra)2, -Rb-O-Rc-C(O)N(Ra)2, -Rb -N(Ra)C(O)ORa, -Rb-N(Ra)C(O)Ra, -Rb-N(Ra)S(O)tRa (where t is 1 or 2), -Rb-S(O)tRa (where t is 1 or 2), -Rb-S(O)tORa (where t is 1 or 2), and -Rb-S(O)tN(Ra)2 (where t is 1 or 2); wherein each Ra is independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl, wherein each Ra may optionally be substituted with the following, where the valence permits: alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thio (= S), cyano (-CN), nitro (-NO2), imino (=N-H), oxime (=N-OH), hydrazine (=N-NH2), -Rb-ORa, -Rb-OC(O)-Ra, -Rb-OC(O)-ORa, -Rb-OC(O)-N(Ra)2, -Rb-N(Ra)2, -Rb-C(O)Ra, -Rb-C(O)ORa, -Rb-C(O)N(Ra)2, -Rb-O-Rc-C(O)N(Ra)2, -Rb-N(Ra)C(O)ORa, -Rb-N(Ra)C(O)Ra, -Rb-N(Ra)S(O)tRa (where t is 1 or 2), -Rb-S(O)tRa (where t is 1 or 2), -Rb-S(O)tORa (where t is 1 or 2) and -Rb-S(O)tN(Ra)2 (where t is 1 or 2); and wherein each Rb is independently selected from a direct bond or a straight-chain or branched alkylene, alkenyl, or ynylene chain, and each Rc is a straight-chain or branched alkylene, alkenyl, or ynylene chain. Those skilled in the art will understand that the substituents themselves may be substituted if appropriate.

[0042] As used herein, the terms “optional” or “optionally” indicate that the events or circumstances described below may or may not occur.And the description includes both the occurrence and non-occurrence of the event or situation. For example, "optionally substituted aryl" means that the aryl group may or may not be substituted, and the description includes both substituted and unsubstituted aryl groups.

[0043] The phrases "parenteral administration" and "administered via a parenteral route" as used herein mean administration methods that are normally administered by injection other than enteral and topical administration, and include, but are not limited to, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, tracheal, subcutaneous, subepidermal, intra-articular, subcapsular, subarachnoid, intraspinal, and intrasternal injections and infusions.

[0044] The phrase "pharmaceutically acceptable" herein is used to mean those compounds, materials, compositions, and / or dosage forms that are suitable for contact with human and animal tissues without excessive toxicity, irritation, allergic reactions, or other problems or complications, to the extent of reasonable medical judgment, and in proportion to a reasonable benefit / risk ratio.

[0045] As used herein, the phrase “pharmaceuticalally acceptable excipient” or “pharmaceuticalally acceptable carrier” means a pharmaceutically acceptable material, composition, or medium, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material. Each carrier must be “acceptable” in the sense that it is compatible with other components of the formulation and is harmless to the patient. Some examples of materials that can serve as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose, and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose, etc. (3) cellulose acetate and cellulose acetate; (4) powdered tragacanth gum; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository wax; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerol, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffers, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotropic saline; (18) Ringer's solution; (19) ethanol; (20) phosphate buffer solution; and (21) other non-toxic and compatible substances used in pharmaceutical preparations.

[0046] The terms “object,” “individual,” and “patient” are used interchangeably and refer to humans as well as non-human mammals (e.g., non-human primates, canines, equines, felines, suidae, bovids, ungulates, rabbits, etc.). In various embodiments, the object may be a hospitalized patient under the care of a physician or other healthcare worker, or an outpatient.Or individuals in other clinical situations (e.g., adult men, adult women, adolescent men, adolescent women, male children, female children). In some embodiments, the subject may not be under the care or prescription of a physician or other healthcare worker.

[0047] As used herein, the phrase “subject in need” means a subject suffering from a lesion for which the compound or salt described herein is intended for prophylactic or therapeutic treatment, or at risk of such lesion as described below.

[0048] The term “administer (administered / administers / administering)” is defined as the administration of the composition to a subject by a route known in the art, including but not limited to intravenous, intra-arterial, oral, parenteral, buccal, transdermal, transrectal, intramuscular, subcutaneous, intraosseous, transmucosal, or intraperitoneal administration. In some embodiments, an oral route of administration of the composition may be used. The term “administer” of a compound should be understood to mean the provision of the compound of the invention or a prodrug of the compound of the invention to an individual in need.

[0049] The term “effective amount” or “therapeutic effective amount” means the amount of the compound or salt described herein sufficient to achieve a predetermined application, including but not limited to the treatment of a disease, as defined below. Therapeutic effective amounts may vary depending on the predetermined application (in vitro or in vivo); or the subject and disease condition being treated, such as the subject’s weight and age, the severity of the disease condition; the manner of administration, etc., which can be readily determined by those skilled in the art. The term may also be applied to doses that can induce a specific response in target cells, such as reduced proliferation or downregulation of the activity of a target protein. Specific doses may vary depending on the particular compound selected, the dosing regimen to be followed, whether it is administered in combination with other compounds, the timing of administration, the tissue to which it is administered, and the physical delivery system in which it is carried.

[0050] As used herein, “treatment / treating” means a method for obtaining a beneficial or desired outcome with respect to a disease, symptom, or medical condition, including but not limited to therapeutic benefits and / or preventive benefits. In some embodiments, treatment involves administering a compound or composition disclosed herein to a subject. Therapeutic benefits may include the eradication or improvement of the underlying symptom being treated. Furthermore, therapeutic benefits can be achieved by eradicating or improving one or more physiological symptoms associated with the underlying condition, such as by observing improvement in the subject, even if the subject may still suffer from the underlying condition. In some embodiments, for preventative benefits, the composition is applied to a subject at risk of exhibiting a specific disease, or a subject reporting one or more physiological symptoms of a disease, even if the disease may not yet have been diagnosed. Treatment may include, for example, reducing, delaying, or alleviating the severity of one or more symptoms of the disease or disorder.Or it may include reducing the frequency of symptoms experienced by a patient as a disease, defect, symptom, or adverse condition. Treatment may be used herein to refer to a method of treatment or improvement resulting in a certain level of disease or ailment, and may be considered as a range of results directed toward said target, including but not limited to complete prevention of the ailment.

[0051] In some embodiments, the term “prevent / preventing,” as used in relation to a disease or ailment, may refer to, in a statistical sample, a reduction in the occurrence of the ailment or ailment in a treated sample relative to an untreated control sample, or, relative to an untreated control sample, delaying the onset of one or more symptoms of the ailment or ailment or reducing the severity of said one or more symptoms.

[0052] “Therapeutic effect,” as used herein, encompasses the therapeutic benefits and / or preventive benefits described above. Preventive effects include delaying or eliminating the onset of a disease or ailment, delaying or eliminating the onset of symptoms of a disease or ailment, slowing, stopping, or reversing the progression of a disease or ailment, or any combination thereof.

[0053] The term “selective inhibition” as used with respect to a bioactive agent means that the agent preferentially reduces the target signaling activity by interacting directly or indirectly with the target, relative to off-target signaling activity.

[0054] Each maximum numerical limit given in this specification is intended to include each lower numerical limit as expressly stated herein. Each minimum numerical limit given in this specification will include each higher numerical limit as expressly stated herein. Each numerical range given in this specification will include each narrower numerical range falling within these wider numerical ranges as expressly stated herein.

[0055] Section headings used herein are for organizational purposes only and should not be construed as limiting the subject matter described.

[0056] Compounds In one aspect, this disclosure provides compounds represented by the structure of formula (I): , or a pharmaceutically acceptable salt or solvate thereof; wherein Z is selected from and .Where t represents the junction of Z with the imidazole ring; X is selected from O and S; Y is selected from -N(R10)2, -OR 10 and -SR10; A is selected from N and CR18; D is selected from N and CR19; R4 is selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C1-6 cyanoalkyl, C1-6 alkoxyalkyl, C1-6 alkyl-N(R20)2, C3-5 cycloalkyl and 3 to 6 membered heterocyclic rings; R5 is selected from hydrogen and C1-6 alkyl; R6 is selected from hydrogen, C1-6 alkyl, halogen, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C1-6 cyanoalkyl, C1-6 alkoxyalkyl, C1-6 alkyl-N(R20)2, C4-6 cycloalkyl and 3 to 6 membered heterocyclic alkyl. R7 is selected from C3-C12 carbon rings and 5 to 15-membered heterocycles, each optionally substituted by one or more R8s; each R8 is independently selected from halogens, -N(R20)2, -OR20, -SR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N (R20)2, -S(O)R20(=NR20), -NR20S(O)2R20, -C(O)N(R20)2, -C(=NR20)N(R20)2, -C(O)NR20OR20, -N (R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R 20) C(O)OR20, -C(O)R20, -C(O)OR20, -OC(O)R20, -OC(O)N(R20)2, -NO2, =O, =N(R20), =NO(R20), -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-C12 carbon ring and 5 to 12 membered heterocycles, wherein the C3-C12 carbon ring and the 5 to 12 membered heterocycles are each optionally selected from one or more of halogens, -OH, -CN, -NO2, -NH2, oxo groups, C1-10 Alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, and C1-C6 alkoxyalkyl substituents; R9 is selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R20)2, C3-6 carbon ring, and 4- to 6-membered heterocycles.The C3-6 carbon ring and the 4- to 6-membered heterocycles are each optionally substituted by one or more substituents independently selected from halogens, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R20)2, C2-10 alkenyl, and C2-10 alkynyl; each R10 is independently selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, and C1-C6 alkyl-N(R20)2; R17 is selected from hydrogen, halogens, -N(R20)2, and -OR. 20. ‑SR20, ‑S(O) 2(R 20), ‑S(O) 2N(R 20) 2, ‑S(O)N (R20)2, ‑S(O)R 20(=NR20), ‑NR20S(O)2R 20, ‑C(O)N(R20)2, ‑C(=NR 20)N(R20)2, ‑C(O)NR 20OR20, ‑N (R20)C(O)R20, ‑N(R20)C(O)N(R20)2, ‑N(R 20)C(O)OR20, ‑C(O)R20, ‑C(O)OR20, ‑OC(O)R20, ‑OC(O) N(R20)2, -NO2, -CN, C1-6 alkyl, -N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-12 carbon ring and 5 to 12-membered heterocycles; R18 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, -O-C1-10 alkyl, C1-C6 alkyl and C1-C6 haloalkyl; R19 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, -O-C1-10 alkyl, C1-C6 alkyl and C1-C6 haloalkyl; and R20 is independently selected from hydrogen each time it appears; C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-12 carbon ring and 3 to 12-membered heterocycles, each optionally substituted by one or more substituents independently selected from: halogen, -OH, -CN, -NO2, -NH2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 ynyl, C3-12 carbon ring and 3 to 12-membered heterocycles.

[0057] In some embodiments, for compounds or salts of formula (I), formula (II), formula (IIA), formula (IIB) or formula (IIC),A is N. In some cases, A is CR18. In some cases, R18 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NH2, -NH1-10 alkyl, -N(C1-10 alkyl)2, -O-C1-10 alkyl, C1-C6 alkyl, and C1-C6 haloalkyl. In some cases, R18 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NH2, -O-C1-10 alkyl, C1-C6 alkyl, and C1-C6 haloalkyl. In some cases, R18 is selected from hydrogen, halogen, -OH, -CN, -O-C1-10 alkyl, C1-C6 alkyl, and C1-C6 haloalkyl. In some cases, R18 is selected from hydrogen, halogen, -OH, -CN, C1-C6 alkyl, and C1-C6 haloalkyl. In some cases, R18 is selected from hydrogen, halogen, -OH, -CN, C1-C4 alkyl, and C1-C4 haloalkyl. In some cases, R18 is selected from hydrogen, halogen, -OH, -CN, methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, and trifluoroethyl. In some cases, R18 is selected from hydrogen, halogen, -OH, -CN, methyl, and trifluoromethyl. In some cases, R18 is selected from hydrogen, fluorine, -OH, -CN, methyl, and trifluoromethyl. In some cases, R18 is selected from hydrogen, fluorine, -OH, and methyl. In some cases, R18 is selected from hydrogen, fluorine, and methyl. In some cases, R18 is methyl. In some cases, R18 is fluorine.

[0058] In some embodiments, for compounds or salts of formula (I), formula (II), formula (IIA), formula (IIB), or formula (IIC), D is N. In some cases, D is CR19. In some cases, R19 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NH2, -C1-10 alkyl, -N(C1-10 alkyl)2, -O-C1-10 alkyl, C1-C6 alkyl, and C1-C6 haloalkyl. In some cases, R19 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NH2, -O-C1-10 alkyl, C1-C6 alkyl, and C1-C6 haloalkyl. In some cases, R19 is selected from hydrogen, halogen, -OH, -CN, -O-C1-10 alkyl, C1-C6 alkyl, and C1-C6 haloalkyl. In some cases, R19 is selected from hydrogen, halogen, -OH, -CN, C1-C6 alkyl, and C1-C6 haloalkyl. In some cases, R19 is selected from hydrogen, halogen, -OH, -CN, C1-C4 alkyl, and C1-C4 haloalkyl. In some cases, R19 is selected from hydrogen, halogen, -OH, -CN, methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, and trifluoroethyl. In some cases,R19 is selected from hydrogen, halogen, -OH, -CN, methyl, and trifluoromethyl. In some cases, R19 is selected from hydrogen, fluorine, -OH, -CN, methyl, and trifluoromethyl. In some cases, R19 is selected from hydrogen, fluorine, -OH, and methyl. In some cases, R19 is selected from hydrogen, fluorine, and methyl. In some cases, R19 is methyl. In some cases, R19 is fluorine.

[0059] In some embodiments, formula (I) is represented by formula (IA): , or a pharmaceutically acceptable salt or solvation thereof.

[0060] In some embodiments, formula (I) is represented by formula (IB): , or a pharmaceutically acceptable salt or solvation thereof.

[0061] In some embodiments, for compounds or salts of formula (I), formula (IA), or formula (IB), R4 is selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C1-6 cyanoalkyl, C1-6 alkoxyalkyl, and C1-6 alkyl-N(R20)2. In some cases, R4 is selected from hydrogen, C1-6 alkyl, and C1-6 haloalkyl. In some cases, R4 is hydrogen.

[0062] In some embodiments, for compounds or salts of formula (I), formula (IA), or formula (IB), R6 is selected from hydrogen, C1-6 alkyl, halogen, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C1-6 cyanoalkyl, C1-6 alkoxyalkyl, and C1-6 alkyl-N(R20)2. In some cases, R6 is hydrogen.

[0063] In some embodiments, for compounds or salts of formula (I), formula (IA), or formula (IB), R5 is selected from hydrogen and methyl. In some cases, R5 is hydrogen.

[0064] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IC), or formula (II), R9 is selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R2O)2, C3-6 carbon rings, and 4- to 6-membered heterocycles. In some cases, R9 is selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, and C1-C6 alkyl-N (R20)2. In some cases, R9 is selected from hydrogen and C1-6 alkyl. In some cases, R9 is selected from hydrogen and methyl. In some cases, R9 is hydrogen. In some cases, R9 is selected from C3-6 carbon rings and 4- to 6-membered heterocycles.The C3-6 carbon ring and the 4- to 6-membered heterocycle are each optionally substituted by one or more substituents independently selected from: halogen, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R20)2, C2-10 alkenyl, and C2-10 alkynyl. In some cases, R9 is hydrogen. In some cases, R9 is selected from the C3-6 carbon ring and the 4- to 6-membered heterocycle, wherein the C3-6 carbon ring and the 4- to 6-membered heterocycle are each optionally substituted by one or more substituents independently selected from halogen, -OH, C1-10 alkyl, -C1-10 haloalkyl, and -O-C1-10 alkyl.

[0065] In some embodiments, for compounds or salts of formula (I), formula (IB), or formula (ID), each R10 is selected from hydrogen, C1-C6 alkyl, and C1-C6 haloalkyl. In some cases, each R10 is selected from hydrogen and C1-6 alkyl. In some cases, R10 appears at least once as hydrogen. In some cases, each R10 is independently selected from hydrogen, C1-6 alkyl, and C1-C6 alkoxyalkyl. In some cases, each R10 is independently selected from C1-C6 alkoxyalkyl. In some cases, each R10 is independently selected from C1-C2 alkoxyalkyl. In some cases, each R10 is independently selected from

[0066] In some embodiments, formula (I) is represented by formula (IC): Formula (IC), or a pharmaceutically acceptable salt or solvation thereof.

[0067] In some embodiments, formula (I) is represented by formula (ID): Formula (ID), or a pharmaceutically acceptable salt or solvation thereof.

[0068] In some embodiments, for compounds or salts of formula (I), (IA), or (IC), R9 is selected from hydrogen and methyl.

[0069] In some embodiments, for compounds or salts of formula (I), (IB), or (ID), R10 is selected from hydrogen and methyl. In some cases, R10 is hydrogen. In some cases, R10 is methyl.

[0070] In one aspect, this disclosure provides compounds represented by the structure of formula (II): , or a pharmaceutically acceptable salt or solvate thereof; wherein AZ is selected from, where t represents the junction of Z and ; Y is selected from -O-, -NR9-, -S- and -SO2-; each R50 is independently selected from hydrogen, halogen, C1-C6 alkyl; or combined to form; each R51 is independently selected from hydrogen, halogen and C1-C6 alkyl; k is selected from 1 and 2; A is selected from N and CR18; is selected from optionally substituted imidazoles,The imidazole is optionally substituted with one or more R14s; D is selected from N and CR19; R5 is selected from hydrogen and C1-6 alkyl; R7 is selected from hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-C14 carbocyclic rings and 5 to 15-membered heterocycles, each optionally substituted with one or more R8s; each R8 is independently selected from halogens, -N(R20)2, -OR20, -SR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), -NR20S(O)2R20, -C(O)N(R20)2, -C(=NR20)N(R20)2, -C(O)NR20OR20, -N (R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R20)C(O)OR20, -C(O)R20, -C(O)OR20, -OC(O)R20, -OC(O)N(R20)2, -NO2, =O, =N(R20), =NO(R20), -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 Cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-C12 carbon ring and 4 to 12-membered heterocycle, wherein the C1-6 alkyl is optionally substituted with one or more R8*, and wherein the C3-C12 carbon ring and the 4 to 12-membered heterocycle are each optionally substituted with one or more substituents selected from halogen, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl and C1-C6 alkoxyalkyl; Each R8* is independently selected from 4- to 12-membered heterocycles, wherein the 4- to 12-membered heterocycles are optionally substituted by one or more substituents selected from halogens, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, and C1-C6 alkoxyalkyl; R9 is selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R20)2, C3-6 carbon rings, and 4- to 6-membered heterocycles.The C3-6 carbon ring and the 4- to 6-membered heterocycle are each optionally substituted by one or more substituents independently selected from halogens, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R20)2, C2-10 alkenyl, and C2-10 alkynyl; R14 is selected from halogens, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbon rings, and 3- to 12-membered heterocycles; R17 Selected from hydrogen, halogens, -N(R20)2, -OR20, -SR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), -NR20S(O)2R20, -C(O)N(R20)2, -C(=NR20)N(R20)2, -C(O)NR20OR20, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R20)C(O)OR20, -C(O)R20, -C(O)OR20, -OC(O)R20, -OC(O) N(R20)2, -NO2, -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl (see specification 15 / 240 pages, 61 CN 121568943 A), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbon ring and 5 to 12 membered heterocycles; R18 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, -O-C1-10 alkyl, C1-C6 alkyl and C1-C6 haloalkyl; R19 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, -O-C1-10 alkyl, C1-C6 alkyl and C1-C6 haloalkyl; and R20 is independently selected from hydrogen each time it appears; C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-12 carbon ring and 3 to 12 membered heterocycles,Each of them is optionally substituted by one or more substituents independently selected from the following: halogen, -OH, -CN, -NO2, -NH2, -S(O)2 (C1-6 alkyl), C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbocyclic, and 3 to 12-membered heterocycles.

[0071] In some embodiments, for compounds or salts of formula (II), Z is. In some cases, K is 1. In some cases, K is 2. In some cases, Z is.

[0072] In some embodiments, for compounds or salts of formula (II), each R51 is independently selected from hydrogen, halogen, and C1-C6 alkyl. In some cases, each R51 is independently selected from hydrogen, halogen, methyl, ethyl, and isopropyl. In some cases, each R51 is independently selected from hydrogen, F, C1, methyl, ethyl, and isopropyl. In some cases, each R51 is independently selected from hydrogen, F, and methyl. In some cases, each R51 is independently selected from hydrogen and methyl. In some cases, each R51 is independently selected from hydrogen and F. In some cases, each R51 is hydrogen.

[0073] In some embodiments, for compounds or salts of formula (II): Z is selected from, where t represents the junction of Z and; Y is selected from -O-, -NR9-, -S-, and -SO2-; each R50 is independently selected from hydrogen, halogen, C1-C6 alkyl; or combined to form; A is selected from N and CR18; is selected from optionally substituted imidazoles, wherein the imidazole is optionally substituted by one or more R14s; D is selected from N and CR19; R5 is selected from hydrogen and C1-6 alkyl; R7 is selected from hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-C14 carbide rings, and 5 to 15-membered heterocycles.Each of these can be optionally replaced by one or more R8s; each R8 is independently selected from halogens, -N(R20)2, -OR20, -SR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), -NR20S(O)2R20, -C(O)N(R20)2, -C(=NR20)N(R20)2, -C(O)NR20OR20, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R20)C(O)OR20, -C(O)R20, -C(O)OR20, -OC(O)R20, -OC(O)R20, -OC(O) (Instruction manual 16 / 240 pages 62 CN) 121568943 AN(R20)2, -NO2, =O, =N(R20), =NO(R20), -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-C12 carbon ring and 5 to 12 membered heterocycles, wherein the C3-C12 carbon ring and the 5 to 12 membered heterocycles are each optionally substituted by one or more substituents selected from halogen, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl and C1-C6 alkoxyalkyl; R9 is selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R20)2, C3-6 carbon ring, and 4- to 6-membered heterocycles.The C3-6 carbon ring and the 4- to 6-membered heterocycle are each optionally substituted by one or more substituents independently selected from halogens, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R20)2, C2-10 alkenyl, and C2-10 alkynyl; R14 is selected from halogens, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbon rings, and 3- to 12-membered heterocycles; R17 Selected from hydrogen, halogens, -N(R20)2, -OR20, -SR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), -NR20S(O)2R20, -C(O)N(R20)2, -C(=NR20)N(R20)2, -C(O)NR20OR20, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R20)C(O)OR20, -C(O)R20, -C(O)OR20, -OC(O)R20, -OC(O) N(R20)2, -NO2, -CN, C1-6 alkyl, -N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-12 carbon ring and 5 to 12 membered heterocycles; R18 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, -O-C1-10 alkyl, C1-C6 alkyl and C1-C6 haloalkyl; R19 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, -O-C1-10 alkyl, C1-C6 alkyl and C1-C6 haloalkyl; and R20 is independently selected from hydrogen each time it appears; C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-12 carbon ring and 3 to 12-membered heterocycles, each optionally substituted by one or more substituents independently selected from: halogen, -OH, -CN, -NO2, -NH2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 ynyl, C3-12 carbon ring and 3 to 12-membered heterocycles.

[0074] In some embodiments,For compounds or salts of formula (I), (IA), (IB), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG), R5 is selected from hydrogen and C1-C6 alkyl groups. In some cases, R5 is selected from hydrogen and C1-C4 alkyl groups. In some cases, R5 is selected from hydrogen, methyl, ethyl, propyl, and isopropyl. In some cases, R5 is selected from hydrogen, methyl, and ethyl. In some cases, R5 is selected from hydrogen and methyl. In some cases, R5 is hydrogen. In some cases, R5 is methyl.

[0075] In some embodiments, for compounds or salts of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG), R7 is selected from C6-C8 carbon rings and 5- to 6-membered heterocycles, each optionally substituted with one or more R8s. In some cases, R7 is selected from C6-C8 carbon rings, optionally substituted with one or more R8s. In some cases, R7 is selected from C6 carbon rings, optionally substituted with one or more R8s. In some cases, R7 is selected from C6 cycloalkyl groups, optionally substituted with one or more R8s. In some cases, R7 is selected from C7 carbon rings, optionally substituted with one or more R8s. In some cases, R7 is selected from C8 carbon rings, optionally substituted with one or more R8s. In some cases, R7 is, optionally substituted with one or more R8s. In some cases, the C6 carbon ring is substituted at the para position. In some cases, each R8 is independently selected from halogens, -OR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), -NR20S(O)2R20, -C(O)N(R20)2, -C(=NR20)N(R20)2, -C(O)NR20OR20, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R20)C(O)OR20, -C(O)R20, -C(O)OR20, -OC(O) R20, -OC(O)N(R20)2, -NO2, =O, =N(R20), =NO(R20), -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-C12 carbon rings and 5- to 12-membered heterocycles. In some cases,Each R8 is independently selected from halogens, -OR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), -NR20S(O)2R20, -C(O)N(R20)2, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R20)C(O)OR20, -C(O)OR20, -OC(O)R20, -OC(O)N(R20)2, =O, -CN, C1-6 alkyl-N(R20). In some cases, each R8 is independently selected from fluorine, chlorine, -OR20, -S(O)2(R20), -S(O)2N(R20)2, -NR20S(O)2R20, -C(O)N(R20)2, -N(R20)C(O)R20, -C(O)OR20, -OC(O)R20, -OC(O)N(R20)2, =O, -CN, C1-6 alkyl, C3-C12 carbon rings, and 5- to 12-membered heterocycles. In some cases, each R8 is independently selected from fluorine, -OR20, -S(O)2(R20), -S(O)2N(R20)2, =O, and C1-6 alkyl. In some cases, each R8 is independently selected from fluorine, -OR20, -S(O)2(R20), -S(O)2N(R20)2, =O, and C1-4 alkyl. In some cases, each R8 is independently selected from fluorine, -OR20, -S(O)2(R20), -S(O)2N(R20)2, methyl, ethyl, propyl, and isopropyl. In some cases, each R8 is independently selected from fluorine, -OR20, -S(O)2(R20), methyl, and ethyl. In some cases, R8 is -S(O)2(R20). In some cases, each R8 is -OR20. In some cases, each R8 is fluorine. In some cases, each R8 is methyl. In some cases, each R8 is -S(O)2(R20). In some cases, R7 is...

[0076] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG),R8 is independently selected from halogens, -N(R20)2, -OR20, -SR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), -NR20S(O)2R20, -C(O)N(R20)2, -C(=NR20)N(R20)2, -C(O)NR20OR20, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R20)C(O)OR20, -C(O)R20, -C(O)OR20, -OC(O)R20, -OC(O)N(R20)2, -NO2, =O, =N(R 20), = NO(R20), -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-C12 carbon ring and 4 to 12 membered heterocycles, wherein the C1-6 alkyl is optionally substituted by one or more R8*, and wherein the C3-C12 carbon ring and the 4 to 12 membered heterocycles are each optionally substituted by one or more substituents selected from halogen, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl and C1-C6 alkoxyalkyl. In some cases, R8 is independently selected from halogens, -N(R20)2, -OR20, -NR20S(O)2R20, -C(O)N(R20)2, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R20)C(O)OR20, -C(O)R20, -C(O)OR20, -OC(O)R20, -OC(O)N(R20)2, -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C3-C12 carbon ring and 4- to 12-membered heterocycles, wherein the C1-6 alkyl is optionally substituted with one or more R8*, and wherein the C3-C12 carbon ring and the 4- to 12-membered heterocycles are each optionally substituted with one or more substituents selected from halogens, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl and C1-C6 alkoxyalkyl. In some cases,R8 is independently selected from halogens, -N(R20)2, -OR20, -NR20S(O)2R20, -C(O)N(R20)2, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R20)C(O)OR20, -C(O)OR20, -OC(O)N(R20)2, -CN, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkyl, C3-C12 carbon rings and 4- to 12-membered heterocycles, wherein the C1-6 alkyl is optionally substituted by one or more R8*, and wherein the C3-C12 carbon rings and 4- to 12-membered heterocycles are each optionally substituted by one or more of halogens, -OH, -CN, -NO2, -NH2, oxo groups, Substituents of C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl and C1-C6 alkoxyalkyl as specified on page 64 of the specification (18 / 240 pages) CN 121568943 A. In some cases, R8 is independently selected from halogens, -N(R20)2, -OR20, -NR20S(O)2R20, -C(O)N(R20)2, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkyl, C3-C12 carbon rings and 4 to 12-membered heterocycles, wherein the C1-6 alkyl is optionally substituted by one or more R8*, and wherein the C3-C12 carbon rings and 4 to 12-membered heterocycles are each optionally substituted by one or more of halogens, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl and C1-C6 alkoxyalkyl. In some cases, R8 is independently selected from halogens, -N(R20)2, -OR20, -NR20S(O)2R20, -C(O)N(R20)2, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkyl, C3-C8 carbon rings and 4- to 8-membered heterocycles, wherein the C1-6 alkyl is optionally substituted by one or more R8*, and wherein the C3-C8 carbon rings and 4- to 8-membered heterocycles are each optionally substituted by one or more substituents selected from: halogens, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl and C1-C6 alkoxyalkyl. In some cases, R8 is independently selected from halogens, -N(R20)2, -OR20, -NR20S(O)2R20, -C(O)N(R20)2, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkyl, C3-C8 cycloalkyl, and 4- to 8-membered heterocycles.The C1-6 alkyl group is optionally substituted with one or more R8* groups, and the C3-C8 cycloalkyl group and the 4- to 8-membered heterocycle are each optionally substituted with one or more substituents selected from: halogen, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C. In some cases, R8 is independently selected from halogen, -N(R20)2, -OR20, -NR20S(O)2R. 20, -C(O)N(R20)2, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkyl, C3-C8 cycloalkyl and 4 to 8 heteroaryl, wherein the C1-6 alkyl is optionally substituted with one or more R8*, and wherein the C3-C8 cycloalkyl and the 4 to 8 heteroaryl are each optionally substituted with one or more substituents selected from halogen, -OH, -CN, -NO2, -NH2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl and C1-C6 alkoxyalkyl.

[0077] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG), each R8* is independently selected from 4 to 12-membered heterocycles, wherein the 4 to 12-membered heterocycles are optionally substituted by one or more substituents selected from halogens, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, and C1-C6 alkoxyalkyl. In some cases, each R8* is independently selected from 4- to 10-membered heterocycles, wherein the 4- to 10-membered heterocycles are optionally substituted by one or more substituents selected from halogens, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, and C1-C6 alkoxyalkyl. In some cases, each R8* is independently selected from 4- to 10-membered heterocycles, wherein the 4- to 10-membered heterocycles are optionally substituted by one or more substituents selected from F, Cl, -OH, -CN, -NH2, C1-6 alkyl, -C1-6 haloalkyl, -O-C1-6 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, and C1-C6 alkoxyalkyl. In some cases, each R8* is independently selected from 4- to 10-membered heterocycles.The 4- to 10-membered heterocycles are optionally substituted with one or more substituents selected from the following: F, Cl, -OH, -CN, methyl, ethyl, isopropyl, -CH2F, -CHF2, -CHF3, -CH2CF3, -CF2CF3, -OCH3, -OCH2CH3, and -OCH(CH3)2. In some cases, each R8* is independently selected from 4- to 8-membered heterocycles, wherein the 4- to 8-membered heterocycles are optionally substituted with one or more substituents selected from the following: F, Cl, -OH, -CN, -NH2, C1-6 alkyl, -C1-6 haloalkyl, -O-C1-6 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, and C1-C6 alkoxyalkyl. In some cases, each R8* is independently selected from 4- to 8-membered heterocycles, wherein the 4- to 8-membered heterocycles are optionally substituted by one or more substituents selected from: F, Cl, -OH, -CN, methyl, ethyl, isopropyl, -CH2F, -CHF2, -CHF3, -CH2CF3, -CF2CF3, -OCH3, -OCH2CH3, and -OCH(CH3)2.

[0078] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG), R7 is selected from C6-C8 carbon rings and 5- to 6-membered heterocycles, each optionally substituted by one or more R8s. In some cases, R7 is selected from C6-C8 carbon rings, optionally substituted with one or more R8s. In some cases, R7 is selected from C6 carbon rings, optionally substituted with one or more R8s. In some cases, R7 is selected from C6 cycloalkyl groups, optionally substituted with one or more R8s. In some cases, R7 is selected from C7 carbon rings, optionally substituted with one or more R8s. In some cases, R7 is selected from C8 carbon rings, optionally substituted with one or more R8s. In some cases, R7 is selected from C4-C6 carbon rings, optionally substituted with one or more R8s. In some cases, R7 is selected from C5 carbon rings, optionally substituted with one or more R8s. In some cases, R7 is selected from C5 cycloalkyl groups, optionally substituted with one or more R8s. In some cases, R7 is selected from C4 carbon rings, optionally substituted with one or more R8s. In some cases, R7 is selected from C4 cycloalkyl groups, optionally substituted with one or more R8s. In some cases, R7 is selected from , , and , and optionally replaced by one or more R8s. In some cases, R7 is selected from and , and optionally replaced by one or more R8s. In some cases, R7 is selected from and , andIt is optionally substituted by one or more R8s. In some cases, R7 is selected from [selection 1] and [selection 2], and is optionally substituted by one or more R8s. In some cases, R7 is selected from [selection 3], and is optionally substituted by one or more R8s. In some cases, R7 is selected from [selection 4], and is optionally substituted by one or more R8s. In some cases, R7 is selected from [selection 5], and is optionally substituted by one or more R8s. In some cases, the C4 carbon ring is substituted at the para position. In some cases, the C5 carbon ring is substituted at the 3 position. In some cases, the C5 carbon ring is substituted at the 2 position. In some cases, the C6 carbon ring is substituted at the para position.

[0079] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG), each R8 is independently selected from halogens, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, -OR20, -N(R20)2, -NR20S(O)2R20, -N(R20)C(O)R20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), -C(O)N(R20)2, -C(=NR20)N(R20)2, -C(O)NR 20OR20, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R20)C(O)OR20, -C(O)R20, -C(O)OR20, -OC(O)R20, -OC(O)N(R20)2, -NO2, =O, =N(R20), =NO(R20), -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-C12 carbon ring and 4- to 6-membered heterocycles, wherein the 4- to 6-membered heterocycles are optionally selected from one or more halogens, -OH, -CN, -NH2, oxo groups, C1-10 Substituents of alkyl, -C1-10 haloalkyl, and -O-C1-10 alkyl groups; and wherein the C1-6 alkyl group of R8 is optionally substituted with a 4- to 6-membered heterocycle, wherein the 4- to 6-membered heterocycle is optionally substituted with one or more substituents selected from halogens. In some cases,Each R8 is independently selected from halogens, C1-6 alkyl groups, C1-6 haloalkyl groups, C1-6 hydroxyalkyl groups, -OR20, -N(R20)2, -NR20S(O)2R20, -N(R20)C(O)R20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)R20(=NR20), -C(O)N(R20)2, -N(R20) AC(O)R20, -N(R20)C(O)N(R20)2, -N(R20)C(O)OR20, -C(O)OR20, -OC(O)R20, -OC(O)N(R20)2, C3-C12 The carbon ring and a 4- to 6-membered heterocycle, wherein the 4- to 6-membered heterocycle is optionally substituted by one or more substituents selected from halogens, -OH, -CN, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl and -O-C1-10 alkyl; and wherein the C1-6 alkyl of R8 is optionally substituted by a 4- to 6-membered heterocycle, wherein the 4- to 6-membered heterocycle is optionally substituted by one or more substituents selected from halogens. In some cases, each R8 is independently selected from halogens, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, -OR20, -N(R20)2, -NR20S(O)2R20, -NR20S(O)2R20, -N(R20)C(O)R20, -C(O)N(R20)2, and 4- to 6-membered heterocycles, wherein the 4- to 6-membered heterocycles are optionally substituted by one or more substituents selected from halogens, -OH, -CN, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, and -O-C1-10 alkyl; and wherein the C1-6 alkyl of R8 is optionally substituted by a 4- to 6-membered heterocycle, wherein the 4- to 6-membered heterocycle is optionally substituted by one or more substituents selected from halogens. In some cases, each R8 is independently selected from halogens, C1-6 alkyl groups, C1-6 haloalkyl groups, C1-6 hydroxyalkyl groups, -OR20, -N(R20)2, -NR20S(O)2R20, -NR20S(O)2R20, -N(R20)C(O)R20, -C(O)N(R20)2, and 4- to 6-membered heterocycles, wherein the 4- to 6-membered heterocycles are optionally substituted by one or more substituents selected from halogens, -OH, -CN, -NH2, oxo groups, C1-6 alkyl groups, -C1-6 haloalkyl groups, and -O-C1-6 alkyl groups; and wherein the C1-6 alkyl group of R8 is optionally substituted by a 4- to 6-membered heterocycle, wherein the 4- to 6-membered heterocycle is optionally substituted by one or more substituents selected from F and Cl. In some cases,Each R8 is independently selected from halogens, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, -OR20, -C(O)N(R20)2 and 4- to 6-membered heterocycles, wherein the 4- to 6-membered heterocycles are optionally substituted by one or more substituents selected from halogens, -OH, -CN, -NH2, oxo, C1-6 alkyl, -C1-6 haloalkyl and -O-C1-6 alkyl; and wherein the C1-6 alkyl of R8 is optionally substituted by a 4- to 6-membered heterocycle, wherein the 4- to 6-membered heterocycle is optionally substituted by one or more substituents selected from F and Cl. In some cases, each R8 is independently selected from halogens, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, -OR20, -C(O)N(R20)2, and 4- to 6-membered heterocycles, wherein the 4- to 6-membered heterocycles are optionally substituted by one or more substituents selected from F, Cl, -OH, C1-6 alkyl, -C1-6 haloalkyl, and -O-C1-6 alkyl; and wherein the C1-6 alkyl of R8 is optionally substituted by a 4- to 6-membered heterocycle, wherein the 4- to 6-membered heterocycle is optionally substituted by one or more substituents selected from F and Cl. In some cases, each R8 is independently selected from F, ... (See specification 21 / 240, page 67, CN 121568943 A). In some cases, R7 is...

[0080] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG), R7 is as specified in CN 121568943 A, page 22 / 240 of the specification, which is optionally substituted with one or more R8s. In some cases, R7 is, which is optionally substituted with one or two R8s. In some cases, each R8 is independently selected from halogens, C1-6 haloalkyl groups, -OR20, -N(R20)2, -NR20S(O)2R20, C1-6 alkyl-N(R20)2, -C(O)N(R20)2, and 5- to 6-membered heterocycles, wherein the 5- to 6-membered heterocycles are optionally substituted by one or more substituents selected from halogens, -OH, -CN, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, and -O-C1-10 alkyl. In some cases, each R8 is independently selected from -N(R20)2 and C1-6 alkyl-N(R20)2. In some cases, each R8 is independently selected from -N(R20)2. In some cases, each R8 is independently selected from fluorine, -CH3, -CF3, -OH, -OCH3, etc. In some cases, R7 is selected from... In some cases, each R8 is independently selected from halogens and C1-6 haloalkyl groups. In some cases,Each R8 is independently selected from fluorine and -CF3. In some cases, R7 is selected from and (see specification 23 / 240, page 69, CN 121568943 A). In some cases, each R8 is independently selected from -OR20. In some cases, R20 is independently selected from C1-6 alkyl each time it appears, wherein the C1-6 alkyl is optionally substituted by one or more substituents independently selected from halogens and -O-C1-10 alkyl. In some cases, each R8 is independently selected from -OCH3, , . In some cases, R7 is selected from, and . In some cases, each R8 is independently selected from -N(R20)2. In some cases, R20 is independently selected from hydrogen and C1-6 alkyl each time it appears, wherein the C1-6 alkyl is optionally substituted by one or more substituents independently selected from halogens. In some cases, each R20 is different. In some cases, each R8 is independently selected from and . In some cases, R7 is selected from and . In some cases, each R8 is independently selected from -NR20S(O)2R20. In some cases, each R8 is independently selected from -NHS(O)2R20. In some cases, R20 is independently selected from C1-6 alkyl each time it appears, wherein the C1-6 alkyl is optionally substituted by one or more substituents independently selected from -O-C1-10 alkyl. In some cases, each R8 is independently selected from and. In some cases, R7 is selected from and. In some cases, each R8 is independently selected from -C(O)N(R20)2. In some cases, R20 is independently selected from hydrogen and C1-6 alkyl each time it appears. In some cases, each R8 is independently selected from. In some cases, R7 is. In some cases, each R8 is independently selected from 5- to 6-membered heterocycles, wherein the 5- to 6-membered heterocycles are optionally substituted by one or more substituents selected from halogens, C1-10 alkyl, -C1-10 haloalkyl, and -O-C1-10 alkyl. In some cases, each R8 is independently selected from 5- to 6-membered heterocycles, wherein the 5- to 6-membered heterocycle is optionally substituted with one or more substituents selected from halogens. In some cases, each R8 is independently selected from. In some cases, R7 is.

[0081] In some embodiments, for compounds or salts of formulas (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG), R7 is selected from the specification, pages 24 / 240, 70 CN 121568943 A, and, which is optionally substituted with one or more R8s. In some cases, R7 is selected from and and, which is optionally substituted with one or more R8s. In some cases,R7 is selected from and , and is optionally replaced by one or more R8s. In some cases, R7 is selected from and , and is optionally replaced by one or more R8s. In some cases, R7 is selected from and is optionally replaced by one or more R8s. In some cases, R7 is selected from and is optionally replaced by one or more R8s. In some cases, R7 is , and is optionally replaced by one or two R8s. In some cases, each R8 is independently selected from halogens, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, -OR20, -N(R20)2, -NR 20S(O)2R 20, -NR20S(O)2R 20, -N(R20)C(O) R20, -C(O)N(R20)2, and 4- to 6-membered heterocycles, wherein the 4- to 6-membered heterocycles are optionally substituted by one or more substituents selected from halogens, -OH, -CN, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, and -O-C1-10 alkyl; and wherein the C1-6 alkyl of R8 is optionally substituted by a 4- to 6-membered heterocycle, wherein the 4- to 6-membered heterocycle is optionally substituted by one or more substituents selected from halogens. In some cases, each R8 is independently selected from halogens, C1-6 alkyl groups, C1-6 haloalkyl groups, C1-6 hydroxyalkyl groups, -OR20, -N(R20)2, -NR20S(O)2R20, -NR20S(O)2R20, -N(R20)C(O)R20, -C(O)N(R20)2, and 4- to 6-membered heterocycles, wherein the 4- to 6-membered heterocycles are optionally substituted by one or more substituents selected from halogens, -OH, -CN, -NH2, oxo groups, C1-6 alkyl groups, -C1-6 haloalkyl groups, and -O-C1-6 alkyl groups; and wherein the C1-6 alkyl group of R8 is optionally substituted by a 4- to 6-membered heterocycle, wherein the 4- to 6-membered heterocycle is optionally substituted by one or more substituents selected from F and Cl. In some cases, each R8 is independently selected from halogens, C1-6 alkyl groups, C1-6 haloalkyl groups, C1-6 hydroxyalkyl groups, -OR20, -C(O)N(R20)2, and 4- to 6-membered heterocycles, wherein the 4- to 6-membered heterocycles are optionally substituted by one or more substituents selected from halogens, -OH, -CN, -NH2, oxo, C1-6 alkyl, -C1-6 haloalkyl, and -O-C1-6 alkyl; and wherein the C1-6 alkyl group of R8 is optionally substituted by a 4- to 6-membered heterocycle, wherein the 4- to 6-membered heterocycle is optionally substituted by one or more substituents selected from F and Cl. In some cases, each R8 is independently selected from halogens, C1-6 alkyl groups, C1-6 haloalkyl groups, C1-6 hydroxyalkyl groups, -OR20, -C(O)N(R20)2, and 4- to 6-membered heterocycles.The 4- to 6-membered heterocycle is optionally substituted with one or more substituents selected from F, Cl, -OH, C1-6 alkyl, -C1-6 haloalkyl, and -O-C1-6 alkyl; and the C1-6 alkyl of R8 is optionally substituted with a 4- to 6-membered heterocycle, wherein the 4- to 6-membered heterocycle is optionally substituted with one or more substituents selected from F and Cl. In some cases, each R8 is independently selected from F, (see specification 25 / 240, page 71, CN 121568943 A). In some cases, R7 is (see specification 26 / 240, page 72, CN 121568943 A). In some cases, each R8 is independently selected from halogens and C1-6 haloalkyls. In some cases, each R8 is independently selected from fluorine and -CF3. In some cases, R7 is selected from [missing information]. In some cases, each R8 is independently selected from -OR20. In some cases, R20 is independently selected from C1-6 alkyl groups each time it appears, wherein the C1-6 alkyl group is optionally substituted by one or more substituents independently selected from halogens and -O-C1-10 alkyl groups. In some cases, each R8 is independently selected from -OCH3, , . In some cases, R7 is selected from , and . In some cases, each R8 is independently selected from -N(R20)2. In some cases, R20 is independently selected from hydrogen and C1-6 alkyl groups each time it appears, wherein the C1-6 alkyl group is optionally substituted by one or more substituents independently selected from halogens. In some cases, each R20 is different. In some cases, each R8 is independently selected from and . In some cases, R7 is selected from and . In some cases, each R8 is independently selected from -NR20S(O)2R20. In some cases, each R8 is independently selected from -NHS(O)2R20. In some cases, R20 is independently selected from C1-6 alkyl groups each time it appears, wherein the C1-6 alkyl group is optionally substituted with one or more substituents independently selected from -O-C1-10 alkyl groups. In some cases, each R8 is independently selected from -C(O)N(R20)2. In some cases, R20 is independently selected from hydrogen and C1-6 alkyl groups each time it appears. In some cases, each R8 is independently selected from -C(O)N(R20)2. In some cases, R20 is independently selected from hydrogen and C1-6 alkyl groups each time it appears. In some cases, each R8 is independently selected from -C1-10 alkyl groups. In some cases, R7 is -C1-10 alkyl groups. In some cases, each R8 is independently selected from 5- to 6-membered heterocycles, wherein the 5- to 6-membered heterocycles are optionally substituted with one or more substituents selected from halogens, C1-10 alkyl groups, -C1-10 haloalkyl groups, and -O-C1-10 alkyl groups. In some cases, each R8 is independently selected from 5- to 6-membered heterocycles.The 5- or 6-membered heterocycle is optionally substituted with one or more substituents selected from halogens. In some cases, each R8 is independently selected. In some cases, R7 is.

[0082] In some embodiments, for compounds or salts of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG), R7 is selected from a 5- or 6-membered heterocycle, optionally substituted with one or more R8s. In some cases, R7 is selected from a 5-membered heterocycle, optionally substituted with one or more R8s. In some cases, R7 is selected from a 6-membered heterocycle, optionally substituted with one or more R8s. In some cases, the heterocycle of R7 has at least one nitrogen atom. In some cases, the heterocycle of R7 has at least one oxygen atom. In some cases, the heterocycle of R7 has at least one sulfur atom. In some cases, each R8 is independently selected from halogens, -OR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), -NR20S(O)2R20, -C(O)N(R20)2, -C(=NR20)N(R20)2, -C(O)NR20OR20, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R20)C(O)OR20, -C(O)R20, -C (O)OR20, -OC(O)R20, -OC(O)N(R20)2, -NO2, =O, =N(R20), =NO(R20), -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-C12 carbon ring and 5 to 12 membered heterocycles. In some cases, each R8 is independently selected from halogens, -OR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), -NR20S(O)2R20, -C(O)N(R20)2, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R20)C(O)OR20, -C(O)OR20, -OC(O)R20, -OC(O)N(R20)2, =O, -CN, C1-6 alkyl-N(R20).Each R8 is independently selected from fluorine, chlorine, -OR20, -S(O)2(R20), -S(O)2N(R20)2, -NR20S(O)2R20, -C(O)N(R20)2, -N(R20)C(O)R20, -C(O)OR20, -OC(O)R20, -OC(O)N(R20)2, =O, -CN, C1-6 alkyl, C3-C12 carbon rings, and 5 to 12-membered heterocycles. In some cases, each R8 is independently selected from fluorine, -OR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), =O, and C1-6 alkyl. In some cases, each R8 is independently selected from fluorine, -OR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), =O, and C1-4 alkyl. In some cases, each R8 is independently selected from fluorine, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), methyl, ethyl, propyl, isopropyl, and =O. In some cases, each R8 is independently selected from -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), and =O. In some cases, each R8 is independently selected from -S(O)2(R 20) and =O. In some cases, each R8 is independently selected from fluorine, methyl, -S(O)2(R 20), and =O. In some cases, each R8 is -S(O)2(R 20). In some cases, each R8 is =O. In some cases, each R8 is methyl. In some cases, each R8 is fluorine. In some cases, R7 is selected from [missing information - likely a specific ingredient or compound]. In some cases, R7 is [missing information - likely a specific ingredient or compound]. In some cases, R7 is [missing information - likely a specific ingredient or compound]. In some cases, R7 is [missing information - likely a specific ingredient or compound]. In some cases, R7 is [missing information - likely a specific ingredient or compound].

[0083] In some embodiments, R7 is not substituted for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG). In some cases, R7 is substituted.

[0084] In some embodiments, R7 is not substituted for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG).R7 is substituted with at least one R8 group. In some cases, R7 is substituted with at least two R8 groups. In some cases, R7 is substituted with at least three R8 groups. In some embodiments, for compounds or salts of formula (I), R7 is substituted with no more than three R8 groups. In some cases, R7 is substituted with no more than two R8 groups. In some cases, R7 is substituted with no more than one R8 group. In some embodiments, for compounds or salts of formula (I), R7 is substituted with three R8 groups. In some cases, R7 is substituted with two R8 groups. In some cases, R7 is substituted with one R8 group.

[0085] In some embodiments, for compounds or salts of formulas (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG), R7 is selected from optionally substituted saturated 4- to 8-membered heterocycles. In some cases, the saturated 4- to 8-membered heterocycle is optionally substituted with one or more R8 atoms. In some cases, R7 is selected from optionally substituted saturated 5-membered heterocycles. In some cases, the 5-membered heterocycle is optionally substituted with one or more R8 atoms. In some cases, R7 is selected from optionally substituted saturated 6-membered heterocycles. In some cases, the 6-membered heterocycle is optionally substituted with one or more R8 atoms. In some cases, R7 is selected from optionally substituted saturated 4- to 6-membered heterocycles. In some cases, R7 is selected from optionally substituted saturated 5- to 6-membered heterocycles. In some cases, R7 is selected from optionally substituted saturated 4- to 6-membered heterocycles. In some cases, R7 is selected from optionally substituted saturated 5- to 6-membered heterocycles. In some cases, R7 is selected from optionally substituted saturated 6-membered heterocycles. In some cases, R7 is selected from optionally substituted saturated 4- to 6-membered heterocycles, wherein the saturated 4- to 6-membered heterocycle has at least one heteroatom selected from oxygen, nitrogen, and sulfur. In some cases, the saturated 4- to 6-membered heterocycle has at most one heteroatom. In some cases, R7 is selected from , , , , , , , , and , wherein each is optionally substituted by one or more substituents independently selected from R8. In some cases, R7 is selected from , , , , , , , and , wherein each is optionally substituted by one or more substituents independently selected from R8. In some cases, R7 is selected from , , and , wherein each is optionally substituted by one or more substituents independently selected from R8. In some cases, R7 is selected from , and .

[0086] In some embodiments,For compounds or salts of formulas (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG), R7 is selected from a saturated 4- to 8-membered heterocycle that is optionally substituted. In some cases, the saturated 4- to 8-membered heterocycle is optionally substituted with one or more R8s. In some cases, R7 is selected from a saturated 5-membered heterocycle that is optionally substituted. In some cases, the 5-membered heterocycle is optionally substituted with one or more R8s. In some cases, R7 is selected from a saturated 6-membered heterocycle that is optionally substituted. In some cases, the 6-membered heterocycle is optionally substituted with one or more R8s. In some cases, R7 is selected from a saturated 4- to 6-membered heterocycle that is optionally substituted. In some cases, R7 is selected from a saturated 5- to 6-membered heterocycle that is optionally substituted. In some cases, R7 is selected from a saturated 4-membered heterocycle that is optionally substituted. In some cases, R7 is selected from a saturated 5-membered heterocycle that is optionally substituted. In some cases, R7 is selected from saturated 6-membered heterocycles that are optionally substituted. In some cases, R7 is selected from saturated 4- to 6-membered heterocycles that are optionally substituted, wherein the saturated 4- to 6-membered heterocycle has at least one heteroatom selected from oxygen, nitrogen, and sulfur. In some cases, the saturated 4- to 6-membered heterocycle has at most one heteroatom. In some cases, R7 is selected from , , , , , , , , , and , wherein each is optionally substituted by one or more substituents independently selected from R8. In some cases, R7 is selected from , , and , wherein each is optionally substituted by one or more substituents independently selected from R8. In some cases, R7 is selected from , , and , wherein each is optionally substituted by one or more substituents independently selected from R8. In some cases, R7 is selected from , , and (see page 30 / 240 of the specification, CN 121568943 A).

[0087] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG), R7 is selected from optionally substituted saturated 4- to 6-membered heterocycles, wherein the optionally substituted saturated 4- to 6-membered heterocycles contain at least one nitrogen atom. In some cases, the optionally substituted saturated 4- to 6-membered heterocycles contain only one nitrogen atom. In some cases, the optionally substituted saturated 4- to 6-membered heterocycles contain at most one nitrogen atom. In some cases, R7 is selected from [missing information - likely a specific type of R8], [missing information - likely a specific type of R8], and [missing information - likely a specific type of R8], wherein each is optionally substituted by one or more substituents independently selected from R8. In some cases, R7 is selected from [missing information - likely a specific type of R8], [missing information - likely a specific type of R8], [missing information - likely a specific type of R8], and [missing information - likely a specific type of R8].Each of these is optionally substituted with one or more substituents selected from halogens, -C(O)R20, and -S(O)2(R20). In some cases, R7 is selected from , , and , wherein each is substituted with -S(O)2(R20). In some cases, R7 is selected from , and , wherein each is substituted with -S(O)2(R20). In some cases, each R20 is independently selected from hydrogen; C1-6 alkyl and C3-12 carbon ring, wherein the C1-6 alkyl is optionally substituted with one or more -O-C1-10 alkyl. In some cases, each R20 is independently selected from hydrogen; C1-6 alkyl and C3-6 carbon ring. In some cases, each R20 is independently selected from C1-6 alkyl and C3-6 carbon ring. In some cases, each R20 is independently selected from C1-6 alkyl. In some cases, each R20 is independently selected from C3-6 carbon rings each time it appears. In some cases, R7 is selected from , ... Each of these is optionally substituted with one or more substituents independently selected from R8. In some cases, R7 is a 4- to 8-membered saturated heterocycle of a β-lactam, wherein each is optionally substituted with one or more substituents independently selected from R8. In some cases, R7 is selected from [specifications omitted], wherein each is optionally substituted with one or more substituents independently selected from R8. In some cases, R7 is [specifications omitted], wherein each is optionally substituted with one or more substituents independently selected from R8. In some cases, each R8 is selected from C1-6 alkyl, =O, and saturated 4- to 8-membered heterocycles. In some cases, each R8 is selected from C1-6 alkyl and =O. In some cases, [specifications omitted]Each R8 is selected from C1-6 alkyl and =O. In some cases, R7 is selected from , , , , , , and . In some cases, R7 is selected from , , , , , , , , , , and .

[0089] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF) or formula (IIG), R7 is selected from saturated 4- to 6-membered heterocycles, wherein the saturated 4- to 6-membered heterocycle contains at least one nitrogen atom and is substituted with at least one oxo group, and is further optionally substituted with one or more R8s. In some cases, R7 is selected from , , , and , wherein each is substituted with at least one oxo group and one or more substituents independently selected from R8. In some cases, R7 is selected from [ ] and [ ], wherein each is substituted with at least one oxo group, and [ ] is further optionally substituted with one or more substituents independently selected from R8. In some cases, R7 is [ ], which is substituted with at least one oxo group, and is further optionally substituted with one or more substituents independently selected from R8. In some cases, each R8 is selected from C1-6 alkyl, =O, and saturated 4 to 8-membered heterocycles. In some cases, each R8 is selected from C1-6 alkyl and =O. In some cases, each R8 is selected from C1-6 alkyl. In some cases, each R8 is selected from =O. In some cases, R7 is selected from [ ], [ ], [ ], [ ], [ ], [ ], and [ ]. In some cases, R7 is selected from [ ], [ ], [ ], [ ], and [ ].

[0090] In some embodiments, for compounds or salts of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG), R7 is selected from saturated 7- to 8-membered spiroheterocycles that are optionally substituted. In some cases, the spiroheterocycle has at least one nitrogen atom. In some cases, the spiroheterocycle has at least one oxygen atom. In some cases, R7 is selected from [R8] and [R8], each optionally substituted with one or more substituents independently selected from R8. In some cases, R7 is selected from [R8] and [R8], optionally substituted with one or more substituents independently selected from R8. In some cases, [R8]Each R8 is independently selected from halogens, -OR20, -SR20, -N(R20)2, -NO2, -CN, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkoxyalkyl, C1-6 alkyl, -C(O)R20, -C(O)OR20, -C(O)N(R20)2, -S(O)2(R20), -S(O)(R20), -S(O)2(NR202), -S(O)(NR20)R20 and -S(O)(NR20)N(R20)2. In some cases, each R8 is independently selected from C1-6 alkyl, -S(O)2(R 20), -S(O)(R20), -S(O)2(NR 202), -S(O)(NR20)R20, and -S(O)(NR20)N(R20)2. In some cases, each R8 is independently selected from C1-6 alkyl and -S(O)2(R 20). In some cases, R7 is...

[0091] In some embodiments, for compounds or salts of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG), R7 is selected from optionally substituted saturated 4- to 6-membered heterocycles, wherein the optionally substituted saturated 4- to 6-membered heterocycles contain at least one nitrogen atom and are substituted with at least one halogen and at least one -S(O)2 (R2O). In some cases, R7 is...

[0092] In some embodiments, for compounds or salts of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG), R7 is selected from optionally substituted saturated 6-membered heterocycles and C6 cycloalkyl groups substituted with one or more R8s. In some cases, the saturated 6-membered heterocycle contains one nitrogen atom. In some cases, the saturated 6-membered heterocycle contains only one nitrogen atom and no other heteroatoms. In some cases, R7 is selected from and , each optionally substituted with one or more substituents independently selected from: R8; and C6 cycloalkyl groups substituted with one or more R8s. In some cases, R7 is selected from (which is optionally substituted with -C(O)R2O and -S(O)2(R2O)); and C6 cycloalkyl groups substituted with one or more halogens. In some cases, R7 is selected from (optionally substituted with -S(O)2(R 20)); and C6 cycloalkyl groups substituted with one or more halogens. In some cases,R7 is selected from , , , , , , .

[0093] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF) or formula (IIG), R7 is selected from optionally substituted saturated 6-membered heterocycles and optionally substituted C4 cycloalkyl groups, each optionally substituted by one or more substituents independently selected from: halogen, C1-6 haloalkyl, C1-6 alkoxyalkyl, -S(O)2(R20), -S(O)(R20), -S(O)2(NR202), -S(O)(NR20)R20 and -S(O)(NR20)N(R20)2. In some cases, R7 is selected from optionally substituted saturated 6-membered heterocycles and unsubstituted C4 cycloalkyl groups, wherein the saturated 6-membered heterocycle is optionally substituted by one or more substituents independently selected from -S(O)2(R20). In some cases, R7 is selected from unsubstituted C4 cycloalkyl groups, and , each optionally substituted by -S(O)2(R20) and a halogen. In some cases, R7 is selected from unsubstituted C4 cycloalkyl groups, (see specification 35 / 240 pages 81 CN 121568943 A), each optionally substituted by -S(O)2(R20). In some cases, R7 is selected from , , , , . In some cases, R7 is selected from , , , and .

[0094] In some embodiments, for compounds or salts of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG), R7 is selected from optionally substituted saturated 4- to 8-membered heterocycles, wherein the optionally substituted saturated 4- to 8-membered heterocycles contain at least one oxygen atom. In some cases, the optionally substituted saturated 4- to 8-membered heterocycles contain only one oxygen atom. In some cases, the optionally substituted saturated 4- to 6-membered heterocycles contain at most one oxygen atom. In some cases, R7 is selected from R8, R9, R1, R2, and R3, wherein each is optionally substituted by one or more substituents independently selected from R8. In some cases, R7 is selected from optionally substituted saturated 4- to 6-membered heterocycles, wherein the optionally substituted saturated 4- to 6-membered heterocycles contain at least one oxygen atom. In some cases, R7 is selected from R8, R9, and R1, each optionally substituted with one or more substituents independently selected from R8. In some cases, R7 is R8, optionally substituted with one or more substituents independently selected from R8. In some cases, R7 is R8, optionally substituted with one or more substituents independently selected from R8.

[0095] In some embodiments,For compounds or salts of formulas (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG), R7 is an optionally substituted 6-membered saturated heterocycle containing one oxygen atom and no other heteroatoms. In some cases, the heterocycle is tetrahydropyran. In some cases, each R8 is independently selected from halogens, -OR20, -SR20, -N(R20)2, -NO2, =O, =S, =N(R20)2, -CN, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkoxyalkyl, C1-6 alkyl, -C(O)R20, -C(O)OR20, -C(O)N(R20)2, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -S(O)2(R20), -S(O)(R20), -S(O)2(NR20), 202)-S(O)(NR20)R20 and -S(O)(NR20)N(R20)2. In some cases, each R8 is independently selected from halogens, -OR20, =O, -CN, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkoxyalkyl, and C1-6 alkyl. In some cases, each R8 is independently selected from halogens and C1-6 alkyl. In some cases, the heterocycle is not substituted. In some cases, the heterocycle is substituted. In some cases, R7 is selected from , , , , and.

[0096] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG), R7 is selected from optionally substituted saturated 8-membered heterocycles, wherein the optionally substituted saturated 8-membered heterocycles contain at least one oxygen atom. In some cases, the saturated 8-membered heterocycle is a bridging heterocycle. In some cases, R7 is.

[0097] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG), R7 is selected from optionally substituted saturated 4- to 6-membered heterocycles, wherein the optionally substituted saturated 4- to 6-membered heterocycles contain at least one sulfur atom. In some cases, the optionally substituted saturated 4- to 6-membered heterocycles contain only one sulfur atom. In some cases,The optionally substituted saturated 4- to 6-membered heterocycles contain at most one sulfur atom. In some cases, R7 is selected from [selection 1] and [selection 2], wherein each is optionally substituted by one or more substituents independently selected from R8. In some cases, R7 is selected from [selection 3], [selection 4], and [selection 5], wherein each is optionally substituted by one or more substituents independently selected from R8. In some cases, R7 is selected from [selection 5], [selection 6], and [selection 7]. In some cases, R7 is selected from [selection 8].

[0098] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG), each R8 is independently selected from halogens, -OR20, =O, C1-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 alkyl, -C(O)R20, -C(O)OR20, -C(O)N(R20)2, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -S(O)2(R20), -S(O)(R20), -S(O)(NR20)R20, -S(O)2(NR20 2), and -S(O)(NR20)N(R20)2. In some cases, each R8 is independently selected from halogens, -OR20, =O, C1-6 hydroxyalkyl, C1-6 alkyl, -C(O)R20, -C(O)OR20, -C(O)N(R20)2, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -S(O)2(R20), -S(O)(R20), -S(O)(NR20)R20 and -S(O)(NR20)N(R20)2. In some cases, each R8 is independently selected from -C(O)R20, -C(O)N(R20)2, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -S(O)2(R20), -S(O)(R20), -S(O)(NR20)R20, and -S(O)(NR20)N(R20)2. In some cases, each R8 is independently selected from -C(O)R20, -C(O)N(R20)2, -S(O)2(R20), and -S(O)(NR20)R20. In some cases,Each R8 is independently selected from halogen, -OR20, C1-6 hydroxyalkyl, C1-6 haloalkyl, C1-6 alkyl, -C(O)R20, -C(O)OR20, -C(O)N(R20)2, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -S(O)2(R20), -S(O)(R20), -S(O)(NR20)R20 and -S(O)(NR20)N(R20)2. In some cases, each R8 is independently selected from halogens, -OR20, =O, C1-6 hydroxyalkyl, C1 haloalkyl, C3-6 haloalkyl, C1-6 alkyl, -C(O)R20, -C(O)OR20, -C(O)N(R20)2, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -S(O)2(R20), -S(O)(R20), -S(O)(NR20)R20 and -S(O)(NR20)N(R20)2. In some cases, R8 is selected from halogens, =O, C1-6 hydroxyalkyl, C1 haloalkyl, C1-6 alkyl, -C(O)R20, -S(O)2(R20), -S(O)(R20), -S(O)(NR20)R20, and -S(O)(NR20)N(R20)2. In some cases, R8 is selected from =O, -C(O)R20, -S(O)2(R20), -S(O)(R20), -S(O)(NR20)R20, and -S(O)(NR20)N(R20)2. In some cases, R8 is selected from -S(O)2(R20), -S(O)2(NR202), -S(O)(NR20)R20, and -S(O)(NR20)N(R20)2. In some cases, R8 is selected from -S(O)2(R20). In some cases, R8 is selected from -C(O)N(R20)2, -S(O)2(R20), -S(O)(NR20)R20, and -C(O)R20. In some cases, R8 is -S(O)2(NR20). In some cases, R8 is selected from -S(O)2(R20) and -C(O)R20. In some cases, R8 is -C(O)N(R20)2. In some cases, R8 is -S(O)2(R20). In some cases, R8 is -S(O)(NR20)R20. In some cases, R8 is selected from halogens, -OR20, and =O. In some cases, R8 is selected from C1-6 hydroxyalkyl, C1-6 haloalkyl, and C1-6 alkyl groups. In some cases, R8 is selected from halogens. In some cases,Each R20 is independently selected, each time it appears, from hydrogen; C1-6 alkyl, C3-12 carbon ring, and 3 to 12-membered heterocycles. In some cases, each R20 is independently selected, each time it appears, from hydrogen; C1-6 alkyl and C3-12 carbon ring, wherein the C1-6 alkyl is optionally substituted with one or more -O-C1-10 alkyl groups. In some cases, R20 is a 3 to 6-membered heterocycle, which is optionally substituted with one or more substituents independently selected from halogens, -OH, -CN, -NO2, -NH2, C1-10 alkyl, -C1-10 haloalkyl, and -O-C1-10 alkyl groups. In some cases, each R20 is independently selected, each time it appears, from hydrogen and C1-6 alkyl. In some cases, each R20 is independently selected, each time it appears, from hydrogen, C1-6 alkyl, C3-12 carbon ring, and 3 to 12-membered heterocycles. In some cases, each R20 is independently selected, each time it appears, from hydrogen and C1-6 alkyl. In some cases, R7 is selected from CN 121568943 A, page 38 / 240 of the specification. In some cases, R7 is selected from [missing information - likely a specific type of document]. In some cases, R7 is selected from [missing information - likely a specific type of document]. In some cases, R7 is selected from [missing information - likely a specific type of document]. In some cases, R7 is selected from [missing information - likely a specific type of document]. In some cases, R7 is selected from [missing information - likely a specific type of document]. In some cases, R7 is selected from [missing information - likely a specific type of document]. In some cases, R7 is selected from [missing information - likely a specific type of document]. In some cases, R7 is selected from [missing information - likely a specific type of document]. In some cases, R7 is selected from [missing information - likely a specific type of document].

[0099] In some embodiments, for compounds or salts of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG), R7 is selected from 5- to 10-membered heterocycles, each optionally substituted with one or more R8s. In some cases, R7 is selected from , , , , , , , , , , , , , , , , , , , and , each optionally substituted with one or more R8s. In some cases, the heterocycle has one oxygen atom. In some cases, the heterocycle has one nitrogen atom. In some cases, the heterocycle has only one heteroatom. In some cases, the heterocycle has only two heteroatoms. In some cases, the heterocycle has only three heteroatoms. In some cases, the heterocycle has one sulfur atom. In some cases, each R8 is independently selected from halogens, -OR20, -S(O)2(R20), -C(O)OR20, =O, C1-6 alkyl, and C1-6 haloalkyl. In some cases,Each R8 is independently selected from =O, -S(O)2 (C1-6 alkyl), -CF3, -CH3, -C(O)OC1-6 alkyl, -OMe, and. In some cases, R7 is selected from, ... In some cases, R7 is selected from , , , , , , , , , , , , , , , , , , and , each optionally substituted by one or more R8. In some cases, R7 is selected from , , , , , , , , , , , , , , , and , each optionally substituted by one or more R8. In some cases, R7 is selected from , , , , , , , , and , each optionally substituted by one or more R8. In some cases, R7 is selected from , , , , , , , , and , each optionally substituted by one or more R8. In some cases, R7 is selected from , , , , and , each optionally substituted by one or more R8. In some cases, the heterocycle has one oxygen atom. In some cases, the heterocycle has one nitrogen atom. In some cases, the heterocycle has only one heteroatom. In some cases, the heterocycle has only two heteroatoms. In some cases, the heterocycle has only three heteroatoms. In some cases, the heterocycle has one sulfur atom. In some cases, each R8 is independently selected from halogens, -OR20, -N(R20)2, -S(O)2(R20), -C(O)OR20, =O, C1-6 alkyl, C1-6 haloalkyl, and 4- to 6-membered heterocycles, wherein the 4- to 6-membered heterocycles are optionally substituted by one or more substituents selected from halogens. In some cases, each R8 is independently selected from [missing information - likely a specific type of halogen]. In some cases, R7 is selected from [missing information - likely a specific type of halogen].

[0101] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG), R7 is selected from 6-membered heterocycles.Each of these components is optionally substituted with one or more R8 atoms. In some cases, the heterocycle has one oxygen atom. In some cases, the heterocycle has one nitrogen atom. In some cases, the heterocycle has one sulfur atom. In some cases, the heterocycle has only one heteroatom. In some cases, the heterocycle has only two heteroatoms. In some cases, the heterocycle has only three heteroatoms. In some cases, R7 is selected from 6-membered heteroaryl groups, which are optionally substituted with one or more R8 atoms. In some cases, the heteroaryl group has one oxygen atom. In some cases, the heteroaryl group has one nitrogen atom. In some cases, the heteroaryl group has one sulfur atom. In some cases, the heteroaryl group has only one heteroatom. In some cases, the heteroaryl group has only two heteroatoms. In some cases, the heteroaryl group has only three heteroatoms. In some cases, the heteroaryl group has one sulfur atom. In some cases, the 6-membered heteroaryl group has one nitrogen atom. In some cases, R7 is selected from [specification details 42 / 240 pages 88 CN 121568943 A], each optionally substituted with one or more R8 atoms. In some cases, R7 is selected from and , each optionally substituted by one or more R8s. In some cases, each R8 is independently selected from halogens, -OR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), -CN, =O, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, and C1-6 alkyl. In some cases, each R8 is independently selected from halogens, -S(O)2(R20), =O, C1-6 alkyl, and C1-6 haloalkyl. In some cases, R20 is a C1-6 alkyl. In some cases, each R8 is independently selected from CF3, Me, =O, or -S(O)2 (C1-6 alkyl). In some cases, R7 is selected from [1], [2], and [3].

[0102] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG), R7 is selected from 9- to 10-membered heterocycles, each optionally substituted with one or more R8s. In some cases, R7 is selected from 9-membered heterocycles, optionally substituted with one or more R8s. In some cases, R7 is selected from 10-membered heterocycles, optionally substituted with one or more R8s. In some cases, the 9- to 10-membered heterocycle is bicyclic. In some cases, the 9- to 10-membered heterocycle is fused heterocycle. In some cases, the 9- to 10-membered heterocycle is aromatic. In some cases, the 9- to 10-membered heterocycle is non-aromatic. In some cases,Nine- or ten-membered heterocycles are fully saturated. In some cases, nine- or ten-membered heterocycles are partially saturated. In some cases, nine- or ten-membered heterocycles are unsaturated. In some cases, the heterocycle has one oxygen atom. In some cases, the heterocycle has one nitrogen atom. In some cases, the heterocycle has one sulfur atom. In some cases, the heterocycle has only one heteroatom. In some cases, the heterocycle has only two heteroatoms. In some cases, the heterocycle has only three heteroatoms. In some cases, the heterocycle has only four heteroatoms. In some cases, the heterocycle has different combinations of heteroatoms. In some cases, nine- or ten-membered heterocycles are not fully saturated. In some cases, R7 is selected from , , , , , , , , , , and , each optionally substituted by one or more R8. In some cases, R7 is , which is optionally substituted by one or more R8. In some cases, R7 is selected from , , , , , , , , , and , each optionally substituted by one or more R8. In some cases, R7 is selected from and , each optionally substituted with one or more R8s. In some cases, R7 is selected from , ... In some cases, each R8 is independently selected from halogens, -OR20, -S(O)2(R20), -N(R20)2, -C(O)OR20, =O, C1-6 alkyl, and C1-6 haloalkyl. In some cases, each R8 is independently selected from =O, -S(O)2(C1-6 alkyl), -CF3, -NHCH3, -N(CH3)2, -CH3, -C(O)OC1-6 alkyl, -OMe, and. In some cases, each R20 is a C1-6 alkyl, wherein each is optionally substituted by one, two, or three substituents independently selected from halogens, -OH, and -O-C1-6 alkyl. In some cases, each R20 is methyl, ethyl, tert-butyl, and. In some cases, R7 is selected from [missing information]. [Specification 44 / 240 pages 90 CN 121568943 A] In some cases, R7 is selected from [missing information].

[0103] In some embodiments,For compounds or salts of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG), R8 is selected from -S(O)2 (NR 20 2) and -S(O)2 (R 20). In some cases, R8 is selected from -S(O)2 (NR 20 2). In some cases, R20 is independently selected from hydrogen each time it appears; C1-6 alkyl and 3 to 6-membered heterocycles, each optionally substituted by one or more substituents independently selected from: halogen, -OH, -CN, -NO2, -NH2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbon ring and 3 to 12-membered heterocycles. In some cases, R20 is independently selected from hydrogen and C1-6 alkyl each time it appears. In some cases, R20 is independently selected from C1-6 alkyl each time it appears. In some cases, R8 is selected from and. In some cases, R7 is. In some cases, R7 is.

[0104] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF) or formula (IIG), R8 is selected from -S(O)2(R20). In some cases, R20 is a 3- to 6-membered heterocycle, optionally substituted with one or more substituents independently selected from: halogen, -OH, -CN, -NO2, -NH2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbon ring, and 3- to 12-membered heterocycles. In some cases, R20 is a 3- to 6-membered heterocycle, optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NH2, C1-10 alkyl, -C1-10 haloalkyl, and -O-C1-10 alkyl. In some cases, R20 is a 3- to 6-membered heterocycle. In some cases, R20 is a 6-membered heterocycle. In some cases, R20 is a saturated 6-membered heterocycle. In some cases, the heterocycle contains at least one oxygen atom. In some cases, the heterocycle contains at least one nitrogen atom. In some cases, the heterocycle comprises at least one oxygen atom and at least one nitrogen atom. In some cases, R8 is [specifically, R7]. In some cases, R7 is selected from [specifically, R7].

[0105] In some embodiments,For compounds or salts of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG), R8 is selected from -C(O)R20. In some cases, R20 is independently selected from C1-6 alkyl groups each time it appears, optionally substituted by one or more substituents independently selected from: halogen, -OH, -CN, -NO2, -NH2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbon ring, and 3 to 12-membered heterocycles. In some cases, R20 is independently selected each time it appears from a C1-6 alkyl group, optionally substituted with one or more substituents independently selected from -O-C1-10 alkyl groups and 3 to 12-membered heterocycles. In some cases, R20 is independently selected each time it appears from a C1-6 alkyl group, optionally substituted with one or more substituents independently selected from halogens, -OH, -CN, -NO2, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 ynyl, C3-12 carbon rings and 3 to 12-membered heterocycles. In some cases, R20 is independently selected each time it appears from a C1-6 alkyl group, optionally substituted with 3 to 6-membered heterocycles. In some cases, R20 is independently selected each time it appears from a C1-6 alkyl group optionally substituted with a 6-membered heterocycle. In some cases, the heterocycle contains at least one oxygen atom. In some cases, the heterocycle contains at least one nitrogen atom. In some cases, the heterocycle contains at least one oxygen atom and at least one nitrogen atom. In some cases, the 6-membered heterocycle is selected from morpholine. In some cases, R8 is. In some cases, R8 is selected from. In some cases, R8 is selected from. In some cases, R7 is selected from. In some cases, R7 is selected from.

[0106] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF) or formula (IIG), R7 is represented by ; wherein B is selected from an unsubstituted 5- to 6-membered heterocycle. In some cases, R7 is represented by , wherein C is selected from a C5-6 saturated carbide ring, and R20 is selected from a C1-6 alkyl substituted with an -O-C1-10 alkyl group. In some cases, R7 is represented by , wherein B is selected from an unsubstituted 5- to 6-membered heterocycle. In some cases, R7 is denoted by , where B is selected from 4- to 6-membered heterocycles having at least one sulfur atom, wherein the 4- to 6-membered heterocycle is substituted with two =O atoms. In some cases, R7 is denoted by .Wherein B is selected from unsubstituted 4- to 6-membered heterocycles having at least one oxygen atom.

[0107] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF) or formula (IIG), R8 is selected from -S(O)2 (R2O). In some cases, R20 is independently selected from hydrogen each time it appears; C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-12 carbon ring and 3 to 12-membered heterocycles, each optionally substituted by one or more substituents independently selected from halogens, -OH, -CN, -NO2, -NH2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 ynyl, C3-12 carbon ring and 3 to 12-membered heterocycles. In some cases, R20 is independently selected from C1-6 alkyl and C3-12 carbon rings each time it appears, each optionally substituted by one or more substituents independently selected from the following: halogen, -OH, -CN, -NO2, -NH2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 ynyl, C3-12 carbon ring, and 3 to 12 membered heterocycles. In some cases, R20 is independently selected from C1-6 alkyl and C3-12 carbon rings each time it appears, each optionally substituted by one or more substituents independently selected from the following: halogen, -OH, -CN, -NO2, -NH2, C1-10 alkyl, -C1-10 haloalkyl, and -O-C1-10 alkyl. In some cases, R20 is independently selected from C1-6 alkyl groups each time it appears, optionally substituted by one or more substituents independently selected from: halogen, -OH, -CN, -NO2, -NH2, -C1-10 haloalkyl, and -O-C1-10 alkyl. In some cases, R20 is independently selected from C1-6 alkyl groups each time it appears, optionally substituted by one or more -O-C1-10 alkyl groups. In some cases, R20 is independently selected from C1-6 alkyl groups each time it appears. In some cases, R20 is independently selected from methyl, ethyl, and propyl groups each time it appears. In some cases, R20 is independently selected from a C3-6 carbon ring each time it appears, and is optionally substituted by one or more substituents independently selected from halogens, -OH, -CN, -NO2, -NH2, C1-10 alkyl, -C1-10 haloalkyl, and -O-C1-10 alkyl. In some cases, R20 is independently selected from a C3-6 carbon ring each time it appears.It is optionally substituted by one or more substituents independently selected from halogens, C1-10 alkyl groups, -C1-10 haloalkyl groups, and -O-C1-10 alkyl groups. In some cases, R20 is independently selected from C3-6 carbon rings each time it appears. In some cases, R8 is selected from , , , , , and . In some cases, R8 is selected from , , , , , and .

[0108] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG), R7 is selected from substituted C6 cycloalkyl groups and optionally substituted saturated 6-membered heterocycles. In some cases, the heterocycle has at least one nitrogen atom. In some cases, the heterocycle has at least one oxygen atom. In some cases, the heterocycle is not substituted. In some cases, the heterocycle is substituted. In some cases, the heterocycle is selected from tetrahydropyran and piperidine. In some cases, each R8 is independently selected from halogen, -C(O)N(R20)2, -S(O)2(R20), and -S(O)2(NR202). In some cases, R7 is selected from , , , and .

[0109] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG), each R8 is independently selected from -C(O)R20, -C(O)N(R20)2, -S(O)2(R20), and -S(O)(NR20)R20. In some cases, each R8 is independently selected from -C(O)N(R20)2 and -S(O)2(R20) and -S(O)(NR20)R20. In some cases, each R8 is -C(O)N(R20)2. In some cases, each R8 is -S(O)(NR20)R20. (See specification 47 / 240 pages 93 CN 121568943 A (O)(NR20)R20.) In some cases, R20 is independently selected from hydrogen each time it appears; a C1-6 alkyl group and a C3-12 carbon ring, each optionally substituted by one or more substituents independently selected from: halogen, -OH, -CN, -NO2, -NH2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 ynyl, C3-12 carbon ring, and 3 to 12-membered heterocycles. In some cases, R20 is independently selected from C1-6 alkyl groups each time it appears.It is optionally substituted by one or more substituents independently selected from the following: halogen, -OH, -CN, -NO2, -NH2, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbon ring, and 3 to 12-membered heterocycles. In some cases, R20 is independently selected from C1-6 alkyl in each occurrence, and is optionally substituted by one or more substituents independently selected from the following: halogen, -OH, -CN, -NO2, -NH2, -O-C1-10 alkyl. In some cases, R20 is independently selected from C1-6 alkyl in each occurrence. In some cases, R20 is methyl. In some cases, R8 is selected from. In some cases, R8 is selected from. In some cases, R8 is selected from.

[0110] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG), R7 is selected from C6 cycloalkyl groups optionally substituted with one or more R8s. In some cases, R8 is independently selected each time it appears from halogens, C1-6 haloalkyl groups, -C(O)R20, -C(O)OR20, -C(O)N(R20)2, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -S(O)2(R20), -S(O)(R20), and -S(O)2(NR202). In some cases, R8 is selected from halogens, C1-6 haloalkyl groups, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -S(O)2(R20), -S(O)(R20), and -S(O)2(NR202) each time it appears. In some cases, R8 is selected from halogens, C1-6 haloalkyl groups, -N(R20)C(O)R20, and -N(R20)C(O)N(R20)2 each time it appears. In some cases, R8 is selected from halogens and C1-6 haloalkyl groups each time it appears. In some cases, R8 is selected from -N(R20)C(O)R20 and -N(R20)C(O)N(R20)2 each time it appears. In some cases, R8 is selected from halogens each time it appears. In some cases, R8 is independently selected from halogens, C1-6 haloalkyl groups, -C(O)R20, -C(O)OR20, -C(O)N(R20)2, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -S(O)2(R20), -S(O)(R20), -S(O)(NR20)R20, and -S(O)(NR20)N(R20)2. In some cases,R8 is independently selected each time it appears from halogens, C1-6 haloalkyl groups, -C(O)R20, -S(O)2(R20), -S(O)(R20), -S(O)(NR20)R20, and -S(O)(NR20)N(R20)2. In some cases, R8 is independently selected each time it appears from halogens, -C(O)R20, and -S(O)2(R20). In some cases, R20 is independently selected each time it appears from hydrogen and C1-6 alkyl groups. In some cases, R20 is independently selected each time it appears from hydrogen and C1-6 alkyl groups. In some cases, R8 is independently selected from -OR20, -SR20, -N(R20)2, -NO2, =O, =S, =N(R20), -CN, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, and C1-6 alkyl each time it appears. In some cases, R8 is selected from -OR20, -SR20, -N(R20)2, -NO2, =O, =S, =N(R20), and -CN each time it appears. In some cases, R8 is selected from -OR20, -SR20, and -N(R20)2 each time it appears. In some cases, R8 is selected from -OR20 each time it appears. In some cases, R20 is independently selected from hydrogen and C1-6 alkyl each time it appears. In some cases, R20 is independently selected from hydrogen and C1-6 alkyl each time it appears.

[0111] In some embodiments, for compounds or salts of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG), R7 is selected from C6 cycloalkyl groups substituted with one or more R8s. In some cases, R7 is substituted with one or more R8s. In some cases, R7 is substituted with two R8s. In some cases, R8 is independently selected from halogens and, in each occurrence, from C1-6 haloalkyl groups. In some cases, R7 is selected from...

[0112] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG), R7 is selected from C8-10 cycloalkyl groups, each optionally substituted with one or more R8 groups. In some cases, R7 is selected from [a specific group], optionally substituted with one or more R8 groups. In some cases, R7 is selected from C8 cycloalkyl groups, optionally substituted with one or more R8 groups. In some cases, C8 cycloalkyl groups are selected from [a specific group], optionally substituted with one or more R8 groups. In some cases, R7 is [a specific group].It is optionally substituted with one or more R8s. In some cases, R7 is selected from C10 cycloalkyl groups, which is optionally substituted with one or more R8s. In some cases, R7 is selected from [specific compounds], which is optionally substituted with one or more R8s. In some cases, R7 is selected from [specific compounds], which is optionally substituted with one or more R8s. In some cases, each R8 is independently selected from halogens, -OR20, -N(R20)2, =O, -CN, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkoxyalkyl, C1-6 alkyl, -C(O)R20, -C(O)OR20, -C(O)N(R20)2, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -S(O)2(R20), -S(O)(R20), -S(O)2(NR202), -S(O)(NR20)R20, -S(O)(NR20)N(R20)2 and 4 to 8-membered heterocycles each time it appears. In some cases, each R8 is independently selected from -OR20, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkoxyalkyl, and C1-6 alkyl in each occurrence. In some cases, each R8 is independently selected from -OR20 and C1-6 alkyl in each occurrence. In some cases, each R8 is independently selected from -OH and -O-C1-6 alkyl in each occurrence. In some cases, R7 is. In some cases, R7 is.

[0113] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG), R7 is selected from C3-5 cycloalkyl, C7-8 cycloalkyl, and C9-10 cycloalkyl, each optionally substituted by one or more R8s. In some cases, R7 is selected from C3 cycloalkyl, C5 cycloalkyl, C7-8 cycloalkyl, and C9-10 cycloalkyl, each optionally substituted with one or more R8s. In some cases, R7 is selected from [missing information - likely C3 cycloalkyl, C5 cycloalkyl, C7-8 cycloalkyl, and C9-10 cycloalkyl, each optionally substituted with one or more R8s.]R8 is independently selected from each halogen, -OR20, -SR20, -N(R20)2, -NO2, =O, =S, =N(R20)2, -CN, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkoxyalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, -C(O)R20, -C(O)OR20, -C(O)N(R20)2, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -S(O)2(R20), -S(O)(R20), -S(O)2(NR202), -S(O)(NR20)R20 and -S(O)(NR20)N(R20)2. In some cases, R8 is independently selected from each halogen, -SR20, -N(R20)2, -NO2, =O, =S, =N(R20), -CN, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkoxyalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, -C(O)R20, -C(O)OR20, -C(O)N(R20)2, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -S(O)2(R20), -S(O)(R20), -S(O)2(NR202), -S(O)(NR20)R20 and -S(O)(NR20)N(R20)2. In some cases, R8 is selected from -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -S(O)2(R20), -S(O)(R20), -S(O)2(NR202), -S(O)(NR20)R20, and -S(O)(NR20)N(R20)2. In some cases, R20 is selected from C1-6 alkyl, C2-6 alkenyl, and C2-6 ynyl, each optionally substituted by one or more substituents independently selected from: halogen, -OH, -CN, -NO2, -NH2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 ynyl, C3-12 carbon ring, and 3 to 12 membered heterocycles. In some cases, R20 is selected from C1-6 alkyl, C2-6 alkenyl, and C2-6 ynyl groups, each optionally substituted by one or more substituents independently selected from halogens, -OH, -CN, -NO2, -NH2, C1-10 alkyl, and -C1-10 haloalkyl groups. In some cases, when R1 is N, R3 is imidazole, R7 is C4 cycloalkyl, and R8 is -OR20, R20 is selected from C1 alkyl, C3-6 alkyl, C2-6 alkenyl, and C2-6 ynyl groups.Each of these groups is optionally substituted by one or more substituents independently selected from the following: halogen, -OH, -CN, -NO2, -NH2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 ynyl, C3-12 carbon ring, and 3 to 12-membered heterocycles. In some cases, when R1 is N, R3 is imidazole, R7 is C4 cycloalkyl, and R8 is -OR20, R20 is selected from C1-6 alkyl, C2-6 alkenyl, and C2-6 ynyl, each of which is optionally substituted by one or more substituents independently selected from the following: halogen, -OH, -CN, -NO2, -NH2, C1-10 alkyl, -C1-10 haloalkyl, -O-C2-10 alkyl, C2-10 alkenyl, C2-10 ynyl, C3-12 carbon ring, and 3 to 12-membered heterocycles. In some cases, R7 is, and .

[0114] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG), R7 is selected from optionally substituted C5 cycloalkyl groups. In some cases, the C5 cycloalkyl group is substituted. In some cases, R7 is a C5 cycloalkyl group substituted with one or more fluorine atoms. In some cases, R7 is selected from

[0115] . In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG), each R8 is independently selected each time it appears from halogen, -OR20, -SR20, -N(R20)2, -NO2, =O, =S, =N(R20), -CN, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkoxyalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, -C(O)R20, -C(O)OR20, -C(O)N(R20)2, -N(R 20)C(O)R20, -N(R20)C(O)N(R20)2, -S(O)2(R20), -S(O)(R20), -S(O)2(NR202), -S(O)(NR20)R20 and -S(O)(NR20)N(R20)2. Specification 50 / 240 pages 96 CN 121568943 A

[0116] In some embodiments,For compounds or salts of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG), R7 is selected from optionally substituted 5- to 6-membered heteroaryl groups. In some cases, R7 is selected from optionally substituted 6-membered heteroaryl groups. In some cases, R7 is selected from optionally substituted pyridines. In some cases, each R8 is selected from halogens, -N(R20)2, OR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20 (=NR20), -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, and C1-6 alkyl. In some cases, each R8 is selected from halogens, -OR20, -CN, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, and C1-6 alkyl. In some cases, R7 is selected from...

[0117] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF) or formula (IIG), R7 is selected from optionally substituted phenyl groups. In some cases, each R8 is selected from halogens, -N(R20)2, -OR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), -NR20S(O)2R20, -C(O)N(R20)2, -C(=NR20)N(R20)2, -C(O)NR20OR20, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R20)C(O)OR20, -C(O)R20, -C(O)OR20, -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl. In some cases, each R8 is selected from halogen, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl. In some cases, each R20 is selected from hydrogen and C1-6 alkyl. In some cases, R7 is selected from phenyl, optionally substituted with one or more substituents selected from halogen and C1-6 hydroxyalkyl. In some cases, R7 is selected from , , , and .

[0118] In some embodiments,For compounds or salts of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG), R7 is selected from optionally substituted phenyl groups. In some cases, R7 is optionally substituted with one or more R8 groups. In some cases, each R8 is independently selected from halogens and -S(O)2 (R2O). In some cases, each R8 is independently selected from halogens and -S(O)2 (CH3). In some cases, R7 is selected from […].

[0119] In some embodiments, for compounds or salts of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG), R7 is selected from C8-C12 carbon rings, optionally substituted with one or more R8s. In some cases, the carbon ring is bicyclic. In some cases, the carbon ring is non-aromatic. In some cases, R7 is selected from C9 carbon rings, optionally substituted with one or more R8s. In some cases, R7 is... In some cases, R7 is...

[0120] In some embodiments, for compounds or salts of formulas (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG), R7 is selected from C5-C10 carbon rings and 5- to 10-membered heterocycles, each optionally substituted with one or more R8s. In some cases, the carbon ring is bicyclic. In some cases, the carbon ring is monocyclic. In some cases, the heterocycle is monocyclic. In some cases, R7 is selected from [missing information - likely a specific type of carbon ring], ... In some cases, R7 is selected from , , and , each optionally substituted by one or more R8s. In some cases, R7 is selected from and , each optionally substituted by one or more R8s. In some cases, R7 is , each optionally substituted by one or more R8s. In some cases, the heterocyclic ring is bicyclic. In some cases,Each R8 is independently selected from halogens, -N(R20)2, -OR20, -S(O)2(R20), -NR20S(O)2R20, -C(O)N(R20)2, C1-6 haloalkyl, C1-6 alkyl, and =O. In some cases, each R8 is independently selected from fluorine, -S(O)2(C1-6 alkyl), -C(O)NHCH3, -NHS(O)2C1-6 alkyl, -NHC1-6 alkyl, -NHS(O)2C1-6 alkyl-O-C1-6 alkyl, =O, -OMe, -CF3, and -CH3. In some cases, R7 is selected from... In some cases, R7 is selected from...

[0121] In one aspect, this disclosure provides compounds represented by the structure of formula (II): , or a pharmaceutically acceptable salt or solvate thereof; wherein AZ is selected from, wherein t represents the junction between Z and; Y is selected from -O-, -NR9-, -S- and -SO2-; each R50 is independently selected from hydrogen, halogen, C1-C6 alkyl; or combined to form; each R51 is independently selected from hydrogen, halogen and C1-C6 alkyl; k is selected from 1 and 2; A is selected from N and CR18; is selected from optionally substituted imidazoles, wherein the imidazoles are optionally substituted by one or more R14s; D is selected from N and CR19; R5 is selected from hydrogen and C1-6 alkyl; R7 is selected from hydrogen; and C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-C14 carbocyclic and 5 to 15-membered heterocycles, each optionally substituted by one or more R8s; Each R8 is independently selected from halogens, -N(R20)2, -OR20, -SR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), -NR20S(O)2R20, -C(O)N(R20)2, -C(=NR20)N(R20)2, -C(O)NR20OR20, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R20)C(O)OR20, -C(O)R20, -C(O)OR20, -OC(O)R20, -OC(O)N(R20)20, -NO2, =O, =N(R 20), =NO(R20), -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-C12 carbon rings and 4 to 12 membered heterocycles,The C1-6 alkyl group is optionally substituted with one or more R8* groups, and the C3-C12 carbon ring and the 4- to 12-membered heterocycle are each optionally substituted with one or more substituents selected from halogens, -OH, -CN, -NO2, -NH2, oxoyl, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, and C1-C6 alkoxyalkyl; each R8* is independently selected from 4- to 12-membered heterocycles, wherein the 4- to 12-membered heterocycles are optionally substituted with one or more substituents selected from halogens, -OH, -CN, -NO2, -NH2, oxoyl, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, and C1-C6 alkoxyalkyl. R9 is selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R20)2, C3-6 carbon ring, and 4- to 6-membered heterocycles.The C3-6 carbon ring and the 4- to 6-membered heterocycle are each optionally substituted by one or more substituents independently selected from halogens, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R20)2, C2-10 alkenyl, and C2-10 alkynyl; R14 is selected from halogens, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbon rings, and 3- to 12-membered heterocycles; R17 Selected from hydrogen, halogens, -N(R20)2, -OR20, -SR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N(R20)2, -S(O)R20(=NR20), -NR20S(O)2R20, -C(O)N(R20)2, -C(=NR20)N(R20)2, -C(O)NR20OR20, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R20)C(O)OR20, -C(O)R20, -C(O)OR20, -OC(O)R20, -OC(O) N(R20)2, -NO2, -CN, C1-6 alkyl, -N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-12 carbon ring and 5 to 12 membered heterocycles; Specification 54 / 240 pages 100 CN 121568943 A R18 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, -O-C1-10 alkyl, C1-C6 alkyl and C1-C6 haloalkyl; R19 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, -O-C1-10 alkyl, C1-C6 alkyl and C1-C6 haloalkyl; and R20 is independently selected from hydrogen each time it appears; C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-12 carbon ring and 3 to 12 membered heterocycles,Each of them may optionally be substituted by one or more substituents independently selected from the following: halogen, -OH, -CN, -NO2, -NH2, -S(O)2 (C1-6 alkyl), C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbon ring and 3 to 12 membered heterocycles.

[0122] In some embodiments, for compounds or salts of formula (II): Z is selected from, where t represents the junction between Z and; Y is selected from -O-, -NR9-, -S-, and -SO2-; each R50 is independently selected from hydrogen, halogen, C1-C6 alkyl; or combined to form; A is selected from N and CR18; is selected from optionally substituted imidazoles, wherein the imidazole is optionally substituted by one or more R14s; D is selected from N and CR19; R5 is selected from hydrogen and C1-6 alkyl; R7 is selected from hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-C14 carbocyclic and 5 to 15-membered heterocycles, each optionally substituted by one or more R8s; each R8 is independently selected from halogen, -N(R20)2, -OR20, -SR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N (R20)2, -S(O)R20(=NR20), -NR20S(O)2R20, -C(O)N(R20)2, -C(=NR20)N(R20)2, -C(O)NR20OR20, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R20)C(O)OR20, -C(O)R20, -C(O)OR20, -OC(O)R20, -OC(O)N(R20)2, -NO2, =O, =N(R20), =NO(R20), -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 The ring is composed of cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-C12 carbon ring, and 5- to 12-membered heterocycles, wherein the C3-C12 carbon ring and the 5- to 12-membered heterocycles are each optionally substituted by one or more substituents selected from halogen, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, and C1-C6 alkoxyalkyl; R9 is selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R20)2, C3-6 carbon ring, and 4- to 6-membered heterocycles.The C3-6 carbon ring and the 4- to 6-membered heterocycle are each optionally substituted by one or more substituents independently selected from halogens, -OH, -CN, -NO2, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R20)2, C2-10 alkenyl, and C2-10 alkynyl; R14 is selected from halogens, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbon rings, and 3- to 12-membered heterocycles; R17 Selected from hydrogen, halogens, -N(R20)2, -OR20, -SR20, -S(O)2(R20), -S(O)2N(R20)2, -S(O)N (R20)2, -S(O)R20(=NR20), -NR20S(O)2R20, -C(O)N(R20)2, -C(=NR20)N(R20)2, -C(O)NR20OR20, -N(R20)C(O)R20, -N(R20)C(O)N(R20)2, -N(R 20) C(O)OR20, -C(O)R20, -C(O)OR20, -OC(O)R20, -OC(O)N(R20)2, -NO2, -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbon ring and 5 to 12 membered heterocycles; R18 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, -O-C1-10 alkyl, C1-C6 alkyl and C1-C6 haloalkyl; R19 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, -O-C1-10 alkyl, C1-C6 alkyl, and C1-C6 haloalkyl; and R20 is independently selected from hydrogen each time it appears; C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-12 carbon ring, and 3 to 12 membered heterocycles.Each of them is optionally substituted by one or more substituents independently selected from: halogen, -OH, -CN, -NO2, -NH2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbide ring, and 3 to 12-membered heterocycles.

[0123] In some embodiments, for compounds or salts of formula (II), is selected from optionally substituted imidazoles, wherein the imidazoles are optionally substituted by one or more R14s. In some cases, is selected from , and , wherein q represents the connection point with Z, and wherein each is optionally substituted by one or more R14s. In some cases, is selected from , and , each of which is unsubstituted.

[0124] In some embodiments, for compounds or salts of formula (II), R14 is selected from halogens, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C3-12 carbon rings, and 3- to 12-membered heterocycles. In some cases, R14 is selected from halogens, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, and C3-6 carbon rings. In some cases, R14 is selected from halogens, -OH, -CN, -NO2, -NH2, -NHC1-10 alkyl, -N(C1-10 alkyl)2, C1-10 alkyl, -C1-10 haloalkyl, -O-C1-10 alkyl, C3-12 carbon rings, and 3- to 12-membered heterocycles. In some embodiments, R14 is selected from halogens, C1-10 alkyl groups, -C1-10 haloalkyl groups, -O-C1-10 alkyl groups, and C3-6 carbon rings. In some embodiments, R14 is selected from halogens, C1-10 alkyl groups, and C3-6 carbon rings. In some embodiments, R14 is selected from halogens and C1-10 alkyl groups.

[0125] In some embodiments, for compounds or salts of formula (II), Y is selected from -O-, -NR9-, -S-, and -SO2. In some embodiments, Y is -O-. In some embodiments, Y is -NR9-. In some embodiments, Y is -S-. In some embodiments, Y is -SO2. In some embodiments, Y is selected from -O- and -NR9-.

[0126] In some embodiments, for compounds or salts of formula (II), R9 is selected from hydrogen, C1-C6 alkyl groups, C1-C6 haloalkyl groups, and C3-6 carbon rings. In some cases, R9 is selected from hydrogen and C1-C6 alkyl. In some cases, R9 is hydrogen. In some cases, R9 is C1-C6 alkyl.

[0127] In some embodiments, for compounds or salts of formula (II), each R50 is independently selected from hydrogen, halogen, and C1-C6 alkyl. In some cases, each R50 is combined to form. In some cases,Each R50 is hydrogen. Specification 56 / 240 pages 102 CN 121568943 A

[0128] In some embodiments, for compounds or salts of formula (II), Z is. In some cases, Z is selected from. In some cases, Z is selected from. In some cases, Z is selected from. In some cases, Z is selected from. In some cases, Z is selected from.

[0129] In some embodiments, for compounds or salts of formula (II), Z is selected from, where t represents the connection point between Z and. In some cases, Z is selected from, where t represents the connection point between Z and. In some cases, Z is selected from, where t represents the connection point between Z and.

[0130] In some embodiments, for compounds or salts of formula (II), Z is selected from, where t represents the connection point between Z and.

[0131] In some embodiments, for compounds or salts of formula (II), R9 is selected from hydrogen, C1-C6 alkyl and C3-6 carbon ring.

[0132] In some embodiments, formula (II) is represented by formula (IIA): , or a pharmaceutically acceptable salt or solvation thereof.

[0133] In some embodiments, formula (II) is represented by formula (IIB): , or a pharmaceutically acceptable salt or solvation thereof.

[0134] In some embodiments, formula (II) is represented by formula (IIC): , or a pharmaceutically acceptable salt or solvation thereof.

[0135] In some embodiments, for compounds or salts of formula (II), formula (IIA), formula (IIB), or formula (IIC), A is selected from N and CH. In some cases, A is CH. In some cases, A is N.

[0136] In some embodiments, for compounds or salts of formula (II), formula (IIA), formula (IIB), or formula (IIC), A is selected from N, CF, and CH. In some cases, A is selected from N and CF. In some cases, A is selected from CF and CH. In some cases, A is CH. In some cases, A is N. In some cases, A is CF.

[0137] In some embodiments, for compounds or salts of formula (II), formula (IIA), formula (IIB), or formula (IIC), D is selected from N and CH. In some cases, D is CH. In some cases, D is N.

[0138] In some embodiments, for compounds or salts of formula (II), formula (IIA), formula (IIB), or formula (IIC), D is selected from N, CF, and CH. In some cases, D is selected from N and CF. In some cases, D is selected from CF and CH. In some cases, D is CH. In some cases, D is N. In some cases, D is CF.

[0139] In some embodiments,For compounds or salts of formula (II), (IIA), (IIB), or (IIC), R17 is selected from hydrogen, halogen, -N(R20)2, -OR 20, -NO2, -CN, C1-6 alkyl-N(R20)2, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 cyanoalkyl, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 carbon ring, and 5- to 6-membered heterocycles. In some cases, R17 is selected from hydrogen, halogen, -N(R20)2, -OR 20, -CN, C1-6 haloalkyl, C1-6 alkyl, C3-6 carbon ring, and 5- to 6-membered heterocycles. In some cases, R17 is selected from hydrogen, halogen, -O-C1-6 alkyl, C1-6 haloalkyl, C1-6 alkyl, and C3-6 carbon ring. In some cases, R17 is selected from hydrogen, -Br, -OCH3, -CF3, methyl, and cyclopropyl. In some cases, R17 is hydrogen. In some cases, R17 is a halogen. In some cases, R17 is a C1-6 haloalkyl. In some cases, R17 is selected from halogen and C1-6 haloalkyl. In some cases, R17 is -O-C1-6 alkyl. In some cases, R17 is a C3-6 carbon ring. In some cases, R17 is a C1-6 alkyl. In some cases, R17 is selected from hydrogen and C1-6 alkyl. In some cases, R17 is selected from hydrogen, C1-6 alkyl, and saturated C3-6 carbon ring.

[0140] In some embodiments, formula (II) or formula (IIA) is represented by formula (IID): (See specification 58 / 240 pages 104 CN 121568943 A), or a pharmaceutically acceptable salt or solvation thereof.

[0141] In some embodiments, formula (II) or formula (IIB) is represented by formula (IIE): , or a pharmaceutically acceptable salt or solvation thereof.

[0142] In some embodiments, formula (II) or formula (IIC) is represented by formula (IIF): , or a pharmaceutically acceptable salt or solvation thereof.

[0143] In some embodiments, formula (II) is represented by formula (IIF): , or a pharmaceutically acceptable salt or solvation thereof.

[0144] In some embodiments, for compounds or salts of formula (II), formula (IID), formula (IIE), formula (IIF), or formula (IIG), R17 is selected from hydrogen, halogen, -OR2O, C1-6 alkyl, C1-6 haloalkyl, saturated C3-6 carbon ring. In some cases, R17 is selected from hydrogen, F, Cl, Br, -OCH3, -CF3, methyl, and cyclopropyl. In some cases, R17 is hydrogen. In some cases, R17 is a halogen. In some cases, R17 is a C1-6 haloalkyl. In some cases, R17 is selected from halogens and C1-6 haloalkyl. In some cases, R17 is -O-C1-6 alkyl. In some cases,R17 is a saturated C3-6 carbon ring. In some cases, R17 is a C1-6 alkyl group. In some cases, R17 is selected from hydrogen and C1-6 alkyl groups. In some cases, R17 is selected from hydrogen, C1-6 alkyl groups, and saturated C3-6 carbon rings.

[0145] In some embodiments, for compounds or salts of formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG), each R8 is independently selected from halogens, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, -OR2O, -N(R2O)2, -NR20S(O)2R2O, -N(R2O)C(O)R2O, -C(O)N(R2O)2, and 4- to 6-membered heterocycles, wherein the 4- to 6-membered heterocycles are optionally replaced by one or more selected from halogens, -OH, -CN, -NH2, oxo, C1-6 alkyl, -C1-6 haloalkyl, and - The C1-6 alkyl group of R8 is substituted with a substituent; and wherein the C1-6 alkyl group of R8 is optionally substituted with a 4- to 6-membered heterocycle, wherein the 4- to 6-membered heterocycle is optionally substituted with one or more substituents selected from halogens. In some cases, each R20 is independently selected from hydrogen each time it appears; the C1-6 alkyl group, the C3-6 carbon ring, and the 4- to 5-membered heterocycle are each optionally substituted with one or more substituents independently selected from halogens, -OH, -CN, -NH2, -S(O)2(C1-6 alkyl), C1-6 alkyl, -C1-6 haloalkyl, -O-C1-6 alkyl, C3-6 carbon ring, and the 4- to 5-membered heterocycle. In some cases, each R8 is independently selected from F, methyl, ethyl, etc.

[0146] In some embodiments, for compounds or salts of formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG), R7 is selected from C4-C6 carbon rings, which are optionally substituted with one or more R8s. In some cases, R7 is selected from [missing information], [missing information], and [missing information], which are optionally substituted with one or more R8s. In some cases, R7 is [missing information], which is optionally substituted with one or more R8s. In some cases, R7 is [missing information], which is substituted with one R8. In some cases, each R8 is independently selected from halogens, C1-6 alkyl groups, C1-6 haloalkyl groups, C1-6 hydroxyalkyl groups, -OR20, -N(R20)2, -NR20S(O)2R20, -N(R20)C(O)R20, -C(O)N(R20)2, -S(O)2(R20), and 4 to 6 membered heterocycles.The 4- to 6-membered heterocycle is optionally substituted with one or more substituents selected from halogens, -OH, -CN, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl, and -O-C1-10 alkyl; and the C1-6 alkyl of R8 is optionally substituted with a 4- to 6-membered heterocycle, wherein the 4- to 6-membered heterocycle is optionally substituted with one or more substituents selected from halogens. In some cases, each R8 is independently selected from F, methyl, ethyl, etc. In some cases, each R8 is independently selected from -OR20. In some cases, each R8 is independently selected from -OR20, wherein R20 is selected from C1-6 alkyl, wherein the C1-6 alkyl is substituted by one or more substituents independently selected from halogens, -OH, -CN, -C1-10 haloalkyl, -S(O)2(C1-6 alkyl), -O-C1-10 alkyl, C3-5 carbon rings, and 4- to 5-membered heterocycles. In some cases, each R8 is independently selected from [missing information - likely a specific type of alkyl group]. In some cases, each R8 is independently selected from [missing information - likely a specific type of alkyl group]. In some cases, each R8 is independently selected from [missing information - likely a specific type of alkyl group]. In some cases, each R8 is independently selected from -OR20, wherein R20 is selected from C1-6 alkyl, wherein the C1-6 alkyl is substituted by one or more substituents independently selected from halogens. In some cases, each R8 is independently selected from , , and . In some cases, each R8 is independently selected from -OR20, wherein R20 is selected from C1-6 alkyl, wherein the C1-6 alkyl is substituted by one or more substituents independently selected from -S(O)2(C1-6 alkyl). In some cases, each R8 is . In some cases, each R8 is independently selected from -OR20, wherein R20 is selected from C1-6 alkyl, wherein the C1-6 alkyl is substituted by one or more substituents independently selected from 5-membered heterocycles. In some cases, the heterocycle contains one oxygen atom. In some cases, each R8 is . In some embodiments, for compounds or salts of formula (II), (IID), (IIE), (IIF), or (IIG), R7 is selected from a C4-C7 carbon ring, optionally substituted with one or more R8s. In some cases, R7 is selected from a C4-C6 carbon ring, optionally substituted with one or more R8s. In some cases, R7 is selected from [missing information - likely a specific type of compound], ...It is optionally replaced by one or more R8s. In some cases, R7 is selected from , and , and is optionally replaced by one or more R8s. In some cases, R7 is selected from , and is optionally replaced by one or more R8s. In some cases, R7 is selected from , and is optionally replaced by one or more R8s. In some cases, each R8 is independently selected from halogens, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, -OR20, -N(R20)2, -NR 20S(O)2R 20, -N(R20)C(O)R20, -C(O)N (R20)2, -S(O)2(R 20) and 4- to 6-membered heterocycles, wherein the 4- to 6-membered heterocycles are optionally substituted by one or more substituents selected from halogens, -OH, -CN, -NH2, oxo, C1-10 alkyl, -C1-10 haloalkyl and -O-C1-10 alkyl; and wherein the C1-6 alkyl of R8 is optionally substituted by a 4- to 6-membered heterocycle, wherein the 4- to 6-membered heterocycle is optionally substituted by one or more substituents selected from halogens. In some cases, each R8 is independently selected from F, methyl, ethyl, (see specification 62 / 240 page 108 CN 121568943 A). In some cases, R7 is. In some cases, each R8 is independently selected from C1-6 hydroxyalkyl, C1-6 alkyl, and C1-6 haloalkyl. In some cases, R7 is selected from, , , , , , and. In some cases, each R8 is independently selected from C1-6 alkyl. In some cases, R7 is selected from, and.

[0147] In some embodiments, for compounds or salts of formula (II), formula (IID), formula (IIE), formula (IIF), or formula (IIG), R7 is (see specification 63 / 240 page 109 CN 121568943 A, specification 64 / 240 page 110 CN 121568943 A).

[0148] In some embodiments, for compounds or salts of formula (II), formula (IID), formula (IIE), formula (IIF), or formula (IIG), R7 is selected from CN 121568943 A, page 65 / 240 of the specification.

[0149] In some embodiments, for compounds or salts of formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG), R7 is. In some cases, R7 is selected from. In some cases, R7 is. In some cases, R7 is selected from, and. In some cases, R7 is. In some cases, R7 is. In some cases,R7, as specified in the specification (page 66 / 240, CN 121568943 A), is substituted with at least one R8 selected from C1-6 alkyl, C1-6 hydroxyalkyl, and C1-6 haloalkyl groups. In some cases, R7 is selected from [specific group]. In some cases, R7 is substituted with at least one R8 selected from -S(O)2(R20). In some cases, R7 is [specific group]. In some cases, R7 is substituted with at least one R8 selected from -N(R20)2. In some cases, R7 is selected from [specific group].

[0150] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG), R7 is selected from CN 121568943 A on page 67 / 240 of the specification and CN 121568943 A on page 68 / 240 of the specification. In some cases, R7 is selected from CN 121568943 A on page 69 / 240 of the specification and CN 121568943 A on page 70 / 240 of the specification. In some cases, R7 is selected from CN 121568943 A on page 71 / 240 of the specification. In some cases, R7 is selected from CN 121568943 A, page 72 / 240. In some cases, R7 is selected from CN 121568943 A, page 73 / 240.

[0151] In some embodiments, for compounds or salts of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG), each R8 is independently selected from fluorine, oxo group, CN 121568943 A, page 74 / 240. In some cases, each R8 is independently selected from fluorine, oxo group, CN 121568943 A, page 75 / 240. In some cases, each R8 is independently selected from fluorine. In some cases, each R8 is independently selected from fluorine.

[0152] In some embodiments, for compounds or salts of formulas (II), (IIA), (IIB), and (IIC), A is selected from N and CR18. In some cases, D is selected from N and CR19. In some cases, A is N.And D is N. In some cases, A is N and D is CR19. In some cases, A is CR18 and D is selected from N. In some cases, A is CR18 and D is selected from CR19. In some cases, R17 is selected from hydrogen, halogen, -OMe, C1-6 haloalkyl, C1-6 alkyl and C3 carbon ring. In some cases, R18 is selected from hydrogen and halogen. In some cases, R19 is selected from hydrogen and halogen.

[0153] In some embodiments, for compounds or salts of formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF) or formula (IIG), the substituents are selected from the compounds in the Example section.

[0154] In some embodiments, compounds of formula (II), formula (IIA), or formula (IID) are selected from the specification, page 76 / 240, 122 CN 121568943 A, and, or pharmaceutically acceptable salts of any of them.

[0155] Chemical entities having carbon-carbon double bonds or carbon-nitrogen double bonds may exist in Z or E forms (or cis or trans forms). In addition, some chemical entities may exist in various tautomeric forms. Unless otherwise specified, the compounds described herein are also intended to include all Z, E, and tautomeric forms.

[0156] An “isomer” is a different compound having the same molecular formula. A “stereoisomer” is an isomer that differs only in the way the atoms are arranged in space. An “enantiomer” is a pair of stereoisomers that are non-overlapping mirror images of each other. A 1:1 mixture of a pair of enantiomers is a “racemic” mixture. When appropriate, the term “(±)” is used to specify a racemic mixture. A “diastereomer” or “diastereomer” is a stereoisomer having at least two asymmetric atoms, but which are not mirror images of each other. Absolute stereochemistry is specified according to the Cahn-Ingold-Prelog R-S system. When a compound is a pure enantiomer, the stereochemistry at each chiral carbon can be specified using R or S. Resolved compounds with unknown absolute configurations can be specified as (+) or (-) depending on the direction (right-handed or left-handed) in which they rotate plane-polarized light at the wavelength of the sodium D line. Some compounds described herein contain one or more asymmetric centers, thus producing enantiomers, diastereomers, and other stereoisomers whose asymmetric centers can be defined as (R)- or (S)- in terms of absolute stereochemistry. The chemical entities, pharmaceutical compositions, and methods of the present invention are intended to include all such possible stereoisomers, including racemic mixtures, optically pure forms, mixtures of diastereomers, and mixtures of intermediates. Optically active (R)-isomers and (S)-isomers can be prepared using chiral synthons or chiral reagents.Alternatively, conventional techniques can be used for resolution. The optical activity of the compound can be analyzed by any suitable method, including but not limited to chiral chromatography and polarization assays, and the degree of dominance of one stereoisomer relative to another can be determined.

[0157] When stereochemistry is not specified, molecules having a stereocenter as described herein include isomers, such as enantiomers and diastereomers; mixtures of enantiomers, including racemates; mixtures of diastereomers; and other mixtures thereof, provided they can be prepared by those skilled in the art through conventional experiments. In some embodiments, a single enantiomer or diastereomer, i.e., the optically active form, can be obtained by asymmetric synthesis or by resolving a mixture of racemates or diastereomers. If possible, the resolution of a mixture of racemates or diastereomers can be achieved, for example, by conventional methods such as crystallization in the presence of a resolving agent, or by chromatography using, for example, a chiral high-performance liquid chromatography (HPLC) column. Furthermore, a mixture of two enantiomers rich in one of the two enantiomers can be purified by recrystallization and / or wet milling to provide a further optically enriched form of the major enantiomer.

[0158] In some embodiments, the compositions of this disclosure may comprise two or more enantiomers or diastereomers of the compound, wherein a single enantiomer or diastereomer accounts for at least about 70% by weight, at least about 80% by weight, at least about 90% by weight, at least about 98% by weight, or at least about 99% by weight or more of the total weight of all stereoisomers. Methods for producing substantially pure enantiomers are well known to those skilled in the art. For example, a single stereoisomer substantially free of its stereoisomers (see specification 77 / 240 pages 123 CN 121568943 A). For example, an enantiomer can be obtained by resolving a racemic mixture using methods such as forming a diastereomer using an optically active resolving agent (Stereochemistry of Carbon Compounds, (1962), EL Eliel, McGraw Hill; Lochmuller (1975) J. Chromatogr., 113(3): 283-302). Racemic mixtures of chiral compounds can be separated and isolated by any suitable method, including but not limited to: (1) forming ionic diastereomeric salts with the chiral compound and separating them by fractional crystallization or other methods; (2) forming diastereomeric compounds with a chiral derivatizing agent, separating the diastereomers, and converting them into pure stereoisomers; and (3) directly separating substantially pure or enriched stereoisomers under chiral conditions. Another method for separating enantiomers is to use a Diacel chiral column and eluent with an organic mobile phase.Such as by Chiral Technologies (www.chiraltech.com) on a service charge basis.

[0159] “Tautomer” refers to a molecule in which a proton is likely to move from one atom of the molecule to another atom of the same molecule. In some embodiments, the compounds provided herein are present in tautomer form. In cases where tautomerism is possible, a chemical equilibrium of tautomers will exist. The precise ratio of tautomers depends on several factors, including physical state, temperature, solvent, and pH. Some examples of tautomer equilibria include: .

[0160] In some embodiments, the compounds disclosed herein are used in different enriched isotopic forms, for example, enriched in terms of the content of 2H, 3H, 11C, 13C, and / or 14C. In a particular embodiment, the compound is deuterated at at least one position. Such deuterated forms can be prepared by the procedures described in U.S. Patent Nos. 5,846,514 and 6,334,997. As described in U.S. Patents 5,846,514 and 6,334,997, deuteration can improve metabolic stability and / or efficacy, thereby increasing the duration of drug action.

[0161] Unless otherwise stated, the compounds described herein are intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the structure of the invention, except that hydrogen is replaced by deuterium or tritium, or carbon is replaced by 13C or 14C enriched carbon, are within the scope of this disclosure.

[0162] The compounds of this disclosure optionally contain atomic isotopes in non-natural proportions at one or more atoms constituting such compounds. For example, the compounds may be labeled with isotopes such as deuterium (2H), tritium (3H), iodine-125 (125I), or carbon-14 (14C). Isotopic substitutions using 2H, 11C, 13C, 14C, 15C, 12N, 13N, 15N, 16N, 16O, 17O, 14F, 15F, 16F, 17F, 18F, 33S, 34S, 35S, 36S, 35Cl, 37Cl, 79Br, 81Br, and 125I are all taken into consideration. All isotopic variations of the compounds of the present invention, whether or not radioactive, are covered within the scope of the present invention. Specification 78 / 240 pages 124 CN 121568943 A

[0163] In some embodiments, some or all of the 1H atoms of the compounds disclosed herein are replaced by 2H atoms. Methods for synthesizing deuterium-containing compounds are known in the art, and are described only by way of non-limiting examples.The following synthetic methods are included.

[0164] Deuterium-substituted compounds were synthesized using various methods such as those described in the following: Dean, Dennis C., ed. Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [Curr., Pharm. Des., 2000; 6(10)] 2000, p. 110; George W.; Varma, Rajender S. The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21; and Evans, E. Anthony. Synthesis of radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32.

[0165] Deuteration starting materials are readily available and can be synthesized using the methods described herein to provide the synthesis of deuterium-containing compounds. A wide variety of deuterium-containing reagents and building blocks are commercially available from chemical suppliers such as Aldrich Chemical Co.

[0166] The compounds of the present invention also include crystalline and amorphous forms of these compounds, pharmaceutically acceptable salts, and active metabolites of these compounds having the same type of activity, including, for example, polymorphs, pseudopolymorphs, solvates, hydrates, unsolvated polymorphs (including anhydrous forms), conformational polymorphs and amorphous forms of the compounds, and mixtures thereof.

[0167] This disclosure includes salts of the compounds described herein, particularly pharmaceutically acceptable salts. Compounds of this disclosure having sufficiently acidic functional groups, sufficiently basic functional groups, or both, can react with a number of inorganic bases and any of inorganic and organic acids to form salts. Alternatively, compounds with an inherently charged band, such as those having a quaternary nitrogen, can form salts with suitable counterions such as halide ions such as bromide, chloride, or fluoride ions, particularly bromide ions.

[0168] The methods and compositions described herein include the use of amorphous forms as well as crystalline forms (also known as polymorphs). The compounds described herein may be in pharmaceutically acceptable salt forms. Similarly, in some embodiments, active metabolites of these compounds having the same type of activity are included within the scope of this disclosure. Furthermore,The compounds described herein may exist in unsolvated form as well as in solvated form with pharmaceutically acceptable solvents such as water, ethanol, etc. The solvated form of the compounds provided herein is also considered to be disclosed herein.

[0169] In some embodiments, the compound or a salt of the compound may be a prodrug, for example, wherein the hydroxyl group in the parent compound is presented as an ester or carbonate, or the carboxylic acid present in the parent compound is presented as an ester. The term "prodrug" is intended to cover compounds that are converted into the pharmaceutical agents disclosed herein under physiological conditions. One method for preparing a prodrug involves hydrolyzing one or more selected portions of the desired molecule under physiological conditions to expose them. In other embodiments, the prodrug is converted by the enzymatic activity of a host animal, such as specific target cells in the host animal. For example, esters or carbonates (e.g., esters or carbonates of alcohols or carboxylic acids, and esters of phosphonates) are preferred prodrugs of this disclosure.

[0170] Prodrugs are often useful because, in some cases, they may be easier to administer than the parent drug. They may achieve bioavailability, for example, by oral administration, which is not possible with the parent drug. Prodrugs can help enhance the cellular permeability of the compound relative to the parent drug. Compared to the parent drug, the prodrug may also have improved solubility in the pharmaceutical composition. The prodrug may be designed as a reversible drug derivative to act as a modulator to enhance drug transport to site-specific tissues or increase drug retention within cells.

[0171] In some embodiments, the prodrug is designed to increase the lipophilicity of the agent. In some embodiments,The design of the prodrug increases its effective water solubility. See, for example, Fedorak et al., Am. J. Physiol., 269:G210-218 (1995); McLoed et al., Gastroenterol, 106:405-413 (1994); Hochhaus et al., Biomed. Chrom., 6:283-286 (1992); J. Larsen and H. Bundgaard, Int. J. Pharmaceutics, 37, 87, 79 / 240 pages, 125 CN 121568943 A (1987); J. Larsen et al., Int. J. Pharmaceutics, 47, 103 (1988); Sinkula et al., J. Pharm. Sci., 64:181-210 (1975); T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Volume 14 of the A.C.S. Symposium Series; and Edward B. Roche, Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987, all of which are incorporated herein by reference in this disclosure. According to another embodiment, this disclosure provides a method for producing compounds as defined above. The compounds can be synthesized using conventional techniques. Advantageously, these compounds are conveniently synthesized from readily available starting materials.

[0172] Synthetic chemical transformations and methods that can be used to synthesize the compounds described herein are known in the art.And including, for example, those described in R. Larock, Comprehensive Organic Transformations (1989); TW Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 2nd edition (1991); L. Fieser and M. Fieser, Fieser and Fieser's Reagents for Organic Synthesis (1994); and L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis (1995).

[0173] Pharmaceutical formulations containing compounds or salts of any of the formulas or sub-formulas described herein (e.g., formulas (I), (IA), (IB), (IC), or (ID) etc.)) can be formulated into any suitable pharmaceutical formulation. Pharmaceutical formulations of this disclosure typically contain an active ingredient (e.g., a compound or salt of any of the formulas described herein) and one or more pharmaceutically acceptable excipients or carriers, including but not limited to: inert solid diluents and fillers, diluents, sterile aqueous solutions and various organic solvents, penetration enhancers, antioxidants, solubilizers, and excipients.

[0174] In some embodiments, a compound or salt of any of the formulas or subformulas described herein is formulated with an agent that inhibits the degradation of said compound or salt. In some embodiments, the compound or salt is formulated with one or more antioxidants. Acceptable antioxidants include, but are not limited to, citric acid, d,1-α-tocopherol, BHA, BHT, monothioglycerol, ascorbate palmitate, ascorbic acid, and propyl gallate. In some embodiments, the formulation contains 0.1 to 30%, 0.5 to 25%, 1 to 20%, 5 to 15%, or 7 to 12% (wt / wt) CCI-779, 0.5 to 50%, 1 to 40%, 5 to 35%, 10 to 25%, or 15 to 20% (wt / wt) of a water-soluble polymer, 0.5 to 10%, 1 to 8%, or 3 to 5% (wt / wt) of a surfactant, and 0.001% to 1%, 0.01% to 1%, or 0.1% to 0.5%. (wt / wt) antioxidant. In some embodiments, the antioxidant in the formulation of the present invention will be used at a concentration ranging from 0.001% to 3% wt / wt.

[0175] In some embodiments,Compounds or salts of any of the formulas or sub-formulas described herein are formulated with a pH adjuster to maintain a pH of about 4 to about 6. Acceptable pH adjusters include, but are not limited to, citric acid, sodium citrate, dilute HCl, and other weak acids or bases capable of buffering solutions containing compounds or salts of the present disclosure to a pH in the range of about 4 to about 6.

[0176] In some embodiments, compounds or salts of any of the formulas or sub-formulas described herein are formulated with a chelating agent or other material capable of binding metal ions, such as ethylenediaminetetraacetic acid (EDTA) and its salts, which can enhance the stability of compounds or salts of any of the formulas described herein.

[0177] Pharmaceutical formulations may be provided in any suitable form, depending on the route of administration. In some embodiments, the pharmaceutical compositions disclosed herein may be formulated into dosage forms for administration to a subject. In some embodiments, the pharmaceutical compositions are formulated for oral, intravenous, intra-arterial, aerosol, parenteral, buccal, topical, transdermal, rectal, intramuscular, subcutaneous, intraosseous, intranasal, intrapulmonary, mucosal, inhalation, and / or intraperitoneal administration. In some embodiments, the dosage form is formulated for oral administration. For example, the pharmaceutical composition may be formulated as a pill, tablet, capsule, inhaler, liquid suspension, liquid emulsion, gel, or powder. In some embodiments, the pharmaceutical composition may be formulated as a unit dose in liquid, gel, semi-liquid, semi-solid, or solid form.

[0178] The amount of any compound or salt of any of the formulas or sub-formulas described herein will depend on the mammal being treated, the severity of the condition or disease, the rate of administration, the disposal of any compound or salt of any of the formulas or sub-formulas described herein, and the judgment of the prescribing physician.

[0179] In some embodiments, a pharmaceutically acceptable carrier for any compound or salt of any of the formulas or sub-formulas described herein may include a physiologically acceptable compound that is an antioxidant.

[0180] In some embodiments, this disclosure provides a pharmaceutical composition for oral administration, the pharmaceutical composition comprising at least one compound or salt of any of the formulas or sub-formulas described herein and a pharmaceutical excipient suitable for oral administration. The composition may be in solid, liquid, gel, semi-liquid, or semi-solid form. In some embodiments, the composition further comprises a second agent.

[0181] Pharmaceutical compositions of the present disclosure suitable for oral administration may be presented in discrete dosage forms, such as hard or soft capsules, flat capsules, lozenges, sugar tablets, or tablets.These dosage forms may be liquids or aerosols (each containing a predetermined amount of an active ingredient in powder or granule form), solutions, or suspensions in aqueous or non-aqueous liquids, oil-in-water emulsions, or water-in-oil liquid emulsions, or dispersible powders or granules, or syrups or elixirs. Such dosage forms can be prepared by any of pharmaceutical methods that typically include the step of associating one or more active ingredients with a carrier. Generally, compositions are prepared by uniformly and tightly blending one or more active ingredients with a liquid carrier or a finely dispersed solid carrier, or both, followed by shaping the product into the desired appearance, if necessary. For example, tablets can be prepared by compression or molding, optionally with one or more excipients. Compressed tablets can be prepared by compressing one or more active ingredients in a free-flowing form (such as powder or granules) optionally mixed with excipients such as, but not limited to, binders, lubricants, inert diluents, and / or surfactants or dispersants, in a suitable machine. Molded tablets can be prepared by molding a powder of any of the formulas or sub-formulas described herein, moistened with an inert liquid diluent, in a suitable machine.

[0182] In some embodiments, this disclosure provides a pharmaceutical composition for injection containing a compound or salt of any of the formulas described herein and a pharmaceutical excipient suitable for injection. The components and amounts of the agents in the composition are as described herein.

[0183] In some embodiments, the compound or salt of any of the formulas or sub-formulas described herein can be formulated as an aqueous or oily suspension; an emulsion containing sesame oil, corn oil, cottonseed oil, or peanut oil; and elixirs, mannitol, dextrose, or sterile aqueous solutions and similar pharmaceutical carriers for injection.

[0184] Aqueous solutions in saline are also conventionally used for injection. Ethanol, glycerol, propylene glycol, liquid polyethylene glycol, etc. (and suitable mixtures thereof), cyclodextrin derivatives, and vegetable oils may also be used. Suitable flowability can be achieved, for example, by using a coating such as lecithin, in the case of a dispersion, by maintaining the desired particle size.And maintained by the use of surfactants. The antimicrobial effect can be achieved by various antibacterial and antifungal agents such as parabens, chlorobutanol, phenol, sorbic acid, thimerosal, etc.

[0185] The pharmaceutical composition can also be prepared from compounds or salts of any of the formulas or subformulas described herein, and one or more pharmaceutically acceptable excipients suitable for transdermal, inhalation, sublingual, buccal, rectal, intraosseous, intraocular, intranasal, epidural, or spinal administration. The preparation of such pharmaceutical compositions is well known in the art. See, for example, Anderson, Philip O.; Knoben, James E.; Troutman, William G., eds., Handbook of Clinical Drug Data, 10th edition, McGraw-Hill, 2002; Pratt and Taylor, eds., Principles of Drug Action, 3rd edition, Churchill Livingston, New York, 1990; Katzung, ed., Basic and Clinical Manual, 81 / 240 pages, 127 CN 121568943 A Pharmacology, 9th edition, McGraw-Hill, 2003; Goodman and Gilman, eds., The Pharmacological Basis of Therapeutics, 10th edition, McGraw-Hill, 2001; Remingtons Pharmaceutical Sciences, 20th edition, Lippincott Williams & Wilkins, 2000; Martindale, The Extra Pharmacopoeia, 32nd edition (The Pharmaceutical Press, London, 1999).

[0186] This disclosure also provides kits. Kits may include a compound or salt of any of the formulas or subforms described herein and one or more additional agents in a suitable package, and may include written materials such as instructions for use, clinical study discussions, a list of side effects, etc. Such kits may also include information indicating or determining the activity and / or benefits of the composition, and / or describing administration, application, side effects, drug interactions, such as scientific references, package inserts, clinical trial results and / or summaries of this information; or other information useful to healthcare providers. Such information may be based on the results of various studies, such as those using laboratory animals.Studies involving in vivo models and studies based on human clinical trials. The kit may also contain another agent. In some embodiments, the compound or salt of any of the formulas or sub-formulas described herein and the agent are provided as a separate composition in a separate container within the kit. In some embodiments, the compound or salt of any of the formulas or sub-formulas described herein and the agent are provided as a single composition in a container within the kit. Suitable packaging and additional supplies (e.g., measuring cups for liquid formulations, foil packaging materials to minimize air exposure, etc.) are known in the art and may be included in the kit. The kits described herein may be available, sold and / or marketed to healthcare providers, including physicians, nurses, pharmacists, prescribing officers, etc. In some embodiments, the kit may also be sold directly to consumers.

[0187] Therapeutic applications In one aspect, this disclosure provides a method of inhibiting CD38, comprising administering a compound or salt of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF) or formula (IIG). In some cases, the method includes inhibiting CD38 by administering a pharmaceutical composition comprising a compound or salt of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG), and a pharmaceutically acceptable excipient thereof.

[0188] In some aspects,This disclosure provides a method for treating a disease or condition. The method includes administering the disclosed compound or salt or pharmaceutical composition to a subject in need. The disease or condition is selected from: neurodegenerative diseases, type 1 diabetes, insulin resistance, Leber hereditary amaurosis, Parkinson's disease, amyotrophic lateral sclerosis, chronic lymphocytic leukemia, periodontal disease, psoriasis, UV-induced skin damage, radiation protection, diabetic neuropathy, hyperpigmentation, pellagra, hereditary niacin deficiency, diabetes, Huntington's disease, bipolar disorder, schizophrenia, postmenopausal osteoporosis, optic neuropathy, neurocognitive impairment, multiple sclerosis, Alzheimer's disease, fatty degeneration, NASH, hearing loss, dyslipidemia, end-stage renal disease, metabolic syndrome, obesity, sarcopenic obesity, gout, irritable bowel syndrome, colitis, COPD, asthma, cystic fibrosis, pancreatitis, and idiopathic pulmonary fibrosis. Organ reperfusion injury, stroke, muscular dystrophy, cardiac hypertrophy, CHF, leishmaniasis, tuberculosis, Hansen's disease, hypoxic pulmonary vasoconstriction, hypertension, clear cell renal cell carcinoma, small pulmonary cell carcinoma, exercise intolerance, epilepsy, sleep disorders, ataxia-telangiectasia, rheumatoid arthritis, lupus, alcohol intolerance, hyperphosphatemia, acute lung injury, and ARDS. In some cases, the disease or condition is a neurodegenerative disease. In some cases, the disease or condition is muscular dystrophy. In some cases, the disease or condition is a metabolic disorder. In some cases, the disease or condition is fibrosis. In some cases, the disease or condition is Duchenne muscular dystrophy. In some cases, the disease or condition is systemic sclerosis. In some cases, the disease or condition is selected from encephalopathy, vascular disease, liver disease, muscle disease, pancreatic disease, adipose tissue-related disease, and inflammation-related disease. Instructions for Use, 82 / 240 pages, 128 CN 121568943 A

[0189] In some cases, a compound or salt of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG) is applied to a subject in need to inhibit CD38 and thereby increase NAD+ levels. In some cases, increasing NAD+ levels may help treat diseases or conditions that have been shown to benefit from NAD+, including mitochondrial-related diseases or conditions.

[0190] In some embodiments, a compound or salt of formula (I), formula (IA), formula (IB), formula (IC), formula (ID), formula (II), formula (IIA), formula (IIB), formula (IIC), formula (IID), formula (IIE), formula (IIF), or formula (IIG) is applied to a subject in need,Used for the treatment and / or prevention of neurodegenerative diseases, type 1 diabetes, insulin resistance, Leber hereditary amaurosis, Parkinson's disease, amyotrophic lateral sclerosis, chronic lymphocytic leukemia, periodontitis, psoriasis, UV-induced skin damage, radiation protection, diabetic neuropathy, hyperpigmentation, pellagra, hereditary niacin deficiency, diabetes, Huntington's disease, bipolar disorder, schizophrenia, postmenopausal osteoporosis, optic neuropathy, neurocognitive impairment, multiple sclerosis, Alzheimer's disease, fatty degeneration, NASH, hearing loss, dyslipidemia, end-stage renal disease, metabolic syndrome, obesity, sarcopenic obesity, gout, irritable bowel syndrome, colitis, COPD, asthma, cystic fibrosis, pancreatitis, idiopathic pulmonary fibrosis, organ reperfusion injury, stroke, muscular dystrophy, cardiac hypertrophy, CHF, leishmaniasis, and tuberculosis. Hansen's disease, hypoxic pulmonary vasoconstriction, hypertension, clear cell renal cell carcinoma, small lung cell carcinoma, exercise intolerance, epilepsy, sleep disorders, ataxia-telangiectasia, rheumatoid arthritis, lupus, alcohol intolerance, hyperphosphatemia, acute lung injury, and ARDS.

[0191] In some cases, a pharmaceutical composition comprising a compound or salt of formula (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIF), or (IIG) and a pharmaceutically acceptable excipient is administered to a subject in need for the treatment of the disease or condition described herein.

[0192] In some embodiments, the compound is selected from , , , and , or salts thereof.

[0193] Preparation of the Compounds The compounds disclosed herein can generally be prepared by a variety of methods well known to those skilled in the art of organic synthesis. For example, the compounds of this disclosure can be synthesized using the methods described herein as well as synthetic methods known in the field of synthetic organic chemistry, or variations thereof as understood by those skilled in the art.

[0194] Synthesis schemes of compounds of general formula (I) and sub-formula Synthesis scheme I Specification 83 / 240 pages 129 CN 121568943 A

[0195] Synthesis schemes of compounds of formula (II) and sub-formula Synthesis scheme II

[0196] First, the corresponding phenol and primary alcohol can be subjected to a Mitsunobu reaction using triphenylphosphine to generate the desired ether. Then, intramolecular Buckwald coupling can be performed using a palladium catalyst and a base to generate the desired oxo-nitrogen hybrid. It can be saponified with lithium hydroxide to generate the corresponding lithium carboxylate. Then, it can be coupled with the desired amine using amide coupling conditions.To generate the final synthetic compound.

[0197] Synthesis Scheme III Specification 84 / 240 pages 130 CN 121568943 A

[0198] The corresponding phenol and primary alcohol can be reacted with triphenylphosphine using a Mitsunobu reaction to generate the desired ether. This can then be intramolecularly Buckwald coupled using a palladium catalyst and a base to generate the desired oxo-nitrogen hybrid. This can be saponified with lithium hydroxide to generate the corresponding lithium carboxylate. It can then be coupled with the desired amine using amide coupling conditions to generate the final synthetic compound.

[0199] Synthesis Scheme IV

[0200] The corresponding phenol can be coupled with a chloroacetyl group to generate the desired ether. It can be deprotected and cyclized using an acid to generate a cyclic imine. Reaction with tosmic yields the desired imidazole compound. This can be saponified with lithium hydroxide to generate the corresponding lithium carboxylate. It can then be coupled with the desired amine using amide coupling conditions to generate the final synthetic compound.

[0201] Synthesis Scheme V

[0202] First, the corresponding aromatic aldehyde is condensed with ethanolamine to generate the desired imine. Then, it is reacted with Tosmic to generate the substituted imidazole compound. Mitsunobu of phenol and alcohol using triphenylphosphine generates an oxonium-nitrogen hybrid. Saponification with lithium hydroxide generates the corresponding lithium carboxylate salt. It can then be coupled with the desired amine under amide coupling conditions to generate the final synthetic compound. Specification 85 / 240 pages 131 CN 121568943 A

[0203] Synthesis Scheme VI

[0204] First, the corresponding F aromatic ester is reacted with a protected glycine derivative under SNAr conditions. Then, the isolated nitro compound is reduced with iron and acetic acid, which is catalytically cyclized to form a bicyclic substance. Then, it is oxidized with hydrogen peroxide to a suitable quinoxaline. It is reacted with Tosmic to generate the desired fused imidazole ring system. Saponification with lithium hydroxide generates the corresponding lithium carboxylate salt. Then, it can be coupled with the desired amine using amide coupling conditions to generate the final synthetic compound.

[0205] Synthesis Scheme VII

[0206] First, the corresponding primary alcohol is converted to the corresponding chloride using thionyl chloride. It can be reacted with a base with a substituted phenol to generate the desired ether. Then, intramolecular Buchwald coupling can be performed using a palladium catalyst and a base to generate the desired oxazine-heptanine, and the acid generated by the attempt to isolate it is immediately coupled with the desired amine using amide coupling conditions to generate the final synthetic compound.

[0207] Synthesis Scheme VIII Specification 86 / 240 pages 132 CN 121568943 A

[0208] First, the corresponding amide is reacted with iodomethane and potassium carbonate to generate an N-methylated compound, which was confirmed by NOESY. Saponification with lithium hydroxide,The corresponding lithium carboxylate salt is generated. It can then be coupled with the desired amine under amide coupling conditions to generate the final synthetic compound.

[0209] Synthetic Scheme IX

[0210] First, the corresponding aromatic aldehyde is condensed with 3-amino-1-propanol to generate the desired imine. It is then reacted with TosMIC to generate a substituted imidazole compound. The Mitsunobu reaction of phenol and alcohol using triphenylphosphine generates an 8-membered heterocycle. It is saponified with lithium hydroxide to generate the corresponding lithium carboxylate salt. It can then be coupled with the desired amine under amide coupling conditions to generate the final synthetic compound.

[0211] Synthetic Scheme X

[0212] First, the corresponding amide is reacted with POCl3 to generate a chlorinated compound. It is then reacted with the corresponding amine to generate the desired aniline-substituted compound. It is saponified with lithium hydroxide to generate the corresponding lithium carboxylate salt. It can then be coupled with the desired amine under amide coupling conditions to generate the final synthetic compound.

[0213] Synthesis Scheme XI Specification 87 / 240 pages 133 CN 121568943 A

[0214] First, the corresponding lithium salt is coupled with protected cyclohexylamine to generate an amide using TCFH and NMI amide coupling conditions. Then, the amide is deprotected using HCl in IPA and the amine isolated as an HCl salt. It can be reacted with the corresponding sulfonyl chloride / acyl chloride to generate the final synthetic compound.

[0215] Synthesis Scheme XII

[0216] First, the corresponding aromatic aldehyde is condensed with 2-methylallylamine to generate the desired imine. Then, it is reacted with TosMIC to generate a substituted imidazole compound. Acid-catalyzed cyclization generates a 7-membered heterocycle. It is saponified with lithium hydroxide to generate the corresponding lithium carboxylate salt. It can then be coupled with the desired amine using amide coupling conditions to generate the final synthetic compound.

[0217] Synthesis Scheme XIII

[0218] A substituted phenol can be reacted with a base alkyl chloride to generate the desired ether, the ester of which is immediately hydrolyzed after separation. It can then be coupled with the desired amine under amide coupling conditions to generate a cyclized precursor. It can then be subjected to an SNAr reaction with cesium carbonate to generate the final synthetic compound.

[0219] Synthesis Scheme XIV Specification 88 / 240 pages 134 CN 121568943 A

[0220] First, the corresponding lithium carboxylate can be coupled with an aromatic amine to generate the desired amide. It can then be coupled with the desired amine / alcohol to generate the final synthetic compound.

[0221] Synthesis Scheme XV

[0222] First, the corresponding aromatic aldehyde is condensed with a 2-substituted amino alcohol to generate the desired imine. It is then reacted with TosMIC to generate a substituted imidazole compound. DIAD reacts with the Mitsunobu of triphenylphosphine to generate a 7-membered heterocycle. It is saponified with lithium hydroxide to generate the corresponding lithium carboxylate. Then,The desired amine can be coupled using amide coupling conditions to generate the final synthetic compound.

[0223] Synthetic Scheme XVI

[0224] First, the corresponding phenol is formylated using HMTA and TFA and hydrolyzed with water. Then, the aromatic aldehyde is condensed with ethanolamine to generate the desired imine. Then it is reacted with Tosmic to generate a substituted imidazole compound. Mitsunobu of phenol and alcohol using triphenylphosphine generates an oxonium aliphatic compound. Saponification with lithium hydroxide to generate the corresponding lithium carboxylate salt. Then, the desired amine can be coupled using amide coupling conditions to generate the final synthetic compound.

[0225] Synthetic Scheme XVII Specification 89 / 240 pages 135 CN 121568943 A

[0226] First, the corresponding lithium salt is coupled with functionalized trans-cyclohexylamine using TCFH and NMI amide coupling conditions to generate an amide. Then the ester is saponified with lithium hydroxide to generate the lithium salt. The amide can be reacted with the corresponding amine under amide coupling conditions to generate the final synthetic compound.

[0227] General Procedure General Procedure A The corresponding amine (1.0 equivalent) and aldehyde (1.0 equivalent) are dissolved in methanol (0.2–1.0 mmol) and stirred at 40 °C for 1–72 h. The reaction mixture is concentrated under reduced pressure to obtain the desired product, which is used directly in the next reaction.

[0228] General Procedure B 4-Toluenesulfonylmethyl isocyanate (1.2 equivalent) is added in portions to a suspension of the corresponding imine (1.0 equivalent) and potassium carbonate (2.2 equivalent) in DME and methanol (~5:3 ratio, 0.1–1.0 mmol) and stirred until the reaction is complete, 18–216 h. The reactants are directly loaded into an appropriately sized SCX-2 column. The column is washed with methanol (2 CV) and then eluted with a methanol solution of 2 M ammonia (2 CV). The eluent was concentrated to dryness under reduced pressure and, if necessary, further purified by normal-phase chromatography on silica or reversed-phase column chromatography on C18 (in some cases, grinding from DMSO / water is also possible) to obtain the desired product.

[0229] General Procedure C: Diisopropyl azodicarboxylate (1.5 equivalents) was added to a solution of the corresponding phenol (1.0 equivalents) and triphenylphosphine (1.2 equivalents) in THF (0.05–0.2 mmol) and stirred until the reaction was complete, 16–48 h. If the reaction was observed to stall after 18 h, additional reagents (0.5 equivalents) and (0.6 equivalents) were added, respectively. The reactants were loaded directly into an appropriately sized SCX-2 column. The column was washed with methanol (2 CV) and then eluted with a methanol solution of 2 M ammonia (2 CV). The eluent was concentrated to dryness under reduced pressure.If necessary, further purification can be achieved by normal-phase chromatography on silica and / or reversed-phase column chromatography on C18 (in some cases, grinding from DMSO / water is also possible) to provide the desired product.

[0230] General Procedure D: A solution of lithium hydroxide monohydrate (1.0–1.05 equivalents) in water (0.5–2 mL) is added to a suspension of the corresponding ester (1.0 equivalents) in tetrahydrofuran (2–6 mL) (sometimes acetonitrile (0.5 mL) is used as a co-solvent or to replace tetrahydrofuran), and the mixture is stirred at room temperature until the reaction is complete, 1–120 h. When the reaction stops, lithium hydroxide monohydrate (0.5–1.0 equivalents) is added further. The reaction mixture is then concentrated under reduced pressure to obtain the desired product, which can be used directly for further conversion without further purification.

[0231] General Procedure E: 1-Methylimidazole (4.5 equivalents) was added to a suspension of lithium carboxylate (1 equivalent), the corresponding amine or amine hydrochloride (1.1 equivalent), and chloro-N,N,N',N'-tetramethylformamidin hexafluorophosphate (1.2-2.2 equivalents) in MeCN (1-5 mL), and stirred at 25°C for 16 h. The crude mixture was diluted with water (10 volumes), and if a precipitate appeared, the solid was filtered and washed with water to obtain the desired product. If no precipitate appeared, the solution was extracted with ethyl acetate (2 x 10 volumes). The combined organic layers were washed with brine (15 volumes), dried (Na2SO4), filtered, and concentrated under reduced pressure to obtain the crude product. It was purified by reversed-phase column chromatography on C18 with gradient elution of MeCN (0.1% NH3) (5% to 95% v / v) in water (0.1% NH3), and further purified by preparative HPLC if necessary to provide the desired product.

[0232] General Procedure F: Hexamethylenetetramine (2.0–4.6 equivalents) was added to a suspension of the corresponding phenol (1.0 equivalent) and trifluoroacetic acid (5.0–7.0 mL), and the mixture was heated at 73 °C for 18–68 h. It was cooled to room temperature, and water (6 times the TFA volume) was slowly added, followed by heating at 80 °C for 2 h or stirring at room temperature for 1 h. It was cooled, filtered, and the resulting precipitate was dried, and further purified by normal-phase chromatography on silica if necessary to obtain the desired product.

[0233] General procedure G: 4-(dibenzylamino)cyclohexanone (1.0 equivalent), the corresponding amine hydrochloride (1.0-1.2 equivalent), and acetic acid (1.03-1.15 equivalent) were dissolved in DCM (5 mL / mmol) and stirred at room temperature for 4-96 h. Sodium cyanoborohydride (2.0 equivalent) was then added.The mixture was stirred at room temperature for 24 h. It was concentrated under reduced pressure to obtain a crude product. It was purified by reversed-phase column chromatography on C18 with gradient elution of MeCN (0.1% NH3) (5% to 95% v / v) in water (0.1% NH3) to obtain the desired product.

[0234] General Procedure H The dibenzylated cyclohexylamine derivative (1.0 equivalent) and palladium hydroxide / carbon (10% loaded, 0.2 equivalent) were suspended in IPA (5-6 mL) and stirred under H2 atmosphere for 18-42 h. It was filtered through diatomaceous earth, washed with IPA, and the combined organic fractions were concentrated under reduced pressure to obtain the desired product.

[0235] General Procedure I Sodium hydride (60% dispersed in mineral oil, 2.4 equivalent) was added to a solution of the corresponding alcohol (1.2 equivalent) in anhydrous NMP (10 mL) under N2 atmosphere and stirred at room temperature for 30 min. Add 1-fluoro-4-nitrobenzene (1 equivalent) and stir for 15–60 min. Quench the reaction mixture with H2O and purify directly by column chromatography on C18 with gradient elution of MeCN (0.1% NH3) (5% to 95%; v / v) in water (0.1% NH3) to obtain the desired product.

[0236] General Procedure J: Dissolve the corresponding substituted nitrobenzene (1.0 equivalent) and 5% rhodium / alumina (10 mol%) in IPA (12 mL) in an ASynt autoclave and stir the resulting mixture at room temperature. Then pressurize the apparatus with H2 to about 10 bar and heat to 80 °C for 18 h. Allow the vessel to cool and then reduce the pressure. Filter the reaction mixture through diatomaceous earth and wash it with IPA, DCM, MeOH, and MeCN. Concentrate the combined filtrates under reduced pressure to obtain the desired product.

[0237] General Procedure K: The corresponding substituted nitrobenzene (1.0 equivalent) and Nishimura catalyst (15 mol%) were suspended in IPA (~5.5 mL / mmol) and stirred for 22 h under H2 atmosphere. The mixture was filtered through diatomaceous earth, washed with IPA, DCM, MeOH, and MeCN, and the combined organic fractions were concentrated under reduced pressure to obtain the desired product.

[0238] General Procedure L: The corresponding alcohol (2.05 equivalent), N,N-diisopropylethylamine (3.05 equivalent), cesium fluoride (1 equivalent), and 2-chloro-5-nitropyrimidine (1 equivalent) were suspended in DMSO (6 mL) and stirred at room temperature for 0.5–16 h. The mixture was diluted with H2O and purified directly by column chromatography on C18 with gradient elution of MeCN (0.1% NH3) (5% to 95%; v / v) in water (0.1% NH3).To obtain the desired product.

[0239] General Procedure M Specification 91 / 240 pages 137 CN 121568943 A The corresponding nitro compound (1 equivalent) and palladium supported on activated carbon (10% loaded, paste, 10 mol%) were suspended in IPA (4–8 mL) and stirred for 1–41 h under H2 atmosphere. It was filtered through diatomaceous earth, washed with IPA, DCM and MeOH, and the combined organic fractions were concentrated under reduced pressure to obtain the desired product.

[0240] Examples The following examples are provided to illustrate and not limit the claimed invention. It will be appreciated that these preparation methods are illustrative and not limiting. Numerous other methods for producing the compounds described herein will be available to those skilled in the art using the teachings provided herein.

[0241] Example 1: General analytical method. Deuterated dimethyl sulfoxide, deuterated acetone, deuterated acetonitrile, deuterated water, or deuterated chloroform were used as solvents for 1H, 13C, and 19F NMR analysis on a JEOL ECZ400s 400 MHz NMR spectrometer. The shift (δ) of each signal was measured in parts per million (ppm) relative to the residual solvent peak, and multiplicity and associated coupling constants (J) were reported where applicable.

[0242] Example 2: Waters Acquity UPLC-MS analytical method. UPLC-MS analysis was performed on a Waters Acquity UPLC system consisting of an Acquity I-Class sample manager-FL, an Acquity I-Class binary solvent manager, and an Acquity UPLC column manager. UV detection was provided using an Acquity UPLC PDA detector (scanning from 210 to 400 nm), mass detection was performed using an Acquity QDa detector (mass scanning from 100 to 1250 Da; both positive and negative modes were used), and ELS detection was performed using an Acquity UPLC ELS detector.

[0243] Samples were prepared by dissolving (with or without sonication) in 1 mL of 50% (v / v) acetonitrile aqueous solution. The resulting solution was then filtered through a 0.2 μm syringe filter and submitted for analysis. All solvents (containing 36% ammonia aqueous solution) were purchased as HPLC grade.

[0244] The specific differences between the methods are as follows: Alkaline 2 min on a Waters Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 μm), 0.1% ammonia solution [elution buffer A]; 0.1% ammonia in MeCN solution [elution buffer B]; flow rate 0.8 mL / min; column oven 50℃; sample manager 20℃; injection volume 2 μL.And a 1.5-minute equilibration time between samples.

[0245]

[0246] Alkaline 4 min on a Waters Acquity UPLC BEH C18 column (2.1×50 mm, 1.7 μm), 0.1% ammonia solution [elution A]; 0.1% ammonia in MeCN solution [elution B]; flow rate 0.8 mL / min; column oven 50℃; sample manager 20℃; injection volume 2 μL, and a 1.5-minute equilibration time between samples. Instructions for use, page 92 / 240, 138 CN 121568943 A

[0247]

[0248] Alkaline 6 min on a Waters Acquity UPLC BEH C18 column (2.1×50 mm, 1.7 μm), 0.1% ammonia solution [elution A]; 0.1% ammonia in MeCN solution [elution B]; flow rate 0.8 mL / min; column oven 50℃; sample manager 20℃; injection volume 2 μL, and equilibration time of 1.5 min between samples.

[0249]

[0250] Acidity 2 min On a Waters Acquity UPLC BEH C18 column (2.1×50 mm, 1.7 μm), 0.1% v / v formic acid in 10 mM ammonium formate [elution A]; 0.1% v / v formic acid in MeCN solution [elution B]; flow rate 0.8 mL / min; column temperature oven 50°C; sample manager 20°C; injection volume 2 μL, and equilibration time of 1.5 min between samples.

[0251]

[0252] Chiral preparative HPLC purification method A (PMA) Specification 93 / 240 pages 139 CN 121568943 A

[0253] Purification method B (PMB)

[0254] Example 3: Synthesis of compounds Synthesis scheme I: General synthesis scheme of compounds of formula (IID)

[0255] Synthesis of methyl 4-hydroxy-3-(((2-hydroxyethyl)imino)methyl)benzoate 1 Specification 94 / 240 pages 140 CN 121568943 A

[0256] A methanol (5 mL) solution of methyl 3-formyl-4-hydroxybenzoate (834 mg, 4.63 mmol) was added to a stirred solution of ethanolamine (0.28 mL, 4.63 mmol) in methanol (5 mL), and the reaction mixture was heated to 40 °C and stirred for 16 h. The reaction mixture was concentrated under reduced pressure to give the desired product, methyl 4-hydroxy-3-(((2-hydroxyethyl)imino)methyl)benzoate 1 (1.03 g, 4.38 mmol), as a yellow solid.95% yield). ¹H NMR (400 MHz, DMSO-D6) δ 8.63 (s, ¹H), 8.07 (d, J = 2.4 Hz, ¹H), 7.82 (dd, J = 9.0, 2.4 Hz, ¹H), 6.76 (d, J = 8.9 Hz, ¹H), 4.93 (t, J = 4.5 Hz, ¹H), 3.79 (s, 3H), 3.69–3.62 (m, 4H). No phenolic protons were observed. UPLC-MS (basic 2 min): rt = 0.68 min, m / z (ES+) 224.1 [M+H]+.

[0257] Methyl 4-hydroxy-3-(1-(2-hydroxyethyl)-1H-imidazol-5-yl)benzoate 2

[0258] 4-Toluenesulfonylmethyl isocyanate (1.03 g, 5.26 mmol) and potassium carbonate (1.33 g, 9.64 mmol) were added to a suspension of methyl 4-hydroxy-3-(((2-hydroxyethyl)imino)methyl)benzoate 1 (1.03 g, 4.38 mmol) in dimethoxyethane (12 mL) and methanol (3 mL). The reaction mixture was stirred at room temperature for 9 days under a nitrogen atmosphere. The reactants were directly loaded onto an SCX-2 column (10 g). The column was washed with methanol (2 CV) and then eluted with a methanol solution of 2 M ammonia (2 CV). The eluent was concentrated to dryness under reduced pressure to give the desired product, methyl 4-hydroxy-3-(1-(2-hydroxyethyl)-1H-imidazol-5-yl)benzoate 2 (987 mg, 3.65 mmol, 83% yield), as a grayish-white solid. 1H NMR (400 MHz, DMSO‑D6) δ 7.86 (dd, J = 8.5, 2.3 Hz, 1H), 7.74 (d, J = 2.2 Hz, 1H), 7.70 (d, J = 1.1 Hz, 1H), 7.01 (d, J = 8.6 Hz, 1H), 6.85 (d, J = 1.1 Hz, 1H), 3.88 (t, J = 5.8 Hz, 2H), 3.79 (s, 3H), 3.44 (t, J = 5.8 Hz, 2H). UPLC-MS (alkaline 2 min): rt = 0.61 min, m / z (ES+) 263.0 [M+H]+.

[0259] 5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinyl-10-carboxylic acid methyl ester 3

[0260] at 0 °C,Methyl 4-hydroxy-3-(1-(2-hydroxyethyl)-1H-imidazol-5-yl)benzoate 2 (150 mg, 0.572 mmol) and triphenylphosphine (180 mg, 0.686 mmol) were added to a solution of THF (4.65 mL) along with diisopropyl azodicarboxylate (0.17 mL, 0.875 mmol). The reaction mixture was heated to room temperature and stirred for 16 h. The reactants were then directly loaded onto an SCX-2 column (1 g). The column was washed with methanol (2 CV) and then eluted with a 2 M ammonia-methanol solution (2 CV). The eluent was concentrated to dryness under reduced pressure to obtain the desired product, 5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinyl-10-carboxylic acid methyl ester 3, which was a grayish-white solid (134 mg, 0.521 mmol, 91% yield). 1H NMR (400 MHz, DMSO‑D6) δ 8.34 (d , J = 2.2 Hz, 1H) , 7.79 (d , J = 1.1 Hz, 1H) , 7.73 (dd , J = 8.6, 2.2 Hz, 1H) , 7.55 (d , J = 1.1 Hz, 1H), 7.10 (d, J = 8.6 Hz, 1H), 4.53 – 4.44 (m, 4H), 3.85 (s, 3H). UPLC‑MS (basic 2 min): rt=0.89 min, m / z (ES+) 245.2 [M +H]+.

[0261] Lithium 5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxaza-10-carboxylate 4

[0262] Lithium hydroxide monohydrate (23 mg, 0.543 mmol) was added to a solution of methyl 5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxaza-10-carboxylate 3 (133 mg, 0.517 mmol) in THF (2 mL), water (1 mL), and MeCN (0.5 mL). The reaction mixture was stirred at room temperature for 22 h, and then concentrated under reduced pressure to obtain the desired product, lithium 5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxaza-10-carboxylate 4 (122 mg, 0.517 mmol), as a pale gray solid.99% yield). 1H NMR (400 MHz, DMSO‑D6) δ 8.24 (d , J = 2.0 Hz, 1H) , 7.72 (d , J = 1.1 Hz, 1H) , 7.64 (dd , J = 8.3, 1.9 Hz, 1H) , 7.38 (d , J = 1.1 Hz, 1H), 6.85 (d, J = 8.3 Hz, 1H), 4.46 – 4.41 (m, 2H), 4.40 – 4.34 (m, 2H).

[0263] Methyl 3-((2-ethoxy-2-oxoethyl)amino)-4-nitrobenzene 5

[0264] A suspension of methyl 3-fluoro-4-nitrobenzene (1.92 g, 9.63 mmol), glycine ethyl ester hydrochloride (1.61 g, 11.6 mmol), and potassium carbonate (3.19 g, 23.1 mmol) in MeCN (49 mL) was heated at 70 °C for 24 h. 100 mL of water was added, and the mixture was extracted with EtOAc (3 x 100 mL). The organic extracts were combined and washed with water (40 mL), then with brine (40 mL), dried (Na2SO4) and evaporated to give the desired product 3-((2-ethoxy-2-oxoethyl)amino)-4-nitrobenzoate 5 (2.61 g, 8.32 mmol, 86% yield) as an orange solid. ¹H NMR (400 MHz, DMSO-D6) δ 8.41 (t, J = 5.8 Hz, ¹H), 8.21 (d, J = 8.8 Hz, ¹H), 7.37 (d, J = 1.7 Hz, ¹H), 7.22 (dd, J = 8.8, 1.7 Hz, ¹H), 4.33 (d, J = 5.8 Hz, 2H), 4.19 (q, J = 7.1 Hz, 2H), 3.87 (s, 3H), 1.23 (t, J = 7.1 Hz, 3H). UPLC-MS (alkaline 2 min): rt = 1.08 min, m / z (ES+) not observed.

[0265] 2-Oxo-1,2,3,4-Tetrahydroquinoxalo-6-carboxylic acid methyl ester 6 Specification 96 / 240 pages 142 CN 121568943 A

[0266] 3-((2-ethoxy-2-oxoethyl)amino)-4-nitrobenzene methyl ester 5 (2.52 g, 8.57 mmol) and iron (1.72 g,A suspension of 30.9 mmol in acetic acid (34 mL) and water (5 mL) was heated at 70 °C for 2 h. The mixture was cooled to 0 °C, water (6 mL) was added, and the mixture was stirred for 30 min. The solid was collected by filtration, washed with water (60 mL), re-slurryed with water (20 mL), collected, and vacuum dried (45 °C) to give the desired product, methyl 2-oxo-1,2,3,4-tetrahydroquinoxaloline-6-carboxylate 6 (1.31 g, 6.35 mmol, 74% yield), as a purple solid. 1H NMR (400 MHz, DMSO‑D6) δ 10.58 (s, 1H), 7.28 (d, J = 1.9 Hz, 1H), 7.23 (dd, J = 8.1, 1.8 Hz, 1H), 6.79 (d, J = 8.1 Hz, 1H) , 6.25 (s, 1H) , 3.81 – 3.75 (m, 5H). UPLC‑MS (basic 2 min): rt=0.73 min, m / z (ES+) 207.2 [M+H]+.

[0267] 2-Hydroxyquinoxaline-6-carboxylic acid methyl ester 7

[0268] A suspension of 2-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid methyl ester 6 (106 mg, 0.494 mmol) and 35 wt.% aqueous hydrogen peroxide solution (200 µL, 2.00 mmol) in methanol (2 mL) was stirred for 48 h. A solution of sodium sulfite (188 mg, 1.49 mmol) in water (3 mL) was added, and the precipitate was collected, washed with water, and dried to give the desired product 2-hydroxyquinoxaline-6-carboxylic acid methyl ester 7 (54 mg, 0.264 mmol, 54% yield) as an orange-brown solid. 1H NMR (400 MHz, DMSO‑D6) δ 12.77 – 12.48 (m, 1H) , 8.35 – 7.89 (m, 3H) , 7.42 – 7.09 (m, 1H) , 3.84 (s, 3H). UPLC‑MS (acidic 2 min): rt=0.77 min, m / z (ES+) 205.1 [M+H]+.

[0269] 4-O-4,5-dihydroimidazo[1,5-a]quinoxaline-8-carboxylic acid methyl ester 8

[0270] 4M potassium carbonate aqueous solution (1.4 mL, 5.49 mmol) was added to a suspension of 2-hydroxyquinoxaline-6-carboxylic acid methyl ester 7 (507 mg, 2.38 mmol) and 4-toluenesulfonyl methyl isocyanate (698 mg, 3.58 mmol) in DMSO (8 mL).The mixture was stirred for 3 days. Water (3 mL) was added, and the precipitate was collected, washed with water, and dried. The solid was stirred in DCM (10 mL) for 1 h. The solid was collected, washed with DCM (5 mL), then washed with MTBE (5 mL), and dried to give the desired product, methyl 4-oxo-4,5-dihydroimidazole[1,5-a]quinoxaloline-8-carboxylate 8 (454 mg, 1.87 mmol, 78% yield), as a pale orange solid. 1H NMR (400 MHz, DMSO‑D6) δ 11.71 (s, 1H) , 9.26 (d, J = 0.9 Hz, 1H) , 8.74 (d , J = 1.7 Hz, 1H) , 7.95 (dd , J = 8.5, 1.8 Hz, 1H) , 7.90 (d, J = 0.8 Hz, 1H), 7.39 (d, J = 8.6 Hz, 1H), 3.90 (s, 3H). UPLC‑MS (basic 2 min): rt= 0.73 min, m / z (ES+) 244.1 [M+H]+.

[0271] Lithium 4-oxo-4,5-dihydroimidazo[1,5-a]quinoxaline-8-carboxylate 9 Specification 97 / 240 pages 143 CN 121568943 A

[0272] A mixture of methyl 4-oxo-4,5-dihydroimidazo[1,5-a]quinoxaline-8-carboxylate 8 (47 mg, 0.186 mmol) in THF (0.40 mL) and lithium hydroxide (16 mg, 0.371 mmol) in water (0.40 mL) was stirred at 20°C for 4 days. The solvent was concentrated under reduced pressure to give the desired product, lithium 4-oxo-4,5-dihydroimidazo[1,5-a]quinoxaline-8-carboxylate 9 (44 mg, 0.187 mmol, 100% yield), as a yellowish-brown solid. ¹H NMR (400 MHz, DMSO-D6) δ 8.90 (s, ¹H), 8.45 (d, J = 1.6 Hz, ¹H), 7.79 (dd, J = 8.3, 1.6 Hz, ¹H), 7.66 (s, ¹H), 7.11 (dd, J = 14.0, 7.9 Hz, ¹H). No NH signal was observed. UPLC-MS (alkaline 2 min): rt = 0.18 min, m / z (ES+) 230.2 [M+H]+.

[0273] 4-(2-(1H-imidazol-2-yl)ethoxy)-3-bromobenzoate methyl ester 10

[0274] At 0°C, to 2-(1H-imidazol-2-yl)ethanol (121 mg,1.08 mmol of methyl 3-bromo-4-hydroxybenzoate (250 mg, 1.08 mmol) and triphenylphosphine (341 mg, 1.30 mmol) were added to a solution of THF (10 mL) with diisopropyl azodicarboxylate (0.33 mL, 1.66 mmol). The reaction mixture was heated to room temperature and stirred for 16 h. The reaction mixture was concentrated under reduced pressure, dissolved in a minimal amount of MeCN, and loaded into an SCX-2 column (2 g). The column was washed with methanol (2 CV) and then eluted with a methanol solution of 2 M ammonia (2 CV). The eluent was concentrated to dryness under reduced pressure, and the resulting residue was purified by column chromatography on silica with gradient elution of MeOH (0% to 10%; v / v) in DCM to give the desired product, methyl 4-(2-(1H-imidazol-2-yl)ethoxy)-3-bromobenzoate 10 (250 mg, 0.730 mmol, 68% yield), as a white solid. 1H NMR (400 MHz, DMSO‑D6) δ 11.80 (s, 1H) , 8.07 (d, J = 2.1 Hz, 1H) , 7.94 (dd, J = 8.7, 2.2 Hz, 1H) , 7.27 (d, J = 8.7 Hz, 1H) , 7.02 (bs, 1H) , 6.80 (bs, 1H) , 4.46 (t, J = 7.0 Hz, 2H) , 3.83 (s, 3H) , 3.13 (t, J = 7.0 Hz, 2H). UPLC‑MS (basic 2 min): rt=0.98 min, m / z (ES+) 326.9 [M+H]+.

[0275] Methyl 4,5-dihydrobenzo[b]imidazo[1,2-d][1,4]oxazolidinyl-9-carboxylic acid ester 11

[0276] Under a nitrogen atmosphere, a suspension of AdBrettPhos Pd G3 (39 mg, 0.0384 mmol), tripotassium phosphate (490 mg, 2.31 mmol) and methyl 4-(2-(1H-imidazol-2-yl)ethoxy)-3-bromobenzoate 10 (250 mg, 0.769 mmol) in 1,4-dioxane (7.5 mL) was stirred at 100 °C for 16 h, and a portion of Me4tButylXPhos Pd G3 (65 mg, 0.0769 mmol) was added, and the reaction was stirred for 2 h. Add another portion of Me4tButylXPhos Pd G3 (65 mg, instruction manual page 98 / 240, 144 CN 121568943 A 0.0769 mmol), and stir the reaction mixture for 64 h.The reaction mixture was cooled to room temperature and then filtered through filter paper, with the filter cake washed with methanol. The filtrate was concentrated under reduced pressure, then redissolved in methanol (5.0 mL) and loaded onto an SCX-2 column (10 g). The column was washed with methanol (2 CV), and the compound was eluted with a methanol solution of 2 M ammonia (2 CV). The eluent was concentrated to dryness under reduced pressure, and the crude residue was purified by column chromatography on silica with gradient elution of MeOH (0% to 10%; v / v) in DCM to give the desired product, methyl 4,5-dihydrobenzo[b]imidazo[1,2-d][1,4]oxazine-9-carboxylic acid 11 (42 mg, 0.169 mmol, 22% yield), as an orange oil. ¹H NMR (400 MHz, chloroform-D₃) δ 8.04 (d, J = 2.1 Hz, ¹H), 7.94 (dd, J = 8.4, 2.1 Hz, ¹H), 7.29–7.23 (m, 2H), 7.10 (d, J = 1.5 Hz, ¹H), 4.65 (t, J = 6.1 Hz, 2H), 3.92 (s, 3H), 3.15 (t, J = 6.1 Hz, 2H). UPLC-MS (alkaline 2 min): rt = 0.88 min, m / z (ES⁺) 245.3 [M⁺H]⁺.

[0277] Lithium 4,5-dihydrobenzo[b]imidazo[1,2-d][1,4]oxazolidinium-9-carboxylate 12

[0278] Lithium hydroxide (7.6 mg, 0.181 mmol) was added to a suspension of methyl 4,5-dihydrobenzo[b]imidazo[1,2-d][1,4]oxazolidinium-9-carboxylate 11 (42 mg, 0.172 mmol) in MeCN (1 mL) and water (0.50 mL), and the reaction mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure to give the desired product, lithium 4,5-dihydrobenzo[b]imidazo[1,2-d][1,4]oxazolidinium-9-carboxylate 12 (41 mg, 0.169 mmol, 100% yield), which was a yellow oil. The crude product was ready for use without further purification. UPLC-MS (alkaline 2 min): rt = 0.38 min, m / z (ES+) 231.2 [M+H]+.

[0279] 5-(2-chloroethyl)-1H-imidazolium 13

[0280] At 0 °C, thionyl chloride (6.2 mL, 86.2 mmol) was slowly added to 2-(1H-imidazolium-5-yl)ethanol (250 mg, 2.23 mmol). After the addition was complete, the mixture was heated to 70 °C.Continue for 1 h. The reaction mixture was concentrated under reduced pressure to give the desired product, 5-(2-chloroethyl)-1H-imidazole 13 (300 mg, 1.84 mmol, 82% yield), as a yellow gel. ¹H NMR (400 MHz, DMSO-D6) δ 9.05 (d, J = 1.4 Hz, 1H), 7.54 (q, J = 1.0 Hz, 1H), 4.85 (s, 1H), 3.93 (t, J = 6.5 Hz, 2H), 3.13 (td, J = 6.6, 0.9 Hz, 2H). UPLC-MS (alkaline 2 min): rt = 0.61 min, m / z (ES+) 130.9, 132.9 [M+H]+.

[0281] 4-(2-(1H-imidazol-5-yl)ethoxy)-3-bromobenzoate methyl ester 14 Specification 99 / 240 pages 145 CN 121568943 A

[0282] 5-(2-chloroethyl)-1H-imidazolium 13 (257 mg, 1.97 mmol), methyl 3-bromo-4-hydroxybenzoate (350 mg, 1.51 mmol), sodium iodide (23 mg, 0.151 mmol), and potassium carbonate (628 mg, 4.54 mmol) in DMF (6 mL) were heated to 80 °C and stirred for 18 h. The reaction mixture was directly loaded onto an SCX-2 column (1 g). The column was washed with methanol (2 CV) and then eluted with a methanol solution of 2 M ammonia (2 CV). The eluent was concentrated to dryness under reduced pressure, and the crude residue was purified by column chromatography on a C18 column using a gradient elution of MeCN (0.1% NH3) (0% to 90% v / v) in water (0.1% NH3) to give the desired product, methyl 4-(2-(1H-imidazol-5-yl)ethoxy)-3-bromobenzoate 14 (170 mg, 0.507 mmol), as a yellow gel.33% yield). ¹H NMR (400 MHz, chloroform-D₃) δ 8.24 (d, J = 2.1 Hz, ¹H), 7.96 (dd, J = 8.6, 2.1 Hz, ¹H), 7.62 (d, J = 1.1 Hz, ¹H), 6.97 (t, J = 0.9 Hz, ¹H), 6.91 (d, J = 8.7 Hz, ¹H), 4.31 (t, J = 5.9 Hz, 2H), 3.89 (s, 3H), 3.20 (td, J = 6.0, 0.8 Hz, 2H). NH₃ was not observed. UPLC-MS (alkaline 2 min): rt = 0.94 min, m / z (ES+) 327.2 [M+H]+.

[0283] Methyl 5-methyl-4-oxo-4,5-dihydroimidazo[1,5-a]quinoxaline-8-carboxylate 15

[0284] A mixture of methyl 4-oxo-4,5-dihydroimidazo[1,5-a]quinoxaline-8-carboxylate 8 (149 mg, 0.588 mmol), methyl iodoforme (110 µL, 1.77 mmol) and potassium carbonate (134 mg, 0.970 mmol) in MeCN (1.2 mL) was stirred at 20 °C for 6 days. The mixture was partially evaporated (only 160 mbar), the solid was collected, washed with water, then with methanol, and finally dried to give the desired product, methyl 5-methyl-4-oxo-4,5-dihydroimidazole[1,5-a]quinoxaline-8-carboxylic acid ester 15 (94 mg, 0.365 mmol, 62% yield), as a light brown solid. 1H NMR (400 MHz, DMSO‑D6) δ 9.29 (s, 1H) , 8.79 (d , J = 1.9 Hz, 1H) , 8.03 (dd , J = 8.8, 1.9 Hz, 1H) , 7.92 (s, 1H) , 7.66 (d , J = 8 .8 Hz, 1H), 3.92 (s, 3H), 3.59 (s, 3H). UPLC‑MS (basic 2 min): rt=0.82 min, m / z (ES+) 258.0 [M+H]+.

[0285] Lithium 5-methyl-4-oxo-4,5-dihydroimidazo[1,5-a]quinoxaline-8-carboxylate 16

[0286] Methyl 5-methyl-4-oxo-4,5-dihydroimidazo[1,5-a]quinoxaline-8-carboxylate 15 (92 mg, 0.342 mmol) and lithium hydroxide (15 mg,A mixture of 0.359 mmol of the product (see product manual, page 100 / 240, CN 121568943 A) in methanol (0.30 mL), THF (0.60 mL), and water (0.30 mL) was stirred at 20 °C for 5 days. The mixture was evaporated, and the solid was freeze-dried to give the desired product, lithium 5-methyl-4-oxo-4,5-dihydroimidazolo[1,5-a]quinoxaloline-8-carboxylic acid 16 (113 mg, 0.449 mmol, 100% yield), as a light brown solid. 1H NMR (400 MHz, DMSO‑D6) δ 8.94 (s, 1H) , 8.63 (s, 1H) , 8.13 – 8.06 (m, 1H) , 7.94 (s, 1H) , 7.61 – 7.54 (m, 1H) , 3.70 (s, 3H). UPLC‑MS (acidic 2 min): rt= 0.69 min, m / z (ES+) 244.2 [M+H]+.

[0287] (Z)-4-hydroxy-3-(((3-hydroxypropyl)imino)methyl)benzoate 17

[0288] A solution of 3-amino-1-propanol (0.085 mL, 1.11 mmol) in methanol (3 mL) was added dropwise to a stirred suspension of methyl 3-formyl-4-hydroxybenzoate (200 mg, 1.11 mmol) in methanol (3 mL). The resulting yellow solution was heated at 40 °C for 18 h. The reaction mixture was concentrated under reduced pressure to give the desired product (Z)-4-hydroxy-3-(((3-hydroxypropyl)imino)methyl)benzoate 17 (260 mg, 1.07 mmol, 97% yield) as a yellow solid. ¹H NMR (400 MHz, chloroform-D₃) δ 8.39 (s, ¹H), 8.02–7.94 (m, 2H), 6.94 (d, J = 8.7 Hz, ¹H), 4.82 (s, 2H), 3.89 (s, 3H), 3.84–3.72 (m, 4H), 1.98 (p, J = 6.4 Hz, 2H). ⁻¹OH was not observed. UPLC-MS (acidic 2 min): rt = 0.65 min, m / z (ES⁺) 238.1 [M⁺H]⁺.

[0289] Methyl 4-hydroxy-3-(1-(3-hydroxypropyl)-1H-imidazol-5-yl)benzoate 18

[0290] Methyl (Z)-4-hydroxy-3-(((3-hydroxypropyl)imino)methyl)benzoate 17 (260 mg,4-Toluenesulfonylmethyl isocyanate (244 mg, 1.25 mmol) and potassium carbonate (317 mg, 2.29 mmol) were added to a suspension of dimethoxyethane (5 mL) and methanol (3 mL), and the reaction mixture was stirred at room temperature for 20 h under a nitrogen atmosphere. The reaction mixture was directly loaded into an SCX-2 column (2 g). The column was washed with methanol (2 CV), and the compound was eluted with a methanol solution of 2 M ammonia (2 CV). The eluent was concentrated under reduced pressure to give the desired product, methyl 4-hydroxy-3-(1-(3-hydroxypropyl)-1H-imidazol-5-yl)benzoate 18 (320 mg, 1.01 mmol, 97% yield), as a yellow oil. ¹H NMR (400 MHz, DMSO-D₆) δ 7.85 (dd, J = 8.5, 2.3 Hz, ¹H), 7.74–7.66 (m, 2H), 7.01 (d, J = 8.6 Hz, 1H), 6.85 (d, J = 1.1 Hz, 1H), 3.92 (dd, J = 7.9, 6.6 Hz, 2H), 3.79 (s, 3H), 3.23 (t, J = 6.2 Hz, 2H), 1.60 (dq, J = 7.9, 6.3 Hz, 2H). ⁻¹OH was not observed. UPLC-MS (alkaline 2 min): rt = 0.62 min, m / z (ES+) 277.2 [M+H]+.

[0291] 6,7-dihydro-5H-benzo[b]imidazo[5,1-d][1,5]oxaconine-11-carboxylic acid methyl ester 19 Specification 101 / 240 pages 147 CN 121568943 A

[0292] At 0 °C, diisopropyl azodicarboxylate (0.30 mL, 1.54 mmol) was added to a solution of methyl 4-hydroxy-3-(1-(3-hydroxypropyl)-1H-imidazo-5-yl)benzoate 18 (320 mg, 1.01 mmol) and triphenylphosphine (317 mg, 1.21 mmol) in THF (10 mL). The reaction mixture was stirred at room temperature for 18 h. Triphenylphosphine (264 mg, 1.01 mmol) and diisopropyl azodicarboxylate (0.20 mL, 1.01 mmol) were added at room temperature, and the resulting reaction mixture was stirred at 40 °C for 20 h. The reaction mixture was then directly loaded onto an SCX-2 column (2 g). The column was washed with methanol (2 CV).The compound was then eluted with a methanol solution of 2 M ammonia (2 CV). The eluent was concentrated under reduced pressure. The residue was purified by column chromatography on a C18 with gradient elution of MeCN (0.1% NH3) (0% to 60% v / v) in water (0.1% NH3) to give the desired product, methyl 6,7-dihydro-5H-benzo[b]imidazo[5,1-d][1,5]oxacoxine-11-carboxylic acid 19 (60 mg, 0.144 mmol, 14% yield), as a yellow solid. 1H NMR (400 MHz, chloroform‑D3) δ 8 .16 – 8 .02 (m , 1H) , 7.95 (dd , J = 8.6, 2.2 Hz, 1H) , 7.56 (d , J = 1.1 Hz, 1H) , 7.25 (d , J = 1.1 Hz, 1H) , 7.08 – 6.98 (m, 1H) , 4.23 – 4.15 (m, 2H) , 4.14 – 4.06 (m, 2H) , 3.90 (s , 3H) , 2.04 (p, J = 5.6 Hz, 2H). UPLC-MS (alkaline 2 min): rt = 0.91 min, m / z (ES+) 259.3 [M+H]+.

[0293] Lithium 6,7-dihydro-5H-benzo[b]imidazo[5,1-d][1,5]oxacoxine-11-carboxylate 20

[0294] Lithium hydroxide (9.7 mg, 0.232 mmol) was added to a solution of methyl 6,7-dihydro-5H-benzo[b]imidazo[5,1-d][1,5]oxacoxine-11-carboxylate 19 (60 mg, 0.232 mmol) in THF (3 mL) and water (2 mL), and the reaction mixture was stirred at room temperature for 18 h. The reaction mixture was concentrated under reduced pressure to give the desired product, 6,7-dihydro-5H-benzo[b]imidazo[5,1-d][1,5]oxaconine-11-carboxylic acid lithium 20 (70 mg, 0.280 mmol), as a dark solid.100% yield). ¹H NMR (400 MHz, DMSO-D6) δ 7.83 – 7.79 (m, 2H), 7.71 (d, J = 1.2 Hz, 1H), 6.98 – 6.93 (m, 2H), 4.11 (t, J = 5.4 Hz, 2H), 4.06 – 3.96 (m, 2H), 1.91 (p, J = 5.4 Hz, 2H).

[0295] 4-chloroimidazolo[1,5-a]quinoxaline-8-carboxylic acid methyl ester 21 Specification 102 / 240 pages 148 CN 121568943 A

[0296] A solution of 4-oxo-4,5-dihydroimidazolo[1,5-a]quinoxaline-8-carboxylic acid methyl ester 8 (450 mg, 1.85 mmol) in phosphorus oxychloride (10 mL, 107 mmol) and N,N-dimethylformamide (20 µL, 0.257 mmol) was heated at 105 °C for 18 h. Then, phosphorus oxychloride (5.0 mL, 52.2 mmol) and N,N-dimethylformamide (20 µL, 0.257 mmol) were added, and the mixture was heated for 5 days. Phosphorus oxychloride (6.0 mL, 62.6 mmol) and N,N-dimethylformamide (20 µL, 0.257 mmol) were added, and the mixture was heated for 18 h. Phosphorus oxychloride (5.0 mL, 52.2 mmol) and N,N-dimethylformamide (0.50 mL) were then added, and the mixture was heated for 2 days. The reaction mixture was concentrated under reduced pressure, quenched with cold water and a saturated aqueous solution of NaHCO3, and extracted with ethyl acetate. The organic phase was dried (Na2SO4), filtered, and concentrated under reduced pressure to give the desired product, methyl 4-chloroimidazolo[1,5-a]quinoxaloline-8-carboxylic acid ester 21 (330 mg, 1.05 mmol, 57% yield), as a brown solid. 1H NMR (400 MHz, DMSO‑D6) δ 9.64 (d, J = 0.7 Hz, 1H), 8.98 (d, J = 1.7 Hz, 1H), 8.12 (dd, J = 8.4, 1.8 Hz, 1H), 8.05 (d, J = 0.6 Hz, 1H), 8.02 – 7.87 (m, 1H), 3.96 (s, 3H). UPLC‑MS (basic 2 min): rt=0.97 min, m / z (ES+) 262.2,264.1 [M+H]+.

[0297] ((1r,4r)-4-(5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinyl-10-carboxamido)cyclohexyl)tert-butyl carbamate 22

[0298] The desired product [(1r,4r)-4-(5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinyl-10-carboxylic acid lithium 4 and trans-4-(boc-amino)cyclohexylamine]tert-butyl carbamate 22 (367 mg, 0.860 mmol, 60% yield) was prepared as a grayish-white solid from lithium 4, 5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinyl-10-carboxamido)cyclohexyl]carbamate 22 (367 mg, 0.860 mmol, 60% yield). 1H NMR (400 MHz, DMSO‑D6) δ 8.26 – 8.18 (m, 2H), 7.77 (d, J = 1.1 Hz, 1H), 7.65 (dd, J = 8.6, 2.2 Hz, 1H), 7.61 (d, J = 1.2 Hz, 1H), 7.03 (d, J = 8.6 Hz, 1H), 6.76 (d, J = 8.0 Hz, 1H), 4.51 – 4.39 (m, 4H), 3.77 – 3.65 (m, 1H), 3.26 – 3.14 (m, 1H), 1.89 – 1.77 (m, 4H), 1.46 – 1.17 (m, 13H). UPLC-MS (alkaline 2 min): rt = 0.99 min, m / z (ES+) 427.3 [M+H]+.

[0299] N-((1r,4r)-4-aminocyclohexyl)-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinyl-10-carboxamide hydrochloride 23

[0300] A suspension of ((1r,4r)-4-(5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinyl-10-carboxamide)cyclohexyl)carbamate tert-butyl ester 22 (367 mg, 0.860 mmol) in IPA (15 mL) was treated dropwise with 6M hydrogen chloride solution in IPA (2.4 mL, 12.0 mmol), and the resulting mixture was heated at 55 °C for 18 h. Then, it was concentrated under reduced pressure, ground with diethyl ether, and filtered to obtain the desired product N-((1r,4r)-4-aminocyclohexyl)-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinyl-10-carboxamide hydrochloride 23 (295 mg), which was a white solid.0.813 Instructions for use, 103 / 240 pages, 149 CN 121568943 A mmol, 60% yield). 1H NMR (400 MHz, DMSO‑D6) δ 9.10 (s, 1H) , 8.59 – 8.47 (m, 2H) , 8.43 (d , J = 2.2 Hz , 1H) , 8.19 – 7.96 (m , 3H) , 7.84 (dd , J = 8.7 , 2.2 Hz, 1H), 7.14 (d, J = 8.6 Hz, 1H), 4.73 – 4.66 (m, 2H), 4.61 – 4.55 (m, 2H), 3.83 – 3.70 (m, 1H), 3.06 – 2.90 (m, 1H) , 2 .08 – 1.87 (m, 4H), 1.58 – 1.40 (m, 4H). UPLC-MS (alkaline 4 min): rt = 0.94 min, m / z (ES+) 327.1 [M+H]+.

[0301] Methyl benzoate (E)-4-hydroxy-3-(((2-methylallyl)imino)methyl)benzoate 24

[0302] 2-methylallylamine (99 mg, 1.39 mmol) and methyl 3-formyl-4-hydroxybenzoate (834 mg, 4.63 mmol) in methanol (5 mL) were heated at 40 °C for 72 h. The reaction mixture was concentrated under reduced pressure to give the desired product (E)-4-hydroxy-3-(((2-methylallyl)imino)methyl)benzoate 24 (350 mg, 1.05 mmol, 76% yield), which was a yellow oil. ¹H NMR (400 MHz, DMSO-D6) δ 8.71 (s, ¹H), 8.12 (d, J = 2.3 Hz, ¹H), 7.88 (dd, J = 8.8, 2.3 Hz, ¹H), 6.89 (d, J = 8.8 Hz, ¹H), 4.94–4.84 (m, 2H), 4.19 (s, 2H), 3.81 (s, 3H), 1.77 (t, J = 1.1 Hz, 3H). OH was not observed. UPLC-MS (alkaline 2 min): rt = 1.06 min.m / z (ES+) 234.1 [M+H]+. Methyl 4-hydroxy-3-(1-(2-methylallyl)-1H-imidazol-5-yl)benzoate 25

[0303] 4-Toluenesulfonylmethyl isocyanate (246 mg, 1.26 mmol) and potassium carbonate (319 mg, 2.31 mmol) were added to a suspension of (E)-4-hydroxy-3-(((2-methylallyl)imino)methyl)benzoate 24 (350 mg, 1.05 mmol) in dimethoxyethane (5 mL) and methanol (3 mL). The reaction mixture was stirred at room temperature for 68 h under a nitrogen atmosphere. The reaction mixture was directly loaded onto an SCX-2 column (20 g). The column was washed with methanol (2 CV) and then eluted with a methanol solution of 2 M ammonia (2 CV). The eluent was concentrated under reduced pressure to give the desired product, methyl 4-hydroxy-3-(1-(2-methylallyl)-1H-imidazol-5-yl)benzoate 25 (270 mg, 0.992 mmol, 94% yield), as a grayish-white solid. ¹H NMR (400 MHz, DMSO-D₆) δ 7.83 (dd, J = 8.5, 2.3 Hz, ¹H), 7.72 – 7.65 (m, 2H), 7.01 (d, J = 8.5 Hz, 1H), 6.93 (d, J = 1.1 Hz, 1H), 4.72 – 4.66 (m, 1H), 4.48 (s, 2H), 4.30 (s, 1H), 3.79 (s, 3H), 1.47 (s, 3H). OH⁻ was not observed. UPLC-MS (alkaline, 2 min): rt = 0.80 min, m / z (ES⁺) 273.0 [M⁺H]⁺.

[0304] Methyl 6,6-dimethyl-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinyl-10-carboxylic acid 26 Specification 104 / 240 pages 150 CN 121568943 A

[0305] At 80 °C, methanesulfonic acid (66 µL, 1.01 mmol) was added to a suspension of methyl 4-hydroxy-3-(1-(2-methylallyl)-1H-imidazol-5-yl)benzoate 25 (250 mg, 0.918 mmol) in toluene (30 mL) and stirred for 68 h. It was then cooled and concentrated under reduced pressure to give a brown solid. The crude substance was purified by column chromatography on C18 with gradient elution of MeCN (0.1% NH3) (5% to 95%; v / v) in water (0.1% NH3).The desired product, methyl 6,6-dimethyl-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinyl-10-carboxylate 26 (31 mg, 0.102 mmol, 11% yield), was obtained as a yellow oil. 1H NMR (400 MHz, DMSO‑D6) δ 8.09 (d , J = 2.2 Hz, 1H) , 7.85 (dd , J = 8.4, 2.2 Hz, 1H) , 7.81 (d , J = 1.1 Hz, 1H) , 7.36 (d , J = 1.0 Hz, 1H), 7.12 (d, J = 8.4 Hz, 1H), 4.17 (s, 2H), 3.85 (s, 3H), 1.33 (s, 6H). UPLC‑MS (basic 2 min): rt=0.97 min, m / z (ES+) 273.3 [M+H]+.

[0306] Lithium 6,6-dimethyl-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinium-10-carboxylate 27

[0307] A solution of lithium hydroxide (4.4 mg, 0.104 mmol) in water (0.80 mL) was added to a solution of methyl 6,6-dimethyl-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinium-10-carboxylate 26 (30 mg, 0.0992 mmol) in THF (2 mL), and stirred at 25 °C for 18 h. The product was concentrated under reduced pressure to give the desired product, lithium 6,6-dimethyl-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazine-10-carboxylic acid 27, which was a yellow solid (30 mg, 0.0976 mmol, 98% yield). 1H NMR (400 MHz, DMSO‑D6) δ 7.92 (d, J = 2.0 Hz, 1H), 7.76 (d, J = 1.0 Hz, 1H), 7.73 (dd, J = 8.2, 2.0 Hz, 1H), 7.14 (d, J = 1 .0 Hz, 1H), 6.86 (d, J = 8.2 Hz, 1H), 3.99 (s, 2H), 1.31 (s, 6H). UPLC‑MS (basic 2 min): rt=0.63 min,m / z (ES+) 259.0 [M+H]+.

[0308] 5-(2-(1H-imidazol-5-yl)ethoxy)-6-bromopyridinecarboxylate lithium 28

[0309] 5-(2-chloroethyl)-1H-imidazolium 13 (338 mg, 2.59 mmol), methyl 6-bromo-5-hydroxypyridine-2-carboxylate (150 mg, 0.646 mmol), sodium iodide (9.7 mg, 0.0646 mmol) and potassium carbonate (268 mg, 1.94 mmol) in DMF (6 mL) were heated to 80 °C and stirred for 18 h. Then, a solution of 5-(2-chloroethyl)-1H-imidazole 13 (178 mg, 1.29 mmol) in DMF (1 mL) and potassium carbonate (268 mg, 1.94 mmol) were added, and the reaction was heated for another 48 h. The reaction mixture was purified directly by column chromatography on a C18 column using a gradient elution of MeCN (0.1% NH3) (0% to 50%; v / v) in water (0.1% NH3) to give a mixture (195 mg) of hydrolyzed acid and methyl ester as a yellow gel. The product was dissolved in THF (2 mL), water (1 mL), and MeCN (2 mL), and lithium hydroxide (9.8 mg, 0.233 mmol) was added. The reaction mixture was stirred at room temperature for 3 h, and then concentrated under reduced pressure to give the desired product, lithium 5-(2-(1H-imidazol-5-yl)ethoxy)-6-bromopyridinecarboxylate 28 (185 mg, 0.372 mmol, 58%), as a dark brown gel. UPLC-MS (alkaline 2 min): rt = 0.45 min, m / z (ES+) not observed.

[0310] (R)-5-(2-(1H-imidazol-5-yl)ethoxy)-6-bromo-N-(tetrahydro-2H-pyran-3-yl)pyridine amide 29

[0311] The desired product (R)-5-(2-(1H-imidazol-5-yl)ethoxy)-6-bromopyridinecarboxylate 29 (55 mg, 0.100 mmol, 27% yield) was prepared from lithium 5-(2-(1H-imidazol-5-yl)ethoxy)-6-bromo-N-(tetrahydro-2H-pyran-3-yl)pyridine amide 29, which was a yellow gel, according to general procedure E. UPLC-MS (acidic 2 min): rt = 0.71 min, m / z (ES+) 395.3,397.3 [M+H]+.

[0312] N-(2-chlorobenzo[d]thiazo-5-yl)-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinium-10-carboxylate 30

[0313] The desired product N-(2-chlorobenzo[d]thiazo-5-yl)-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinium-10-carboxylate 30 (663 mg, 1.55 mmol, 82% yield) was prepared from lithium 4 of 5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinium-10-carboxylate in a light yellow solid by general procedure E. 1H NMR (400 MHz, DMSO‑D6) δ 10.49 (s, 1H) , 8.50 (d, J = 2.0 Hz, 1H) , 8.43 (d, J = 2.3 Hz, 1H) , 8.07 (d , J = 8.8 Hz, 1H) , 7.95 (s, 1H) , 7.87 (dd , J = 8.9, 2.1 Hz, 1H) , 7.82 (dd , J = 8.6 , 2.2 Hz , 1H) , 7.79 – 7.75 (m , 1H) , 7.15 (d , J = 8.5 Hz , 1H) , 4.56 – 4.48 (m, 4H). UPLC-MS (alkaline 4 min): rt=1.62 min, m / z (ES+) 397.0, 399.0 [M+H]+.

[0314] (E)-4-hydroxy-3-(((1-hydroxy-2-methylpropane-2-yl)imino)methyl)benzoate 31

[0315] 2-amino-2-methyl-1-propanol (0.11 mL, 1.11 mmol) and 3-formyl-4-hydroxybenzoate (200 mg, 1.11 mmol) in methanol (5 mL) were heated to 40 °C for 3 h. Instructions 106 / 240 pages 152 CN 121568943 A The reaction mixture was concentrated under reduced pressure to give the desired product, methyl (E)-4-hydroxy-3-(((1-hydroxy-2-methylpropane-2-yl)imino)methyl)benzoate 31 (275 mg, 1.08 mmol), as a yellow solid.98% yield). ¹H NMR (400 MHz, DMSO-D6) δ 8.69 (s, 1H), 8.14 (d, J = 2.4 Hz, 1H), 7.78 (ddd, J = 9.1, 2.4, 0.8 Hz, 1H), 6.65 (d, J = 9.0 Hz, 1H), 5.18 (s, 1H), 3.78 (s, 3H), 3.40 (s, 2H), 1.30 (d, J = 0.7 Hz, 6H). UPLC-MS (alkaline 2 min): rt = 0.81 min, m / z (ES+) 252.1 [M+H]+.

[0316] Methyl 4-hydroxy-3-(1-(1-hydroxy-2-methylpropane-2-yl)-1H-imidazol-5-yl)benzoate

[0317] At 25 °C, 4-toluenesulfonyl methyl isonitrile (256 mg, 1.31 mmol) was added to a suspension of (E)-4-hydroxy-3-(((1-hydroxy-2-methylpropane-2-yl)imino)methyl)benzoate 31 (275 mg, 1.09 mmol) and potassium carbonate (333 mg, 2.41 mmol) in dimethoxyethane (5 mL) and methanol (3 mL), and stirred for 18 h. The reactants were directly loaded onto an SCX-2 column (10 g). The column was washed with methanol (2 CV), and then the compound was eluted with a methanol solution of 2 M ammonia (2 CV). The eluent was concentrated to dryness under reduced pressure to give the crude product. It was purified by column chromatography on a C18 column with gradient elution of MeCN (0.1% NH3) (5% to 40% v / v) in water (0.1% NH3), and concentrated under reduced pressure. The resulting solid was ground with MeCN to give the desired product, methyl 4-hydroxy-3-(1-(1-hydroxy-2-methylpropane-2-yl)-1H-imidazol-5-yl)benzoate (245 mg, 0.844 mmol, 77% yield), as a white solid. ¹H NMR (400 MHz, DMSO-D6) δ 7.84 (dd, J = 8.5, 2.3 Hz, ¹H), 7.76–7.70 (m, 2H), 6.92 (d, J = 8.4 Hz, 1H), 6.64 (d, J = 1.2 Hz, 1H), 3.78 (s, 3H), 3.42 (s, 2H), 1.30 (s, 6H). 2OH was not observed. UPLC-MS (alkaline 2 min): rt = 0.74 min.m / z (ES+) 291.1 [M+H]+.

[0318] Methyl 5,5-dimethyl-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinyl-10-carboxylic acid

[0319] At 25°C, diisopropyl azodicarboxylic acid (0.25 mL, 1.27 mmol) was added to a suspension of triphenylphosphine (266 mg, 1.01 mmol) and methyl 4-hydroxy-3-(1-(1-hydroxy-2-methylpropane-2-yl)-1H-imidazo-5-yl)benzoate (245 mg, 0.844 mmol) in THF (13 mL) and stirred for 68 h. The reaction mixture was directly loaded onto an SCX-2 column (10 g). The column was washed with MeOH (2 CV) and then eluted with a methanol solution of 2 M ammonia (2 CV). The eluent was concentrated to dryness under reduced pressure to give the desired product, methyl 5,5-dimethyl-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinyl-10-carboxylate, as a white solid (229 mg, 0.841 mmol, 99% yield). 1H NMR (400 MHz, DMSO‑D6) δ 8.37 (t, J = 2.0 Hz, 1H) , 8.06 (t, J = 1.4 Hz, 1H) , 7.77 – 7.69 (m, 1H) , 7.51 (t, J = 1.5 Hz, 1H) , 7.13 (dd, J = 8.5, 1.7 Hz, 1H), 4.28 (s, 2H), 3.85 (s, 3H), 1.59 (s, 6H). UPLC‑MS (basic 2 min): rt=0.97 min, m / z (ES+) 273.3 [M+H]+. Instructions for Use 107 / 240 pages 153 CN 121568943 A

[0320] Lithium 5,5-dimethyl-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinium-10-carboxylate

[0321] At 25°C, a solution of lithium hydroxide (37 mg, 0.883 mmol) in water (1.5 mL) was added to a solution of methyl 5,5-dimethyl-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinium-10-carboxylate (229 mg, 0.841 mmol) in THF (6 mL), and stirred for 48 h. The product was concentrated under reduced pressure to obtain the desired product, lithium 5,5-dimethyl-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazine-10-carboxylate (235 mg, 0.845 mmol), which was a grayish-white solid.100% yield). 1H NMR (400 MHz, DMSO‑D6) δ 8.28 (d , J = 1.8 Hz, 1H) , 7.99 (d , J = 1.1 Hz, 1H) , 7.63 (dd , J = 8.3, 1.9 Hz, 1H) , 7.34 (d , J = 1.1 Hz, 1H), 6.86 (d, J = 8.3 Hz, 1H), 4.16 (s, 2H), 1.57 (s, 6H). UPLC-MS (alkaline 2 min): rt = 0.65 min, m / z (ES+) 259.1 [M+H]+ methyl 3-bromo-5-formyl-4-hydroxybenzoate

[0322] Hexamethylenetetramine (1.40 g, 9.95 mmol) was added to a suspension of methyl 3-bromo-4-hydroxybenzoate (500 mg, 2.16 mmol) and trifluoroacetic acid (5.0 mL, 65.3 mmol), and the mixture was heated at 73 °C for 18 h. It was cooled to room temperature, and water (30 mL) was slowly added, followed by heating at 80 °C for 2 h. It was cooled, and the resulting precipitate was filtered and dried to give the desired product, methyl 3-bromo-5-formyl-4-hydroxybenzoate (570 mg, 1.76 mmol, 81% yield), as a grayish-white solid. 1H NMR (400 MHz, DMSO-D6) δ 10.16 (s, 1H), 8.35 (d, J = 2.2 Hz, 1H), 8.31 (d, J = 2.2 Hz, 1H), 3.86 (s, 3H). UPLC-MS (alkaline 2 min): rt = 0.69 min, m / z (ES+) not observed.

[0323] Methyl 3-bromo-4-hydroxy-5-(((2-hydroxyethyl)imino)methyl)benzoate

[0324] Ethanolamine (0.11 mL, 1.76 mmol) in methanol (10 mL) and methyl 3-bromo-5-formyl-4-hydroxybenzoate (570 mg, 1.76 mmol) were heated to 40 °C for 68 h. The reaction mixture was concentrated under reduced pressure to give the desired product, methyl (E)-3-bromo-4-hydroxy-5-(((2-hydroxyethyl)imino)methyl)benzoate (680 mg, 1.76 mmol), as a yellow solid.100% yield). ¹H NMR (400 MHz, DMSO-D6) δ 8.68 (s, 1H), 8.07 (d, J = 2.3 Hz, 1H), 8.04 (d, J = 2.3 Hz, 1H), 5.13 (s, 1H), 3.77 (s, 3H), 3.73 – 3.62 (m, 5H).

[0325] Methyl 3-bromo-4-hydroxy-5-(1-(2-hydroxyethyl)-1H-imidazol-5-yl)benzoate

[0326] At 25°C, 4-toluenesulfonylmethylisocyanate (422 mg, 2.16 mmol) was added to a suspension of (E)-3-bromo-4-hydroxy-5-(((2-hydroxyethyl)imino)methyl)benzoate (680 mg, 1.80 mmol) and potassium carbonate (547 mg, 3.96 mmol) in dimethoxyethane (10 mL) and methanol (6 mL), and stirred for 18 h. The mixture was then filtered and concentrated under reduced pressure to obtain the crude product. It was purified by column chromatography on C18 with gradient elution of MeCN (0.1% NH3) (5% to 25% v / v) in water (0.1% NH3) to give the desired product, methyl 3-bromo-4-hydroxy-5-(1-(2-hydroxyethyl)-1H-imidazol-5-yl)benzoate (518 mg, 1.37 mmol, 76% yield), as a white solid. ¹H NMR (400 MHz, DMSO-D₆) δ 7.84 (d, J = 2.5 Hz, ¹H), 7.58 (d, J = 1.2 Hz, ¹H), 7.43 (d, J = 2.5 Hz, ¹H), 6.58 (d, J = 1.2 Hz, ¹H), 5.79 (s, ¹H), 3.87 (t, J = 5.6 Hz, 2H), 3.66 (s, 3H), 3.57 (t, J = 5.6 Hz, 2H). ¹OH was not observed. UPLC-MS (alkaline 2 min): rt = 0.68 min, m / z (ES+) 341.2, 343.2 [M+H]+.

[0327] 8-bromo-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinyl-10-carboxylic acid methyl ester

[0328] At 0 °C, diisopropyl azodicarboxylic acid (0.36 mL,1.84 mmol) of methyl 3-bromo-4-hydroxy-5-(1-(2-hydroxyethyl)-1H-imidazol-5-yl)benzoate (465 mg, 1.23 mmol) and triphenylphosphine (386 mg, 1.47 mmol) in THF (25 mL) were added, and the reaction was stirred at room temperature for 18 h. Then, triphenylphosphine (193 mg, 0.74 mmol) and diisopropyl azodicarboxylate (0.18 mL, 0.92 mmol) were added, and the reaction was stirred for 2 h. The reaction mixture was loaded onto an SCX-2 column (20 g). The column was washed with MeOH (2 CV), and then eluted with a 2 M ammonia solution in methanol (2 CV). The eluent was concentrated to dryness under reduced pressure to give the crude product. The product was suspended in DMSO, ground with water, filtered, and vacuum dried to give the desired product, methyl 8-bromo-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinyl-10-carboxylate, as a yellow solid (174 mg, 0.538 mmol, 44% yield). 1H NMR (400 MHz, DMSO‑D6) δ 8.30 (d, J = 2.1 Hz, 1H) , 7.98 (d, J = 2.0 Hz, 1H) , 7.84 (d, J = 1.1 Hz, 1H) , 7.60 (d , J = 1.1 Hz, 1H) , 4.63 – 4.56 (m, 2H), 4.56 – 4.49 (m, 2H), 3.86 (s, 3H). UPLC‑MS (basic 2 min): rt=0.99 min, m / z (ES+) 322.9, 324.8 [M+H]+.

[0329] Lithium 8-bromo-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinium-10-carboxylate specification 109 / 240 pages 155 CN 121568943 A

[0330] At 25°C, lithium hydroxide (23 mg, 0.552 mmol) in water (1 mL) was added to a solution of methyl 8-bromo-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinium-10-carboxylate (170 mg, 0.526 mmol) in THF (4 mL), and stirred for 68 h. The product was concentrated under reduced pressure to obtain the desired product, lithium 8-bromo-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazine-10-carboxylate (174 mg, 0.525 mmol), which was an orange solid.99% yield). ¹H NMR (400 MHz, DMSO-D6) δ 8.16 (d, J = 1.8 Hz, ¹H), 7.92 (d, J = 1.8 Hz, ¹H), 7.78 (d, J = 1.1 Hz, ¹H), 7.39 (d, J = 1.1 Hz, ¹H), 4.51 – 4.40 (m, 4H). UPLC-MS (alkaline 2 min): rt = 0.64 min, m / z (ES+) 308.9, 310.8 [M+H]+.

[0331] Methyl 3-formyl-4-hydroxy-5-methylbenzoate

[0332] Hexamethylenetetramine (1.94 g, 13.8 mmol) was added to a suspension of methyl 4-hydroxy-3-methylbenzoate (500 mg, 3.01 mmol) and trifluoroacetic acid (6.9 mL, 90.0 mmol), and the mixture was heated at 73 °C for 18 h. It was cooled to room temperature, and water (35 mL) was slowly added, and then heated at 80 °C for 2 h. It was cooled, and the resulting precipitate was filtered and dried to give methyl 3-formyl-4-hydroxy-5-methylbenzoate (317 mg, 1.29 mmol, 43% yield) as a pale yellow solid. ¹H NMR (400 MHz, DMSO-D6) δ 11.46 (s, ¹H), 10.14 (s, ¹H), 8.26 (d, J = 2.3 Hz, ¹H), 8.03 (dd, J = 2.3, 1.0 Hz, ¹H), 3.85 (s, ³H), 2.25 (s, ³H). UPLC-MS (alkaline 4 min): rt = 0.87 min, m / z (ES+) 193.1 [M-H]−.

[0333] Methyl benzoate (E)-4-hydroxy-3-(((2-hydroxyethyl)imino)methyl)-5-methylbenzoate

[0334] Ethanolamine (0.061 mL, 1.01 mmol) and methyl 3-formyl-4-hydroxy-5-methylbenzoate (249 mg, 1.01 mmol) in methanol (5 mL) were heated to 40 °C for 18 h. The reaction mixture was concentrated under reduced pressure to give the desired product (E)-4-hydroxy-3-(((2-hydroxyethyl)imino)methyl)-5-methylbenzoate (242 mg, 1.01 mmol) as a yellow solid.100% yield). ¹H NMR (400 MHz, DMSO-D6) δ 8.60 (s, ¹H), 7.92 (d, J = 2.7 Hz, ¹H), 7.75 – 7.72 (m, ¹H), 3.78 (s, ³H), 3.69 – 3.62 (m, 4H), 2.13 (s, ³H). No 2 OH was observed. (See specification 110 / 240 pages, 156 CN 121568943 A)

[0335] Methyl 4-hydroxy-3-(1-(2-hydroxyethyl)-1H-imidazol-5-yl)-5-methylbenzoate

[0336] At 25 °C, 4-toluenesulfonyl methyl isonitrile (239 mg, 1.22 mmol) was added to a suspension of (E)-4-hydroxy-3-(((2-hydroxyethyl)imino)methyl)-5-methylbenzoate (242 mg, 1.02 mmol) and potassium carbonate (310 mg, 2.24 mmol) in dimethoxyethane (2.5 mL) and methanol (1 mL), and stirred for 18 h. The reaction mixture was loaded into an SCX-2 column (20 g). The column was washed with MeOH (2 CV) and then eluted with a methanol solution of 2 M ammonia (2 CV). The eluent was concentrated to dryness under reduced pressure to give the desired product, methyl 4-hydroxy-3-(1-(2-hydroxyethyl)-1H-imidazol-5-yl)-5-methylbenzoate (249 mg, 0.685 mmol, 67% yield), as a light yellow solid. ¹H NMR (400 MHz, DMSO-D₆) δ 7.74 (dd, J = 2.4, 0.8 Hz, ¹H), 7.71 (d, J = 1.1 Hz, ¹H), 7.55 (d, J = 2.3 Hz, ¹H), 6.81 (d, J = 1.1 Hz, ¹H), 4.10 (s, ¹H), 3.83 (t, J = 5.7 Hz, 2H), 3.77 (s, 3H), 3.46 (t, J = 5.8 Hz, 2H), 2.22 (s, 3H). ¹OH was not observed. UPLC-MS (alkaline 4 min): rt = 0.93 min, m / z (ES+) 277.0 [M+H]+.

[0337] 8-Methyl-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazine-10-carboxylic acid methyl ester

[0338] Diisopropyl azodiacetic acid (0.27 mL,1.36 mmol) of methyl 4-hydroxy-3-(1-(2-hydroxyethyl)-1H-imidazol-5-yl)-5-methylbenzoate (249 mg, 0.90 mmol) and triphenylphosphine (284 mg, 1.08 mmol) in THF (4.5 mL) were added, and the reaction was stirred at room temperature for 18 h. The reaction mixture was loaded onto an SCX-2 column (10 g). The column was washed with MeOH (2 CV) and then eluted with a 2 M ammonia-methanol solution (2 CV). The eluent was concentrated to dryness under reduced pressure to give the crude product. It was purified by column chromatography on silica with gradient elution of MeOH (0% to 10%; v / v) in DCM to give the crude product. It was purified by column chromatography on C18 with gradient elution of MeCN (0.1% NH3) (5% to 90% v / v) in water (0.1% NH3) to give the desired product, methyl 8-methyl-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinyl-10-carboxylic acid (97 mg, 0.376 mmol, 42% yield), as a grayish-white solid. 1H NMR (400 MHz, DMSO‑D6) δ 8.17 (dd , J = 2.2, 0.6 Hz, 1H) , 7.79 (d , J = 1.1 Hz, 1H) , 7.68 (dd, J = 2.2, 0.9 Hz, 1H) , 7.49 (d, J = 1.1 Hz, 1H), 4.52 – 4.46 (m, 4H), 3.84 (s, 3H), 2.25 (s, 3H). UPLC‑MS (basic 4 min): rt=1.43 min, m / z (ES+) 259.1 [M+H]+.

[0339] Lithium 8-methyl-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinium-10-carboxylate specification 111 / 240 pages 157 CN 121568943 A

[0340] At 25°C, lithium hydroxide (18 mg, 0.432 mmol) in water (1 mL) was added to a solution of methyl 8-methyl-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinium-10-carboxylate (97 mg, 0.376 mmol) in THF (4 mL), and stirred for 18 h. Then lithium hydroxide (18 mg, 0.432 mmol) was added, and the reaction was stirred for 5 h. The product was concentrated under reduced pressure to obtain the desired product, lithium 8-methyl-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazine-10-carboxylate (120 mg), which was a pale yellow solid.0.376 mmol, 99% yield). ¹H NMR (400 MHz, DMSO-D6) δ 8.01 (d, J = 2.0 Hz, ¹H), 7.72 (d, J = 1.1 Hz, ¹H), 7.59–7.55 (m, ¹H), 7.30 (d, J = 1.1 Hz, ¹H), 4.39 (s, 4H), 2.19 (s, 3H). UPLC-MS (alkaline 4 min): rt = 0.68 min, m / z (ES+) 243.1 [M-H]−.

[0341] Methyl 3-formyl-4-hydroxy-5-methoxybenzoate

[0342] Hexamethylenetetramine (1.77 g, 12.6 mmol) was added to a suspension of methyl 4-hydroxy-3-methoxybenzoate (500 mg, 2.74 mmol) and trifluoroacetic acid (6.3 mL, 82.3 mmol), and the mixture was heated at 73 °C for 18 h. It was cooled to room temperature, and water (31 mL) was slowly added, followed by heating at 80 °C for 2 h. It was cooled, and the resulting precipitate was filtered and dried to give methyl 3-formyl-4-hydroxy-5-methoxybenzoate (388 mg, 1.85 mmol, 67% yield) as a white solid. ¹H NMR (400 MHz, DMSO-D6) δ 11.08 (s, ¹H), 10.32 (s, ¹H), 7.90 (d, J = 2.0 Hz, ¹H), 7.65 (d, J = 2.0 Hz, ¹H), 3.93 (s, 3H), 3.84 (s, 3H). UPLC-MS (alkaline 4 min): rt = 0.68 min, m / z (ES+) 210.1 [M+H]+.

[0343] Methyl (E)-4-hydroxy-3-((((2-hydroxyethyl)imino)methyl)-5-methoxybenzoate

[0344] Ethanolamine (0.11 mL, 1.85 mmol) and methyl 3-formyl-4-hydroxy-5-methoxybenzoate (388 mg, 1.85 mmol) in methanol (9 mL) were heated to 40 °C for 96 h. The reaction mixture was concentrated under reduced pressure to give the desired product (E)-4-hydroxy-3-(((2-hydroxyethyl)imino)methyl)-5-methoxybenzoate (466 mg, 1.84 mmol) as a yellow solid.100% yield). ¹H NMR (400 MHz, DMSO-D6) δ 8.55 (s, ¹H), 7.69 (d, J = 2.0 Hz, ¹H), 7.19 (d, J = 2.1 Hz, ¹H), 5.05–4.98 (m, ¹H), 3.77 (s, 3H), 3.74 (s, 3H), 3.67–3.62 (m, 4H). No ¹OH was observed.

[0345] Methyl 4-hydroxy-3-(1-(2-hydroxyethyl)-1H-imidazol-5-yl)-5-methoxybenzoate

[0346] At 25 °C, 4-toluenesulfonylmethylisocyanate (431 mg, 2.21 mmol) was added to a suspension of (E)-4-hydroxy-3-(((2-hydroxyethyl)imino)methyl)-5-methoxybenzoate (466 mg, 1.84 mmol) and potassium carbonate (560 mg, 4.05 mmol) in dimethoxyethane (7.5 mL) and methanol (3 mL), and stirred for 18 h. The reaction mixture was loaded onto an SCX-2 column (20 g). The column was washed with MeOH (2 CV) and then eluted with a methanol solution of 2 M ammonia (2 CV). The eluent was concentrated to dryness under reduced pressure to give the desired product, methyl 4-hydroxy-3-(1-(2-hydroxyethyl)-1H-imidazol-5-yl)-5-methoxybenzoate (534 mg, 1.75 mmol, 95% yield), as a pale yellow solid. ¹H NMR (400 MHz, DMSO-D₆) δ 7.71 (d, J = 1.1 Hz, ¹H), 7.52 (d, J = 2.0 Hz, ¹H), 7.42 (d, J = 2.0 Hz, ¹H), 6.84 (d, J = 1.1 Hz, ¹H), 3.91 (s, 3H), 3.86 (t, J = 5.8 Hz, 2H), 3.81 (s, 3H), 3.41 (t, J = 5.8 Hz, 2H). 2OH was not observed. UPLC-MS (alkaline 4 min): rt = 0.74 min, m / z (ES⁺) 293.3 [M⁺H]⁺.

[0347] 8-Methoxy-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinyl-10-carboxylic acid methyl ester

[0348] Diisopropyl azodiacetic acid (0.54 mL,2.74 mmol) of methyl 4-hydroxy-3-(1-(2-hydroxyethyl)-1H-imidazol-5-yl)-5-methoxybenzoate (534 mg, 1.83 mmol) and triphenylphosphine (575 mg, 2.19 mmol) in THF (9 mL) were added, and the reaction was stirred at room temperature for 18 h. The reaction mixture was loaded onto an SCX-2 column (10 g). The column was washed with MeOH (2 CV) and then eluted with a 2 M ammonia solution in methanol (2 CV). The eluent was concentrated to dryness under reduced pressure to give the crude product. It was purified by column chromatography on C18 with gradient elution of MeCN (0.1% NH3) (5% to 90% v / v) in water (0.1% NH3) to give the desired product, methyl 8-methoxy-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinyl-10-carboxylic acid (274 mg, 0.959 mmol, 52% yield), as a grayish-white solid. 1H NMR (400 MHz, DMSO‑D6) δ 7.94 (d , J = 2.0 Hz, 1H) , 7.80 (d , J = 1.1 Hz , 1H) , 7.51 (d , J = 1.1 Hz , 1H) , 7.35 (d , J = 2.0 Hz , 1H), 4.48 (s, 4H), 3.86 (s, 3H), 3.84 (s, 3H). UPLC‑MS (basic 4 min): rt=1.18 min, m / z (ES+) 275.0 [M+H]+.

[0349] Lithium 8-methoxy-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinium-10-carboxylate specification 113 / 240 pages 159 CN 121568943 A

[0350] At 25°C, lithium hydroxide (48 mg, 1.15 mmol) in water (1 mL) was added to a solution of methyl 8-methoxy-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinium-10-carboxylate (274 mg, 0.999 mmol) in THF (4 mL), and stirred for 68 h. The product was concentrated under reduced pressure to obtain the desired product, lithium 8-methoxy-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazine-10-carboxylate (287 mg, 0.999 mmol), which was an orange solid.99% yield). ¹H NMR (400 MHz, DMSO-D6) δ 8.01 (d, J = 2.0 Hz, ¹H), 7.72 (d, J = 1.1 Hz, ¹H), 7.59–7.55 (m, ¹H), 7.30 (d, J = 1.1 Hz, ¹H), 4.39 (s, 4H), 2.19 (s, 3H). UPLC-MS (alkaline 4 min): rt = 0.68 min, m / z (ES+) 243.1 [M+H]−.

[0351] Methyl 3-formyl-4-hydroxy-5-(trifluoromethyl)benzoate

[0352] Hexamethylenetetramine (1.46 g, 10.4 mmol) was added to a suspension of methyl 4-hydroxy-3-(trifluoromethyl)benzoate (500 mg, 2.27 mmol) and trifluoroacetic acid (5.3 mL, 68.6 mmol), and the mixture was heated at 73 °C for 42 h. It was cooled to room temperature, and water (30 mL) was slowly added, and then stirred at 25 °C for 1 h. It was cooled, and the resulting precipitate was filtered to give a crude product. It was purified by column chromatography on silica with gradient elution of EtOAc (0% to 50%; v / v) in isohexane to give the desired product, methyl 3-formyl-4-hydroxy-5-(trifluoromethyl)benzoate (278 mg, 1.09 mmol, 48% yield), as a white solid. ¹H NMR (400 MHz, DMSO-D₆) δ 10.19 (s, ¹H), 8.60 (d, J = 2.3 Hz, ¹H), 8.29 (d, J = 2.2 Hz, ¹H), 3.88 (s, ³H). No OH was observed. UPLC-MS (alkaline 2 min): rt = 0.76 min, m / z (ES⁺) 247.1 [M⁻H]⁻.

[0353] Methyl (E)-4-hydroxy-3-(((2-hydroxyethyl)imino)methyl)-5-(trifluoromethyl)benzoate

[0354] Ethanolamine (0.066 mL, 1.09 mmol) and methyl 3-formyl-4-hydroxy-5-(trifluoromethyl)benzoate (278 mg, 1.09 mmol) in methanol (5 mL) were heated to 40 °C for 1 h. The reaction mixture was concentrated under reduced pressure to give the desired product (E)-4-hydroxy-3-(((2-hydroxyethyl)imino)methyl)-5-(trifluoromethyl)benzoate (320 mg, 1.07 mmol) as a yellow solid.98% yield). ¹H NMR (400 MHz, DMSO-D6) δ 8.69 (s, ¹H), 8.24 (d, J = 2.5 Hz, ¹H), 7.98 (d, J = 2.5 Hz, ¹H), 5.02 (s, ¹H), 3.77 (s, ³H), 3.65 (s, ⁴H). No ¹OH was observed. (See specification 114 / 240 pages, CN 121568943 A).

[0355] Methyl 4-hydroxy-3-(1-(2-hydroxyethyl)-1H-imidazol-5-yl)-5-(trifluoromethyl)benzoate

[0356] 4-Toluenesulfonylmethylisocyanate (250 mg, 1.28 mmol) was added to a suspension of (E)-4-hydroxy-3-(((2-hydroxyethyl)imino)methyl)-5-(trifluoromethyl)benzoate (320 mg, 1.07 mmol) and potassium carbonate (324 mg, 2.34 mmol) in dimethoxyethane (5 mL) and methanol (3 mL) at 25 °C, and stirred for 18 h. The reaction mixture was loaded onto an SCX-2 column (10 g). The column was washed with MeOH (2 CV), and the compound was eluted with a methanol solution of 2 M ammonia (2 CV). The eluent was concentrated to dryness under reduced pressure to give the crude product. It was purified by column chromatography on C18 with gradient elution of MeCN (0.1% NH3) (5% to 40% v / v) in water (0.1% NH3) to give the desired product, methyl 4-hydroxy-3-(1-(2-hydroxyethyl)-1H-imidazol-5-yl)-5-(trifluoromethyl)benzoate (255 mg, 0.757 mmol, 71% yield), as a white solid. ¹H NMR (400 MHz, DMSO-D₆) δ 8.58 (s, ¹H), 7.94 (d, J = 2.5 Hz, ¹H), 7.74 (d, J = 2.6 Hz, ¹H), 7.32 (d, J = 1.4 Hz, ¹H), 4.03 (t, J = 5.3 Hz, 2H), 3.73 (s, 3H), 3.55 (t, J = 5.4 Hz, 2H). 2OH was not observed. UPLC-MS (alkaline, 2 min): rt = 0.74 min, m / z (ES⁺) 330.9 [M⁺H]⁺.

[0357] 8-(trifluoromethyl)-5,6-dihydrobenzo[f]imidazo[1,5-d][1,4]oxazolidinyl-10-carboxylic acid methyl ester

[0358] Diisopropyl azodiacetic acid (0.22 mL,1.12 mmol) was added to a solution of methyl 4-hydroxy-3-(1-(2-hydroxyethyl)-1H-imidazol-5-yl)-5-(trifluoromethyl)benzoate (252 mg, 0.748 mmol) and triphenylphosphine (235 mg, 0.897 mmol) in THF (13 mL), and the reaction was stirred at room temperature for 1...

Claims

1. A compound of formula (I): ， Or its pharmaceutically acceptable salts or solvates; wherein Z is selected from and , where t represents the connection point between Z and the imidazole ring; X is selected from O and S; Y is selected from -N(R) 10 )2、-OR 10 and -SR 10 ; A is selected from N and CR. 18 ; D is selected from N and CR. 19 ; R 4 Selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 aminoalkyl, C 1-6 Cyanoalkyl, C 1-6 Alkoxyalkyl, C 1-6 Alkyl-N(R) 20 2. C3-5 cycloalkyl groups and 3 to 6-membered heterocycles; R 5 Selected from hydrogen and C 1-6 alkyl; R 6 Selected from hydrogen, C 1-6 Alkyl, halogen, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 aminoalkyl, C 1-6 Cyanoalkyl, C 1-6 Alkoxyalkyl, C 1-6 Alkyl-N(R) 20 2. C 4-6 cycloalkyl and 3- to 6-membered heterocyclic alkyl; R 7 Selected from C3-C 12 Carbon rings and 5 to 15-membered heterocycles, each optionally separated by one or more R 8 replace; Each R 8 Independently selected from halogens, -N(R) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C3-C 12 Carbon rings and 5- to 12-membered heterocycles, wherein the C3-C 12 The carbocyclic ring and the 5- to 12-membered heterocycle are each optionally surrounded by one or more elements selected from halogens, -OH, -CN, -NO2, -NH2, oxo groups, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Substituents of alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl and C1-C6 alkoxyalkyl groups; R 9 Selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R) 20 2. C 3-6 Carbon rings and 4- to 6-membered heterocycles, wherein the C 3-6 The carbocyclic ring and the 4- to 6-membered heterocycle are each optionally selected independently from one or more halogens, -OH, -CN, -NO2, -NH2, oxo groups, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R) 20 2. C 2-10 alkenyl, C 2-10 Substitution of the alkynyl group; Each R 10 Independently selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl and C1-C6 alkyl-N(R) 20 )2; R 17 Selected from hydrogen, halogens, -N(R) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、-CN、C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Carbon rings and 5 to 12-membered heterocycles; R 18 Selected from hydrogen, halogens, -OH, -CN, -NO2, -NH2, -NHC 1-10 Alkyl, -N(C) 1-10 Alkyl)2, -OC 1-10 Alkyl, C1-C6 alkyl and C1-C6 haloalkyl; R 19 Selected from hydrogen, halogens, -OH, -CN, -NO2, -NH2, -NHC 1-10 Alkyl, -N(C) 1-10 Alkyl)2, -OC 1-10 Alkyl, C1-C6 alkyl, and C1-C6 haloalkyl; and R 20 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 The carbocyclic ring and 3 to 12-membered heterocycles are each optionally substituted by one or more substituents independently selected from the following: halogen, -OH, -CN, -NO2, -NH2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 3-12 Carbon rings and 3 to 12-membered heterocycles.

2. The compound or salt according to claim 1, wherein formula (I) is represented by formula (IA): ， Or its pharmaceutically acceptable salts or solvates.

3. The compound or salt according to claim 1, wherein formula (I) is represented by formula (IB): ， Or its pharmaceutically acceptable salts or solvates.

4. The compound or salt according to any one of claims 1-3, wherein R 18 and R 19 Each is independently selected from hydrogen and halogens.

5. The compound or salt according to any one of claims 1-4, wherein R 4 Selected from hydrogen and C 1-6 alkyl.

6. The compound or salt according to any one of claims 1-5, wherein R 4 It is hydrogen.

7. The compound or salt according to any one of claims 1-6, wherein R 6 It is hydrogen.

8. The compound or salt according to any one of claims 1-7, wherein R 5 Selected from hydrogen and methyl.

9. The compound or salt according to any one of claims 1-7, wherein R 5 It is hydrogen.

10. The compound or salt according to any one of claims 1, 2, or 4-9, wherein R 9 Selected from hydrogen and C 1-6 alkyl.

11. The compound or salt according to any one of claims 1, 2, or 4-10, wherein R 9 Selected from hydrogen and methyl.

12. The compound or salt according to any one of claims 1, 2, or 4-11, wherein R 9 It is hydrogen.

13. The compound or salt according to any one of claims 1 or 3-9, wherein each R 10 Independently selected from hydrogen, C 1-6 Alkyl and C1-C6 alkoxyalkyl.

14. The compound or salt according to claim 13, wherein R appears at least once. 10 It is hydrogen.

15. The compound or salt according to claim 1, wherein formula (I) is represented by formula (IC): Formula (IC), Or its pharmaceutically acceptable salts or solvates.

16. The compound or salt according to claim 1, wherein formula (I) is represented by formula (ID): Expression (ID), Or its pharmaceutically acceptable salts or solvates.

17. The compound or salt according to claim 15, wherein R 9 Selected from hydrogen and methyl.

18. The compound or salt according to claim 16, wherein R 10 Selected from hydrogen, methyl and C1-C6 alkoxyalkyl.

19. The compound or salt according to any one of claims 1-18, wherein R 7 Selected from C6-C8 carbon rings and 5- to 6-membered heterocycles, each optionally separated by one or more R 8 replace.

20. The compound or salt according to any one of claims 1-19, wherein R 7 Selected from C6-C8 carbon rings, which are optionally separated by one or more R 8 replace.

21. The compound or salt according to claim 20, wherein R 7 Selected from C6 carbon rings, which are optionally separated by one or more R 8 replace.

22. The compound or salt according to any one of claims 1-21, wherein R 7 yes It is optionally controlled by one or more R 8 replace.

23. The compound or salt according to any one of claims 1-22, wherein each R 8 Independently selected from halogens, C 1-6 Halogenated alkyl groups, -OR 20 -N(R) 20 )2、-NR 20 S(O)2R 20 -C(O)N(R) 20 )2 and 5 to 6 membered heterocycles, wherein the 5 to 6 membered heterocycles are optionally composed of one or more elements selected from halogens, -OH, -CN, -NH2, oxo groups, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups and -OC 1-10 Alkyl substituents.

24. The compound or salt according to claim 23, wherein R 7 Selected from , , , , , , , , , and .

25. The compound or salt according to any one of claims 1-21, wherein R 7 yes It is optionally controlled by one or more R 8 replace.

26. The compound or salt according to any one of claims 1-21 or 25, wherein each R 8 Independently selected from halogens and -S(O)2(R 20 ).

27. The compound or salt according to claim 26, wherein R 7 Selected from and .

28. The compound or salt according to any one of claims 1-18, wherein R 7 Selected from C9 carbon rings, which are optionally separated by one or more R 8 replace.

29. The compound or salt according to claim 28, wherein R 7 yes .

30. The compound or salt according to any one of claims 1-18, wherein R 7 Selected from 5- to 10-membered heterocycles, each optionally bounded by one or more R... 8 replace.

31. The compound or salt of claim 30, wherein R 7 Selected from , , , , , , , , , , , , , , and Each of them is optionally controlled by one or more R 8 replace.

32. The compound or salt according to any one of claims 30-31, wherein each R 8 Independently selected from halogens, -OR 20 -S(O)2(R 20 -C(O)OR 20 =O,C 1-6 Alkyl and C 1-6 Halogenated alkyl groups.

33. The compound or salt according to any one of claims 30-32, wherein R 7 Selected from .

34. The compound or salt according to any one of claims 1-19, wherein R 7 Selected from 5- to 6-membered saturated heterocycles, each optionally separated by one or more R 8 replace.

35. The compound or salt according to claim 34, wherein each R 8 Independently selected from -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 ) and =O.

36. The compound or salt according to claim 35, wherein each R 8 Independently selected from -S(O)2(R 20 ) and =O.

37. The compound or salt according to any one of claims 34-36, wherein R 7 Selected from , and .

38. The compound or salt according to any one of claims 1-19, wherein R 7 Selected from 5 to 6 heteroaryl groups that are optionally substituted.

39. The compound or salt according to claim 38, wherein R 7 Selected from 6-membered heteroaryl groups that are optionally substituted.

40. The compound or salt according to claim 39, wherein R 7 Selected from pyridines that are optionally substituted.

41. The compound or salt according to any one of claims 38-40, wherein each R 8 Selected from halogens, -N(R) 20 )2、-OR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Halogenated alkyl and C 1-6 alkyl.

42. The compound or salt according to claim 41, wherein each R 8 Selected from halogens, -OR 20 -CN,C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Halogenated alkyl and C 1-6 alkyl.

43. The compound or salt according to any one of claims 38-42, wherein R 7 Selected from .

44. The compound or salt according to any one of claims 1-19, wherein R 7 Selected from 6-membered heterocycles, which are optionally bounded by one or more R 8 replace.

45. The compound or salt according to claim 44, wherein the 6-membered heterocycle has a nitrogen atom.

46. ​​The compound or salt according to any one of claims 1-19, wherein R 7 Selected from 6-membered heteroaryl groups, which are optionally bounded by one or more R groups 8 replace.

47. The compound or salt according to claim 46, wherein the 6-membered heteroaryl group has a nitrogen atom.

48. The compound or salt according to any one of claims 44-47, wherein each R 8 Independently selected from halogens, -OR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Halogenated alkyl and C 1-6 alkyl.

49. The compound or salt according to any one of claims 44-48, wherein each R 8 Independently selected from halogens, -S(O)2(R 20 =O,C 1-6 Alkyl and C 1-6 Halogenated alkyl groups.

50. The compound or salt according to any one of claims 44 to 49, wherein R 7 Selected from , and .

51. The compound or salt according to any one of claims 1-18, wherein R 7 Selected from 9- to 10-membered heterocycles, each optionally bounded by one or more R... 8 replace.

52. The compound or salt according to claim 51, wherein the 9- or 10-membered heterocycle is a bicyclic ring.

53. The compound or salt according to claim 51 or 52, wherein R 7 Selected from , , , , , , , , , and Each of them is optionally controlled by one or more R 8 replace.

54. The compound or salt according to any one of claims 51-53, wherein each R 8 Independently selected from halogens, -OR 20 -S(O)2(R 20 -C(O)OR 20 =O,C 1-6 Alkyl and C 1-6 Halogenated alkyl groups.

55. The compound or salt according to any one of claims 51-53, wherein each R 8 Independently selected from =O, -S(O)2(C 1-6 Alkyl groups, -CF3, -CH3, -C(O)OC 1-6 Alkyl, -OMe and .

56. The compound or salt according to any one of claims 51-55, wherein R 7 Selected from .

57. The compound or salt according to any one of claims 1-19, wherein R 7 Selected from phenyl, which is optionally coated with one or more R 8 replace.

58. The compound or salt according to claim 57, wherein each R 8 Selected from halogens, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Halogenated alkyl and C 1-6 alkyl.

59. The compound or salt according to claim 57 or 58, wherein R 7 Selected optionally by one or more of halogens and C 1-6 A phenyl group substituted with a hydroxyalkyl group.

60. The compound or salt according to any one of claims 57-59, wherein R 7 Selected from , , , and .

61. A compound of formula (II): ， Or its pharmaceutically acceptable salts or solvates; wherein Z is selected from , where t represents Z and Connection points between them; Y is selected from -O-, -NR 9 -, -S- and -SO2-; Each R 50 Independently selected from hydrogen, halogens, and C1-C6 alkyl groups; or combined to form ; Each R 51 Independently selected from hydrogen, halogens, and C1-C6 alkyl groups; k is selected from 1 and 2; A is selected from N and CR. 18 ; Selected from imidazoles that are optionally substituted, wherein the imidazoles are optionally substituted with one or more R 14 replace; D is selected from N and CR. 19 ; R 5 Selected from hydrogen and C 1-6 alkyl; R 7 Selected from hydrogen; and C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C3-C 14 Carbon rings and 5 to 15-membered heterocycles, each optionally separated by one or more R 8 replace; Each R 8 Independently selected from halogens, -N(R) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、=O、=N(R 20 =NO(R) 20 -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C3-C 12 Carbon rings and 4- to 12-membered heterocycles, wherein the C 1-6 Alkyl groups are optionally surrounded by one or more R 8 * Replacement, and wherein the C3-C 12 The carbocyclic ring and the 4- to 12-membered heterocycle are each optionally surrounded by one or more elements selected from halogens, -OH, -CN, -NO2, -NH2, oxo groups, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Substituents of alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl and C1-C6 alkoxyalkyl groups; Each R 8 *Independently selected from 4- to 12-membered heterocycles, wherein the 4- to 12-membered heterocycle is optionally composed of one or more elements selected from halogen, -OH, -CN, -NO2, -NH2, oxo group, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Substituents of alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl and C1-C6 alkoxyalkyl groups; R 9 Selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R) 20 2. C 3-6 Carbon rings and 4- to 6-membered heterocycles, wherein the C 3-6 The carbocyclic ring and the 4- to 6-membered heterocycle are each optionally selected independently from one or more halogens, -OH, -CN, -NO2, -NH2, oxo groups, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 cyanoalkyl, C1-C6 alkoxyalkyl, C1-C6 alkyl-N(R) 20 2. C 2-10 alkenyl and C 2-10 Substitution of the alkynyl group; Each R 14 Independently selected from halogens, -OH, -CN, -NO2, -NH2, -NHC 1-10 Alkyl, -N(C) 1-10 Alkyl)2, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 3-12 Carbon rings and 3 to 12-membered heterocycles; R 17 Selected from hydrogen, halogens, -N(R) 20 )2、-OR 20 -SR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -NR 20 S(O)2R 20 -C(O)N(R) 20 )2、-C(=NR 20 )N(R 20 )2、-C(O)NR 20 OR 20 -N(R) 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -C(O)R 20 -C(O)OR 20 -OC(O)R 20 -OC(O)N(R) 20 )2、-NO2、-CN、C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Carbon rings and 5 to 12-membered heterocycles; R 18 Selected from hydrogen, halogens, -OH, -CN, -NO2, -NH2, -NHC 1-10 Alkyl, -N(C) 1-10 Alkyl)2, -OC 1-10 Alkyl, C1-C6 alkyl and C1-C6 haloalkyl; R 19 Selected from hydrogen, halogens, -OH, -CN, -NO2, -NH2, -NHC 1-10 Alkyl, -N(C) 1-10 Alkyl)2, -OC 1-10 Alkyl, C1-C6 alkyl, and C1-C6 haloalkyl; and R 20 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 The carbocyclic ring and 3 to 12-membered heterocycles are each optionally substituted by one or more substituents independently selected from the following: halogen, -OH, -CN, -NO2, -NH2, -S(O)2(C 1-6 Alkyl), C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups, -OC 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 3-12 Carbon rings and 3 to 12-membered heterocycles.

62. The compound or salt according to claim 61, wherein Z is .

63. The compound or salt according to claim 61 or 62, wherein Z is .

64. The compound or salt according to claim 61, wherein formula (II) is represented by formula (IIA): ， Or its pharmaceutically acceptable salts or solvates.

65. The compound or salt according to claim 61, wherein formula (II) is represented by formula (IIB): ， Or its pharmaceutically acceptable salts or solvates.

66. The compound or salt according to claim 61, wherein formula (II) is represented by formula (IIC): ， Or its pharmaceutically acceptable salts or solvates.

67. The compound or salt according to any one of claims 61 to 66, wherein A is selected from N, CF and CH.

68. The compound or salt according to claim 67, wherein A is CH.

69. The compound or salt according to claim 67, wherein A is N.

70. The compound or salt according to any one of claims 61 to 69, wherein D is selected from N, CF and CH.

71. The compound or salt according to claim 70, wherein D is CH.

72. The compound or salt according to claim 70, wherein D is N.

73. The compound or salt according to any one of claims 61 to 64, wherein formula (II) is represented by formula (IID): ， Or its pharmaceutically acceptable salts or solvates.

74. The compound or salt according to any one of claims 61 to 63 or 65, wherein formula (II) is represented by formula (IIIE): ， Or its pharmaceutically acceptable salts or solvates.

75. The compound or salt according to any one of claims 61 to 63 or 66, wherein formula (II) is represented by formula (IIF): ， Or its pharmaceutically acceptable salts or solvates.

76. The compound or salt according to claim 61, wherein formula (II) is represented by formula (IIF): ， Or its pharmaceutically acceptable salts or solvates.

77. The compound or salt according to any one of claims 61 to 76, wherein R 5 Selected from hydrogen and methyl.

78. The compound or salt according to any one of claims 61 to 77, wherein R 5 It is hydrogen.

79. The compound or salt according to any one of claims 61 to 78, wherein R 7 Selected from C6-C8 carbon rings and 5- to 6-membered heterocycles, each optionally separated by one or more R 8 replace.

80. The compound or salt according to any one of claims 61 to 79, wherein R 7 Selected from C6-C8 carbon rings, which are optionally separated by one or more R 8 replace.

81. The compound or salt according to any one of claims 61 to 78, wherein R 7 Selected from C4-C7 carbon rings, optionally separated by one or more R 8 replace.

82. The compound or salt according to any one of claims 61 to 81, wherein R 7 Selected from , , and It is optionally controlled by one or more R 8 replace.

83. The compound or salt according to any one of claims 61 to 82, wherein each R 8 Independently selected from halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, -OR 20 -N(R) 20 )2、-NR 20 S(O)2R 20 -N(R) 20 )C(O)R 20 -C(O)N(R) 20 )2、-S(O)2(R 20 ) and 4 to 6-membered heterocycles, wherein the 4 to 6-membered heterocycles are optionally composed of one or more elements selected from halogens, -OH, -CN, -NH2, oxo groups, C 1-10 Alkyl, -C 1-10 Halogenated alkyl groups and -OC 1-10 Alkyl substituents; and wherein R 8 The C mentioned 1-6 The alkyl group is optionally substituted with a 4- to 6-membered heterocycle, wherein the 4- to 6-membered heterocycle is optionally substituted with one or more substituents selected from halogens.

84. The compound or salt according to any one of claims 61 to 83, wherein each R 8 Independently selected from F, methyl, ethyl, .

85. The compound or salt according to any one of claims 61 to 84, wherein R 7 Selected from .

86. The compound or salt according to any one of claims 61 to 81, wherein R 7 Selected from optionally substituted phenyl groups, which are optionally converted to one or more R groups. 8 replace.

87. The compound or salt according to any one of claims 61 to 81 or 86, wherein each R 8 Independently selected from halogens, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Haloalkyl, C 1-6 alkyl.

88. The compound or salt according to claim 86 or 87, wherein R 7 Selected optionally by one or more of halogens and C 1-6 A phenyl group substituted with a hydroxyalkyl group.

89. The compound or salt according to claim 88, wherein R 7 Selected from , , , and .

90. The compound or salt according to any one of claims 61 to 81, wherein R 7 yes It is optionally controlled by one or more R 8 replace.

91. The compound or salt according to any one of claims 61 to 81 or 90, wherein each R 8 Independently selected from halogens and -S(O)2(R 20 ).

92. The compound or salt according to claim 90 or 91, wherein R 7 Selected from and .

93. The compound or salt according to any one of claims 61 to 78, wherein R 7 Selected from C9 carbon rings, which are optionally separated by one or more R 8 replace.

94. The compound or salt according to claim 93, wherein R 7 yes .

95. The compound or salt according to any one of claims 61 to 78, wherein R 7 Selected from 5- to 10-membered heterocycles, each optionally bounded by one or more R... 8 replace.

96. The compound or salt according to claim 95, wherein R 7 Selected from , , , , , , , , , , , , , , , , and Each of them is optionally controlled by one or more R 8 replace.

97. The compound or salt according to any one of claims 61 to 78, 95 or 96, wherein each R 8 Independently selected from halogens, -OR 20 -N(R) 20 )2、-S(O)2(R 20 -C(O)OR 20 =O,C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyl alkyl and 4 to 6-membered heterocycles, wherein the 4 to 6-membered heterocycles are optionally selected from one or more halogens and -C 1-3 Substituents of haloalkyl groups.

98. The compound or salt according to any one of claims 61 to 78 or 95 to 97, wherein each R 8 Selected independently , , , , , , , , , , , , , , , , , and .

99. The compound or salt according to claim 98, wherein R 7 Selected from .

100. The compound or salt according to any one of claims 61 to 79, wherein R 7 Selected from 5- to 6-membered saturated heterocycles, each optionally separated by one or more R 8 replace.

101. The compound or salt according to any one of claims 61 to 79 or 100, wherein each R 8 Independently selected from -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 ) and =O.

102. The compound or salt according to claim 101, wherein each R 8 Independently selected from -S(O)2(R 20 ) and =O.

103. The compound or salt according to any one of claims 61 to 79 or 100 to 102, wherein R 7 Selected from , and .

104. The compound or salt according to any one of claims 61 to 79, wherein R 7 Selected from 5 to 6 heteroaryl groups that are optionally substituted.

105. The compound or salt according to claim 104, wherein R 7 Selected from optionally substituted 6-membered heteroaryl groups, which are optionally substituted with one or more R 8 replace.

106. The compound or salt according to claim 105, wherein R 7 Selected from optionally substituted pyridines, which are optionally substituted with one or more R 8 replace.

107. The compound or salt according to any one of claims 61 to 79 or 104 to 106, wherein each R 8 Independently selected from halogens, -N(R) 20 )2、-OR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Halogenated alkyl and C 1-6 alkyl.

108. The compound or salt according to claim 107, wherein each R 8 Selected from halogens, -OR 20 -CN,C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Halogenated alkyl and C 1-6 alkyl.

109. The compound or salt according to any one of claims 61 to 79 or 104 to 108, wherein R 7 Selected from .

110. The compound or salt according to any one of claims 61 to 79, wherein R 7 Selected from 6-membered heterocycles, which are optionally bounded by one or more R 8 replace.

111. The compound or salt of claim 110, wherein the 6-membered heterocycle has a nitrogen atom.

112. The compound or salt according to any one of claims 61 to 79, wherein R 7 Selected from 6-membered heteroaryl groups, which are optionally bounded by one or more R groups 8 replace.

113. The compound or salt according to claim 112, wherein the 6-membered heteroaryl group has a nitrogen atom.

114. The compound or salt according to any one of claims 61 to 79 or 110 to 113, wherein each R 8 Independently selected from halogens, -OR 20 -S(O)2(R 20 -S(O)2N(R) 20 )2、-S(O)N(R 20 )2、-S(O)R 20 (=NR 20 -CN, C 1-6 Alkyl-N(R) 20 2. C 1-6 aminoalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Halogenated alkyl and C 1-6 alkyl.

115. The compound or salt according to any one of claims 61 to 79 or 110 to 114, wherein each R 8 Independently selected from halogens, -S(O)2(R 20 =O,C 1-6 Alkyl and C 1-6 Halogenated alkyl groups.

116. The compound or salt according to any one of claims 61 to 79 or 110 to 114, wherein R 7 Selected from , and .

117. The compound or salt according to any one of claims 61 to 78, wherein R 7 Selected from 9- to 10-membered heterocycles, each optionally bounded by one or more R... 8 replace.

118. The compound or salt according to claim 117, wherein the 9- or 10-membered heterocycle is a bicyclic ring.

119. The compound or salt according to claim 117 or 118, wherein R 7 Selected from , , , , , , , , , and Each of them is optionally controlled by one or more R 8 replace.

120. The compound or salt according to any one of claims 61 to 78 or 117 to 119, wherein each R 8 Independently selected from halogens, -OR 20 -S(O)2(R 20 -C(O)OR 20 =O,C 1-6 Alkyl and C 1-6 Halogenated alkyl groups.

121. The compound or salt according to any one of claims 61 to 78 or 117 to 120, wherein each R 8 Independently selected from =O, -S(O)2(C 1-6 Alkyl groups, -CF3, -CH3, -C(O)OC 1-6 Alkyl, -OMe and .

122. The compound or salt according to any one of claims 61 to 78 or 117 to 121, wherein R 7 Selected from , , , , , , , , , , , , , , and .

123. The compound or salt according to any one of claims 61 to 72 or 77 to 122, wherein R 17 Selected from hydrogen, halogens, -OR 20 C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and saturated C 3-6 Carbon ring.

124. The compound or salt according to any one of claims 61 to 82, wherein R 7 yes .

125. The compound or salt according to any one of claims 61 to 82 or 124, wherein R 7 Selected from .

126. The compound or salt according to any one of claims 61 to 82 or 125, wherein R 7 yes .

127. The compound or salt according to any one of claims 61 to 82 or 125, wherein R 7 Selected from , and .

128. The compound or salt according to any one of claims 61 to 82 or 125, wherein R 7 yes .

129. The compound or salt according to any one of claims 61 to 82, 124 or 125, wherein R 7 yes .

130. The compound or salt according to any one of claims 61 to 82, wherein R 7 yes It is selected from at least one of C 1-6 Alkyl, C 1-6 Hydroxyalkyl and C 1-6 R of haloalkyl 8 replace.

131. The compound or salt according to any one of claims 61 to 82 or 130, wherein R 7 Selected from , , , , , , , and .

132. The compound or salt according to any one of claims 61 to 82, wherein R 7 yes It is selected from at least one of -S(O)2(R 20 R 8 replace.

133. The compound or salt according to any one of claims 61 to 82 or 132, wherein R 7 yes .

134. The compound or salt according to any one of claims 61 to 82, wherein R 7 yes It is selected from at least one of -N(R) 20 )2 of R 8 replace.

135. The compound or salt according to any one of claims 61 to 82 or 134, wherein R 7 Selected from , , , , , , and .

136. The compound or salt according to claim 1, selected from: , , , , , and or its pharmaceutically acceptable salts or solvates.

137. The compound or salt according to claim 61, selected from: or its pharmaceutically acceptable salts or solvates.

138. A pharmaceutical composition comprising: a compound or salt according to any one of claims 1 to 137 and at least one pharmaceutically acceptable excipient.

139. Use of the compound or salt according to any one of claims 1 to 137 or the pharmaceutical composition according to claim 138 for the treatment of a disease or condition.

140. A method of treating a disease or ailment, the method comprising administering to a subject in need a therapeutically effective amount of a compound or salt according to any one of claims 1 to 137 or a pharmaceutical composition according to claim 138.

141. The method of claim 140, wherein the object benefits from the suppression of CD38.

142. The method of claim 140 or 141, wherein the method results in the suppression of CD38 in the target.

143. The method according to any one of claims 140 to 142, wherein the disease or condition is selected from: neurodegenerative diseases, type 1 diabetes, insulin resistance, Leber hereditary amaurosis, Parkinson's disease, amyotrophic lateral sclerosis, chronic lymphocytic leukemia, periodontitis, psoriasis, UV skin damage, radiation protection, diabetic neuropathy, hyperpigmentation, pellagra, hereditary niacin deficiency, diabetes, Huntington's disease, bipolar disorder, schizophrenia, postmenopausal osteoporosis, optic neuropathy, neurocognitive impairment, multiple sclerosis, Alzheimer's disease, fatty degeneration, NASH, hearing loss, dyslipidemia, end-stage renal disease, metabolic syndrome, obesity, sarcopenic obesity, gout, irritable bowel syndrome, colitis, COPD, asthma, cystic fibrosis, pancreatitis, idiopathic pulmonary fibrosis, organ reperfusion injury, stroke, muscular dystrophy, cardiac hypertrophy, CHF, leishmaniasis, tuberculosis, Hansen's disease, hypoxic pulmonary vasoconstriction, hypertension, clear cell renal cell carcinoma, small lung cell carcinoma, exercise intolerance, epilepsy, sleep disorders, ataxia-telangiectasia, rheumatoid arthritis, lupus, alcohol intolerance, hyperphosphatemia, acute lung injury, and ARDS.

144. The method according to any one of claims 140 to 143, wherein the disease or condition is a neurodegenerative disease.

145. The method according to any one of claims 140 to 143, wherein the disease or condition is muscular dystrophy.

146. The method according to any one of claims 140 to 143, wherein the disease or condition is a metabolic disorder.

147. The method according to any one of claims 140 to 143, wherein the disease or condition is fibrosis.

148. The method according to any one of claims 140 to 143, wherein the disease or condition is Duchenne muscular dystrophy.

149. The method according to any one of claims 140 to 143, wherein the disease or condition is systemic sclerosis.

150. The method according to any one of claims 140 to 143, wherein the disease or symptom is selected from encephalopathy, vascular disease, liver disease, muscle disease, pancreatic disease, adipose tissue disease, and inflammation-related disease.

151. A method for regulating CD38 in a subject, comprising administering to the subject a compound or salt according to any one of claims 1 to 137 or a pharmaceutical composition according to claim 138.

152. The method of claim 151, further comprising treating the subject with a disease or condition selected from: neurodegenerative diseases, type 1 diabetes, insulin resistance, Leber hereditary amaurosis, Parkinson's disease, amyotrophic lateral sclerosis, chronic lymphocytic leukemia, periodontitis, psoriasis, UV-induced skin damage, radiation protection, diabetic neuropathy, hyperpigmentation, pellagra, hereditary niacin deficiency, diabetes, Huntington's disease, bipolar disorder, schizophrenia, postmenopausal osteoporosis, optic neuropathy, neurocognitive impairment, multiple sclerosis, Alzheimer's disease, fatty degeneration Sexual dysfunction, NASH, hearing loss, dyslipidemia, end-stage renal disease, metabolic syndrome, obesity, sarcopenic obesity, gout, irritable bowel syndrome, colitis, COPD, asthma, cystic fibrosis, pancreatitis, idiopathic pulmonary fibrosis, organ reperfusion injury, stroke, muscular dystrophy, cardiac hypertrophy, CHF, leishmaniasis, tuberculosis, Hansen's disease, hypoxic pulmonary vasoconstriction, hypertension, clear cell renal cell carcinoma, small lung cell carcinoma, exercise intolerance, epilepsy, sleep disorders, ataxia-telangiectasia, rheumatoid arthritis, lupus, alcohol intolerance, hyperphosphatemia, acute lung injury, and ARDS.