Nk3 modulators and their uses

Claims

1. Compound characterized by having Formula (I): Formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein: Z is a bivalent group selected from -S-, -N=C(R5)-, C(R5)=N- or -C(R5)=C(R5)-; R1 is a pyrazole, wherein said pyrazole is optionally substituted with 1-3 groups selected independently from R6; R2 is C1-C10 alkyl, C1-C10 heteroalkyl, -C(=O)OR7, C(=O)N(R8)(R7), -N(R8)(R7), -C(=NR9)N(R8)(R7), N(R7)C(=NR9)N(R8)(R7), C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C12 cycloalkyl or 3- to 15-membered heterocycloalkyl, wherein the aryl and heteroaryl are optionally substituted with 1-4 groups selected independently of R10, and the alkyl, heteroalkyl, cycloalkyl and heterocycloalkyl are optionally substituted with 1-4 groups selected independently of oxo and R10; R3 is halogen, cyano, -C(=O)OH, -C(=O)O(C1-C6 alkyl), C1C6 alkyl, C1-C6 alkenyl, -O(C1-C6 alkyl), C3-C6 cycloalkyl or C1-C6 haloalkyl;Each R4 is independently hydrogen, halogen, C1-C6 alkyl, -O-C1-C6 alkyl, C1-C6 haloalkyl or -O-(C1-C6 haloalkyl); L is a linkage, C1-C2 alkylene or C3-C6 cycloalkylene, wherein said alkylene or cycloalkylene is optionally substituted with 1 or 2 -OH groups; each R5 is independently hydrogen, cyano, halogen, C1-C6 alkyl, -O(C1-C6 alkyl), C3-C6 cycloalkyl, C1-C6 haloalkyl or -O(C1-C6 haloalkyl); Petition 870250094509, dated 10 / 16 / 2025, p. 24 / 64 2 / 40 each R6 is selected independently from the group consisting of halogen, hydroxy, cyano, amino, C1-C6 alkyl, C1C6 hydroxyalkyl, C1-C6 aminoalkyl, -O(C1-C6 alkyl), -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, C3-C6 cycloalkyl, -CH2-(C3-6 cycloalkyl), -O-(C3-6 cycloalkyl), C1-C6 haloalkyl and -O(C1-C6 haloalkyl);wherein, if an R6 is attached to a nitrogen atom, then it is selected from the group consisting of C1-C6 alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C3-C6 cycloalkyl, -CH2(C3-6 cycloalkyl) and C1-C6 haloalkyl; each R7 is independently hydrogen or C1-C6 alkyl, wherein said alkyl is optionally substituted with 1-2 hydroxy groups; R8 is hydrogen, C1-C10 alkyl, C1-C10 heteroalkyl, C1-C10 alkenyl, C1-C10 alkynyl, C3-C12 cycloalkyl, 3- to 15-membered heterocycloalkyl, C6-C10 aryl or 5- to 10-membered heteroaryl; wherein the aryl and heteroaryl groups are optionally replaced with 16 groups selected independently of R11, and the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl and heterocycloalkyl groups are optionally replaced with 1-6 groups selected independently of oxo and R11;or an R7 and an R8 bonded to the same nitrogen atom join to form a 3- to 15-membered heterocycloalkyl that is optionally substituted with 1-6 groups selected independently from oxo and R11; R9 is hydrogen, -C(O)OR12, -C(O)N(R12)2, -S(O)2R12, S(O)2N(R12)2 or C1-C6 alkyl; each R10 is independently selected from hydroxy, amino, cyano, fluorine, -C(=O)OR12, -C(=O)N(R12)2, C1-C4 alkyl, C1-C4 haloalkyl, -O(C1-C6 alkyl), -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, C3-C6 cycloalkyl, wherein said alkyl, haloalkyl or cycloalkyl is optionally substituted with 1-2 groups selected from hydroxy, amino, cyano, fluorine, -C(=O)OR12 and Petition 870250094509, dated 10 / 16 / 2025, p. 25 / 64 3 / 40 C(=O)N(R12)2;Each R11 is independently selected from the group consisting of halogen, hydroxyl, amino, cyano, -S(=O)2(R13), N(R12)S(=O)2(R13), -S(=O)(R13), -N(R12)S(=O)(R13), -C(=O)R13, ​​N(R12)C(=O)R13, ​​C1-C6 alkyl, -O(C1-C6 alkyl), -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-C10 aryl and 5- to 10-membered heteroaryl, wherein the aryl and heteroaryl are optionally substituted with 1-4 independently selected groups. R14, and the alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl and heterocycloalkyl groups are optionally substituted with 1-4 groups selected independently from oxo and R14; or two R11 groups attached to the same carbon or nitrogen atom join to form a 3- to 6-membered C3-C6 cycloalkyl or heterocycloalkyl group, wherein the cycloalkyl and heterocycloalkyl groups are optionally substituted with 1-4 groups selected independently from oxo and R14;Each R12 is independently hydrogen or C1-C6 alkyl; each R13 is independently hydroxy, amino, C1-C6 alkyl, O(C1-C6 alkyl), -NH(C1-C6 alkyl), -N(Cx-C6 alkyl)2, C1-C6 haloalkyl, C3-C6 cycloalkyl or 3- to 6-membered heterocycloalkyl; and each R14 is independently cyano, amino, hydroxy, C(=O)OR12, -C(=O)N(R12)2, C1-C6 alkyl, -O(Cx-C6 alkyl), -NR12(C1C6 alkyl), aryl, heteroaryl, C3-C6 cycloalkyl or 3- to 6-membered heterocycloalkyl, where each alkyl is optionally substituted with 1-2 hydroxy groups.

2. Compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: R3 is halogen, cyano, C1-C6 alkyl, C3-C6 cycloalkyl or C1C6 haloalkyl. Petition 870250094509, dated 10 / 16 / 2025, p. 26 / 64 4 / 40 3. Compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: R3 is fluorine, chlorine, cyano, methyl, ethyl, vinyl, -OMe, C(=O)OH, trifluoromethyl, difluoromethyl or cyclopropyl.

4. A compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: R3 is chlorine, cyano, methyl or ethyl.

5. A compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: each R4 is independently hydrogen, fluorine or methyl.

6. A compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: each R4 is hydrogen.

7. A compound according to any one of claims 1 to 6, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: Z is -C(R5)=C(R5)- or -S-.

8. Compound according to claim 7, characterized by having the structure of Formula (IIa): Formula (IIa), or a pharmaceutically acceptable salt or solvate thereof.

9. Compound according to claim 7, characterized by having the structure of Formula (IIb): Petition 870250094509, dated 10 / 16 / 2025, p. 27 / 64 5 / 40 Formula (IIb), or a pharmaceutically acceptable salt or solvate thereof.

10. A compound according to any one of claims 1 to 6, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: Z is -N=C(R5)- or -C(R5)=N-.

11. Compound according to claim 10, characterized by having the structure of Formula (IIc): Formula (IIc), or a pharmaceutically acceptable salt or solvate thereof.

12. Compound according to claim 10, characterized by having the structure of Formula (IId): Formula (IId), or a pharmaceutically acceptable salt or solvate thereof.

13. A compound according to any one of claims 1 to 12, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: L is a C1 alkylene bond.

14. Compound, according to any of the claims Petition 870250094509, of 10 / 16 / 2025, p. 28 / 64 6 / 40 1 to 13, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: R2 is -C(O) (OR7) or -C(O)N(R8) (R7) .

15. Compound according to any one of claims 1 to 13, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: R2 is a 5- to 10-membered heteroaryl or a 3- to 15-membered heterocycloalkyl.

16. Compound according to any one of claims 1 to 13, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: R2 is a 5- to 6-membered heteroaryl or a 3- to 8-membered heterocycloalkyl.

17. Compound according to any one of claims 1 to 7, characterized by having the structure of Formula (III): or a pharmaceutically acceptable salt or solvate thereof.

18. Compound according to claim 17, characterized by having the structure of Formula (IVa): or a pharmaceutically acceptable salt or solvate thereof.

19. A compound according to any one of claims 1 to 18, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: Petition 870250094509, 10 / 16 / 2025, page 29 / 64 7 / 40 R1 is optionally replaced with 1-3 R6 groups selected independently from the group consisting of methyl, ethyl, cyano, fluorine, chlorine, -OMe, cyclopropyl, -CH2-cyclopropyl, trifluoromethyl and difluoromethyl; wherein, when an R6 is attached to a nitrogen atom, it is selected from the group consisting of methyl, ethyl, cyclopropyl, -CH2-cyclopropyl, trifluoromethyl, trifluoroethyl and difluoromethyl.

20. A compound according to any one of claims 1 to 19, or a pharmaceutically acceptable salt or solvate thereof, characterized in that:

21. A compound according to any one of claims 1 to 20, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: R1 is optionally substituted with 1-2 R6 groups selected independently from the group consisting of methyl, cyano, fluorine, chlorine, -OMe, cyclopropyl, -CH2-cyclopropyl and difluoromethyl; wherein, when an R6 is attached to a nitrogen atom, it is methyl, cyclopropyl or -CH2-cyclopropyl.

22. Compound according to claim 20, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: Petition 870250094509, 10 / 16 / 2025, page 30 / 64 8 / 40 fluorine, chlorine, cyano, cyclopropyl, -CH2-cyclopropyl or methyl; wherein, when an R6 is attached to a nitrogen atom, it is methyl, cyclopropyl or CH2-cyclopropyl.

23. Compound according to claim 20, or a pharmaceutically acceptable salt or solvate thereof, characterized by R6 is independently fluorine, chlorine, cyano, cyclopropyl, CH2-cyclopropyl or methyl.

24. Compound according to claim 20, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: R6 is methyl, cyclopropyl or -CH2-cyclopropyl.

25. Compound, according to any one of claims 1 to 4, characterized by having the structure of Formula (VIa): Petition 870250094509, dated 10 / 16 / 2025, p. 31 / 64 9 / 40 or a pharmaceutically acceptable salt or solvate thereof.

26. Compound according to any one of claims 1 to 4, characterized by having the structure of Formula (VIIa): or a pharmaceutically acceptable salt or solvate thereof.

27. Compound according to claim 25 or 26, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: each R6 is independently halogen, cyano, C1-6 alkyl, C1-6 fluoroalkyl, C3-6 cycloalkyl or -CH2-(C3-6 cycloalkyl); wherein, when an R6 is attached to a nitrogen atom, it is C1-6 alkyl, C1-6 fluoroalkyl, C3-6 cycloalkyl or -CH2-(C3-6 cycloalkyl).

28. A compound according to claim 24 or 25, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: each R6 is independently fluorine, chlorine, cyano, cyclopropyl, -CH2-cyclopropyl or methyl; wherein, when an R6 is attached to a nitrogen atom, it is methyl, cyclopropyl or CH2-cyclopropyl.

29. Compound, according to any of the claims Petition 870250094509, of 10 / 16 / 2025, pp. 32 / 64 10 / 40 1 to 28, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: each R5 is independently hydrogen or fluorine.

30. Compound according to claim 28, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: each R5 is hydrogen.

31. A compound according to any one of claims 1 to 14 or 17 to 30, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: each R7 is independently hydrogen or C1-C6 alkyl.

32. A compound according to any one of claims 1 to 14 or 17 to 31, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: R8 is a 3 to 15 member C1-C10 alkyl, C1-C10 heteroalkyl, C3-C12 cycloalkyl or heterocycloalkyl; wherein alkyl, heteroalkyl, cycloalkyl or heterocycloalkyl is optionally substituted with 1-6 independently selected oxo groups and R11.

33. Compound according to claim 32, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: R8 is a 3- to 15-membered C1-C10 alkyl, C3-C12 cycloalkyl or heterocycloalkyl; wherein alkyl, cycloalkyl or heterocycloalkyl is optionally substituted with 1-6 independently selected oxo groups and R11.

34. Compound according to claim 32 or 33, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: R8 is a 3- to 12-membered C3-C10 cycloalkyl or heterocycloalkyl; wherein the cycloalkyl or heterocycloalkyl is optionally substituted with 1-6 independently selected oxo groups and R11. Petition 870250094509, 10 / 16 / 2025, p. 33 / 64 11 / 40 35. A compound according to any one of claims 32 to 34, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: R8 is a C3-C10 monocyclic cycloalkyl, a fused C5-C10 bicyclic cycloalkyl, a bridged C5-C10 bicyclic cycloalkyl, a spirocyclic C5-C10 bicyclic cycloalkyl, a monocyclic 3- to 12-membered cycloalkyl heterocycloalkyl, a fused 5- to 12-membered bicyclic cycloalkyl heterocycloalkyl, a bridged 5- to 12-membered bicyclic heterocycloalkyl, or a spirocyclic 5- to 12-membered bicyclic heterocycloalkyl; wherein the cycloalkyl or heterocycloalkyl is optionally substituted with 1-6 groups selected independently from oxo and R11.

36. A compound according to any one of claims 32 to 35, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: R8 is a fused C5-C10 bicyclic cycloalkyl, a bridged C5-C10 bicyclic cycloalkyl, a spirocyclic C5-C10 bicyclic cycloalkyl, a fused 5- to 12-membered bicyclic cycloalkyl heterocycloalkyl, a bridged 5- to 12-membered bicyclic cycloalkyl heterocycloalkyl, or a spirocyclic 5- to 12-membered bicyclic cycloalkyl heterocycloalkyl; wherein the cycloalkyl or heterocycloalkyl is optionally substituted with 1-6 groups selected independently from oxo and R11.

37. A compound according to any one of claims 31 to 35, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: R8 is a C5-C10 cycloalkyl bicyclic spirocyclic or 5- to 12-membered cycloalkyl bicyclic spirocyclic; wherein the cycloalkyl or heterocycloalkyl is optionally substituted with 1-6 independently selected oxo groups and R11.

38. Compound, according to any one of claims 1 to 13 or 17 to 30, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: an R7 and an R8 attached to the same nitrogen atom join to form a 3- to 15-membered heterocycloalkyl that is optionally substituted with 1-6 independently selected oxo groups and R11.

39. Compound according to claim 38, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: an R7 and an R8 linked to the same nitrogen atom join to form a fused 5- to 12-membered bicyclic heterocycloalkyl, a bridged 5- to 12-membered bicyclic heterocycloalkyl or a spirocyclic 5- to 12-membered bicyclic heterocycloalkyl; wherein the heterocycloalkyl is optionally substituted with 1-6 groups independently selected from oxo and R11.

40. Compound according to claim 38 or 39, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: an R7 and an R8 linked to the same nitrogen atom join to form a 5- to 12-membered bicyclic bridged heterocycloalkyl or a 5- to 12-membered bicyclic spirocyclic heterocycloalkyl; wherein the heterocycloalkyl is optionally substituted with 1-6 independently selected oxo groups and R11.

41. A compound according to any one of claims 38 to 40, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: an R7 and an R8 attached to the same nitrogen atom join to form a 5- to 12-membered bicyclic spirocyclic heterocycloalkyl; wherein the heterocycloalkyl is optionally substituted with 1-6 independently selected oxo groups and R11.

42. Compound, according to any one of claims 1 to 13 or 17 to 41, or a pharmaceutically graded salt or solvate. Petition 870250094509, dated 10 / 16 / 2025, p. 35 / 64 13 / 40 acceptable thereof, characterized in that: each R11 is independently selected from the group consisting of halogen, hydroxy, amino, cyano, -S(=O)2(R13), N(R12)S(=O)2(R13), -S(=O)(R13), -N(R12)S(=O)(R13), -C(=O)R13, ​​N(R12)C(=O)R13, ​​C1-C6 alkyl, -O(C1-C6 alkyl), -NH(C1-C6 alkyl), N(C1-C6 alkyl)2, C1-C6 haloalkyl, C3-C8 cycloalkyl, 3- to 10-membered heterocycloalkyl, C6 aryl and 5- to 6-membered heteroaryl, wherein the aryl and heteroaryl are optionally substituted with 1-4 independently selected groups R14, and the alkyl, haloalkyl, cycloalkyl and heterocycloalkyl groups are optionally replaced with 1-4 groups selected independently from oxo and R14;or two R11 groups attached to the same carbon or nitrogen atom join to form a 3- to 6-membered C3-C6 cycloalkyl or heterocycloalkyl group, wherein the cycloalkyl and heterocycloalkyl groups are optionally substituted with 1-4 groups selected independently from oxo and R14; and each occurrence of R14 is independently cyano, amino, hydroxy, -C(=O)OR12, -C(=O)N(R12)2, Cx-Cs alkyl, -O(C1-C6 alkyl), -NR12(C1-C6 alkyl), aryl, heteroaryl, 3- to 6-membered C3-C6 cycloalkyl or heterocycloalkyl group, wherein each alkyl group is optionally substituted with 1-2 hydroxyl groups.

43. A compound according to claim 42, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: each R11 is independently selected from the group consisting of fluorine, hydroxyl, amino, -S(=O)2(R13), N(R12)S(=O)2(R13), -S(=O)(R13), -N(R12)S(=O)(R13), -C(=O)R13, ​​N(R12)C(=O)R13, ​​C1-C6 alkyl, -O(C1-C6 alkyl), -NH(Cx-C6 alkyl), C1-C6 haloalkyl, C3-C8 cycloalkyl, 3- to 10-membered heterocycloalkyl, phenyl, and 5- to 6-membered heteroaryl, wherein the phenyl and heteroaryl are optionally substituted with 1-4 independently selected groups. R14, and the alkyl, haloalkyl, Petition 870250094509, of 10 / 16 / 2025, p. 36 / 64 14 / 40 cycloalkyl and heterocycloalkyl are optionally replaced with 1-4 groups selected independently from oxo and R14.

44. A compound according to any one of claims 1 to 13 or 17 to 41, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: each R11 is independently selected from the group consisting of halogen, hydroxy, amino, cyano, -S(=O)2(R13), N(R12)S(=O)2(R13), -S(=O)(R13), -N(R12)S(=O)(R13), -C(=O)R13, ​​N(R12)C(=O)R13, ​​C1-C6 alkyl, -O(C1-C6 alkyl), -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, C1-C6 haloalkyl, C3-C8 cycloalkyl, 3- to 10-membered heterocycloalkyl and 5- to 10-membered heteroaryl, wherein the heteroaryl is optionally substituted with 14 groups selected independently of R14, and alkyl, haloalkyl, cycloalkyl and heterocycloalkyl are optionally substituted with 1-4 groups selected independently of oxo and R14;or two R11 groups linked to the same carbon or nitrogen atom join to form a 3- to 6-membered C3-C6 cycloalkyl or heterocycloalkyl group, wherein the cycloalkyl and heterocycloalkyl groups are optionally substituted with 1-4 groups selected independently from oxo and R14; each R12 is independently hydrogen or C1-C6 alkyl; each R13 is independently hydroxy, amino, C1-C6 alkyl, O(C1-C6 alkyl), -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2 or C1-C6 haloalkyl; and each R14 is independently cyano, amino, hydroxy, C(=O)OR12, -C(=O)N(R12)2, C1-C6 alkyl, -O(C1-C6 alkyl) or NR12(C1-C6 alkyl), wherein each alkyl group is optionally substituted with 1-2 hydroxy groups.

45. Compound, according to any one of claims 17 to 18 or 25 to 28, or a pharmaceutically acceptable salt or solvate thereof, characterized in that: Petition 870250094509, 10 / 16 / 2025, p. 37 / 64 15 / 40 Petition 870250094509, 10 / 16 / 2025, p. 38 / 64 16 / 40 Petition 870250094509, 10 / 16 / 2025, p. 39 / 64 17 / 40 Petition 870250094509, 10 / 16 / 2025, p. 40 / 64 18 / 40 ο ο , ; .

46. ​​A compound, according to any one of claims 1 to 12, or a pharmaceutically acceptable salt or solvate thereof, Petition 870250094509, dated 10 / 16 / 2025, p. 41 / 64 19 / 40 characterized in that: Petition 870250094509, dated 10 / 16 / 2025, p. 42 / 64 20 / 40 Petition 870250094509, dated 10 / 16 / 2025, p. 43 / 64 21 / 40 Petition 870250094509, dated 10 / 16 / 2025, p. 44 / 64 22 / 40 47. Compound, according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, characterized in that the compound is a compound depicted in the table. (Applicant 870250094509, 10 / 16 / 2025, p. 45 / 64 23 / 40; Petition 870250094509, 10 / 16 / 2025, p. 46 / 64 24 / 40; Petition 870250094509, 10 / 16 / 2025, p. 47 / 64 25 / 40; Petition 870250094509, 10 / 16 / 2025, p.) 48 / 64 26 / 40 Petition 870250094509, dated 10 / 16 / 2025, p. 49 / 64 27 / 40 Petition 870250094509, dated 10 / 16 / 2025, p. 50 / 64 28 / 40 Petition 870250094509, dated 10 / 16 / 2025, p. 51 / 64 29 / 40 Petition 870250094509, dated 10 / 16 / 2025, p. 52 / 64 30 / 40 Petition 870250094509, dated 10 / 16 / 2025, p. 53 / 64 31 / 40 Petition 870250094509, dated 10 / 16 / 2025, p. 54 / 64 32 / 40 Petition 870250094509, dated 10 / 16 / 2025, p. 55 / 64 33 / 40 Petition 870250094509, dated 10 / 16 / 2025, p. 56 / 64 34 / 40 Petition 870250094509, dated 10 / 16 / 2025, p. 57 / 64 35 / 40 Petition 870250094509, dated 10 / 16 / 2025, p. 58 / 64 36 / 40 Cl F o HO. J'NA Cl F eW ho-2 -nAf Cl F HO, b.nv~f HO HO HO^' Cl F NA Cl F n,nv-f Cl F NAF Petition 870250094509, dated 10 / 16 / 2025, page 59 / 64 37 / 40 Petition 870250094509, dated 10 / 16 / 2025, page 60 / 64 38 / 40 Petition 870250094509, dated 10 / 16 / 2025, page 61 / 64 39 / 40.

48. Pharmaceutical composition characterized by comprising a compound, as defined in any one of claims 1 to 47, or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient.

49. A method for treating a disease or disorder in a needy individual, characterized by comprising administering to the individual a therapeutically effective amount of a compound, as defined in any one of claims 1 to 47, or a pharmaceutically acceptable salt or solvate thereof, or of the pharmaceutical composition as defined in claim 48.

50. Method according to claim 49, characterized in that the disease or disorder is a neurokinin 3 (NK3) receptor-dependent disease or disorder.

51. A method according to claim 49 or 50, characterized in that the disease or disorder is selected from the group consisting of: migraine, medication overuse headache, cluster headache, general headache, trigeminal neuralgia, orofacial pain, and combinations thereof.

52. A method, according to any one of claims 49 to 51, characterized in that the disease or disorder is selected from the group consisting of: migraine, medication overuse headache, cluster headache, general headache, and combinations thereof.

53. A method, according to any one of claims 49 to 52, characterized in that the disease or disorder is migraine.

54. A method according to any one of claims 49 to 53, characterized by further comprising the administration of a therapeutically effective amount of an additional therapeutic agent.

55. Method according to claim 54, characterized by the fact that the additional therapeutic agent is selected from: beta-blockers such as, for example, propranolol, nadolol, timolol, metoprolol and atenolol; antidepressants such as, for example, amitriptyline and venlafaxine; anticonvulsants such as, for example, valproate and topiramate; phenothiazine antiemetics such as, for example, prochlorperazine; non-phenothiazine antiemetics such as, for example, metoclopramide; non-steroidal anti-inflammatory drugs (NSAIDs) such as, for example, aspirin, ibuprofen and naproxen; acetaminophen; caffeine; Ergot alkaloids such as ergotamine and dihydroergotamine (DHE); dithanes such as lasmiditan; dithanes such as almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan;Calcitonin gene-related peptide (CGRP) receptor antagonists such as ubrogepant, rimegepant, atogepant, and zavegepant; antibodies to CGRP such as erenumab, fremanezumab, galcanezumab, and eptinezumab; and combinations thereof.