Aryl ether analogs as inhibitors of menin-mll interaction

By developing aryl ether analog compounds to inhibit the interaction between menin and MLL, the problem of limited treatment options in existing technologies has been solved, providing a new approach to treat MLL-r leukemia and other diseases, and achieving selective inhibition and apoptosis induction of MLL-r leukemia cells.

CN122121871APending Publication Date: 2026-05-29SEDAX PHARM CO LTD
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
SEDAX PHARM CO LTD
Filing Date
2024-08-28
Publication Date
2026-05-29

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Abstract

The present disclosure relates to inhibitors of the interaction of menin with MLL and MLL fusion proteins of the formula (I), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, pharmaceutical compositions containing the same, and their use in the treatment of cancers and other diseases mediated by the menin-MLL interaction. Formula (I).
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Claims

1. A compound having formula (I), Equation (I), Its stereoisomers or pharmaceutically acceptable salts, wherein: W is either N or CH; Y is either N or CH; R 1 It is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C 12 cycloalkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclic, wherein the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C 12 cycloalkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclic group may optionally be surrounded by one or more halogroups, OH, oxogroups, CN, C1-C6 alkyl, C1-C6 alkoxy, C6-C 10 aryl, 5- to 10-membered heteroaryl, or N(R) 4a ')(R 4b ')replace; R 2 It is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C 12 cycloalkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclic, wherein the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C 12 cycloalkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclic group may optionally be replaced by one or more halogen groups, OH, oxo groups, CN, or N(R) groups. 4a ')(R 4b ')replace; R 1 and R 2 Optionally, a 3- to 12-membered heterocyclic group is formed, wherein the heterocyclic group is optionally substituted by one or more C1-C6 alkyl groups, halogroups, OH groups, or CN groups; Z is O, CH2, or NH; Ring A is a 6- to 10-membered aryl or a 6- to 10-membered heteroaryl, wherein the 6- to 10-membered aryl or 6- to 10-membered heteroaryl may optionally be substituted by one or more C1-C6 alkyl, halogroup, OH, CN, or C1-C6 alkoxy groups; X 3 It is H, C1-C6 alkyl, wherein the C1-C6 alkyl is optionally replaced by one or more halogroups, 3 to 12-membered heterocyclic groups, S(=O)2R 4a OR 4a , Oxide group, CN, C(=O)N(R) 4a (R) 4b ), or N(R) 4a (R) 4b )replace; R 3 It is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C 12 cycloalkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclic, wherein the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C 12 cycloalkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclic group optionally surrounded by one or more R 3a Replace, or R 3 A 3- to 12-membered heterocyclic group is formed with a carbon atom adjacent to the nitrogen atom it is attached to, wherein the 3- to 12-membered heterocyclic group is optionally surrounded by one or more R atoms. 3a replace; Each R 3a Independently, it is a halogenated group, OR 4a , Oxide group, C(O)O(R) 4a ), CN, C(=O)N(R 4a (R) 4b ), OC(O)N(R 4a (R) 4b ), S(=O)2R 4b '、N(R 4a (R) 4b C1-C6 alkyl, C3-C 12 Cycloalkyl, C1-C6 alkoxy, C6-C 10 aryl, 3- to 12-membered heterocyclic, or 5- to 10-membered heteroaryl, wherein the C1-C6 alkyl, C3-C 12 cycloalkyl, C6-C 10 The aryl, 3- to 12-membered heterocyclic, or 5- to 10-membered heteroaryl groups may optionally be substituted by one or more substituents independently selected from the following: halogenated, O(R) 4a '), oxo group, CN, C(O)OR 4a '、OC(O)N(R 4a ')(R 4b '), N(R 4a ')(R 4b '), N(R 4a ')C(O)(R 4b '), N(R 4a ')C(O)O(R 4b '), optionally O(R 4a ) substituted C1-C6 alkyl groups, and optionally substituted oxo groups of 3 to 12-membered heterocyclic groups; Each R 4a Independently H, CN, or optionally H, CN, C6-C 10 Aryl or N(R) 4a ')(R 4b ') substituted C1-C6 alkyl groups; Each R 4b Independently, H, S(=O)2R 4b '、C(O)OR 4b '、C(O)R 4b '、C(O)NR 4a 'R 4b '、C(O)CH2-N(R 4a ')(R 4b '), C1-C6 alkyl, C3-C 12 cycloalkyl, C 6-10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclic group, wherein the C1-C6 alkyl group is optionally surrounded by a C1-C6 alkoxy group or a C(O)N(R) group. 4a ')(R 4b ')replace; Each R 4a 'and R 4b Independently, it is H, C1-C6 alkyl, C3-C 12 Cycloalkyl, or 3 to 12-membered heterocyclic groups; and n is 1, 2, or 3.

2. The compound of claim 1, wherein, R 2 It is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C 12 cycloalkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclic, wherein the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C 12 cycloalkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclic group may optionally be replaced by one or more halogen groups, OH, oxo groups, CN, or N(R) groups. 4a ')(R 4b ')replace.

3. The compound according to claim 1 or 2, wherein, R 2 It is a C1-C6 alkyl group, wherein the C1-C6 alkyl group is optionally converted by one or more halogroups, OH, oxogroups, CN, or N(R) groups. 4a ')(R 4b ')replace.

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

5. The compound of claim 1, wherein, R 1 and R 2 Forming groups selected from the following: , ,and .

6. A compound having formula (II), Equation (II), Its stereoisomers or pharmaceutically acceptable salts, wherein: W is either N or CH; Y is either N or CH; R 1 It is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C 12 cycloalkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclic, wherein the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C 12 cycloalkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclic group may optionally be surrounded by one or more halogroups, OH, oxogroups, CN, C1-C6 alkyl, C1-C6 alkoxy, C6-C 10 aryl, 5- to 10-membered heteroaryl, or N(R) 4a ')(R 4b ')replace; Z is O, CH2, or NH; Ring A is a 6- to 10-membered aryl or a 6- to 10-membered heteroaryl, wherein the 6- to 10-membered aryl or 6- to 10-membered heteroaryl may optionally be substituted by one or more C1-C6 alkyl, halogroup, OH, CN, or C1-C6 alkoxy groups; X 3 It is H, C1-C6 alkyl, wherein the C1-C6 alkyl is optionally replaced by one or more halogroups, 3 to 12-membered heterocyclic groups, S(=O)2R 4a OR 4a , Oxide group, CN, C(=O)N(R) 4a (R) 4b ), or N(R) 4a (R) 4b )replace; R 3 It is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C 12 cycloalkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclic, wherein the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C 12 cycloalkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclic group optionally surrounded by one or more R 3a Replace, or R 3 A 3- to 12-membered heterocyclic group is formed with a carbon atom adjacent to the nitrogen atom it is attached to, wherein the 3- to 12-membered heterocyclic group is optionally surrounded by one or more R atoms. 3a replace; Each R 3a Independently, it is a halogenated group, OR 4a , Oxide group, C(O)O(R) 4a ), CN, C(=O)N(R 4a (R) 4b ), OC(O)N(R 4a (R) 4b ), S(=O)2R 4b '、N(R 4a (R) 4b C1-C6 alkyl, C3-C 12 Cycloalkyl, C1-C6 alkoxy, C6-C 10 aryl, 3- to 12-membered heterocyclic, or 5- to 10-membered heteroaryl, wherein the C1-C6 alkyl, C3-C 12 cycloalkyl, C6-C 10 The aryl, 3- to 12-membered heterocyclic, or 5- to 10-membered heteroaryl groups may optionally be substituted by one or more substituents independently selected from the following: halogenated, O(R) 4a '), oxo group, CN, C(O)OR 4a '、OC(O)N(R 4a ')(R 4b '), N(R 4a ')(R 4b '), N(R 4a ')C(O)(R 4b '), N(R 4a ')C(O)O(R 4b '), optionally O(R 4a ) substituted C1-C6 alkyl groups, and optionally substituted oxo groups of 3 to 12-membered heterocyclic groups; Each R 4a Independently H, CN, or optionally H, CN, C6-C 10 Aryl or N(R) 4a ')(R 4b ') substituted C1-C6 alkyl groups; Each R 4b Independently, H, S(=O)2R 4b '、C(O)OR 4b '、C(O)R 4b '、C(O)NR 4a 'R 4b '、C(O)CH2-N(R 4a ')(R 4b '), C1-C6 alkyl, C3-C 12 cycloalkyl, C 6-10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclic group, wherein the C1-C6 alkyl group is optionally surrounded by a C1-C6 alkoxy group or a C(O)N(R) group. 4a ')(R 4b ')replace; Each R 4a 'and R 4b Independently, it is H, C1-C6 alkyl, C3-C 12 Cycloalkyl, or 3 to 12-membered heterocyclic groups; and n is 1, 2, or 3.

7. The compound as claimed in any one of the preceding claims, wherein, W is N.

8. The compound as claimed in any one of the preceding claims, wherein, W is CH.

9. The compound as claimed in any one of the preceding claims, wherein, Y is N.

10. The compound as claimed in any one of the preceding claims, wherein, Y is CH.

11. The compound as claimed in any one of the preceding claims, wherein, R 1 It is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C 12 cycloalkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclic, wherein the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C 12 cycloalkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclic group may optionally be surrounded by one or more halogroups, OH, oxogroups, CN, C1-C6 alkyl, C1-C6 alkoxy, C6-C 10 aryl, 5- to 10-membered heteroaryl, or N(R) 4a ')(R 4b ')replace.

12. The compound as claimed in any one of the preceding claims, wherein, R 1 It is a C1-C6 alkyl, C3-C 12 Cycloalkyl, or 3 to 12-membered heterocyclic groups, wherein the C1-C6 alkyl group, the C3-C6 heterocyclic group, or the C4-C5-C6-C5 ... 12 The cycloalkyl group, or the 3- to 12-membered heterocyclic group, may optionally be surrounded by one or more halogen groups, OH, oxo groups, CN, C1-C6 alkyl groups, C1-C6 alkoxy groups, or C6-C6 alkyl groups. 10 aryl, 5- to 10-membered heteroaryl, or N(R) 4a ')(R 4b ')replace.

13. The compound as claimed in any one of the preceding claims, wherein, R 1 It is a C1-C6 alkyl, C3-C 12 Cycloalkyl, or 3 to 12-membered heterocyclic groups, wherein the C1-C6 alkyl group, the C3-C6 heterocyclic group, or the C4-C5-C6-C5 ... 12 The cycloalkyl group, or the 3 to 12-membered heterocyclic group, may optionally be substituted with one or more halogenated groups.

14. The compound according to any one of claims 1-4 and 6-13, wherein, R 1 It is methyl or ethyl.

15. The compound according to any one of claims 1-4 and 6-13, wherein, R 1 It is isopropyl.

16. The compound according to any one of claims 1-4 and 6-13, wherein, R 1 It is 2,2-difluoroethyl.

17. The compound according to any one of claims 1-4 and 6-13, wherein, R 1 yes , , , , , , , , , , , , , , , or .

18. The compound according to any one of claims 1-4 and 6-13, wherein, R 1 It is -CH2-CN or -CH2-phenyl.

19. The compound according to any one of claims 1-4 and 6-12, wherein, R 1 It is a cyclobutyl group substituted with an OH group and a methyl group, a cyclobutyl group substituted with a CN group and a methyl group, a cyclobutyl group substituted with a methoxy group, a cyclobutyl group substituted with a 1H-pyrazole-1-yl group, a cyclobutyl group substituted with a 1H-imidazol-1-yl group, or a cyclobutyl group substituted with a 1H-imidazol-1-yl group and a methyl group.

20. The compound as claimed in any one of the preceding claims, wherein, Z can be O, CH2, or NH.

21. The compound as claimed in any one of the preceding claims, wherein, Z is O.

22. The compound according to any one of claims 1-20, wherein, Z stands for CH2.

23. The compound according to any one of claims 1-20, wherein, Z is NH.

24. The compound as claimed in any of the preceding claims, wherein, Ring A is a 6- to 10-membered aryl or a 6- to 10-membered heteroaryl, wherein the 6- to 10-membered aryl or 6- to 10-membered heteroaryl may optionally be substituted by one or more C1-C6 alkyl, halogroup, OH, CN, or C1-C6 alkoxy groups.

25. The compound as claimed in any one of the preceding claims, wherein, Ring A is a 6- to 10-membered aryl or a 6- to 10-membered heteroaryl.

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

27. The compound according to any one of claims 1-25, wherein, Ring A is .

28. The compound according to any one of claims 1-25, wherein, Ring A is .

29. The compound as claimed in any one of the preceding claims, wherein, yes , , , ,or .

30. The compound as claimed in any one of the preceding claims, wherein, X 3 It is H, C1-C6 alkyl, wherein the C1-C6 alkyl is optionally replaced by one or more halogroups, 3 to 12-membered heterocyclic groups, S(=O)2R 4a OR 4a , Oxide group, CN, C(=O)N(R) 4a (R) 4b ), or N(R) 4a (R) 4b ) replace, and in which Each R 4a Independently H, CN, or optionally H, CN, C6-C 10 Aryl or N(R) 4a ')(R 4b ') substituted C1-C6 alkyl groups; Each R 4b Independently, H, S(=O)2R 4b '、C(O)OR 4b '、C(O)R 4b '、C(O)NR 4a 'R 4b '、C(O)CH2-N(R 4a ')(R 4b '), C1-C6 alkyl, C3-C 12 cycloalkyl, C 6-10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclic group, wherein the C1-C6 alkyl group is optionally surrounded by a C1-C6 alkoxy group or a C(O)N(R) group. 4a ')(R 4b ')replace.

31. The compound as claimed in any one of the preceding claims, wherein, X 3 It is H or C1-C6 alkyl.

32. The compound according to claims 1-30, wherein, X 3 is -CH2-OCH3, -CH2-CH2-OCH3, -CH2-CH2-CH2-OCH3, -CH2-O-CH2-CHF2, -CH2-CH2-CH2-O-CHF2, -CH2-O-CH2-CH2- N(CH3)2, -CH2-CH2-S(O)2-CH3 or -CH2-CH2-CH2-S(O)2-CH3, -CH2-CH2-NH-C(O)-CH3, -CH2-CH2-NH-S(O)2-CH3, or ,or .

33. The compound according to claims 1-31, wherein, X 3 It is a methyl group.

34. The compound as claimed in any of the preceding claims, wherein, R 3 It is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C 12 cycloalkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclic, wherein the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C 12 cycloalkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclic group optionally surrounded by one or more R 3a Replace, of which: Each R 3a Independently, it is a halogenated group, OR 4a , Oxide group, C(O)O(R) 4a ), CN, C(=O)N(R 4a (R) 4b ), OC(O)N(R 4a (R) 4b ), S(=O)2R 4b '、N(R 4a (R) 4b C1-C6 alkyl, C3-C 12 Cycloalkyl, C1-C6 alkoxy, C6-C 10 aryl, 3- to 12-membered heterocyclic, or 5- to 10-membered heteroaryl, wherein the C1-C6 alkyl, C3-C 12 cycloalkyl, C6-C 10 The aryl, 3- to 12-membered heterocyclic, or 5- to 10-membered heteroaryl groups may optionally be substituted by one or more substituents independently selected from the following: halogenated, O(R) 4a '), oxo group, CN, C(O)OR 4a '、OC(O)N(R 4a ')(R 4b '), N(R 4a ')(R 4b '), N(R 4a ')C(O)(R 4b '), N(R 4a ')C(O)O(R 4b '), optionally O(R 4a ) substituted C1-C6 alkyl groups, and optionally substituted oxo groups of 3 to 12-membered heterocyclic groups; Each R 4a Independently H, CN, or optionally H, CN, C6-C 10 Aryl or N(R) 4a ')(R 4b ') substituted C1-C6 alkyl groups; Each R 4b Independently, H, S(=O)2R 4b '、C(O)OR 4b '、C(O)R 4b '、C(O)NR 4a 'R 4b '、C(O)CH2-N(R 4a ')(R 4b '), C1-C6 alkyl, C3-C 12 cycloalkyl, C 6-10 aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclic group, wherein the C1-C6 alkyl group is optionally surrounded by a C1-C6 alkoxy group or a C(O)N(R) group. 4a ')(R 4b ') replace; and Each R 4a 'and R 4b Independently, it is H, C1-C6 alkyl, C3-C 12 Cycloalkyl or 3 to 12-membered heterocyclic groups.

35. The compound according to any one of claims 1-34, wherein, R 3 It can be optionally controlled by one or more R 3a Substituted C1-C6 alkyl groups, wherein: Each R 3a Independently is N(R) 4a (R) 4b ), S(=O)2R 4b ', or optionally substituted by one or more substituents selected independently from C1-C6 alkyl groups optionally substituted by one or more halogenated groups, and O(R 4a '); Each R 4a and R 4b Independently, it is H or a C1-C6 alkyl group; and Each R 4a 'and R 4b Independently, it is H or C1-C6 alkyl.

36. The compound according to any one of claims 1-35, wherein, R 3 It is methyl, ethyl, or isopropyl.

37. The compound according to any one of claims 1-34, wherein, R 3 is -CH2-CH2-N(CH3)2, -CH2-CH2-CH2-N(CH3)2, -CH2-CH2-CH2-CH2-N(CH3)2, -CH2-CH2-CH2-CH2-CH2-N(CH3)2, -CH2-CH2-S(=O)2Me, or -CH2-CH2-CH2-S(=O)2Me.

38. The compound according to any one of claims 1-34, wherein, R 3 It is H.

39. The compound according to any one of claims 1-34, wherein, R 3 yes , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,or .

40. The compound according to any one of claims 1-34, wherein, R 3 yes , , , , , , , , , , , , , , , , , , , ,or .

41. The compound according to any one of claims 1-34, wherein, R 3 yes , , , , , , , , , , , , , , , , ,or .

42. The compound according to any one of claims 1-34, wherein, R 3 It is H.

43. The compound according to any one of claims 1-33, wherein, R 3 It forms 3 to 12-membered heterocyclic groups with the carbon atom of the nitrogen atom immediately adjacent to it.

44. The compound of claim 43, wherein, yes ,or .

45. The compound as claimed in any one of the preceding claims, wherein, n is 1.

46. ​​The compound as claimed in any one of the preceding claims, wherein, n is 2.

47. The compound as claimed in any of the preceding claims, wherein, n is 3.

48. A compound having formula (III), Equation (III), Its stereoisomers or pharmaceutically acceptable salts, wherein: W is either N or CH; Y is either N or CH; R 1 It is a C1-C6 alkyl or C3-C 12 cycloalkyl, wherein the C1-C6 alkyl or the C3-C 12 The cycloalkyl group may optionally be replaced by one or more halogen groups, C1-C6 alkoxy groups, or C6-C6 alkoxy groups. 10 Aryl, or 5 to 10 heteroaryl substitutions; R 2 It is a C1-C6 alkyl group; Z is O, CH2, or NH; Ring A is a 6- to 10-membered aryl or a 6- to 10-membered heteroaryl; X 3 It is an H or C1-C6 alkyl group; R 3 It is an H or C1-C6 alkyl group, wherein the C1-C6 alkyl group is optionally separated by one or more R groups. 3a Replace, or R 3 It forms 3 to 12-membered heterocyclic groups with the carbon atom immediately adjacent to the nitrogen atom it is attached to; Each R 3a Independently is N(R) 4a (R) 4b ) or a 3- to 12-membered heterocyclic group, wherein the 3- to 12-membered heterocyclic group is optionally substituted by one or more substituents independently selected from: C1-C6 alkyl and O(R 4a '); Each R 4a and R 4b It is independently a C1-C6 alkyl group; R 4a 'Is H; and n is 1 or 2.

49. The compound of claim 48, wherein, W is N.

50. The compound of claim 48, wherein, W is CH.

51. The compound according to any one of claims 48-50, wherein, Y is N.

52. The compound according to any one of claims 48-50, wherein, Y is CH.

53. The compound according to any one of claims 48-52, wherein, R 1 It is a C1-C6 alkyl group that may be optionally substituted with one or more halogroups.

54. The compound according to any one of claims 48-52, wherein, R 1 It is a C3-C that can be optionally substituted with one or more halogenated groups. 12 Cycloalkyl.

55. The compound according to any one of claims 48-54, wherein, R 2 It is a C1-C6 alkyl group.

56. The compound according to any one of claims 48-54, wherein, R 2 It is a C1-C6 alkyl group.

57. The compound according to any one of claims 48-56, wherein, Z is O.

58. The compound according to any one of claims 48-56, wherein, Z is NH.

59. The compound according to any one of claims 48-56, wherein, Z stands for CH2.

60. The compound according to any one of claims 48-59, wherein, Ring A is a 6-membered aryl or a 6-membered heteroaryl.

61. The compound according to any one of claims 48-59, wherein, yes , , , ,or .

62. The compound according to any one of claims 48-61, wherein, X 3 It is H.

63. The compound according to any one of claims 48-61, wherein, X 3 It is a C1-C6 alkyl group.

64. The compound according to any one of claims 48-63, wherein, R 3 It is H.

65. The compound according to any one of claims 48-63, wherein, R 3 It can be optionally controlled by one or more R 3a Substituted C1-C6 alkyl groups.

66. The compound of claim 65, wherein, R 3a It is N(R) 4a (R) 4b ), and each of R 4a and R 4b It is independently a C1-C6 alkyl group.

67. The compound of claim 65, wherein, Each R 3a Independently or optionally composed of one or more alkyl groups selected independently from C1-C6 and O(R) 4a The 3 to 12-membered heterocyclic groups are substituted by the substituents of ').

68. The compound of claim 67, wherein, Each R 3a Independently, it is a 3- to 12-membered heterocyclic group that is optionally substituted by one or more substituents independently selected from C1-C6 alkyl and OH.

69. The compound according to any one of claims 48-63, wherein, R 3 It forms 3 to 12-membered heterocyclic groups with the carbon atom of the nitrogen atom immediately adjacent to it.

70. The compound according to any one of claims 48-69, wherein, n is 1.

71. The compound according to any one of claims 48-69, wherein, n is 2.

72. A compound as shown in Table 1, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

73. A compound as shown in Table 1 or a pharmaceutically acceptable salt thereof.

74. A compound as shown in Table 1.

75. A compound as shown in Table 1 or a pharmaceutically acceptable salt thereof, wherein the salt is hydrochloric acid.

76. The compound as claimed in any of the preceding claims, wherein, This compound can be used to treat cancer, and it minimizes hERG binding.

77. A pharmaceutical composition comprising a compound as described in any one of claims 1 to 49, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

78. A pharmaceutical composition comprising a salt or crystalline form as described in any one of claims 1-48, and at least one pharmaceutically acceptable carrier.

79. A method for inhibiting the interaction between menin and MLL, the method comprising contacting the menin and MLL with a compound as described in any one of claims 1 to 76 or a pharmaceutical composition as described in claim 77 or 78.

80. A method of treating a patient with cancer, the method comprising administering to the patient a compound as described in any one of claims 1 to 76 or a pharmaceutical composition as described in claims 77 or 78.

81. The method of claim 80, wherein, This cancer is a blood cancer.

82. The method of claim 80 or 81, wherein, The cancer is leukemia.

83. The method of claim 80 or 81, wherein, The cancer is lymphoma.

84. The method of claim 80 or 81, wherein, This cancer is mixed lineage leukemia (MLL), MLL-associated leukemia, MLL-related leukemia, MLL-positive leukemia, MLL-induced leukemia, rearranged mixed lineage (KMT2A rearrangement) leukemia (MLL-r), and leukemia associated with MLL rearrangement or MLL Leukemia related to gene rearrangement, acute leukemia, chronic leukemia, indolent leukemia, lymphoblastic leukemia, lymphocytic leukemia, myeloid leukemia, myeloid cell leukemia, childhood leukemia, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), acute granulocytic leukemia, acute non-lymphocytic leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), treatment-related leukemia, myelodysplastic syndromes (MDS), myeloproliferative disorders (MPD), myeloproliferative neoplasms (...). MPN), plasma cell tumor, multiple myeloma, myelodysplastic syndrome, cutaneous T-cell lymphoma, lymphoid tumor, AIDS-related lymphoma, thymoma, thymic carcinoma, mycosis fungoides, Albert-Bazan syndrome, mycosis fungoides, Cezari syndrome, hairy cell leukemia, T-cell prolymphocytic leukemia (T-PLL), large granular lymphocytic leukemia, meningeal leukemia, leukemic meningitis, leukemic meningitis, multiple myeloma, Hodgkin lymphoma, non-Hodgkin lymphoma (malignant lymphoma), or Waldenström macroglobulinemia.

85. The method of claim 80 or 81, wherein, The cancer is acute myeloid leukemia caused by a nucleolar phosphatase (NPM1) mutation. Right now NPM1 mut Acute myeloid leukemia.

86. The method of claim 80 or 81, wherein, The cancer is rearranged mixed lineage (KMT2A rearrangement) leukemia (MLL-r).

87. The compound of any one of claims 1-76 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claims 77 or 78, for use in the treatment or prevention of diseases caused by or related to menin expression, activity, and / or function.

88. The compound of any one of claims 1-76 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claims 77 or 78, for use in the treatment or prevention of cancer.

89. The use of the compound of any one of claims 1-76 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claims 77 or 78, for the treatment or prevention of diseases caused by or related to menin expression, activity, and / or function.

90. Use of the compound of any one of claims 1-76 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claims 77 or 78, in the manufacture of a medicament for the treatment or prevention of diseases caused by or related to menin expression, activity, and / or function.

91. Use of the compound of any one of claims 1-76 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claims 77 or 78, for the treatment or prevention of cancer.

92. Use of the compound of any one of claims 1-76 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claims 77 or 78, in the manufacture of a medicament for the treatment or prevention of cancer.

93. A kit comprising a compound as described in any one of claims 1-76 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described in claims 77 or 78 and instructions for use thereof.