Aryl ether analogs as inhibitors of menin-MLL interaction
Patent Information
- Application Number
- JP2026513290
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-05-24
- Filing Date
- 2024-08-28
- Publication Date
- 2026-09-04
AI Technical Summary
【0016】 本開示の詳細は、以下の添付の説明に記載される。本明細書に記載の方法及び材料と類似の又は均等な方法及び材料を本出願の実施又は試験に使用することができるが、ここでは例示的な方法及び材料を説明する。矛盾が生じた場合、定義を含めて本明細書が優先される。更に、材料、方法及び実施例は、例示に過ぎず、限定を意図しない。本開示の他の特徴、目的及び利点は、説明及び特許請求の範囲から明らかになるであろう。本明細書及び添付の特許請求の範囲では、単数形は、文脈が明らかにそうでないことを示さない限り、複数形も含む。別段定義されない限り、本明細書で使用される全ての技術的用語及び科学的用語は、本開示が属する技術分野の当業者によって一般的に理解される意味と同様の意味を有する。
Smart Images
Figure 2026530173000001_ABST
Abstract
Claims
1. Equation (I) 【Chemistry 1】 (In the formula, W is either N or CH. Y is either N or CH, R １ is H, C １ to C ６ alkyl, C ２ to C ６ alkenyl, C ２ to C ６ alkynyl, C １ to C ６ alkoxy, C ３ to C １２ cycloalkyl, C ６ to C １０ aryl, 5- to 10-membered heteroaryl or 3- to 12-membered heterocyclyl, wherein the C １ to C ６ alkyl, C ２ to C ６ alkenyl, C ２ to C ６ alkynyl, C １ to C ６ alkoxy, C ３ to C １２ cycloalkyl, C ６ to C １０ aryl, 5- to 10-membered heteroaryl and 3- to 12-membered heterocyclyl are each optionally substituted with one or more of halo, OH, oxo, CN, C １ to C ６ alkyl, C １ to C ６ alkoxy, C ６ to C １０ aryl, 5- to 10-membered heteroaryl or N(R ４ａ ')(R ４ｂ '), R ２ H, C １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy, C ３ ~C １２ Cycloalkyl, C ６ ~C １０ The C １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy, C ３ ~C １２ Cycloalkyl, C ６ ~C １０ Aryl, 5-10 membered heteroaryl, or 3-12 membered heterocyclyl may contain one or more halo, OH, oxo, CN, or N(R) ４ａ ')(R ４ｂ It is optionally replaced with '), R １ and R ２ It optionally forms 3- to 12-membered heterocyclines, and the heterocyclines contain one or more C １ ~C ６ It is optionally substituted with alkyl, halo, OH, or CN. Z is O, CH ２ or NH, Ring A is a 6-10 membered aryl or 6-10 membered heteroaryl, and the 6-10 membered aryl or 6-10 membered heteroaryl contains one or more C １ ~C ６ Alkyl, halo, OH, CN, or C １ ~C ６ It is optionally substituted with an alkoxy, X ３ H, C １ ~C ６ Alkyl, and the C １ ~C ６ Alkyl is composed of one or more halos, 3- to 12-membered heterocyclines, and S (=O) ２ R ４ａ , OR ４ａ , oxo, CN, C(=O)N(R ４ａ ) (Caution ４ｂ ) or N(R ４ａ ) (Caution ４ｂ ) is optionally replaced, R ３ is H, C １ to C ６ alkyl, C ２ to C ６ alkenyl, C ２ to C ６ alkynyl, C １ to C ６ alkoxy, C ３ to C １２ cycloalkyl, C ６ to C １０ aryl, 5- to 10-membered heteroaryl or 3- to 12-membered heterocyclyl, and said C １ to C ６ alkyl, C ２ to C ６ alkenyl, C ２ to C ６ alkynyl, C １ to C ６ alkoxy, C ３ to C １２ cycloalkyl, C ６ to C １０ aryl, 5- to 10-membered heteroaryl or 3- to 12-membered heterocyclyl is optionally substituted with one or more R ３ａ , or R ３ It forms a 3- to 12-membered heterocycline with the carbon atom adjacent to the nitrogen atom to which it is bonded, and the 3- to 12-membered heterocycline has one or more R ３ａ It is optionally replaced by Each R ３ａ Independently, Haro, OR ４ａ , oxo, C(O)O(R ４ａ ), CN, C(=O)N(R ４ａ ) (Caution ４ｂ ), OC(O)N(R ４ａ ) (Caution ４ｂ ), S (=O) ２ R ４ｂ ', N (R ４ａ ) (Caution ４ｂ ), C １ ~C ６ Alkyl, C ３ ~C １２ Cycloalkyl, C １ ~C ６ Alkoxy, C ６ ~C １０ The C is an aryl, a 3-12 membered heterocyclyl, or a 5-10 membered heteroaryl. １ ~C ６ Alkyl, C ３ ~C １２ Cycloalkyl, C ６ ~C １０ Aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl is a halo, O(R) ４ａ '), oxo, 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 '), O(R ４ａ C is optionally replaced by ) １ ~C ６ It is optionally substituted with one or more substituents independently selected from 3- to 12-membered heterocyclines that are optionally substituted with alkyl and oxo substituents. Each R ４ａ These are independently H, CN or one or more halos, C ６ ~C １０ Aryl or N(R) ４ａ ')(R ４ｂ C is optionally replaced by '). １ ~C ６ It is alkyl, Each R ４ｂ These are H and S (=O) independently. ２ R ４ｂ ', C(O)OR ４ｂ ', C(O)R ４ｂ ', C(O)NR ４ａ 'R ４ｂ ', C(O)CH ２ -N(R) ４ａ ')(R ４ｂ '), C １ ~C ６ Alkyl, C ３ ~C １２ Cycloalkyl, C ６～１０ The C １ ~C ６ Alkyl is C １ ~C ６ Alkoxy or C(O)N(R) ４ａ ')(R ４ｂ It is optionally replaced with '), Each R ４ａ 'and R ４ｂ ' is independently H, C １ ~C ６ Alkyl, C ３ ~C １２ It is a cycloalkyl or a 3- to 12-membered heterocycline, and n is 1, 2, or 3. Compounds thereof, their stereoisomers, or pharmaceutically acceptable salts.
2. R ２ H, C １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy, C ３ ~C １２ Cycloalkyl, C ６ ~C １０ The C １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy, C ３ ~C １２ Cycloalkyl, C ６ ~C １０ Aryl, 5-10 membered heteroaryl, or 3-12 membered heterocyclyl may contain one or more halo, OH, oxo, CN, or N(R) ４ａ ')(R ４ｂ The compound according to claim 1, which is optionally substituted with ').
3. R ２ C １ ~C ６ Alkyl, and the C １ ~C ６ Alkyl is one or more halo, OH, oxo, CN or N(R) ４ａ ')(R ４ｂ The compound according to claim 1 or 2, which is optionally substituted with ').
4. R ２ The compound according to any one of claims 1 to 3, wherein isopropyl.
5. R １ and R ２ teeth, 【Chemistry 2】 The compound according to claim 1, which forms a group selected from the above.
6. Formula (II) 【Transformation 3】 (In the formula, W is either N or CH. Y is either N or CH, R １ H, C １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy, C ３ ~C １２ Cycloalkyl, C ６ ~C １０ The C １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy, C ３ ~C １２ Cycloalkyl, C ６ ~C １０ Aryl, 5-10 membered heteroaryl, or 3-12 membered heterocyclyl may contain one or more halo, OH, oxo, CN, or C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, C ６ ~C １０ Aryl, 5-10 membered heteroaryl or N(R) ４ａ ')(R ４ｂ It is optionally replaced with '), Z is O, CH ２ or NH, Ring A is a 6-10 membered aryl or 6-10 membered heteroaryl, and the 6-10 membered aryl or 6-10 membered heteroaryl contains one or more C １ ~C ６ Alkyl, halo, OH, CN, or C １ ~C ６ It is optionally substituted with an alkoxy, X ３ H, C １ ~C ６ Alkyl, and the C １ ~C ６ Alkyl is composed of one or more halos, 3- to 12-membered heterocyclines, and S (=O) ２ R ４ａ , OR ４ａ , oxo, CN, C(=O)N(R ４ａ ) (Caution ４ｂ ) or N(R ４ａ ) (Caution ４ｂ ) is optionally replaced, R ３ H, C １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy, C ３ ~C １２ Cycloalkyl, C ６ ~C １０ The C １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy, C ３ ~C １２ Cycloalkyl, C ６ ~C １０ Aryl, 5-10 membered heteroaryl, or 3-12 membered heterocyclyl is one or more R ３ａ It is either optionally replaced by, R ３ It forms a 3- to 12-membered heterocycline with the carbon atom adjacent to the nitrogen atom to which it is bonded, and the 3- to 12-membered heterocycline has one or more R ３ａ It is optionally replaced by Each R ３ａ Independently, Haro, OR ４ａ , oxo, C(O)O(R ４ａ ), CN, C(=O)N(R ４ａ ) (Caution ４ｂ ), OC(O)N(R ４ａ ) (Caution ４ｂ ), S (=O) ２ R ４ｂ ', N (R ４ａ ) (Caution ４ｂ ), C １ ~C ６ Alkyl, C ３ ~C １２ Cycloalkyl, C １ ~C ６ Alkoxy, C ６ ~C １０ The C is an aryl, a 3-12 membered heterocyclyl, or a 5-10 membered heteroaryl. １ ~C ６ Alkyl, C ３ ~C １２ Cycloalkyl, C ６ ~C １０ Aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl is a halo, O(R) ４ａ '), oxo, 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 '), O(R ４ａ C is optionally replaced by ) １ ~C ６ It is optionally substituted with one or more substituents independently selected from 3- to 12-membered heterocyclines that are optionally substituted with alkyl and oxo substituents. Each R ４ａ These are independently H, CN or one or more halos, C ６ ~C １０ Aryl or N(R) ４ａ ')(R ４ｂ C is optionally replaced by '). １ ~C ６ It is alkyl, Each R ４ｂ These are H and S (=O) independently. ２ R ４ｂ ', C(O)OR ４ｂ ', C(O)R ４ｂ ', C(O)NR ４ａ 'R ４ｂ ', C(O)CH ２ -N(R) ４ａ ')(R ４ｂ '), C １ ~C ６ Alkyl, C ３ ~C １２ Cycloalkyl, C ６～１０ The C １ ~C ６ Alkyl is C １ ~C ６ Alkoxy or C(O)N(R) ４ａ ')(R ４ｂ It is optionally replaced with '), Each R ４ａ 'and R ４ｂ ' is independently H, C １ ~C ６ Alkyl, C ３ ~C １２ It is a cycloalkyl or a 3- to 12-membered heterocycline, and n is 1, 2, or 3. Compounds thereof, their stereoisomers, or pharmaceutically acceptable salts.
7. The compound according to any one of claims 1 to 6, wherein W is N.
8. The compound according to any one of claims 1 to 7, wherein W is CH.
9. The compound according to any one of claims 1 to 8, wherein Y is N.
10. The compound according to any one of claims 1 to 9, wherein Y is CH.
11. R １ H, C １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy, C ３ ~C １２ Cycloalkyl, C ６ ~C １０ The C １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy, C ３ ~C １２ Cycloalkyl, C ６ ~C １０ Aryl, 5-10 membered heteroaryl, or 3-12 membered heterocyclyl may contain one or more halo, OH, oxo, CN, or C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, C ６ ~C １０ Aryl, 5-10 membered heteroaryl or N(R) ４ａ ')(R ４ｂ The compound according to any one of claims 1 to 10, which is optionally substituted with ').
12. R １ C １ ~C ６ Alkyl, C ３ ~C １２ The C is a cycloalkyl or a 3- to 12-membered heterocycline. １ ~C ６ alkyl, the C ３ ~C １２ The cycloalkyl or the 3- to 12-membered heterocyclyl comprises one or more halo, OH, oxo, CN, and C. １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, C ６ ~C １０ Aryl, 5-10 membered heteroaryl or N(R) ４ａ ')(R ４ｂ The compound according to any one of claims 1 to 11, wherein it is optionally substituted with ').
13. R １ C １ ~C ６ Alkyl, C ３ ~C １２ The C is a cycloalkyl or a 3- to 12-membered heterocycline. １ ~C ６ alkyl, the C ３ ~C １２ The compound according to any one of claims 1 to 12, wherein the cycloalkyl or the 3- to 12-membered heterocyclyl is optionally substituted with one or more halos.
14. R １ The compound according to any one of claims 1 to 4 or 6 to 13, wherein is methyl or ethyl.
15. R １ The compound according to any one of claims 1 to 4 or 6 to 13, wherein isopropyl.
16. R １ The compound according to any one of claims 1 to 4 or 6 to 13, wherein is 2,2-difluoroethyl.
17. R １ teeth, 【Chemistry 4】 The compound according to any one of claims 1 to 4 or 6 to 13.
18. R １ is, -CH ２ -CN or -CH ２ - A compound according to any one of claims 1 to 4 or 6 to 13, wherein the compound is phenyl.
19. R １ The compound according to any one of claims 1 to 4 or 6 to 12, wherein is a cyclobutyl substituted with one OH and one methyl group, a cyclobutyl substituted with one CN and one methyl group, a cyclobutyl substituted with one methoxy group, a cyclobutyl substituted with one 1H-pyrazole-1-yl group, a cyclobutyl substituted with one 1H-imidazole-1-yl group, or a cyclobutyl substituted with one 1H-imidazole-1-yl group and one methyl group.
20. Z is O, CH ２ The compound according to any one of claims 1 to 19, wherein the compound is NH or NH.
21. The compound according to any one of claims 1 to 20, wherein Z is O.
22. Z is CH ２ The compound according to any one of claims 1 to 20.
23. The compound according to any one of claims 1 to 20, wherein Z is NH.
24. Ring A is a 6-10 membered aryl or 6-10 membered heteroaryl, and the 6-10 membered aryl or 6-10 membered heteroaryl contains one or more C １ ~C ６ Alkyl, halo, OH, CN, or C １ ~C ６ The compound according to any one of claims 1 to 23, wherein it is optionally substituted with an alkoxy.
25. The compound according to any one of claims 1 to 24, wherein ring A is a 6- to 10-membered aryl or a 6- to 10-membered heteroaryl.
26. Ring A is, 【Transformation 5】 The compound according to any one of claims 1 to 25.
27. Ring A is, 【Transformation 6】 The compound according to any one of claims 1 to 25.
28. Ring A is, 【Transformation 7】 The compound according to any one of claims 1 to 25. 【Request Item 29】 【Chemistry 8】 teeth, 【Chemistry 9】 The compound according to any one of claims 1 to 28.
30. X ３ H, C １ ~C ６ Alkyl, and the C １ ~C ６ Alkyl is composed of one or more halos, 3- to 12-membered heterocyclines, and S (=O) ２ R ４ａ , OR ４ａ , oxo, CN, C(=O)N(R ４ａ ) (Caution ４ｂ ) or N(R ４ａ ) (Caution ４ｂ ) is optionally replaced, Each R ４ａ These are independently H, CN or one or more halos, C ６ ~C １０ Aryl or N(R) ４ａ ')(R ４ｂ C is optionally replaced by '). １ ~C ６ It is alkyl, Each R ４ｂ These are H and S (=O) independently. ２ R ４ｂ ', C(O)OR ４ｂ ', C(O)R ４ｂ ', C(O)NR ４ａ 'R ４ｂ ', C(O)CH ２ -N(R) ４ａ ')(R ４ｂ '), C １ ~C ６ Alkyl, C ３ ~C １２ Cycloalkyl, C ６～１０ The C １ ~C ６ Alkyl is C １ ~C ６ Alkoxy or C(O)N(R) ４ａ ')(R ４ｂ The compound according to any one of claims 1 to 29, wherein it is optionally substituted with ').
31. X ３ is H or C １ ~C ６ A compound according to any one of claims 1 to 30, wherein it is alkyl.
32. X ３ は、-CH ２ -OCH ３ 、-CH ２ -CH ２ -OCH ３ 、-CH ２ -CH ２ -CH ２ -OCH ３ 、-CH ２ -O-CH ２ -CHF ２ 、-CH ２ -CH ２ -CH ２ -O-CHF ２ 、-CH ２ -O-CH ２ -CH ２ -N(CH ３ ) ２ 、-CH ２ -CH ２ -S(O) ２ -CH ３ or-CH ２ -CH ２ -CH ２ -S(O) ２ -CH ３ 、-CH ２ -CH ２ -NH-C(O)-CH ３ 、-CH ２ -CH ２ -NH-S(O) ２ -CH ３ 、 or 【Chemistry 10】 The compound according to any one of claims 1 to 30.
33. X ３ The compound according to any one of claims 1 to 31, wherein is methyl.
34. R ３ H, C １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy, C ３ ~C １２ Cycloalkyl, C ６ ~C １０ The C １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy, C ３ ~C １２ Cycloalkyl, C ６ ~C １０ Aryl, 5-10 membered heteroaryl, or 3-12 membered heterocyclyl is one or more R ３ａ It is optionally replaced by Each R ３ａ Independently, Haro, OR ４ａ , oxo, C(O)O(R ４ａ ), CN, C(=O)N(R ４ａ ) (Caution ４ｂ ), OC(O)N(R ４ａ ) (Caution ４ｂ ), S (=O) ２ R ４ｂ ', N (R ４ａ ) (Caution ４ｂ ), C １ ~C ６ Alkyl, C ３ ~C １２ Cycloalkyl, C １ ~C ６ Alkoxy, C ６ ~C １０ The C is an aryl, a 3-12 membered heterocyclyl, or a 5-10 membered heteroaryl. １ ~C ６ Alkyl, C ３ ~C １２ Cycloalkyl, C ６ ~C １０ Aryl, 3-12 membered heterocyclyl, or 5-10 membered heteroaryl is a halo, O(R) ４ａ '), oxo, 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 '), O(R ４ａ C is optionally replaced by ) １ ~C ６ It is optionally substituted with one or more substituents independently selected from 3- to 12-membered heterocyclines that are optionally substituted with alkyl and oxo substituents. Each R ４ａ These are independently H, CN or one or more halos, C ６ ~C １０ Aryl or N(R) ４ａ ')(R ４ｂ C is optionally replaced by '). １ ~C ６ It is alkyl, Each R ４ｂ These are H and S (=O) independently. ２ R ４ｂ ', C(O)OR ４ｂ ', C(O)R ４ｂ ', C(O)NR ４ａ 'R ４ｂ ', C(O)CH ２ -N(R) ４ａ ')(R ４ｂ '), C １ ~C ６ Alkyl, C ３ ~C １２ Cycloalkyl, C ６～１０ The C １ ~C ６ Alkyl is C １ ~C ６ Alkoxy or C(O)N(R) ４ａ ')(R ４ｂ ') is optionally replaced, and Each R ４ａ 'and R ４ｂ ' is independently H, C １ ~C ６ Alkyl, C ３ ~C １２ The compound according to any one of claims 1 to 33, which is a cycloalkyl or a 3- to 12-membered heterocycline.
35. R ３ is one or more R ３ａ C is optionally replaced by １ ~C ６ It is alkyl, Each R ３ａ Independently, N(R) ４ａ ) (Caution ４ｂ ), S (=O) ２ R ４ｂ 'or C which is optionally replaced by one or more halos １ ~C ６ Alkyl and O(R) ４ａ A 3- to 12-membered heterocycline that is optionally substituted with one or more substituents independently selected from '), Each R ４ａ and R ４ｂ H or C １ ~C ６ It is alkyl, and Each R ４ａ 'and R ４ｂ ' is independently H or C １ ~C ６ A compound according to any one of claims 1 to 34, wherein it is alkyl.
36. R ３ The compound according to any one of claims 1 to 35, wherein is methyl, ethyl, or isopropyl.
37. R ３ is, -CH ２ -CH ２ -N(CH ３ ) ２ ien-CH ２ -CH ２ -CH ２ -N(CH ３ ) ２ ien-CH ２ -CH ２ -CH ２ -CH ２ -N(CH ３ ) ２ ien-CH ２ -CH ２ -CH ２ -CH ２ -CH ２ -N(CH ３ ) ２ ien-CH ２ -CH ２ -S (=O) ２ Me or -CH ２ -CH ２ -CH ２ -S (=O) ２ A compound according to any one of claims 1 to 34, wherein the compound is Me.
38. R ３ The compound according to any one of claims 1 to 34, wherein is H.
39. R ３ teeth, 【Chemistry 11】 【Chemistry 12】 The compound according to any one of claims 1 to 34.
40. R ３ teeth, 【Chemistry 13】 The compound according to any one of claims 1 to 34.
41. R ３ teeth, 【Chemistry 14】 The compound according to any one of claims 1 to 34.
42. R ３ The compound according to any one of claims 1 to 34, wherein is H.
43. R ３ The compound according to any one of claims 1 to 33, wherein it forms a 3- to 12-membered heterocycline with a carbon atom adjacent to the nitrogen atom to which it is bonded. 【Request Item 44】 【Chemistry 15】 teeth, 【Chemistry 16】 The compound according to claim 43.
45. The compound according to any one of claims 1 to 44, wherein n is 1.
46. The compound according to any one of claims 1 to 45, wherein n is 2.
47. The compound according to any one of claims 1 to 46, wherein n is 3.
48. Formula (III) 【Chemistry 17】 (In the formula, W is either N or CH. Y is either N or CH, R １ C １ ~C ６ Alkyl or C ３ ~C １２ It is a cycloalkyl, and the C １ ~C ６ Alkyl or the C ３ ~C １２ Cycloalkyl is one or more halos, C １ ~C ６ Alkoxy, C ６ ~C １０ It is optionally substituted with an aryl or a 5- to 10-membered heteroaryl. R ２ C １ ~C ６ It is alkyl, Z is O, CH ２ or NH, Ring A is a 6-10 membered aryl or 6-10 membered heteroaryl. X ３ is H or C １ ~C ６ It is alkyl, R ３ is H or C １ ~C ６ Alkyl, and the C １ ~C ６ Alkyl is one or more R ３ａ It is either optionally replaced by R ３ It forms a 3- to 12-membered heterocycline with the carbon atom adjacent to the nitrogen atom to which it is bonded. Each R ３ａ Independently, N(R) ４ａ ) (Caution ４ｂ ) or a 3- to 12-membered heterocycline, wherein the 3- to 12-membered heterocycline is C １ ~C ６ Alkyl and O(R) ４ａ ') is optionally substituted with one or more substituents independently selected from the original compound. Each R ４ａ and R ４ｂ Independently, C １ ~C ６ It is alkyl, R ４ａ ' is H, and n is either 1 or 2. Compounds thereof, their stereoisomers, or pharmaceutically acceptable salts.
49. The compound according to claim 48, wherein W is N.
50. The compound according to claim 48, wherein W is CH.
51. The compound according to any one of claims 48 to 50, wherein Y is N.
52. The compound according to any one of claims 48 to 50, wherein Y is CH.
53. R １ C is a C that is optionally replaced by one or more halos. １ ~C ６ The compound according to any one of claims 48 to 52, wherein it is alkyl.
54. R １ C is a C that is optionally replaced by one or more halos. ３ ~C １２ A compound according to any one of claims 48 to 52, wherein it is a cycloalkyl compound.
55. R ２ C １ ~C ６ The compound according to any one of claims 48 to 54, wherein it is alkyl.
56. R ２ C １ ~C ６ The compound according to any one of claims 48 to 54, wherein it is alkyl.
57. The compound according to any one of claims 48 to 56, wherein Z is O.
58. The compound according to any one of claims 48 to 56, wherein Z is NH.
59. Z is CH ２ The compound according to any one of claims 48 to 56.
60. The compound according to any one of claims 48 to 59, wherein ring A is a six-membered aryl or a six-membered heteroaryl. 【Request Item 61】 【Chemistry 18】 teeth, 【Chemistry 19】 The compound according to any one of claims 48 to 59.
62. X ３ The compound according to any one of claims 48 to 61, wherein is H.
63. X ３ C １ ~C ６ The compound according to any one of claims 48 to 61, wherein it is alkyl.
64. R ３ The compound according to any one of claims 48 to 63, wherein is H.
65. R ３ is one or more R ３ａ C is optionally replaced by １ ~C ６ The compound according to any one of claims 48 to 63, wherein it is alkyl.
66. R ３ａ N(R) ４ａ ) (Caution ４ｂ ) and each R ４ａ and R ４ｂ Independently, C １ ~C ６ The compound according to claim 65, wherein it is alkyl.
67. Each R ３ａ Independently, C １ ~C ６ Alkyl and O(R) ４ａ The compound according to claim 65, which is a 3- to 12-membered heterocycline that is optionally substituted with one or more substituents independently selected from ').
68. Each R ３ａ Independently, C １ ~C ６ The compound according to claim 67, which is a 3- to 12-membered heterocycline optionally substituted with one or more substituents independently selected from alkyl and OH.
69. R ３ The compound according to any one of claims 48 to 63, wherein it forms a 3- to 12-membered heterocycline with a carbon atom adjacent to the nitrogen atom to which it is bonded.
70. The compound according to any one of claims 48 to 69, wherein n is 1.
71. The compound according to any one of claims 48 to 69, wherein n is 2.
72. Compounds shown in Table 1, their stereoisomers, or pharmaceutically acceptable salts thereof.
73. The compounds shown in Table 1 or their pharmaceutically acceptable salts.
74. The compounds shown in Table 1.
75. A compound or a pharmaceutically acceptable salt thereof, as shown in Table 1, wherein the salt is hydrochloric acid.
76. A compound according to any one of claims 1 to 75, which is useful in the treatment of cancer and minimizes hERG binding.
77. A pharmaceutical composition comprising a compound according to 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 according to any one of claims 1 to 48 and at least one pharmaceutically acceptable carrier.
79. A method for inhibiting the interaction between menine and MLL, comprising contacting the menine and MLL with a compound according to any one of claims 1 to 76 or a pharmaceutical composition according to claim 77 or 78.
80. A method for treating cancer in a patient, comprising administering to the patient a compound according to any one of claims 1 to 76 or a pharmaceutical composition according to claim 77 or 78.
81. The method according to claim 80, wherein the cancer is a blood cancer.
82. The method according to claim 80 or 81, wherein the cancer is leukemia.
83. The method according to claim 80 or 81, wherein the cancer is lymphoma.
84. The aforementioned cancers include mixed lineage leukemia (MLL), MLL-associated leukemia, leukemia associated with MLL, MLL-positive leukemia, MLL-induced leukemia, rearranged mixed lineage (KMT2A rearrangement) leukemia (MLL-r), leukemia associated with MLL rearrangement or rearrangement of the MLL gene, acute leukemia, chronic leukemia, painless leukemia, lymphoblastic leukemia, lymphocytic leukemia, myeloid leukemia, myeloid leukemia, childhood leukemia, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), acute granulocytic leukemia, acute nonlymphoblastic leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), treatment-related leukemia, and myelodysplastic syndrome. The method according to claim 80 or 81, wherein the disease is a group of lymphomas (MDS), myeloproliferative disorder (MPD), myeloproliferative neoplasm (MPN), plasma cell neoplasm, multiple myeloma, myelodysplasia, cutaneous T-cell lymphoma, lymphoid neoplasm, AIDS-associated lymphoma, thymoma, thymic carcinoma, mycosis fungoides, Alibert-Bazin syndrome, granulomatous fungoides, Sézary syndrome, hairy cell leukemia, T-cell prelymphocytic leukemia (T-PLL), large granular lymphocytic leukemia, meningeal leukemia, leukemic pilafenitis, leukemic meningitis, multiple myeloma, Hodgkin lymphoma, non-Hodgkin lymphoma (malignant lymphoma), or Waldenström macroglobulinemia.
85. The aforementioned cancer is an abstract nucleophosmin (NPM1) mutation acute myeloid leukemia (i.e., NPM1 ｍｕｔ The method according to claim 80 or 81, wherein the disease is acute myeloid leukemia.
86. The method according to claim 80 or 81, wherein the cancer is a reconstituted mixed strain (KMT2A reconstituted) leukemia (MLL-r).
87. A compound according to any one of claims 1 to 76 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 77 or 78, for use in the treatment or prevention of diseases caused by or related to the expression, activity and / or function of menin.
88. A compound according to any one of claims 1 to 76 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 77 or 78, for use in the treatment or prevention of cancer.
89. Use of a compound according to any one of claims 1 to 76 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 77 or 78, for the treatment or prevention of diseases caused by or related to the expression, activity and / or function of menin.
90. Use of a compound according to any one of claims 1 to 76 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 77 or 78, in the manufacture of a pharmaceutical for treating or preventing a disease caused by or related to the expression, activity and / or function of menine.
91. Use of a compound according to any one of claims 1 to 76 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 77 or 78, for the treatment or prevention of cancer.
92. Use of a compound according to any one of claims 1 to 76 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 77 or 78, in the manufacture of a pharmaceutical for treating or preventing cancer.
93. A kit comprising a compound according to any one of claims 1 to 76 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 77 or 78, and instructions for use thereof.