Tricyclic quinolone BCL6 bifunctional degrader

Abstract

The present disclosure provides compounds of formula (I) (e.g., formula (I-aa) (e.g., formula (I-aa-1), (I-aa-2), (I-aa-3), (I-aa-4), (I-aa-5), or (I-aa-6)), formula (I-a) (e.g., formula (I-a-1), (I-a-2), (I-a-3), (I-a-4), (I-a-5), or (I-a-6)), formula (I-bb) (e.g., formula (I-bb-1) or (I-bb-2)), or formula (I-b) (e.g., formula (I-b-1) or (I-b-2))), or formula (II), or pharmaceutically acceptable salts thereof, which induce the degradation of the BCL6 protein. These compounds are useful, for example, in treating cancer in a subject (e.g., a human). The present disclosure also provides methods of using and making the compounds, as well as compositions containing the compounds provided herein.

Claims

1. A compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein TBM is (T1), X １ is selected from the group consisting of N and CR ２ and X ２ is CH, Each R ２ is independently selected from the group consisting of H, halo, cyano, C １～３ alkyl, C １～３ haloalkyl, C １～３ alkoxy, C １～３ haloalkoxy, -OH and -NR ｄ R ｅ and is independently selected from the group consisting of: m3 is 0 or 1, X ３ is an alkylene which may be substituted with 1 to 3 Rs ｃ and may be substituted with C １～３ ​ R １ is selected from the group consisting of H and C ３～６ cycloalkyl, m1 is 2, and each A １ is, independently, CH ２ , CHR ４ , or CR ４ R ４ wherein m2 is 1, and A ２ is -O-, One R ３ is (i) 1 to 3 R's ｇ Optionally substituted C ３～６ Cycloalkyl, and (ii)C which may be substituted with 1 to 3 -F １～３ alkyl selected from the group consisting of The other R ３ is H, Each R ４ is independently selected from the group consisting of H, R ａ , and R ｂ and is selected independently from the group consisting of X ａ is selected from the group consisting of N, CH, and CF, X ｂ is selected from the group consisting of N and CR ｘ１ and R ６ and R ｘ１ are each independently selected from the group consisting of H, halo, C １～２ alkyl, C １～２ haloalkyl, C １～２ alkoxy, CN and -C≡CH L is -(L Ａ ) ｎ１ -, and L Ａ and n1 are defined according to (AA) or (BB). (AA) n1 is an integer from 1 to 15, and Each L Ａ is independently selected from the group consisting of L Ａ１ , L Ａ３ , and L Ａ４ , provided that 1 to 3 occurrences of L Ａ are L Ａ４ ; (BB) n1 is an integer from 0 to 20, and Each L Ａ is independently selected from the group consisting of L Ａ１ and L Ａ３ and Each L Ａ１ is independently selected from the group consisting of -CH ２ -, -CHR Ｌ -, and -C(R Ｌ ) ２ -. Each L Ａ３ is independently selected from the group consisting of -N(R ｄ ), -N(R ｂ ), -O-, -S(O) ０～２ -, and C(=O). Each L Ａ４ is (a) C ３～１５ cycloalkylene or 3- to 15-membered heterocyclylene, each of which may be substituted with 1 to 6 substituents independently selected from the group consisting of R ａ and R ｂ cycloalkylene or 3- to 15-membered heterocyclylene which may be substituted, and ３～１５ cycloalkylene or 3- to 15-membered heterocyclylene, and (b) C ６～１５ An arylene or a 5- to 15-membered heteroarylene, each of which may be substituted with 1 to 6 substituents independently selected from the group consisting of R ａ and R ｂ and may be substituted with 1 to 6 substituents independently selected from the group consisting of C ６～１５ arylene or a 5- to 15-membered heteroarylene independently selected from the group consisting of However, L does not include any of O-O, N-O, N-N, N-S(O) ０ , and O-S(O) ０～２ and does not include any bonds Each R Ｌ is independently selected from the group consisting of halo, cyano, -OH, -C １～６ alkoxy, -C １～６ haloalkoxy, NR ｄ R ｅ , C(=O)N(R ｆ ), ２ S(O) ０～２ (C １～６ alkyl), S(O) ０～２ (C １～６ haloalkyl), S(O) １～２ N(R ｆ ), ２ -R ｂ , and C ｃ alkyl which may be substituted with 1 to 6 R １～６ and is independently selected from the group consisting of: Ring C is selected from the group consisting of, where c1 is 0, 1, 2, or 3, Each R Ｙ is independently selected from the group consisting of R ａ and R ｂ ; R ａＮ is C alkyl which may be substituted with H or 1 to 3 R ｃ and １～６ is optionally substituted with H or 1 to 3 R Y １ and Y ２ each independently is N, CH or CR Ｙ wherein yy represents the point of attachment to L, X is CH, C or N, is a single bond or a double bond, L Ｃ is selected from the group consisting of a bond, -CH ２ -, -CHR ａ -, -C(R ａ ) ２ -, -C(=O)-, -N(R ｄ )-, and O, provided that when X is N, L Ｃ is other than O, and When ring C is bonded to -L via a ring nitrogen, X is CH and L Ｃ is a bond, with the further condition that Ｃ ​ Each R ａ is (a) halo; (b) cyano; (c) -OH; (d) oxo; (e) 1 to 6 R's ｃ C which may be substituted with １～６ alkoxy; (f) - NR ｄ R ｅ ; (g) C(=O)C １～６ alkyl; (h) C(=O)C １～６ Haloalkyl; (i) C(=O)OH; (j) C(=O)OC １～６ alkyl; (k) C(=O)OC １～６ Haloalkyl; (l) C(=O)N(R ｆ ) ２ ; (m) S(O) ０～２ (C １～６ alkyl); (n) S(O) ０～２ (C １～６ haloalkyl); (o) S(O) １～２ N(R ｆ ) ２ ; and (p) 1 to 6 Rs each ｃ optionally substituted by C １～６ alkyl, C ２～６ alkenyl or C ２～６ alkynyl independently selected from the group consisting of Each R ｂ is independently selected from the group consisting of - (L ｂ ), ｂ -R ｂ１ and -R ｂ１ and is independently selected from the group consisting of each b is independently 1, 2 or 3, Each -L ｂ is independently selected from the group consisting of -O-, -N(H)-, -N(C １～３ alkyl)-, -S(O) ０～２ -, C(=O) and C １～３ alkylene, Each R ｂ１ is each independently selected from the group consisting of C ｇ cycloalkyl which may be substituted with 1 to 3 R ３～１０ groups, 4- to 10-membered heterocyclyl, C ６～１０ aryl, and 5- to 10-membered heteroaryl, Each R ｃ is independently selected from the group consisting of halo, cyano, -OH, -C １～６ alkoxy, -C １～６ haloalkoxy, -NR ｄ R ｅ , C(=O)C １～６ alkyl, C(=O)C １～６ haloalkyl, C(=O)OC １～６ alkyl, C(=O)OC １～６ haloalkyl, C(=O)OH, C(=O)N(R ｆ ) ２ , S(O) ０～２ (C １～６ alkyl), S(O) ０～２ (C １～６ haloalkyl), and S(O) １～２ N(R ｆ ) ２ ; Each R ｄ and R ｅ is independently selected from the group consisting of H, C(=O)C １～６ alkyl, C(=O)C １～６ haloalkyl, C(=O)OC １～６ alkyl, C(=O)OC １～６ haloalkyl, C(=O)N(R ｆ ) ２ , S(O) １～２ (C １～６ alkyl), S(O) １～２ (C １～６ haloalkyl), S(O) １～２ N(R ｆ ) ２ , and C ｈ alkyl which may be substituted with 1 to 3 R １～６ and is independently selected from the group Each R ｆ is independently selected from the group consisting of C ｈ alkyl which may be substituted with H and 1 to 3 R １～６ groups Each R ｇ is independently selected from the group consisting of R ｈ , oxo, C １～３ alkyl and C １～３ haloalkyl, and Each R ｈ is independently selected from the group consisting of halo, cyano, -OH, -(C ０～３ alkylene)-C １～６ alkoxy, -(C ０～３ alkylene)-C １～６ haloalkoxy, -(C ０～３ alkylene)-NH ２ , -(C ０～３ alkylene)-N(H)(C １～３ alkyl), and -(C ０～３ alkylene)-N(C １～３ alkyl) ２ ; a compound of formula (I), or a pharmaceutically acceptable salt thereof.

2. Ring C is or Ring C is the compound according to claim 1.

3. c1 is 0, or c1 is 1 and R Ｙ is a halo (e.g., -F), a compound according to any one of claims 1 or 2.

4. R ａＮ is C １～３ The compound according to any one of claims 1 to 3, wherein the alkyl is (for example, methyl).

5. The compound according to any one of claims 1 to 4, wherein X is CH.

6. L Ｃ The compound according to any one of claims 1 to 5, wherein L is a bond.

7. The moiety is represented by Table CM-1b: Table CM-1b The compound according to claim 1, selected from the group consisting of the moieties shown.

8. The moiety is or The moiety is the compound according to claim 7.

9. -(A １ ) ｍ１ - is -C(R ４ R ４ )-CH ２ -* (for example, -CF ２ -CH ２ -*) and in the formula, * represents the bonding point to -(A ２ ) ｍ２ -; a compound according to any one of claims 1 to 8.

10. One R ３ is C ３～６ cycloalkyl, and the other R ３ is H, or One R ３ is cyclopropyl, and the other R ３ is H, or One R ３ is cyclopropyl, and the other R ３ is H, and -(A １ ) ｍ１ - is -CF ２ -CH ２ -*, where * represents the bonding point to -(A ２ ) ｍ２ -. The compound according to any one of claims 1 to 9.

11. Each R ３ The compound according to any one of claims 1 to 10, wherein the carbon atom to which each R is attached has an (S)-stereochemical configuration.

12. X １ The compound according to any one of claims 1 to 11, wherein X is CH.

13. X ａ is N, and X ｂ is CH, or X ａ is CH and X ｂ is CH The compound according to any one of claims 1 to 12.

14. R ６ is a halo (e.g., -F, -Cl, -Br) or CN, or R ６ is -F or R ６ is -Cl, The compound according to any one of claims 1 to 13.

15. Each R ２ The compound according to any one of claims 1 to 14, wherein R is H.

16. m3 is 1 and X ３ is C １～３ an alkylene (e.g., methylene, ethylene or isopropylene), or m3 is 0, the compound according to any one of claims 1 to 15.

17. R １ The compound according to any one of claims 1 to 16, wherein R is H.

18. m3 is 1, and X ３ is C alkylene which may be substituted with 1 to 3 Rs ｃ and R １～３ is H or １ ​ m3 is 1, and X ３ is C １～３ is alkylene, and R １ is H the compound according to any one of claims 1 to 15.

19. -(X ３ ) ｍ３ -R １ wherein, R is methyl, ethyl or isopropyl (e.g., methyl), the compound according to any one of claims 1 to 15.

20. TBM is the following: the compound according to any one of claims 1 to 8.

21. m3 is 1, and X ３ is C １～３ is alkylene, and R １ is H, the compound according to claim 20.

22. -(X ３ ) ｍ３ -R １ is methyl, ethyl or isopropyl, the compound according to claim 20 or 21.

23. X ａ is CH or X ａ is N, The compound according to any one of claims 20 to 22.

24. R ６ The compound according to any one of claims 20 to 23, wherein R is -F or -Cl.

25. L is -(L Ａ ) ｎ１ -, and L Ａ and n1 are defined according to (AA), a compound according to any one of claims 1 to 24.

26. n1 is an integer from 1 to 5, or n1 is an integer from 2 to 4 (e.g., 2 or 3), the compound according to any one of claims 1 to 25.

27. L is -L Ａ４ -L Ａ１ -L Ａ４ - ｂｂ ; -L Ａ４ -L Ａ４ - ｂｂ ; -L Ａ４ -L Ａ１ -L Ａ１ -L Ａ４ - ｂｂ ; -L Ａ４ -L Ａ３ -L Ａ４ - ｂｂ ; and -L Ａ４ -L Ａ１ -L Ａ４ -L Ａ３ - ｂｂ selected from the group consisting of, where bb represents the point of attachment to Ring C, the compound according to any one of claims 1 to 26.

28. Each L Ａ４ is independently C ３～１０ cycloalkylene or 4- to 12-membered heterocyclylene, each of which may be substituted with 1 to 6 Rs ａ or Each L Ａ４ is, independently, a 4- to 12- (e.g., 4- to 10-) membered heterocyclylene which may be substituted with 1 to 3 Rs ａ or Each L Ａ４ is, independently, a monocyclic 4- to 6-membered nitrogen-containing heterocyclylene which may be substituted with 1 to 3 R ａ or One L Ａ４ is a monocyclic 4- to 6-membered nitrogen-containing heterocyclylene which may be substituted with 1 to 3 Rs ａ and the other L Ａ４ is a bicyclic 6- to 12 (e.g., 6- to 10)-membered nitrogen-containing heterocyclylene which may be substituted with 1 to 3 Rs ａ or One L Ａ４ is a monocyclic 4- to 6-membered nitrogen-containing heterocyclylene which may be substituted with 1 to 3 Rs ａ and the other L Ａ４ is a bicyclic spirocyclic 6- to 12 (e.g., 6- to 10)-membered nitrogen-containing heterocyclylene which may be substituted with 1 to 3 Rs ａ or Each L Ａ４ contains 1 to 2 ring nitrogen atoms and no further ring heteroatoms, The compound according to claim 27.

29. L Ａ４ each R present thereon ａ is selected independently from the group consisting of -F, CN, C １～３ alkoxy, OH, and C optionally substituted with 1 to 3 F １～３ alkyl, the compound according to claim 28.

30. L is -L Ａ４ -L Ａ１ -L Ａ４ - ｂｂ The compound according to claim 28, wherein it is as described above.

31. L Ａ１ is -CH ２ -, -CHMe- or -CMe ２ -, the compound according to claim 30.

32. L is -L Ａ４ -L Ａ３ -L Ａ４ - ｂｂ The compound according to claim 28, wherein it is as defined above.

33. L Ａ３ The compound according to claim 32, wherein L is -C(=O).

34. L is -L Ａ４ -L Ａ１ -L Ａ４ -L Ａ３ - ｂｂ and L Ａ３ is C(=O), a compound according to claim 28 or 29.

35. L is -L Ａ４ -L Ａ１ -L Ａ１ -L Ａ４ - ｂｂ and L Ａ１ one or both of which is CH ２ The compound according to claim 28, wherein

36. L is -L Ａ４ -L Ａ３ - ｂｂ ; -L Ａ４ -L Ａ１ - ｂｂ ; and -L Ａ４ -L Ａ１ -L Ａ３ - ｂｂ selected from the group consisting of, where bb represents the bonding point to ring C The compound according to any one of claims 1 to 26.

37. L is -L Ａ４ -L Ａ３ - ｂｂ The compound according to claim 36, wherein it is as defined above.

38. L Ａ３ is -NH- or -N(C １～３ alkyl)-(for example, -NH-), the compound according to claim 36 or 37.

39. L Ａ４ is a 4- to 12-membered heterocyclylene optionally substituted with 1 to 6 Rs ａ or L Ａ４ is a 4- to 12- (e.g., 6- to 10-) membered nitrogen-containing heterocyclylene which may be substituted with 1 to 3 Rs ａ or L Ａ４ is a bicyclic spirocyclic 6- to 12- (e.g., 6- to 10-) membered nitrogen-containing heterocyclylene which may be substituted with 1 to 3 Rs ａ or L Ａ４ contains one or two ring nitrogen atoms and no further ring heteroatoms, The compound according to any one of claims 36 to 38.

40. L Ａ４ each R present thereon ａ is selected independently from the group consisting of -F, CN, C １～３ alkoxy, OH, and C optionally substituted with 1 to 3 F １～３ alkyl, the compound according to claim 39.

41. The compound according to any one of claims 1 to 27, wherein L is selected from the group consisting of the moieties shown in Table L or Table L1-a, and bb represents the bonding point to ring C.

42. The compound is a compound of formula (I-aa): or a pharmaceutically acceptable salt thereof, wherein X ａ is N or CH, R ６ is -F or -Cl, m3 is 1, and X ３ is C １～３ is alkylene, and R １ is H, ring C is selected from the group consisting of wherein c1 is 0 or 1, and R Ｙ is selected from the group consisting of halo (e.g., -F), and C which may be substituted with 1 to 3 Fs １～３ alkyl, and R ａＮ is C １～３ alkyl L is -L Ａ４ -L Ａ１ -L Ａ４ - ｂｂ ; -L Ａ４ -L Ａ１ -L Ａ１ -L Ａ４ - ｂｂ ; -L Ａ４ -L Ａ４ - ｂｂ ; -L Ａ４ -C(=O)-L Ａ４ - ｂｂ ; and -L Ａ４ -L Ａ１ -L Ａ４ -C(=O)- ｂｂ selected from the group consisting of, and bb represents the bonding point to ring C L Ａ１ is CH ２ , CHMe, or CMe ２ and Each L Ａ４ is, independently, a 4- to 12-membered nitrogen-containing heterocyclylene which may be substituted with 1 to 3 Rs ａ and is L Ａ４ each R present thereon ａ is independently selected from the group consisting of -F, CN, C １～３ alkoxy, OH, and C optionally substituted with 1 to 3 F １～３ alkyl Is the compound of formula (I-aa) or a pharmaceutically acceptable salt thereof; or The compound is a compound of formula (I-a): or a pharmaceutically acceptable salt thereof, wherein X ａ is N or CH, R ６ is -F or -Cl, m3 is 1, and X ３ is C １～３ is alkylene, and R １ is H ring C is selected from the group consisting of L is -L Ａ４ -L Ａ１ -L Ａ４ - ｂｂ ; -L Ａ４ -L Ａ１ -L Ａ１ -L Ａ４ - ｂｂ ; -L Ａ４ -L Ａ４ - ｂｂ ; -L Ａ４ -C(=O)-L Ａ４ - ｂｂ ; and -L Ａ４ -L Ａ１ -L Ａ４ -C(=O)- ｂｂ selected from the group consisting of, and bb represents the bonding point to ring C L Ａ１ is CH ２ , CHMe, or CMe ２ and Each L Ａ４ is, independently, a 4- to 12-membered nitrogen-containing heterocyclylene which may be substituted with 1 to 3 R's ａ and L Ａ４ each R present thereon ａ is independently selected from the group consisting of -F, CN, C １～３ alkoxy, OH, and C optionally substituted with 1 to 3 F １～３ alkyl Is the compound of formula (I-a) or a pharmaceutically acceptable salt thereof; or The compound is a compound of formula (I-aa-1): or a pharmaceutically acceptable salt thereof, wherein X ａ is N or CH, R ６ is -F or -Cl, m3 is 1, and X ３ is C １～３ is alkylene, and R １ is H ring C is selected from the group consisting of wherein c1 is 0 or 1, and R Ｙ is selected from the group consisting of halo (e.g., -F) and C optionally substituted with 1 to 3 F １～３ alkyl, and R ａＮ is C １～３ alkyl L Ａ１ is CH ２ , CHMe, or CMe ２ and Each L Ａ４ is, independently, a monocyclic 4- to 6-membered nitrogen-containing heterocyclylene which may be substituted with 1 to 3 Rs ａ and is Each L Ａ４ contains 1 to 2 ring nitrogen atoms, does not contain further ring heteroatoms, and L Ａ４ each R present thereon ａ is independently selected from the group consisting of -F, CN, C １～３ alkoxy, OH, and C optionally substituted with 1 to 3 F １～３ alkyl Is the compound of formula (I-aa-1) or a pharmaceutically acceptable salt thereof; or The compound is a compound of formula (I-a-1): or a pharmaceutically acceptable salt thereof, wherein X ａ is N or CH, R ６ is -F or -Cl, m3 is 1, and X ３ is C １～３ is alkylene, and R １ is H, ring C is selected from the group consisting of L Ａ１ is CH ２ , CHMe, or CMe ２ and Each L Ａ４ is, independently, a monocyclic 4- to 6-membered nitrogen-containing heterocyclylene which may be substituted with 1 to 3 Rs ａ and is Each L Ａ４ contains 1 to 2 ring nitrogen atoms, does not contain further ring heteroatoms, and L Ａ４ each R present thereon ａ is independently selected from the group consisting of -F, CN, C １～３ alkoxy, OH, and C optionally substituted with 1 to 3 F １～３ alkyl Is the compound of formula (I-a-1) or a pharmaceutically acceptable salt thereof; or The compound is a compound of formula (I-aa-2): or a pharmaceutically acceptable salt thereof, wherein X ａ is N or CH, R ６ is -F or -Cl, m3 is 1, and X ３ is C １～３ is alkylene, and R １ is H ring C is selected from the group consisting of In the formula, c1 is 0 or 1, and R Ｙ is selected from the group consisting of halo (e.g., -F) and C optionally substituted with 1 to 3 F １～３ alkyl, and R ａＮ is C １～３ alkyl L Ａ１ is CH ２ , CHMe, or CMe ２ and Z １ and Z ２ are independently selected from the group consisting of CH, CR ａ４ , and N Z ３ and Z ４ are independently selected from the group consisting of CH, CR ａ５ , and N, However, Z １ and Z ２ at least one of which is N, and Z ３ and Z ４ at least one of which is N, and when Z ２ is N, Z ３ is CH or CR ａ５ and m4 and m5 are independently selected from the group consisting of 0, 1, and 2, and Each R ａ４ and R ａ５ are independently selected from the group consisting of -F, CN, C １～３ alkoxy, OH, and C optionally substituted with 1 to 3 F １～３ alkyl Is the compound of formula (I-aa-2) or a pharmaceutically acceptable salt thereof; or The compound is a compound of formula (I-a-2): or a pharmaceutically acceptable salt thereof, wherein X ａ is N or CH, R ６ is -F or -Cl, m3 is 1, and X ３ is C １～３ is alkylene, and R １ is H ring C is selected from the group consisting of L Ａ１ is CH ２ , CHMe, or CMe ２ and Z １ and Z ２ are independently selected from the group consisting of CH, CR ａ４ , and N, Z ３ and Z ４ are independently selected from the group consisting of CH, CR ａ５ , and N, However, Z １ and Z ２ at least one of which is N, and Z ３ and Z ４ at least one of which is N, and when Z ２ is N, Z ３ is CH or CR ａ５ and m4 and m5 are independently selected from the group consisting of 0, 1, and 2, and Each R ａ４ and R ａ５ is independently selected from the group consisting of -F, CN, C １～３ alkoxy, OH, and C optionally substituted with 1 to 3 F １～３ alkyl Is the compound of formula (I-a-2) or a pharmaceutically acceptable salt thereof; or The compound is a compound of formula (I-aa-3): or a pharmaceutically acceptable salt thereof, wherein X ａ is N or CH, R ６ is -F or -Cl, m3 is 1, and X ３ is C １～３ is alkylene, and R １ is H ring C is selected from the group consisting of wherein c1 is 0 or 1, and R Ｙ is selected from the group consisting of halo (e.g., -F) and C optionally substituted with 1 to 3 F １～３ alkyl, and R ａＮ is C １～３ alkyl L Ａ１ is CH ２ , CHMe, or CMe ２ and One L Ａ４ is a monocyclic 4- to 6-membered nitrogen-containing heterocyclylene which may be substituted with 1 to 3 Rs ａ and The other L Ａ４ is a bicyclic 6- to 12-membered nitrogen-containing heterocyclylene which may be substituted with 1 to 3 Rs ａ and L Ａ４ each R present thereon ａ is independently selected from the group consisting of -F, CN, C １～３ alkoxy, OH, and C optionally substituted with 1 to 3 F １～３ alkyl Is the compound of formula (I-aa-3) or a pharmaceutically acceptable salt thereof; or The compound is a compound of formula (I-a-3): or a pharmaceutically acceptable salt thereof, wherein X ａ is N or CH, R ６ is -F or -Cl, m3 is 1, and X ３ is C １～３ is alkylene, and R １ is H ring C is selected from the group consisting of L Ａ１ is CH ２ , CHMe, or CMe ２ and One L Ａ４ is a monocyclic 4- to 6-membered nitrogen-containing heterocyclylene which may be substituted with 1 to 3 Rs ａ and The other L Ａ４ is a bicyclic 6- to 12-membered nitrogen-containing heterocyclylene which may be substituted with 1 to 3 Rs ａ and L Ａ４ Each R present thereon ａ is independently selected from the group consisting of -F, CN, C １～３ alkoxy, OH, and C optionally substituted with 1 to 3 F １～３ alkyl Is it a compound of formula (I-a-3) or a pharmaceutically acceptable salt thereof; or The compound is a compound of formula (I-aa-4): Or a pharmaceutically acceptable salt thereof, wherein X ａ is N or CH, R ６ is -F or -Cl, m3 is 1, and X ３ is C １～３ is alkylene, and R １ is H Ring C is Selected from the group consisting of wherein c1 is 0 or 1, and R Ｙ is selected from the group consisting of halo (e.g., -F) and C optionally substituted with 1 to 3 F １～３ alkyl, and R ａＮ is C １～３ alkyl L Ａ１ is CH ２ , CHMe, or CMe ２ and Z １ and Z ２ are independently selected from the group consisting of CH, CR ａ４ , and N, Z ３ and Z ４ are independently selected from the group consisting of CH, CR ａ５ , and N, However, Z １ and Z ２ at least one of which is N, and Z ３ and Z ４ at least one of which is N, and when Z ２ is N, Z ３ is CH or CR ａ５ and m4 and m6 are independently 0 or 1, m5 is 0, 1 or 2, and Each R ａ４ , R ａ５ and R ａ６ are independently selected from the group consisting of -F, CN, C １～３ alkoxy, OH, and C optionally substituted with 1 to 3 F １～３ alkyl Is it a compound of formula (I-aa-4) or a pharmaceutically acceptable salt thereof; or The compound is a compound of formula (I-a-4): Or a pharmaceutically acceptable salt thereof, wherein X ａ is N or CH, R ６ is -F or -Cl, m3 is 1, and X ３ is C １～３ is alkylene, and R １ is H, Ring C is Selected from the group consisting of L Ａ１ is CH ２ , CHMe, or CMe ２ and Z １ and Z ２ are independently selected from the group consisting of CH, CR ａ４ , and N, Z ３ and Z ４ are independently selected from the group consisting of CH, CR ａ５ , and N, However, Z １ and Z ２ at least one of which is N, and Z ３ and Z ４ at least one of which is N, and when Z ２ is N, Z ３ is CH or CR ａ５ and m4 and m6 are independently 0 or 1, m5 is 0, 1 or 2, Each R ａ４ , R ａ５ and R ａ６ are independently selected from the group consisting of -F, CN, C １～３ alkoxy, OH, and C which may be substituted with 1 to 3 F １～３ alkyl Is it a compound of formula (I-a-4) or a pharmaceutically acceptable salt thereof; or The compound is a compound of formula (I-bb): Or a pharmaceutically acceptable salt thereof, wherein X ａ is N or CH, R ６ is -F or -Cl, m3 is 1, and X ３ is C １～３ is alkylene, and R １ is H Ring C is Selected from the group consisting of wherein c1 is 0 or 1, and R Ｙ is selected from the group consisting of halo (e.g., -F) and C optionally substituted with 1 to 3 F １～３ alkyl, and R ａＮ is C １～３ alkyl L is -L Ａ４ -L Ａ３ - ｂｂ or -L Ａ４ -L Ａ１ -L Ａ３ - ｂｂ wherein bb represents the bonding point with ring C and L Ａ４ is a 4- to 12-membered nitrogen-containing heterocyclylene which may be substituted with 1 to 3 Rs ａ and L Ａ４ each R present thereon ａ is independently selected from the group consisting of -F, CN, C １～３ alkoxy, OH, and C optionally substituted with 1 to 3 F １～３ alkyl Is it a compound of formula (I-bb) or a pharmaceutically acceptable salt thereof; or The compound is a compound of formula (I-b): Or a pharmaceutically acceptable salt thereof, wherein X ａ is N or CH, R ６ is -F or -Cl, m3 is 1, and X ３ is C １～３ is alkylene, and R １ is H Ring C is Selected from the group consisting of L is, -L Ａ４ -L Ａ３ - ｂｂ or -L Ａ４ -L Ａ１ -L Ａ３ - ｂｂ and bb represents the bonding point with ring C, and L Ａ４ is a 4- to 12-membered nitrogen-containing heterocyclylene which may be substituted with 1 to 3 Rs ａ and is optionally substituted with 1 to 3 Rs L Ａ４ each R present thereon ａ is independently selected from the group consisting of -F, CN, C １～３ alkoxy, OH, and C optionally substituted with 1 to 3 F １～３ alkyl A compound of formula (I-b) or a pharmaceutically acceptable salt thereof, The compound according to claim 1.

43. The compound according to claim 1, selected from the group consisting of a compound of Table C1 or a pharmaceutically acceptable salt thereof.

44. A pharmaceutical composition comprising a compound according to any one of claims 1 to 43 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient.

45. A method for treating cancer in a subject in need thereof, comprising Administering to the subject a therapeutically effective amount of a compound according to any one of claims 1 to 43 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 44, Said method.

46. The method according to claim 45, wherein the cancer is a blood cancer, breast cancer, gastrointestinal cancer, brain cancer, lung cancer, or a combination thereof.

47. The method according to claim 46, wherein the blood cancer is diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), diffuse histiocytic lymphoma (DHL), intravascular large B-cell lymphoma (IVLBCL), small lymphocyte lymphoma (SLL), Burkitt lymphoma (BL), mantle cell lymphoma (MCL), peripheral T-cell lymphoma (PTCL), chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), or chronic myelogenous leukemia (CML).

48. The blood cancer is selected from the group consisting of DLBCL, FL, MCL, BL, PTCL, and ALL (e.g., B-ALL), or the blood cancer is FL or DLBCL, or the blood cancer is DLBCL, or the blood cancer is FL, or the blood cancer is BL, or the blood cancer is PTCL, or the blood cancer is ALL (e.g., B-ALL), The method according to claim 47.

49. The method according to any one of claims 46 to 48, wherein a therapeutically effective amount of the compound according to any one of claims 1 to 43 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 44 is administered to the subject as a monotherapy.

50. The method according to any one of claims 46 to 48, comprising administering an additional therapy or therapeutic agent to the subject.

51. wherein the additional therapy or therapeutic agent is a PI3K inhibitor, an Abl inhibitor (e.g., a BCR-Abl inhibitor), a BTK inhibitor, a JAK inhibitor, a BRAF inhibitor, a MEK inhibitor, a BCL-2 inhibitor, a Bcl-X Ｌ inhibitor, an XPO1 inhibitor, an inhibitor of polycomb repressive complex 2 (PRC2), an immunomodulatory imide drug, an anti-CD19 therapy, an anti-CD20 therapy, an anti-CD3 therapy, chemotherapy, or a combination thereof, the method of claim 50.

52. A method for treating an autoimmune condition in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound according to any one of claims 1 to 43 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 44, The method.

53. A method for treating a lymphoproliferative disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound according to any one of claims 1 to 43 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 44, The method.

54. A compound of formula (SI): or a salt thereof, wherein ring C is selected from the group consisting of In the formula, c1 is 0 or 1, and R Ｙ is selected from the group consisting of halo (for example, -F) and C optionally substituted with 1 to 3 F １～３ alkyl, and R ａＮ is C １～３ alkyl, and yy represents the bonding point to L L is -L Ａ４ -L Ａ１ -L Ａ４ - ｂｂ ; -L Ａ４ -L Ａ１ -L Ａ１ -L Ａ４ - ｂｂ ; -L Ａ４ -L Ａ４ - ｂｂ ; -L Ａ４ -C(=O)-L Ａ４ - ｂｂ ; and -L Ａ４ -L Ａ１ -L Ａ４ -C(=O)- ｂｂ selected from the group consisting of, bb represents the point of attachment to ring C, and L Ａ１ is CH ２ , CHMe, or CMe ２ and Each L Ａ４ is, independently, a 4- to 12-membered nitrogen-containing heterocyclylene which may be substituted with 1 to 3 Rs ａ and is L Ａ４ Each R present thereon ａ is independently selected from the group consisting of -F, CN, C １～３ alkoxy, OH, and C optionally substituted with 1 to 3 F １～３ alkyl The compound of formula (SI) or a salt thereof; or A compound of formula (SI-A) or formula (SI-B): or a salt thereof, wherein c1 is 0 or 1, R Ｙ is selected from the group consisting of halo (e.g., -F) and C １～３ alkyl which may be substituted with 1 to 3 Fs, R ａＮ is C １～３ alkyl, and L Ａ１ is CH ２ , CHMe, or CMe ２ and Each L Ａ４ is, independently, a 4- to 12-membered nitrogen-containing heterocyclylene which may be substituted with 1 to 3 Rs ａ and is L Ａ４ each R present thereon ａ is selected independently from the group consisting of -F, CN, C １～３ alkoxy, OH, and C optionally substituted with 1 to 3 F １～３ alkyl A compound of formula (SI-A) or formula (SI-B) or a salt thereof; or Compounds of formula (SI-A-1) and formula (SI-B-1): or a salt thereof, wherein c1 is 0 or 1, R Ｙ is selected from the group consisting of halo (e.g., -F) and C optionally substituted with 1 to 3 F １～３ alkyl R ａＮ is C １～３ alkyl, L Ａ１ is CH ２ , CHMe, or CMe ２ and Z ２ , Z ３ , and Z ４ are each independently selected from the group consisting of CH, CR ａ４ , and N, provided that at least one of Z ３ and Z ４ is N, and when Z ２ is N, Z ３ is CH or CR ａ４ , and when Z ３ is N, Z ２ is CH or CR ａ４ . m4 and m5 are independently 0, 1, or 2, and Each R ａ４ and R ａ５ is independently selected from the group consisting of -F, CN, C １～３ alkoxy, OH, and C optionally substituted with 1 to 3 F １～３ alkyl Compounds of formula (SI-A-1) and formula (SI-B-1) or a salt thereof; or A compound of formula (SI-A-2) or formula (SI-B-2): or a salt thereof, wherein c1 is 0 or 1, R Ｙ is selected from the group consisting of halo (e.g., -F) and C １～３ alkyl which may be substituted with 1 to 3 Fs, R ａＮ is C １～３ alkyl, and L Ａ１ is CH ２ , CHMe, or CMe ２ and Z ２ 、Z ３ 、and Z ４ are independently selected from the group consisting of CH, CR ａ４ , and N, provided that at least one of Z ３ and Z ４ is N, and when Z ２ is N, Z ３ is CH or CR ａ４ , and when Z ３ is N, Z ２ is CH or CR ａ４ and m4, m5, and m6 are independently 0, 1, or 2, and Each R ａ４ , R ａ５ and R ａ６ are independently selected from the group consisting of -F, CN, C １～３ alkoxy, OH, and C optionally substituted with 1 to 3 F １～３ alkyl A compound of formula (SI-A-2) or formula (SI-B-2) or a salt thereof.

55. Any of the compounds, compositions, combinations, pharmaceutical compositions, methods, uses, and processes substantially provided herein.

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