Methods and compounds for the treatment of hereditary diseases

Abstract

This invention provides compounds and methods for regulating dmpk expression and treating diseases and conditions in which dmpk plays an active role. [Solution] A transcription modulator molecule is provided having a first end, a second end, and an oligomeric skeleton, wherein a) the first end includes a DNA-binding portion that can non-covalently bind to a nucleotide repeat sequence GAA, b) the second end includes a protein-binding portion that binds to a regulatory molecule that modulates the expression of a gene containing the nucleotide repeat sequence GAA, and c) the oligomeric skeleton includes a linker between the first end and the second end.

Claims

1. A transcription modulator molecule having a first terminal, a second terminal, and an oligomeric skeleton, wherein, a) The first end includes a DNA-binding portion that can non-covalently bind to the nucleotide repeat sequence GAA, b) The second end includes a protein-binding portion that binds to a regulatory molecule that regulates the expression of the gene containing the nucleotide repeat sequence GAA, c) The oligomer skeleton includes a linker between the first end and the second end. Transcription modulator molecule.

2. The transcription modulator molecule according to claim 1, wherein the first end comprises a polyamide selected from the group consisting of linear polyamide, hairpin polyamide, H-pin polyamide, overlap polyamide, slip polyamide, cyclic polyamide, tandem polyamide, and extended polyamide.

3. The transcription modulator molecule according to claim 1 or 2, wherein the first end comprises a linear polyamide.

4. The transcription modulator molecule according to any one of claims 1 to 3, wherein the polyamide can bind DNA with an affinity of less than 500 nM.

5. The first terminus contains -NH-Q-C(O)-, where Q is optionally replaced by C. ６－１０ A transcription modulator molecule according to any one of claims 1 to 4, wherein the molecule is an arylene group, an optionally substituted 4-10 membered heterocyclene group, an optionally substituted 5-10 membered heteroarylene group, or an optionally substituted alkylene group.

6. The transcription modulator molecule according to any one of claims 1 to 5, wherein the first terminus comprises at least three heteroaromatic carboxamide moieties containing at least one heteroatom selected from O, N, and S, and at least one aliphatic amino acid residue selected from the group consisting of glycine, β-alanine, γ-aminobutyric acid, 2,4-diaminobutyric acid, and 5-aminovaleric acid.

7. The transcription modulator molecule according to claim 6, wherein the heteroaromatic carboxamide moiety is a monocyclic or bicyclic moiety.

8. The transcription modulator molecule according to claim 6, wherein the first terminus comprises one or more carboxamide moieties selected from the group consisting of optionally substituted pyrrole carboxamide monomers, optionally substituted imidazole carboxamide monomers, and β-alanine monomers.

9. The first terminus comprises the structure of formula (A-1), or a pharmaceutically acceptable salt thereof: fi １ａ ______ ｐ  １ Formula (A-1) During the ceremony, Each of [A-M] appears p times, where p is an integer in the range of 1 to 10. L １ａ is a single bond, C １－６ alkylene, -NR ａ -C １－６ alkylene-C(O)-, -NR ａ C(O)-, -NR ａ -C １－６ alkylene, -O-, or -O-C １－６ alkylene, and A is a single bond, C １－１０ Alkylene group, optionally substituted C ６－１０ Arylene group, optionally substituted 4-10 membered heterocyclene group, optionally substituted 5-10 membered heteroarylene group, -C １－１０ Alkylene-C(O)-, -C １－１０ Alkylene-NR ａ -, -CO-, -NR ａ -, -CONR ａ -,-CONR ａ C １－４ Alkylene-,-NR ａ CO-C １－４ Alkylene-, -C(O)O-, -O-, -S-, -S(O)-, -S(O) ２ -, -C(=S)-NH-, -C(O)-NH-NH-, -C(O)-N=N-, -C(O)-CH=CH-, (CH ２ ) ０－４ -CH=CH-(CH ２ ) ０－４ , -N(CH ３ )-C １－６ Alkilen, 【Chemistry 1】 , -NH-C １－６ Alkylene-NH-,-O-C １－６ A is selected from the group consisting of alkylene-O-, -NH-N=N-, -NH-C(O)-NH-, and any combination thereof, where at least one A is -CONH-, Each M is replaced by a C of arbitrary choice. ６－１０ The group is an arylene group, an optionally substituted 4-10 membered heterocyclene group, an optionally substituted 5-10 membered heteroarylene group, or an optionally substituted alkylene. E １ is H or -A Ｅ -G, A Ｅ It does not exist, or it is NHKCO. G is replaced by H and C through arbitrary selection. ６－１０ Aryl, optionally substituted 4-10 member heterocyclyl, optionally substituted 5-10 member heteroaryl, optionally substituted C １－６ Alkyl, C ０－４ Alkylene-NHC (=NH)NH,-CN,-C ０－４ Alkylene-C (=NH) (NR) ａ R ｂ ), -C ０－４ Alkylene-C(=N) ＋ H ２ )-(NR ａ R ｂ ), -C １－５ Alkylene-NR ａ R ｂ , C ０－４ Alkylene-NHC (=NH)R ａ , and selected from the group consisting of optionally substituted amines, R ａ and R ｂ Each of these is independently replaced by H and C by any choice. １－６ Alkyl, optionally substituted C ３－１０ Cycloalkyl, optionally substituted C ６－１０ A transcription modulator molecule according to any one of claims 1 to 8, selected from the group consisting of aryls, optionally substituted 4-10 member heterocyclines, and optionally substituted 5-10 member heteroaryls.

10. The first terminus comprises the structure of formula (A-2), or a pharmaceutically acceptable salt thereof: 【Chemistry 2】 During the ceremony, Y １ , Y ２ , Y ３ , and Y ４ Each is independently CH or N, Z １ Z ２ Z ３ , and Z ４ These are each independent of O, S, or NR １Ｄ And, W １ C is a hydrogen atom, optionally substituted with C. １ -C ６ Alkyl, -C(O)-NR １Ｅ R １Ｆ , -NR １Ｅ -C(O)-NR １Ｅ R １Ｆ , or (AA) １－１０ And, W ２ C is a hydrogen atom, optionally substituted with C. １ -C ６ Alkyl, -C(O)-NR １Ｅ R １Ｆ , or (AA) １－１０ And, m1 is 1, 2, 3, or 4. n1 is 0, 1, or 2, and also, AA is an amino acid residue selected from β-alanine, lysine, and arginine. R １Ｄ and R １Ｅ Each of them independently represents hydrogen or C １ -C ６ It is alkyl, and also, R １Ｆ is hydrogen, optionally substituted C １ -C １０ -alkyl, C １ -C １０ -heteroalkyl, PEG １－２０ or one or more AAs, the transcription modulator molecule according to any one of claims 1-8.

11. The transcription modulator molecule according to claim 10, wherein the first terminus comprises the structure of formula (A-3) or a pharmaceutically acceptable salt thereof. 【Transformation 3】

12. Z １ 、Z ２ 、Z ３ 、and Z ４ are each independently NR １Ｄ where R １Ｄ is C １ -C ６ alkyl, the transcription modulator molecule according to claim 10 or 11.

13. Z １ Z ２ Z ３ , and Z ４ Each is independently NCH ３ The transcription modulator molecule according to claim 10 or 11.

14. Z １ and Z ３ Each of these is N, and also Z ２ and Z ４ A transcription modulator molecule according to any one of claims 10-13, wherein each is independently CH or N.

15. Z ２ and Z ４ The transcription modulator molecule according to claim 14, wherein each of them is CH.

16. The transcription modulator molecule according to any one of claims 10-15, wherein the first terminus comprises the structure of formula (A-4). 【Chemistry 4】

17. W １ C is replaced by an optional substitution. １ -C ６ Alkyl, or -C(O)-NR １Ｅ R １Ｆ A transcription modulator molecule according to any one of claims 10-16.

18. W １ Ha-C(O)-NR １Ｅ R １Ｆ And R １Ｅ is hydrogen, and R １Ｆ C is a hydrogen atom, optionally substituted. １ -C １０ Alkyl or PEG １－２０ The transcription modulator molecule according to claim 17.

19. W １ The transcription modulator molecule according to any one of claims 10-16, wherein is hydrogen.

20. A transcription modulator molecule according to any one of claims 10-19, wherein m1 is 2 or 3, and n1 is 0 or 1.

21. The transcription modulator molecule according to claim 20, wherein n1 is 0.

22. The transcription modulator molecule according to claim 20, wherein n1 is 1.

23. The transcription modulator molecule according to any one of claims 1 to 22, wherein the linker has a length of less than about 50 angstroms.

24. The linker has a length of about 15 to 40 angstroms, the transcription modulator molecule according to any one of claims 1 to 22.

25. The linker comprises 5 to 50 chain atoms, the transcription modulator molecule according to any one of claims 1 to 22.

26. The linker includes a multimer having 2 to 50 spacing portions, where the spacing portions are independently -((CR ３ａ R ３ｂ ) ｘ -O) ｙ -, -((CR ３ａ R ３ｂ ) ｘ -NR ４ａ ) ｙ -, -((CR ３ａ R ３ｂ ) ｘ -CH=CH-(CR ３ａ R ３ｂ ) ｘ -O) ｙ -, replaced by optional -C １－１２ Alkyl, optionally substituted C ２－１０ Alkenyl, C substituted by choice ２－１０ Alkinyl, optionally replaced with C ６－１０ Arrine, optionally replaced with C ３－７ Cycloalkylene, optionally substituted 5-10 membered heteroarylene, optionally substituted 4-10 membered heterocycloalkylene, amino acid residue, -O-, -C(O)NR ４ａ -, -NR ４ａ C(O)-, -C(O)-, -NR ４ａ -, -C(O)O-, -O-, -S-, -S(O)-, -SO ２ -, -SO ２ NR ４ａ -, -NR ４ａ SO ２ Selected from the group consisting of -, and -P(O)OH-, and any combination thereof, where, x is independently 2-4, y is independently 1-10, R ３ａ and R ３ｂ Each is independently selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted amino, carboxyl, carboxyl ester, acyl, acyloxy, acylamino, aminoacyl, optionally substituted alkylamide, sulfonyl, optionally substituted thioalkoxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, and optionally substituted heterocyclyl, and R ４ａ Each of these is independently a C that is substituted with hydrogen or optionally. １－６ A transcription modulator molecule according to any one of claims 1 to 22, wherein the molecule is alkyl.

27. The aforementioned oligomer skeleton is -(T １ -V １ ) ａ - (T ２ -V ２ ) ｂ - (T ３ -V ３ ) ｃ - (T ４ -V ４ ) ｄ - (T ５ -V ５ ) ｅ - including, where a, b, c, d, and e are each independently 0 or 1, and the sum of a, b, c, d, and e is between 1 and 5. T １ , T ２ , T ３ , T ４ , and T ５ Each of them was independently replaced by arbitrary choice (C １ -C １２ ) Alkilen, optionally substituted alkenylene, optionally substituted alkinylene, (EA) ｗ (EDA) ｍ (PEG) ｎ (Modified PEG) ｎ (AA) ｐ ,-(CR ２ａ OH) ｈ -, replaced by arbitrary selection (C ６ -C １０ ) Arrinen, optionally replaced with C ３－７ Selected from cycloalkylenes, optionally substituted 5-10 membered heteroarylenes, optionally substituted 4-10 membered heterocycloalkylenes, disulfides, hydrazines, carbohydrates, β-lactams, and esters, m, p, and w are each independent integers between 1 and 20. n is an integer between 1 and 30. h is an integer between 1 and 12. EA has the following structure: 【Transformation 5】 EDA has the following structure: 【Transformation 6】 In the formula, each q is an independent integer between 1 and 6. x are independent integers between 2 and 4. r is either 0 or 1 independently, (PEG) ｎ Ha- (CR ２ａ R ２ｂ -CR ２ａ R ２ｂ -O) ｎ -CR ２ａ R ２ｂ - Having a structure, - (Modified PEG) ｎ (PEG) ｎ at least one of the (CR ２ａ R ２ｂ -CR ２ａ R ２ｂ -O)- to, -(CH ２ -CR ２ａ =CR ２ａ -CH ２ -O)- or -(CR ２ａ R ２ｂ -CR ２ａ R ２ｂ It has a structure that replaces -S)- AA is an amino acid residue, V １ , V ２ , V ３ , V ４ , and V ５ These are independently single bonds, -CO-, and -NR １ａ -, -CONR １ａ -, -NR １ａ CO-, -CONR １ａ C １－４ Alkyl-, -NR １ａ CO-C １－４ Alkyl-, -C(O)O-, -OC(O)-, -O-, -S-, -S(O)-, -SO ２ -, -SO ２ NR １ａ -, -NR １ａ SO ２ Selected from the group consisting of - and -P(O)OH-, R １ａ Each is independently of C, which is substituted with hydrogen or optionally. １－６ It is alkyl, R ２ａ and R ２ｂ A transcription modulator molecule according to any one of claims 1 to 26, wherein each is independently selected from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, halogen, alkoxy, substituted alkoxy, amino, substituted amino, carboxyl, carboxyl ester, acyl, acyloxy, acylamino, aminoacyl, alkylamide, substituted alkylamide, sulfonyl, thioalkoxy, substituted thioalkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, and substituted heterocyclyl.

28. T １ , T ２ , T ３ , T ４ , and T ５ Each is independent of the others, (C １ -C １２ ) alkyl, substituted (C １ -C １２ ) alkyl, (EA) ｗ (EDA) ｍ (PEG) ｎ (Modified PEG) ｎ (AA) ｐ ,-(CR ２ａ OH) ｈ - Optionally substituted phenyl, piperidine-4-amino (P4A), piperidine-3-amino, piperazine, pyrrolidine-3-amino, azetidine-3-amino, para-amino-benzyloxycarbonyl (PAABC), meta-amino-benzyloxycarbonyl (MAABC), para-amino-benzyloxy (PABO), meta-amino-benzyloxy (MABO), para-aminobenzyl, acetal group, disulfide, hydrazine, carbohydrate, β-lactam, ester, (AA) ｐ -MABC- (AA) ｐ (AA) ｐ -MABO- (AA) ｐ (AA) ｐ -PABO-(AA) ｐ , and (AA) ｐ -PABC-(AA) ｐ A transcription modulator molecule according to claim 27, selected from the above.

29. T １ , T ２ , T ３ , T ４ , and T ５ Each is independent of the others, (C １ -C １２ ) alkyl, substituted (C １ -C １２ ) alkyl, (EA) ｗ (EDA) ｍ (PEG) ｎ (Modified PEG) ｎ (AA) ｐ ,-(CR ２ａ OH) ｈ -, replaced by arbitrary selection (C ６ -C １０ A transcription modulator molecule according to claim 27, selected from arylene, a 4-10 member heterocycloalkene, and optionally substituted 5-10 member heteroarylene.

30. T ４ or T ５ (C) was replaced by choice. ６ -C １０ The transcription modulator molecule according to claim 27, wherein it is an arylene.

31. T ４ or T ５ The transcription modulator molecule according to claim 27, wherein is optionally substituted phenylene.

32. The linker is -N(R １ａ ) (CH ２ ) ｘ N(R) １ｂ ) (CH ２ ) ｘ N- is included, where R １ａ and R １ｂ Each of these is independently a C that is substituted with hydrogen or optionally. １ -C ６ A transcription modulator molecule according to any one of claims 1 to 28, wherein x is selected from alkyl groups, and x is independently an integer in the range of 1 to 6.

33. The linker is -(CH ２ -C(O)N(R'')-(CH ２ ) ｑ -N(R')-(CH ２ ) ｑ -N(R'')C(O)-(CH ２ ) ｘ -C(O)N(R'')-A-, -(CH ２ ) ｘ -C(O)N(R'')-(CH ２ CH ２ O) ｙ (CH ２ ) ｘ -C(O)N(R'')-A-, -C(O)N(R'')-(CH ２ ) ｑ -N(R')-(CH ２ ) ｑ -N(R'')C(O)-(CH ２ ) ｘ -A-, -(CH ２ ) ｘ -O-(CH ２ CH ２ O) ｙ - (CH ２ ) ｘ -N(R'')C(O)-(CH ２ ) ｘ -A-, or -N(R'')C(O)-(CH ２ )-C(O)N(R'')-(CH ２ ) ｘ -O(CH ２ CH ２ O) ｙ (CH ２ ) ｘ It contains -A-, where R' is methyl, R'' is hydrogen, x and y are each independently integers from 1 to 10, q is each independently integers from 2 to 10, and A is each independently a single bond, optionally substituted with C １－１２ Alkyl, optionally substituted C ６－１０ Arrine, optionally replaced with C ３－７ A transcription modulator molecule according to any one of claims 1 to 32, selected from a cycloalkylene, an optionally substituted 5-10 member heteroarylene, and an optionally substituted 4-10 member heterocycloalkylene.

34. The transfer modulator molecule according to any one of claims 1 to 33, wherein the linker contains PEG (polyethylene glycol).

35. The transcription modulator molecule according to claim 34, wherein the linker contains 2-20 PEG units.

36. The transcription modulator molecule according to claim 34, wherein the linker comprises 6, 8, 10, or 15 PEG units.

37. The linker is -CO-, -NR １ａ -, -CONR １ａ -, -NR １ａ CO-, -CONR １ａ C １－４ Alkyl-, -NR １ａ CO-C １－４ Alkyl-, -C(O)O-, -OC(O)-, -O-, -S-, -S(O)-, -SO ２ -, -SO ２ NR １ａ -, -NR １ａ SO ２ -, -P(O)OH-, -((CH ２ ) ｘ -O)-,-((CH ２ ) ｙ -NR １ａ ) - Replaced by arbitrary selection - C １－１２ Alkylene, optionally replaced with C ２－１０ Alkenylene, optionally substituted with C ２－１０ Alkynylene, optionally substituted with C ６－１０ Arrine, optionally replaced with C ３－７ The first terminus is linked to a group selected from cycloalkylenes, optionally substituted 5-10 membered heteroarylenes, and optionally substituted 4-10 membered heterocycloalkylenes, where x and y are independently 1-4, and R １ａ Each of these is independently a C that is substituted with hydrogen or optionally. １－６ A transcription modulator molecule according to any one of claims 1 to 36, wherein the molecule is alkyl.

38. The linker is -CO-, -NR １ａ -, C １－１２ Alkyl, -CONR １ａ -, and -NR １ａ The first terminal is connected to a group selected from CO-, where R １ａ Each of these is independently a C that is substituted with hydrogen or optionally. １－６ A transcription modulator molecule according to any one of claims 1 to 36, wherein the molecule is alkyl.

39. The second terminus is replaced by one or more optional C values. ６－１０ Aaryl, replaced by C of any choice ４－１０ A transcription modulator molecule according to any one of claims 1 to 35, comprising a carbon ring, an optionally substituted 4-10 membered heterocycle, or an optionally substituted 5-10 membered heteroaryl.

40. The transcription modulator molecule according to any one of claims 1 to 39, wherein the second terminus comprises at least one 5-10 membered heteroaryl group having at least two nitrogen atoms.

41. The transcription modulator molecule according to any one of claims 1 to 40, wherein the second terminus includes a portion capable of binding to a regulatory protein, and the portion is derived from a compound capable of binding to a regulatory protein.

42. The transcription modulator molecule according to any one of claims 1 to 40, wherein the second terminus comprises at least one group selected from optionally substituted diazine, optionally substituted diazepine, and optionally substituted phenyl.

43. The transcription modulator molecule according to any one of claims 1 to 40, wherein the second terminus includes a portion that binds to a bromodomain protein.

44. The second end comprises a diazine ring or a diazepine ring, and the diazine ring or diazepine ring comprises one or more heteroatoms selected from S, N, and O. ６－１０ A transcription modulator molecule according to any one of claims 1 to 43, wherein it is condensed with an aryl or a 5-10 membered heteroaryl ring.

45. The transcription modulator molecule according to any one of claims 1 to 43, wherein the second terminus comprises a bicyclic or tricyclic structure which is optionally substituted.

46. The transcription modulator molecule according to claim 45, wherein the optionally substituted bicyclic or tricyclic structure comprises a diazepine ring fused with a thiophene ring.

47. The transcription modulator molecule according to claim 46, wherein the second terminus comprises an optionally substituted bicyclic structure, the bicyclic structure comprising a diazepine ring fused with a thiophene ring.

48. The transcription modulator molecule according to claim 45, wherein the second terminus comprises an optionally substituted tricyclic structure, the tricyclic structure being a diazepine ring condensed with thiophene and triazole.

49. The second terminus contains a compound having the structure of formula 7, 【Transformation 7】 During the ceremony, R １ and R ３ Each of these is independently selected from alkoxy, alkyl, amino, halogen, and hydrogen. R ２ These are selected from alkoxy, alkyl, alkenyl, alkynyl, amide, amino, halogen, and hydrogen. R ６ and R ７ Each of these is independently selected from alkyl, alkoxy, amino, halogen, and hydrogen. R ５ It is hydrogen, W is independently selected from C and N, where if W is N, p is 0 or 1, and if W is C, p is 1, and W - (R ４ ) ｐ Regarding this, if W is C, then p is 1, and R ４ If is H, or if W is N, then p is 0, R １ If R is hydrogen, ３ is an alkoxy, and R ３ If R is hydrogen, １ R is selected from amino and alkoxy, ６ and R ７ A transcription modulator molecule according to any one of claims 1-43, wherein at least one of is independently selected from alkyl, alkoxy, amino, and halogen.

50. The transcription modulator molecule according to any one of claims 1 to 43, wherein the second terminus comprises the compound of formula 8. 【Transformation 8】

51. The second terminus comprises a compound having the structure of formula (9-A), or a pharmaceutically acceptable salt thereof. 【Chemistry 9】 During the ceremony, Ring A is either absent or a six-membered monocyclic aryl or heteroaryl. Y is -NH- or -O-, R ９ , R １０ , and R １１ Each of these is independently of hydrogen and optionally substituted C. １－６ Alkyl, C １－６ Haloalkyl, or C １－６ Selected from hydroxyalkyl groups, R １２ It is hydrogen, halogen, -NO ２ , -CN, optionally replaced aryl, optionally replaced C １－６ Alkyl, C １－６ Haloalkyl, or C １－６ Selected from hydroxyalkyl groups, Alternatively, R １２ Ha-NR Ａ R Ｂ And here, R Ａ and R Ｂ Each of these is independently of hydrogen and optionally substituted C. １－６ Alkyl, or C １－６ It is heteroalkyl, A transcription modulator molecule according to any one of claims 1 to 40, wherein x1 is an integer from 1 to 6.

52. The transcription modulator molecule according to claim 51, wherein the second terminus comprises a compound having the structure of formula (9-C) or a pharmaceutically acceptable salt thereof. 【Chemistry 10】

53. The second terminus comprises a compound having the structure of formula (10-A), or a pharmaceutically acceptable salt thereof. 【Chemistry 11】 During the ceremony, Ring B either does not exist, or it is a 5-6 member monocyclic aryl or heteroaryl ring, or a 4-8 member heterocyclic ring. Y is -NH- or -O-, R １３ C is substituted with hydrogen or optionally. １ -C ６ Selected from alkyl groups, R １４ and R １５ Each of these is independently of hydrogen and optionally substituted C. １－６ Alkyl, C １－６ Haloalkyl, or C １－６ Selected from hydroxyalkyl groups, R １６ It is hydrogen, halogen, -NO ２ , -CN, optionally replaced aryl, optionally replaced C １－６ Alkyl, C １－６ Haloalkyl, or C １－６ Selected from hydroxyalkyl groups, Alternatively, R １６ Ha-NR Ａ R Ｂ And here, R Ａ and R Ｂ Each of these is independently of hydrogen and optionally substituted C. １－６ Alkyl, or C １－６ It is heteroalkyl, The transcription modulator molecule according to any one of claims 1 to 43, wherein x² is an integer from 1 to 6.

54. The transcription modulator molecule according to claim 53, wherein the second terminus comprises a compound having the structure of formula (10-B) or a pharmaceutically acceptable salt thereof. 【Chemistry 12】

55. The second terminus contains a compound having the structure of formula (12-A), 【Chemistry 13】 During the ceremony, Ring C is either absent or a monocyclic six-membered aryl or heteroaryl. X １ is CH or N, L ２ is -NRD- or -CRDH-, R ２３ is C １ -C ６ Alkyl or C ３ -C ６ It is a cycloalkyl, and, R ２４ C is a halogen, alkyl, hydroxyalkyl, haloalkyl; optionally substituted. １ -C ６ Alkyl, C １ -C ６ Haloalkyl, or C １ -C ６ It is a hydroxyalkyl, and, R Ｄ is hydrogen or C １－３ A transcription modulator molecule according to any one of claims 1 to 43, wherein the molecule is alkyl.

56. Ring C is 【Chemistry 14】 The transcription modulator molecule according to claim 55.

57. The transcription modulator molecule according to claim 55, wherein ring C is phenyl.

58. The transcription modulator molecule according to claim 55 or 57, wherein the second terminus comprises a compound having the structure of formula (12-B) or a pharmaceutically acceptable salt thereof. 【Chemistry 15】

59. The transcription modulator molecule according to claim 52 or 54, wherein the second terminus comprises a compound having the structure of formula (12-C) or a pharmaceutically acceptable salt thereof. 【Chemistry 16】

60. The second end of the above is 【Chemistry 17】 A transcription modulator molecule according to any one of claims 1 to 43, selected from a pharmaceutically acceptable salt thereof.

61. The aforementioned protein binding portion is [Chemistry 18] A transcription modulator molecule according to any one of claims 1 to 43, or a pharmaceutically acceptable salt thereof.

62. A transcription modulator molecule according to any one of claims 1-61 for use as a pharmaceutical agent.

63. A transcription modulator molecule according to any one of claims 1-62, used in the manufacture of a drug for the prevention or treatment of a disease or illness improved by overexpression of fxn.

64. A transcription modulator molecule according to any one of claims 1 to 63 for use in the treatment of Friedreich's ataxia (FA).

65. A pharmaceutical composition comprising a transcription modulator molecule as described in any one of claims 1 to 64 and a pharmaceutically acceptable carrier.

66. A method for regulating the expression of fxn, comprising the step of contacting fxn with a transcription modulator molecule described in any one of claims 1 to 61.

67. A method for treating a disease caused by the expression of a deficiency fxn, comprising the step of administering a therapeutically effective amount of a transcription modulator molecule according to any one of claims 1-61 to a patient in need.

68. The method according to claim 67, wherein the disease is Friedreich's ataxia.

69. A method for treating a disease caused by the expression of a deficiency fxn, comprising the steps of administering a therapeutically effective amount of a transcription modulator molecule according to any one of claims 1-61 and another therapeutic agent.

70. A method for achieving an effect in a patient, comprising the step of administering to the patient a therapeutically effective amount of a transcription modulator molecule or a salt thereof disclosed herein, wherein the effect is selected from muscle atrophy, ataxia, fasciculations, and dementia.

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