JPWO2019165229A5 - - Google Patents

Description

の化合物、またはその薬学的に許容される塩、溶媒和物、水和物、互変異性体、もしくは立体異性体を開示し、
式中、
Aの各対において、一方のAは水素であり、かつ他方のAは、
（i）R¹、OR¹、NR¹R²、S(O)_qR¹、SO₂R¹R²、NR¹SO₂R²、C(O)R¹、C(O)OR¹、C(O)NR¹R²、NR¹C(O)R²、NR¹C(O)OR²、CF₃、およびOCF₃からなる群より選択される1～5つの置換基で置換されていてもよい、フェニル；
（ii）R¹、OR¹、NR¹R²、S(O)_qR¹、SO₂R¹R²、NR¹SO₂R²、C(O)R¹、C(O)OR¹、C(O)NR¹R²、NR¹C(O)R²、NR¹C(O)OR²、CF₃、およびOCF₃からなる群より選択される1～5つの置換基で置換されていてもよい、ナフチル；
（iii）O、N、およびSからなる群より選択される1～3つのヘテロ原子を有し、R¹、OR¹、NR¹R²、S(O)_qR¹、SO₂R¹R²、NR¹SO₂R²、C(O)R¹、C(O)OR¹、C(O)NR¹R²、NR¹C(O)R²、NR¹C(O)OR²、CF₃、およびOCF₃からなる群より選択される1～3つの置換基で置換されていてもよい、5または6員単環式ヘテロアリール基；ならびに
（iv）O、N、およびSからなる群より選択される1～3つのヘテロ原子を含み；かつ第2の環が第1の環に3～4つの炭素原子を用いて縮合され、かつ二環式ヘテロアリール基が、R¹、OR¹、NR¹R²、S(O)_qR¹、SO₂R¹R²、NR¹SO₂R²、C(O)R¹、C(O)OR¹、C(O)NR¹R²、NR¹C(O)R²、NR¹C(O)OR²、CF₃、およびOCF₃からなる群より選択される1～3つの置換基で置換されていてもよい、8～10員二環式ヘテロアリル基
のうちの1つであり；
ここでYはO、S、NR¹、およびCR¹R²からなる群より選択され、かつここでR¹およびR²は、水素、ニトロ、ヒドロキシル、カルボキシ、アミノ、ハロゲン、シアノ、およびC₁～C₁₄直鎖または分岐アルキル基からなる群より選択され、C₁～C₁₄直鎖または分岐アルキル、ペルハロまでの置換C₁～C₁₄直鎖または分岐アルキル、C₁～C₁₄アルコキシ、水素、ニトロ、ヒドロキシル、カルボキシ、アミノ、C₁～C₁₄アルキルアミノ、C₁～C₁₄ジアルキルアミノ、ハロゲン、およびシアノからなる群より選択される1～3つの置換基で置換されていてもよく；かつ
ここでZは、水素；C₁～C₁₄直鎖、分岐、または環式アルキル；フェニル；アルキル部分がペルハロまでのハロゲンで置換されていてもよい、ベンジル、1～5置換ベンジル、C₁～C₃アルキル-フェニル；ペルハロまでの置換C₁～C₁₄直鎖または分岐アルキル；-(CH₂)_q-Kからなる群より選択され、ここでKは、酸素、窒素、および硫黄より選択される1～4つの原子を含み飽和、部分飽和、もしくは芳香族である5もしくは6員単環式複素環式環、または、O、N、およびSからなる群より選択される1～4つのヘテロ原子を有する8～10員二環式ヘテロアリールであり、ここで該アルキル部分はペルハロまでのハロゲンで置換されていてもよく、かつここで変数qは0～4の範囲の整数であり；
Lはリンカーであり；かつ
Jはブロモドメイン、ブロモドメイン含有タンパク質、およびFKBP12からなる群より選択される標的の結合物質である。
In one aspect, Formulas (I), (IA), and (IB):

or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof,
During the ceremony,
In each pair of A, one A is hydrogen and the other A is
(i) selected from the group consisting ^{of R1} , ^OR1 , ^NR1R2 , S( ^O _{) qR1} , ^SO2R1R2 , ^NR1SO2R2 , ^C ( ^O ) ^R1 , C(O) _OR1 , C(O) ^NR1R2 , ^NR1C (O) ^{R2 , NR1C} ( ^O ) ^OR2 , _CF3 , and _OCF3 ; phenyl, optionally substituted with 1 to 5 substituents;
(ii) selected from the group consisting ^{of R1 , OR1} , ^NR1R2 , S( ^O ) ^qR1 , _{SO2R1R2 ,} ^NR1SO2R2 , C( ^O ) ^R1 , C(O) ^OR1 , C(O) ^{NR1R2 ,} _NR1C (O) ^R2 , ^NR1C ( ^O ) ^OR2 , _CF3 , and _OCF3 ; naphthyl, optionally substituted with 1 to 5 substituents;
（iii）O、N、およびSからなる群より選択される1～3つのヘテロ原子を有し、R ¹ 、OR ¹ 、NR ¹ R ² 、S(O) _q R ¹ 、SO ₂ R ¹ R ² 、NR ¹ SO ₂ R ² 、C(O)R ¹ 、C(O)OR ¹ 、C(O)NR ¹ R ² 、NR ¹ C(O)R ² 、NR ¹ C(O)OR ² 、CF ₃ 、およびOCF ₃からなる群より選択される1～3つの置換基で置換されていてもよい、5または6員単環式ヘテロアリール基；ならびに （iv）O、N、およびSからなる群より選択される1～3つのヘテロ原子を含み；かつ第2の環が第1の環に3～4つの炭素原子を用いて縮合され、かつ二環式ヘテロアリール基が、R ¹ 、OR ¹ 、NR ¹ R ² 、S(O) _q R ¹ 、SO ₂ R ¹ R ² 、NR ¹ SO ₂ R ² 、C(O)R ¹ 、C(O)OR ¹ 、C(O)NR ¹ R ² 、NR ¹ C(O)R ² 、NR ¹ C(O)OR ² 、CF ₃ 、およびOCF ₃からなる群より選択される1～3つの置換基で置換されていてもよい、8～10員二環式ヘテロアリル基のうちの1つであり；
ここでYはO、S、NR ¹ 、およびCR ¹ R ²からなる群より選択され、かつここでR ¹およびR ²は、水素、ニトロ、ヒドロキシル、カルボキシ、アミノ、ハロゲン、シアノ、およびC ₁ ～C ₁₄直鎖または分岐アルキル基からなる群より選択され、C ₁ ～C ₁₄直鎖または分岐アルキル、ペルハロまでの置換C ₁ ～C ₁₄直鎖または分岐アルキル、C ₁ ～C ₁₄アルコキシ、水素、ニトロ、ヒドロキシル、カルボキシ、アミノ、C ₁ ～C ₁₄アルキルアミノ、C ₁ ～C ₁₄ジアルキルアミノ、ハロゲン、およびシアノからなる群より選択される1～3つの置換基で置換されていてもよく；かつここでZは、水素；C ₁ ～C ₁₄直鎖、分岐、または環式アルキル；フェニル；アルキル部分がペルハロまでのハロゲンで置換されていてもよい、ベンジル、1～5置換ベンジル、C ₁ ～C ₃アルキル-フェニル；ペルハロまでの置換C ₁ ～C ₁₄直鎖または分岐アルキル；-(CH ₂ ) _q -Kからなる群より選択され、ここでKは、酸素、窒素、および硫黄より選択される1～4つの原子を含み飽和、部分飽和、もしくは芳香族である5もしくは6員単環式複素環式環、または、O、N、およびSからなる群より選択される1～4つのヘテロ原子を有する8～10員二環式ヘテロアリールであり、ここで該アルキル部分はペルハロまでのハロゲンで置換されていてもよく、かつここで変数qは0～4の範囲の整数であり；
L is a linker; and
J is a target binder selected from the group consisting of bromodomains, bromodomain-containing proteins, and FKBP12.

の化合物、またはその薬学的に許容される塩、溶媒和物、水和物、互変異性体、もしくは立体異性体を開示し、
式中、
Aの各対において、一方のAは水素であり、かつ他方のAは、
（i）R¹、OR¹、NR¹R²、S(O)_qR¹、SO₂R¹R²、NR¹SO₂R²、C(O)R¹、C(O)OR¹、C(O)NR¹R²、NR¹C(O)R²、NR¹C(O)OR²、CF₃、およびOCF₃からなる群より選択される1～5つの置換基で置換されていてもよい、フェニル；
（ii）R¹、OR¹、NR¹R²、S(O)_qR¹、SO₂R¹R²、NR¹SO₂R²、C(O)R¹、C(O)OR¹、C(O)NR¹R²、NR¹C(O)R²、NR¹C(O)OR²、CF₃、およびOCF₃からなる群より選択される1～5つの置換基で置換されていてもよい、ナフチル；
（iii）O、N、およびSからなる群より選択される1～3つのヘテロ原子を有し、R¹、OR¹、NR¹R²、S(O)_qR¹、SO₂R¹R²、NR¹SO₂R²、C(O)R¹、C(O)OR¹、C(O)NR¹R²、NR¹C(O)R²、NR¹C(O)OR²、CF₃、およびOCF₃からなる群より選択される1～3つの置換基で置換されていてもよい、5または6員単環式ヘテロアリール基；ならびに
（iv）O、N、およびSからなる群より選択される1～3つのヘテロ原子を含み；かつ第2の環が第1の環に3～4つの炭素原子を用いて縮合され、かつ二環式ヘテロアリール基が、R¹、OR¹、NR¹R²、S(O)_qR¹、SO₂R¹R²、NR¹SO₂R²、C(O)R¹、C(O)OR¹、C(O)NR¹R²、NR¹C(O)R²、NR¹C(O)OR²、CF₃、およびOCF₃からなる群より選択される1～3つの置換基で置換されていてもよい、8～10員二環式ヘテロアリル基
のうちの1つであり；
ここでYはO、S、NR¹およびCR¹R²からなる群より選択され、かつここでR¹およびR²は、水素、ニトロ、ヒドロキシル、カルボキシ、アミノ、ハロゲン、シアノ、およびC₁～C₁₄直鎖または分岐アルキル基からなる群より選択され、C₁～C₁₄直鎖または分岐アルキル、ペルハロまでの置換C₁～C₁₄直鎖または分岐アルキル、C₁～C₁₄アルコキシ、水素、ニトロ、ヒドロキシル、カルボキシ、アミノ、C₁～C₁₄アルキルアミノ、C₁～C₁₄ジアルキルアミノ、ハロゲン、およびシアノからなる群より選択される1～3つの置換基で置換されていてもよく；かつ
ここでZは、水素；C₁～C₁₄直鎖、分岐、または環式アルキル；フェニル；アルキル部分がペルハロまでのハロゲンで置換されていてもよい、ベンジル、1～5置換ベンジル、C₁～C₃アルキル-フェニル；ペルハロまでの置換C₁～C₁₄直鎖または分岐アルキル；-(CH₂)_q-Kからなる群より選択され、ここでKは、酸素、窒素、および硫黄より選択される1～4つの原子を含み飽和、部分飽和、もしくは芳香族である5もしくは6員単環式複素環式環、または、O、N、およびSからなる群より選択される1～4つのヘテロ原子を有する8～10員二環式ヘテロアリールであり、ここで該アルキル部分はペルハロまでのハロゲンで置換されていてもよく、かつここで変数qは0～4の範囲の整数であり；
Lはリンカーであり；かつ
Jはブロモドメイン、ブロモドメイン含有タンパク質、およびFKBP12からなる群より選択される標的の結合物質である。
In one aspect, formulas (I) and (IA):

or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof,
During the ceremony,
In each pair of A, one A is hydrogen and the other A is
(i) selected from the group consisting ^{of R1} , ^OR1 , ^NR1R2 , S( ^O _{) qR1} , ^SO2R1R2 , ^NR1SO2R2 , ^C ( ^O ) ^R1 , C(O) _OR1 , C(O) ^NR1R2 , ^NR1C (O) ^{R2 , NR1C} ( ^O ) ^OR2 , _CF3 , and _OCF3 ; phenyl, optionally substituted with 1 to 5 substituents;
(ii) selected from the group consisting ^{of R1 , OR1} , ^NR1R2 , S( ^O ) ^qR1 , _{SO2R1R2 ,} ^NR1SO2R2 , C( ^O ) ^R1 , C(O) ^OR1 , C(O) ^{NR1R2 ,} _NR1C (O) ^R2 , ^NR1C ( ^O ) ^OR2 , _CF3 , and _OCF3 ; naphthyl, optionally substituted with 1 to 5 substituents;
（iii）O、N、およびSからなる群より選択される1～3つのヘテロ原子を有し、R ¹ 、OR ¹ 、NR ¹ R ² 、S(O) _q R ¹ 、SO ₂ R ¹ R ² 、NR ¹ SO ₂ R ² 、C(O)R ¹ 、C(O)OR ¹ 、C(O)NR ¹ R ² 、NR ¹ C(O)R ² 、NR ¹ C(O)OR ² 、CF ₃ 、およびOCF ₃からなる群より選択される1～3つの置換基で置換されていてもよい、5または6員単環式ヘテロアリール基；ならびに （iv）O、N、およびSからなる群より選択される1～3つのヘテロ原子を含み；かつ第2の環が第1の環に3～4つの炭素原子を用いて縮合され、かつ二環式ヘテロアリール基が、R ¹ 、OR ¹ 、NR ¹ R ² 、S(O) _q R ¹ 、SO ₂ R ¹ R ² 、NR ¹ SO ₂ R ² 、C(O)R ¹ 、C(O)OR ¹ 、C(O)NR ¹ R ² 、NR ¹ C(O)R ² 、NR ¹ C(O)OR ² 、CF ₃ 、およびOCF ₃からなる群より選択される1～3つの置換基で置換されていてもよい、8～10員二環式ヘテロアリル基のうちの1つであり；
ここでYはO、S、NR ¹およびCR ¹ R ²からなる群より選択され、かつここでR ¹およびR ²は、水素、ニトロ、ヒドロキシル、カルボキシ、アミノ、ハロゲン、シアノ、およびC ₁ ～C ₁₄直鎖または分岐アルキル基からなる群より選択され、C ₁ ～C ₁₄直鎖または分岐アルキル、ペルハロまでの置換C ₁ ～C ₁₄直鎖または分岐アルキル、C ₁ ～C ₁₄アルコキシ、水素、ニトロ、ヒドロキシル、カルボキシ、アミノ、C ₁ ～C ₁₄アルキルアミノ、C ₁ ～C ₁₄ジアルキルアミノ、ハロゲン、およびシアノからなる群より選択される1～3つの置換基で置換されていてもよく；かつここでZは、水素；C ₁ ～C ₁₄直鎖、分岐、または環式アルキル；フェニル；アルキル部分がペルハロまでのハロゲンで置換されていてもよい、ベンジル、1～5置換ベンジル、C ₁ ～C ₃アルキル-フェニル；ペルハロまでの置換C ₁ ～C ₁₄直鎖または分岐アルキル；-(CH ₂ ) _q -Kからなる群より選択され、ここでKは、酸素、窒素、および硫黄より選択される1～4つの原子を含み飽和、部分飽和、もしくは芳香族である5もしくは6員単環式複素環式環、または、O、N、およびSからなる群より選択される1～4つのヘテロ原子を有する8～10員二環式ヘテロアリールであり、ここで該アルキル部分はペルハロまでのハロゲンで置換されていてもよく、かつここで変数qは0～4の範囲の整数であり；
L is a linker; and
J is a target binder selected from the group consisting of bromodomains, bromodomain-containing proteins, and FKBP12.

In some embodiments, Z is selected from the group consisting of : hydrogen; _C1 - _C14 straight chain, branched, or _cyclic alkyl; phenyl; alkyl moiety optionally substituted with halogen up to perhalo, benzyl, 1-5 substituted benzyl, _C1 - _C3 alkyl-phenyl ; substituted _C1 - _C14 straight chain or branched alkyl up to _perhalo ; In some embodiments, K is a 5- or 6-membered monocyclic heterocyclic ring that is saturated, partially saturated, or aromatic containing 1-4 atoms selected from oxygen, nitrogen, and sulfur, or an 8-10 membered bicyclic heteroaryl having 1-4 heteroatoms selected from the group consisting of O, N, and S, wherein the alkyl moiety is optionally substituted with halogen up to perhalo, and where the variable q is an integer ranging from 0-4. In certain embodiments, q is 0. In certain embodiments, q is 1. In certain embodiments, q is two. In one particular embodiment q is three. In one particular embodiment q is four.

Claims (20)

Equation (I), Equation (IA) , or Equation (IB) :

Compounds, or pharmaceutically acceptable salts thereof, solvates, hydrates, tautomers, or stereoisomers thereof:
During the ceremony
In each pair of A, one A is hydrogen and the other A is
(I) R ¹ , OR ¹ , NR ¹ R ² , S (O) _q R ¹ , SO ₂ R ¹ R ² , NR ¹ SO ₂ R ² , C (O) R ¹ , C (O) OR ¹ , Substituted with 1-5 substituents selected from the group consisting of C (O) NR ¹ R ² , NR ¹ C (O) R ² , NR ¹ C (O) OR ² , CF ₃ and OCF ₃ May be phenyl;
(Ii) R ¹ , OR ¹ , NR ¹ R ² , S (O) _q R ¹ , SO ₂ R ¹ R ² , NR ¹ SO ₂ R ² , C (O) R ¹ , C (O) OR ¹ , Substituted with 1-5 substituents selected from the group consisting of C (O) NR ¹ R ² , NR ¹ C (O) R ² , NR ¹ C (O) OR ² , CF ₃ and OCF ₃ May, Naftil;
(Iii) It has 1 to 3 heteroatoms selected from the group consisting of O, N, and S, and has R ¹ , OR ¹ , NR ¹ R ² , S (O) _q R ¹ , SO ₂ R ¹ R. ² , NR ¹ SO ₂ R ² , C (O) R ¹ , C (O) OR ¹ , C (O) NR ¹ R ² , NR ¹ C (O) R ² , NR ¹ C (O) OR ² , A 5- or 6-membered monocyclic heteroaryl group optionally substituted with 1 to 3 substituents selected from the group consisting of CF ₃ and OCF ₃ ; and (iv) consisting of O, N, and S. Contains 1 to 3 heteroatoms selected from the group; and the second ring is fused to the first ring with 3 to 4 carbon atoms, and the bicyclic heteroaryl group is R ¹ , OR. ¹ , NR ¹ R ² , S (O) _q R ¹ , SO ₂ R ¹ R ² , NR ¹ SO ₂ R ² , C (O) R ¹ , C (O) OR ¹ , C (O) NR ¹ R May be substituted with 1-3 substituents selected from the group consisting of ² , NR ¹ C (O) R ² , NR ¹ C (O) OR ² , CF ₃ , and OCF ₃ , 8-10. It is one of the member bicyclic heteroallyl groups;
Where Y is selected from the group consisting of O, S, NR ¹ and CR ¹ R ² , where R ¹ and R ² are hydrogen, nitro, hydroxyl, carboxy, amino, halogen, cyano, and C ₁ Selected from the group consisting of ~ C ₁₄ linear or branched alkyl groups, C ₁ to C ₁₄ linear or branched alkyl, substitutions up to perhalo C ₁ to C ₁₄ linear or branched alkyl, C ₁ to C ₁₄ alkoxy, hydrogen , Nitro, hydroxyl, carboxy, amino, C ₁ to C ₁₄ alkylamino, C ₁ to C ₁₄ dialkylamino, halogen, and may be substituted with 1 to 3 substituents selected from the group consisting of cyano; And here Z is selected from the group consisting of hydrogen; C ₁ to C ₁₄ linear, branched or cyclic alkyl; phenyl; benzyl, 1 to 5 substituted benzyl, C ₁ to C ₃ alkyl-phenyl. Alkyl moieties may be substituted with halogens up to perhalo; substituted C ₁ to C ₁₄ linear or branched alkyl to perhalo; where-(CH ₂ ) _q -K, where K is oxygen, nitrogen, and A 5- or 6-membered monocyclic heterocyclic ring containing 1 to 4 atoms selected from sulfur and being saturated, partially saturated, or aromatic, or selected from the group consisting of O, N, and S 1 It is an 8- to 10-membered bicyclic heteroaryl with up to 4 heteroatoms, where the alkyl moiety may be substituted with halogens up to perhalo, where the variable q is an integer in the range 0-4. And;
L is a linker; and
J is a target binding agent selected from the group consisting of bromodomain, bromodomain-containing protein, and FKBP12. The compound according to claim 1 , wherein J is a bromodomain and / or a binding substance of a bromodomain-containing protein, or a pharmaceutically acceptable salt, solvate, hydrate, homovariant, or steric thereof. The isomer. J is equation (II):

And
During the ceremony
Y1 is the formula:

And
here,
R ⁴ is a hydrogen, optionally substituted alkyl, optionally substituted acyl, or nitrogen protecting group;
L ^1a is an optionally substituted alkylene;
L ⁴¹ is an unsubstituted branched alkylene or a substituted alkylene;
X ⁴ is a halogen, -OR ^f , -SR ^f , or -N (R ^f ) ₂ ;
Ring D is a carbocyclic ring or a heterocyclic ring, wherein the heterocyclic ring contains one heteroatom and the heteroatom is N;
Ring G is a bicyclic heterocyclic ring or a bicyclic heteroaryl ring, where these rings share exactly two atoms;
E is O, S, NR ^E11 , or CHR ^E11 , where R ^E11 is substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or substituted. Is also a good heteroaryl;
Each appearance of R ^D3 is independently hydrogen, halogen, alkyl optionally substituted, heteroalkyl optionally substituted, alkenyl optionally substituted, alkynyl optionally substituted, substituted. Carbocyclyl may be substituted, heterocyclyl which may be substituted, aryl which may be substituted, heteroaryl which may be substituted, acyl which may be substituted, -OR ^f , -SR ^f , -N (R). ^f ) _{Two R D3s that are 2} ^, -NO ₂ , or -CN, or are linked to adjacent atoms together, may be substituted carbocyclyl, optionally substituted heterocyclyl, substituted. Form an aryl, which may be present, or a heteroaryl ring, which may be substituted;
z is 0, 1, or 2; and
d1 is 0, 1, 2, 3, or 4;
^RA12 is hydrogen, halogen, alkyl optionally substituted, alkenyl optionally substituted, alkynyl optionally substituted, carbocyclyl optionally substituted, heterocyclyl optionally substituted, substituted. Aryl may be, heteroaryl which may be substituted, acyl which may be substituted, -OR ^f , -SR ^f , -N (R ^f ) ₂ , -NO ₂ , or -CN;
^RA3 is hydrogen, halogen, alkyl optionally substituted, alkenyl optionally substituted, alkynyl optionally substituted, carbocyclyl optionally substituted, heterocyclyl optionally substituted, substituted. Aryl may be, heteroaryl which may be substituted, acyl which may be substituted, -OR ^f , -SR ^f , -N (R ^f ) ₂ , -NO ₂ , or -CN;
X ¹ is N or CR ⁵ , where R ⁵ is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkynyl. Carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, -OR ^f , -SR ^f , -N (R ^f ) ₂ , -NO ₂ , or -CN;
R ^B41 is hydrogen, halogen, alkyl optionally substituted, alkenyl optionally substituted, alkynyl optionally substituted, carbocyclyl optionally substituted, heterocyclyl optionally substituted, substituted. Aryl may be, heteroaryl which may be substituted, acyl which may be substituted, -OR ^f , -SR ^f , -N (R ^f ) ₂ , -NO ₂ , or -CN;
Ring C is aryl or heteroaryl;
Each appearance of R ^C3 is independent of halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted. Heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, -OR ^f , -SR ^f , -N (R ^f ) ₂ , -NO ₂ , or -CN;
c is 0, 1, 2, 3, or 4;
n1 is 0, 1, 2, 3, or 4;
R ² is a hydrogen, halogen, or optionally substituted alkyl;
Each appearance of R ^f is independent of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted. Heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, oxygen-protecting group, or nitrogen-protecting group, or two. R ^f together form a optionally substituted heterocyclic ring or an optionally substituted heteroaryl ring,
The compound according to claim 2 . J is equation (III):

And
During the ceremony
^RA12 is hydrogen, halogen, alkyl optionally substituted, alkenyl optionally substituted, alkynyl optionally substituted, carbocyclyl optionally substituted, heterocyclyl optionally substituted, substituted. Aryl may be, heteroaryl which may be substituted, acyl which may be substituted, -OR ^f , -SR ^f , -N (R ^f ) ₂ , -NO ₂ , or -CN;
^RA3 is hydrogen, halogen, alkyl optionally substituted, alkenyl optionally substituted, alkynyl optionally substituted, carbocyclyl optionally substituted, heterocyclyl optionally substituted, substituted. Aryl may be, heteroaryl which may be substituted, acyl which may be substituted, -OR ^f , -SR ^f , -N (R ^f ) ₂ , -NO ₂ , or -CN;
X ¹ is N or CR ⁵ , where R ⁵ is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkynyl. Carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, -OR ^f , -SR ^f , -N (R ^f ) ₂ , -NO ₂ , or -CN;
R ^B41 is hydrogen, halogen, alkyl optionally substituted, alkenyl optionally substituted, alkynyl optionally substituted, carbocyclyl optionally substituted, heterocyclyl optionally substituted, substituted. Aryl may be, heteroaryl which may be substituted, acyl which may be substituted, -OR ^f , -SR ^f , -N (R ^f ) ₂ , -NO ₂ , or -CN;
Ring C is aryl or heteroaryl;
Each appearance of R ^C3 is independent of halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted. Heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, -OR ^f , -SR ^f , -N (R ^f ) ₂ , -NO ₂ , or -CN;
c is 0, 1, 2, 3, or 4;
R ¹ is hydrogen, halogen, optionally substituted alkyl, or-(CH ₂ ) _n L ₂ , where n is 0, 1, 2, 3, or 4, and L ₂ is. -C (= O) R ³ , -C (= O) OR ³ , -C (= O) NR ³ R ⁴ , -S (= O) ₂ R ³ , -S (= O) ₂ OR ³ ,- S (= O) ₂ NR ³ R ⁴ , -OR ³ , -NR ³ R ⁴ , -N (R ⁴ ) C (= O) R ³ , optionally substituted carbocyclyl, optionally substituted heterocyclyl , May be substituted aryl, or optionally substituted heteroaryl;
R ² is a hydrogen, halogen, or optionally substituted alkyl;
R ³ and R ⁴ are independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, and optionally substituted. Good heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted acyl, oxygen-protecting group, or nitrogen-protecting group, or R ³ and R ⁴ together. To form a optionally substituted heterocyclic ring or an optionally substituted heteroaryl ring;
Each appearance of R ^f is independent of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted. Heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, oxygen-protecting group, or nitrogen-protecting group, or two. R ^f together form a optionally substituted heterocyclic ring or an optionally substituted heteroaryl ring,
The compound according to claim 2 . J is equation (IV):

And
During the ceremony
R ^M is -CN, -N (R ^f ) ₂ , or -CH ₂ N (R ^f ) ₂ ;
^RA3 is hydrogen, halogen, alkyl optionally substituted, alkenyl optionally substituted, alkynyl optionally substituted, carbocyclyl optionally substituted, heterocyclyl optionally substituted, substituted. Aryl may be, heteroaryl which may be substituted, acyl which may be substituted, -OR ^f , -SR ^f , -N (R ^f ) ₂ , -NO ₂ , or -CN;
X ¹ is N or CR ⁵ , where R ⁵ is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkynyl. Carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, -OR ^f , -SR ^f , -N (R ^f ) ₂ , -NO ₂ , or -CN;
R ^B41 is hydrogen, halogen, alkyl optionally substituted, alkenyl optionally substituted, alkynyl optionally substituted, carbocyclyl optionally substituted, heterocyclyl optionally substituted, substituted. Aryl may be, heteroaryl which may be substituted, acyl which may be substituted, -OR ^f , -SR ^f , -N (R ^f ) ₂ , -NO ₂ , or -CN;
Ring C is aryl or heteroaryl;
Each appearance of R ^C3 is independent of halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted. Heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, -OR ^f , -SR ^f , -N (R ^f ) ₂ , -NO ₂ , or -CN;
c is 0, 1, 2, 3, or 4;
R ¹ is hydrogen, halogen, optionally substituted alkyl, or-(CH ₂ ) _n L ₂ , where n is 0, 1, 2, 3, or 4, and L ₂ is. -C (= O) R ³ , -C (= O) OR ³ , -C (= O) NR ³ R ⁴ , -S (= O) ₂ R ³ , -S (= O) ₂ OR ³ ,- S (= O) ₂ NR ³ R ⁴ , -OR ³ , -NR ³ R ⁴ , -N (R ⁴ ) C (= O) R ³ , optionally substituted carbocyclyl, optionally substituted heterocyclyl , May be substituted aryl, or optionally substituted heteroaryl;
R ² is a hydrogen, halogen, or optionally substituted alkyl;
R ³ and R ⁴ are independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, and optionally substituted. A good heterocyclyl, an aryl which may be substituted, or a heteroaryl which may be substituted, or an acyl, an oxygen-protecting group, or a nitrogen-protecting group which may be substituted, or R ³ and R ⁴ are together. To form a optionally substituted heterocyclic ring or a optionally substituted heteroaryl ring;
Each appearance of R ^f is independent of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted. Heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, oxygen-protecting group, or nitrogen-protecting group, or two. R ^f together form a optionally substituted heterocyclic ring or an optionally substituted heteroaryl ring,
The compound according to claim 2 . J is the formula (V):

And
During the ceremony
X ¹ is N or CR ⁵ ;
R ⁵ is hydrogen, halogen, alkyl optionally substituted, alkenyl optionally substituted, alkynyl optionally substituted, carbocyclyl optionally substituted, heterocyclyl optionally substituted, substituted. Aryl may be, heteroaryl which may be substituted, acyl which may be substituted, -OR ^f , -SR ^f , -N (R ^f ) ₂ , -NO ₂ , or -CN;
R ^B41 is H, alkyl, hydroxylalkyl, aminoalkyl, alkoxyalkyl, haloalkyl, hydroxy, alkoxy, or -COO-R ₃ , each of which may be substituted;
Ring A is aryl or heteroaryl;
Each R ^A41 is independently alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which may be substituted; or any two R ^A41s are each concatenated. Condensed aryl or heteroaryl groups can be formed with the atoms present;
R is alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which may be substituted;
R ¹ is-(CH ₂ ) _n -L ₂ , where n is 0, 1, 2, or 3, and L ₂ is H, -C (= O) R ³ , -C (=). O) OR ³ , -C (= O) NR ³ R ⁴ , -S (= O) ₂ R ³ , -S (= O) ₂ NR ³ R ⁴ -NR ³ R ⁴ , -N (R ⁴ ) C (= O) R ³ , optionally substituted aryl, or optionally substituted heteroaryl; R ² is H, D (deuterium), halogen, or optionally substituted alkyl. can be;
R ³ are independent of each other
(I) H, aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
(Ii) Heterocycloalkyl or substituted heterocycloalkyl;
(Iii) -C ₁ to C ₈ alkyl, -C ₂ to C ₈ alkenyl, or -C ₂ to each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N. C ₈ alkynyl; each may be substituted, -C ₃ to C ₁₂ cycloalkyl, substituted -C ₃ to C ₁₂ cycloalkyl, -C ₃ to C ₁₂ cycloalkenyl, or substituted -C ₃ to C ₁₂ cyclo Alkyne;
(Iv) N = CR ⁴ R ⁶
Selected from the group consisting of;
Each of R ⁴ is independently hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which may be substituted;
Or R ³ and R ⁴ form a 4-10 membered ring with the nitrogen atom to which they are linked;
R ⁶ is alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, or heteroaryl, each of which may be substituted; or R ⁴ and R ⁶ are linked together. Form a 4- to 10-membered ring with carbon atoms;
m is 0, 1, 2, or 3,
The compound according to claim 2 . The compound according to claim 1 , wherein J is a binding substance of FKBP12, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. J is the formula (IX):

Or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.
During the ceremony
Each example of R ^Y1 is independently a halogen, optionally substituted C _1-6 alkyl, -OR ^f , -SR ^f , -N (R ^g ) ₂ , -NO ₂ or -C N. ;
y1 is 0, 1, 2, 3, 4, or 5;
R ^Y is -OR ^f , optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, substituted. Heterocyclyls that may be, aryls that may be substituted, or heteroaryls that may be substituted;
Each example of R ^Y1 is independently a halogen, optionally substituted C _1-6 alkyl, -OR ^f , -SR ^f , -N (R ^g ) ₂ , -NO ₂ or -C N. ;
R ^{Y 2} is hydrogen, optionally substituted acyl, or optionally substituted C _1-6 alkyl;
R ^Y3 is hydrogen, optionally substituted acyl, or optionally substituted C _1-6 alkyl;
R ^f is hydrogen, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, substituted. May be heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen-protecting group if linked to an oxygen atom, or a sulfur-protecting group if linked to a sulfur atom; And
R ^g may be substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted. Aryl, optionally substituted heteroaryl, or a nitrogen-protecting group,
The compound according to claim 7 . J is the formula:

The compound according to claim 1 , which is a compound of the above, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. formula:

,

,or

The compound according to claim 1 , which is a compound thereof or a pharmaceutically acceptable salt thereof. The compound according to claim 1 , wherein in each pair of A, one A is hydrogen and the other A is a halogen-substituted phenyl. The compound of claim 1 , wherein at least two examples of Y are O. The compound according to claim 1 , wherein Z is benzyl. L is bonded, optionally substituted or unsubstituted C One or more chain atoms of _{1 to 12} hydrocarbon chains are independently -C (= O)-, -O-, -S-, -NR ^b- , -N =, or = N-replaced with the hydrocarbon chain, substituted or unsubstituted carbocyclylene, substituted or unsubstituted heterocyclylene, substituted or unsubstituted arylene, substituted or unsubstituted heteroarylene, or substituted. Or it is an unsubstituted heteroalkylene,
Here, each example of R ^b is independently hydrogen, substituted or unsubstituted C _1-6 alkyl, or a nitrogen-protecting group, or optionally two examples of R ^b with their intervening atoms. To form a substituted or unsubstituted heterocyclic ring or a substituted or unsubstituted heteroaryl ring,
The compound according to claim 1, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. L is the formula:

(In the formula, g is 1-5;
p is 2-5;
s is 1-5);

(In the formula, x1 is 1-6;
x2 is 1-6; and
x3 is 1-8);

(In the formula, x1 is 1 to 6; and
x3 is 1-8);

(In the formula, x1 is 1-6;
x2 is 1-6;
x3 is 1-8; and
x4 is 1-3);

(In the formula, x1 is 1-6;
x2 is 1-6;
x3 is 1-8; and
x4 is 1-3);

(In the formula, x1 is 1-6;
x2 is 1-6; and
Each example of x3 is 1-8 independently);

(In the formula, x1 is 1 to 6; and
x3 is 1-8);

(X1 is 2 or 3; and
x3 is 6, 7, or 8);

The compound according to claim 1. L is the formula:

The compound according to claim 15 . formula:

The compound according to claim 1, which is a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. A therapeutically effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt, solvent, hydrate, tautomer, or steric isomer thereof, and optionally pharmaceutically acceptable. A pharmaceutical composition comprising an excipient. Bromodomain, bromodomain in a subject comprising a therapeutically effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or steric isomer thereof. Contains proteins, or pharmaceutical compositions for treating cancers mediated by FKBP12 . 19. The pharmaceutical composition of claim 19 , wherein the cancer is multiple myeloma , leukemia, or lymphoma .