Methods for treating hematological malignancies and ewing's sarcoma

Abstract

To provide methods for treating hematological malignancies such as acute myeloid leukemia or Ewing's sarcoma.SOLUTION: Disclosed is a method for treating acute myeloid leukemia in a subject exhibiting a nucleoporin 98 (NUP98) gene fusion, mutation in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, or mixed lineage leukemia (MLL) gene amplification, comprising a step of administering a menin inhibitor to a subject in need thereof.SELECTED DRAWING: Figure 7A

Description

Technical Field

[0001] Cross-reference This application claims the benefit of U.S. Provisional Patent Application No. 62 / 476,710, filed Mar. 24, 2017; U.S. Provisional Patent Application No. 61 / 561,119, filed Sep. 20, 2017; U.S. Provisional Patent Application No. 62 / 577,640, filed Oct. 26, 2017; and U.S. Provisional Patent Application No. 62 / 635,256, filed Feb. 26, 2018, each of which is incorporated herein by reference in its entirety.

[0002] Sequence Listing This application includes a sequence listing, which is submitted electronically in ASCII format and is incorporated herein by reference in its entirety. The ASCII copy created on Mar. 19, 2018 is named 47535727601_SL.txt and is 15,924 bytes in size.

Background Art

[0003] The mixed-lineage leukemia (MLL) protein is a histone methyltransferase important for the epigenetic control of gene transcription. Protein-protein interactions between MLL and menin have been shown to play important roles in the development of many diseases. The menin protein encoded by the multiple endocrine neoplasia (MEN) gene is a ubiquitously expressed nuclear protein involved in interactions with DNA processing and repair proteins, chromatin modification proteins, and many transcription factors (Non-Patent Document 1). Menin binds to the N-terminus of MLL proteins, including MLL1, MLL2, and MLL fusion proteins.

[0004] Aberrant expression of HOX genes is involved in many diseases, including hematological malignancies such as acute myeloid leukemia (AML) and Ewing sarcoma. Certain hematological malignancies are characterized by the presence of specific genetic abnormalities or mutations, including nucleoporin 98 (NUP98) gene fusions (Non-Patent Document 2), mutations in the nucleophosmin (NPM1) gene (Non-Patent Document 3), mutations in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene (Non-Patent Document 4), or amplification of the mixed-lineage leukemia (MLL) gene (Non-Patent Document 5). Ewing sarcoma exhibits aberrant overexpression of the posterior HOXD genes, particularly the HOXD13 gene. Tumors and cell lines of Ewing sarcoma express high levels of menin and MLL1, which are required for tumor maintenance and progression, and HOXD13 is a downstream target of MLL1 (Non-Patent Document 6).

Prior Art Documents

Non-Patent Documents

[0005]

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

Non-Patent Document 4

Non-Patent Document 5

Non-Patent Document 6

Summary of the Invention

[0006] New therapeutic strategies are urgently needed to treat these diseases. Small molecule inhibitors that block the Menin-MLL interaction are, therefore, valuable targets for treating hematological malignancies and Ewing sarcoma.

[0007] The present disclosure addresses the needs in the art by providing compositions and methods for treating hematological malignancies such as acute myeloid leukemia or Ewing sarcoma using a Menin inhibitor. The Menin inhibitor is capable of inhibiting the protein-protein interaction of Menin with an MLL protein (e.g., MLL1, MLL2, or an MLL fusion protein). The compositions and methods described herein may be useful for treating diseases such as hematological malignancies or Ewing sarcoma by virtue of the activity of Menin, MLL1, and / or MLL2.

[0008] In one aspect, the present disclosure provides a method of treating acute myeloid leukemia in a subject presenting with a nucleoporin 98 (NUP98) gene fusion, a mutation in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, or a mixed lineage leukemia (MLL) gene amplification, the method comprising administering a menin inhibitor to a subject in need thereof. In some embodiments, the subject presents with a nucleoporin 98 (NUP98) gene fusion. In some embodiments, the nucleoporin 98 (NUP98) gene fusion is a gene fusion of NUP98 and a homeodomain partner gene. In some embodiments, the nucleoporin 98 (NUP98) gene fusion is a gene fusion of NUP98 and a non-homeodomain partner gene. In some embodiments, the nucleoporin 98 (NUP98) gene fusion is a gene fusion of NUP98 and a partner gene selected from HOXA9, HOXA11, HOXA13, HOXC11, HOXC13, HOXD11, HOXD13, PMX1, PMX2, HHEX, PHF23, JARID1A, NSD1, NSD3, MLL, SETBP1, LEDGF, CCDC28, HMGB3, IQCG, RAP1GDS1, ADD3, DDX10, TOP1, TOP2B, LNP1, RARG, ANKRD28, and POU1F1. In some embodiments, the subject presents with a mutation in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene. In some embodiments, the mutation in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene is a mutation at R882. In some embodiments, the mutation in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene is not a mutation at R882. In some embodiments, the mutation in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene is a frameshift deletion, a missense mutation, a nonsense mutation, a splice site substitution, a splice site deletion, or a whole gene deletion. In some embodiments, the subject presents with a mixed lineage leukemia (MLL) gene amplification.

[0009] In one aspect, the present disclosure provides a method of treating a subject having acute myeloid leukemia or acute lymphoblastic leukemia, the method comprising: (a) screening the subject for the presence of an MLL rearrangement, a partial tandem duplication of MLL, or an increase in MEIS1 expression level; and (b) administering a menin inhibitor to the subject if it is determined that one or more of an MLL rearrangement, a partial tandem duplication of MLL, or an increase in MEIS1 expression level is present.

[0010] In some embodiments, the menin inhibitor is a compound of formula (I-A),

[0011]

Chemical formula

[0012] In some embodiments, the menin inhibitor is a compound of formula (I-B),

[0013]

Chemical formula

[0014] In some embodiments, R C is -C(O)R 52 , -S(=O)R 52 , -S(=O)2R 52 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , =O, C 1-3 alkyl, and C 1-3 haloalkyl, or two R C groups bonded to different atoms can combine to form a C 1-3 bridge.

[0015] In some embodiments, the menin inhibitor is a compound of formula (II):

[0016]

Chemical formula

[0017] In some embodiments, the menin inhibitor is a compound of formula (III):

[0018]

Chemical formula

[0019]

Chemical formula

[0020] In some embodiments, the menin inhibitor is a compound of formula (IV):

[0021]

Chemical formula

[0022]

Chemical formula

[0023] In some embodiments, the menin inhibitor is a compound of formula (VI):

[0024]

Chemical formula

[0025]

Chemical formula

[0026] In one aspect, the present disclosure provides a method for treating acute myeloid leukemia in a subject having a mutation in the nucleophosmin (NPM1) gene, the method comprising administering to a subject in need thereof a compound of formula (I-A),

[0027]

Chemical formula

[0028] In one aspect, the present disclosure provides a method for treating a hematological malignancy of a subject having a mutation in the nucleophosmin (NPM1) gene, DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, FMS-like tyrosine kinase-3 (FLT3) gene, isocitrate dehydrogenase 1 (IDH1) gene, isocitrate dehydrogenase 2 (IDH2) gene, or a combination thereof, the method comprising administering a compound of formula (I-A) to a subject in need thereof.

[0029] In one aspect, the present disclosure provides a method for treating acute myeloid leukemia of a subject having a mutation in the nucleophosmin (NPM1) gene, the method comprising a compound of formula (I-B),

[0030]

Chemical formula

[0031] In one aspect, the present disclosure provides a method for treating hematological malignancies in a subject having a mutation in the nucleophosmin (NPM1) gene, DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, FMS-like tyrosine kinase-3 (FLT3) gene, isocitrate dehydrogenase 1 (IDH1) gene, isocitrate dehydrogenase 2 (IDH2) gene, or a combination thereof, the method comprising administering a compound of formula (I-B) to a subject in need thereof.

[0032] In some embodiments, R C Is -C(O)R 52 , -S(=O)R 52 , -S(=O)2R 52 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , =O, C1-3 alkyl, and C 1-3 selected from haloalkyl, or two Rs attached to different atoms C groups may combine together to form a C 1-3 bridge.

[0033] In one aspect, the present disclosure provides a method for treating acute myeloid leukemia in a subject having a mutation in the nucleophosmin (NPM1) gene, the method comprising administering to the subject a compound of formula (II),

[0034]

Chemical formula

[0035] In one aspect, the present disclosure provides a method for treating a hematological malignancy in a subject having a mutation in the nucleophosmin (NPM1) gene, DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, FMS-like tyrosine kinase-3 (FLT3) gene, isocitrate dehydrogenase 1 (IDH1) gene, isocitrate dehydrogenase 2 (IDH2) gene, or a combination thereof, the method comprising administering a compound of formula (II) to the subject.

[0036] In one aspect, the present disclosure provides a method for treating a hematological malignancy in a subject having a mutation in the nucleophosmin (NPM1) gene, the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, the FMS-like tyrosine kinase-3 (FLT3) gene, the isocitrate dehydrogenase 1 (IDH1) gene, the isocitrate dehydrogenase 2 (IDH2) gene, or a combination thereof, the method comprising administering to the subject a compound of formula (III),

[0037]

Chemical formula

[0038]

Chemical formula

[0039] In one aspect, the present disclosure provides a method for treating hematological malignancies in a subject having a mutation in the nucleophosmin (NPM1) gene, DNA (cytosine - 5) - methyltransferase 3A (DNMT3A) gene, FMS - like tyrosine kinase - 3 (FLT3) gene, isocitrate dehydrogenase 1 (IDH1) gene, isocitrate dehydrogenase 2 (IDH2) gene, or a combination thereof, the method comprising a compound of formula (IV),

[0040] [Chemistry] or a step of administering to a subject the pharmaceutically acceptable salt or prodrug thereof,

[0041] [Chemistry] is a fused thienyl or fused phenyl group; G a is selected from a C 3-12 carbocyclic ring and a 3- to 12-membered heterocyclic ring, each of which is substituted with -E 1 -R 4a and optionally further substituted with one or more R 50 ; R 2a is selected from hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocycle, optionally substituted heteroaryl, and aralkyl; R 3a and R 3b are each independently selected from hydrogen, alkyl, halo, hydroxy, cyano, amino, alkylamino, dialkylamino, haloalkyl, alkoxy, and haloalkoxy; X a -Y a is selected from -N(R 52 )-C(=O)-, -C(=O)-O-, -C(=O)-N(R 52 )-, -CH2N(R 52 )-CH2-, -C(=O)N(R 52 )-CH2-, -CH2CH2-N(R 52 )-, -CH2N(R 52 )-C(=O)-, and -CH2OCH2-; or X a and Y a do not form a chemical bond, where: X ais selected from hydrogen, alkyl, halo, hydroxy, cyano, amino, alkylamino, dialkylamino, haloalkyl, alkoxy, and haloalkoxy; and, Y a is cyano, hydroxy, and -CH2R 50 selected from; E 1 is absent or selected from -C(=O)-, -C(=O)N(R 52 )-, -[C(R 14a )2] 1-5 O-, -[C(R 14a )2] 1-5 NR 52 -, -[C(R 14a )2] 1-5 -, -CH2(=O)-, and, -S(=O)2-; R 4a is selected from hydrogen, alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocycle, optionally substituted heteroaryl, aralkyl, (heterocycle)alkyl, and (heteroaryl)alkyl; R 14a is selected from hydrogen and alkyl; R 50 is, each time it appears, selected from: halogen, -NO2, -CN, -OR 52 , -SR 52 , -N(R 52 )2, -NR 53 R 54 , -S(=O)R 52 , -S(=O)2R 52 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 )2, -NR 52 S(=O)2NR 53 R 54 , -C(O)R 52 , -C(O)OR52 、 -OC(O)R 52 、 -OC(O)OR 52 、 -OC(O)N(R 52 )2、 -OC(O)NR 53 R 54 、 -NR 52 C(O)R 52 、 -NR 52 C(O)OR 52 、 -NR 52 C(O)N(R 52 )2、 -NR 52 C(O)NR 53 R 54 、 -C(O)N(R 52 )2、 -C(O)NR 53 R 54 、 -P(O)(OR 52 )2、 -P(O)(R 52 )2、 -P(O)(OR 52 )(R 52 )、 -P(O)(NR 52 )(R 52 )、 -NR 52 P(O)(R 52 )、 -P(O)(NR 52 )(OR 52 )、 -P(O)(NR 52 )2、 =O、 =S、 =N(R 52 ); C 1-10 alkyl, C 2-10 alkenyl, and C 2-10 alkynyl, each of which is independently halogen, -NO2, -CN, -OR 52 、 -SR 52 、 -N(R 52 )2、 -NR 53 R 54 、 -S(=O)R 52 、 -S(=O)2R 52 、 -S(=O)2N(R 52 )2、 -S(=O)2NR 53 R 54 、 -NR 52 S(=O)2R 52 、 -NR 52 S(=O)2N(R 52 )2、 -NR 52 S(=O)2NR 53 R54 , -C(O)R 52 , -C(O)OR 52 , -OC(O)R 52 , -OC(O)OR 52 , -OC(O)N(R 52 )2, -OC(O)NR 53 R 54 , -NR 52 C(O)R 52 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 , -C(O)N(R 52 )2, -C(O)NR 53 R 54 , -P(O)(OR 52 )2, -P(O)(R 52 )2, -P(O)(OR 52 )(R 52 ), -P(O)(NR 52 )(R 52 ), -NR 52 P(O)(R 52 ), -P(O)(NR 52 )(OR 52 ), -P(O)(NR 52 )2, =O, =S, =N(R 52 ), C 3-12 A carbon ring, and one or more substituents selected from 3- to 12-membered heterocyclic rings, optionally substituted each time it appears, C 1-10 alkyl, C 2-10 alkenyl, and C 2-10 alkynyl; and, C 3-12 A carbon ring and a 3- to 12-membered heterocyclic ring, wherein each C 50 in R 3-12 The carbon ring and the 3- to 12-membered heterocyclic ring are independently halogen, -NO2, -CN, -OR 52 , -SR 52 , -N(R 52 )2, -NR 53 R 54 , -S(=O)R 52 , -S(=O)2R 52, -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 )2, -NR 52 S(=O)2NR 53 R 54 , -C(O)R 52 , -C(O)OR 52 , -OC(O)R 52 , -OC(O)OR 52 , -OC(O)N(R 52 )2, -OC(O)NR 53 R 54 , -NR 52 C(O)R 52 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 , -C(O)N(R 52 )2, -C(O)NR 53 R 54 , -P(O)(OR 52 )2, -P(O)(R 52 )2, -P(O)(OR 52 )(R 52 ), -P(O)(NR 52 )(R 52 ), -NR 52 P(O)(R 52 ), -P(O)(NR 52 )(OR 52 ), -P(O)(NR 52 )2, =O, =S, =N(R 52 ), C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, and, C 2-6 alkynyl, optionally substituted with one or more substituents selected from R 52 is, each time it appears, hydrogen; and, C 1-20 alkyl, C 2-20 alkenyl, C2-20 Alkynyl, 1- to 6-membered heteroalkyl, C 3-12 Selected from carbocyclic rings and 3- to 12-membered heterocyclic rings, each of which is halogen, -CN, -NO2, -NH2, -NHCH3, -NHCH2CH3, =O, -OH, -OCH3, -OCH2CH3, C 3-12 Optionally substituted by a carbocyclic ring or a 3- to 6-membered heterocyclic ring; and, R 53 and R 54 together with the nitrogen atom to which they are attached form a heterocyclic ring optionally substituted with one or more R 50 s.

[0042] In one aspect, the present disclosure provides a method for treating a hematologic malignancy in a subject having a mutation in the nucleophosmin (NPM1) gene, DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, FMS-like tyrosine kinase-3 (FLT3) gene, isocitrate dehydrogenase 1 (IDH1) gene, isocitrate dehydrogenase 2 (IDH2) gene, or a combination thereof, the method comprising administering to the subject a compound of formula (VI),

[0043]

Chemical formula

[0044]

Chemical formula

[0045] In some embodiments, the hematological malignancy is selected from malignant lymphoma, leukemia, mature B cell neoplasm, mature T cell and natural killer (NK) cell neoplasm, precursor lymphoid neoplasm, Hodgkin's lymphoma (HL), plasma cell neoplasm, mast cell tumor, histiocytic and accessory lymphoid cell neoplasm, immunoproliferative disease, myeloid leukemia, and myelodysplastic syndrome (MDS). In some embodiments, the hematological malignancy is selected from acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia, non-Hodgkin's lymphoma, multiple myeloma, mixed lineage leukemia, and myelodysplastic syndrome. In some embodiments, the hematological malignancy is acute myeloid leukemia. In some embodiments, relapse of the hematological malignancy is prevented.

[0046] In some embodiments, the mutation in the nucleophosmin (NPM1) gene is a mutation in exon 12 of the NPM1 gene. In some embodiments, the mutation in the nucleophosmin (NPM1) gene is a frameshift mutation. In some embodiments, the mutation in the nucleophosmin (NPM1) gene is an insertion of 2 to 9 bases, such as an insertion of 4 bases. In some embodiments, the insertion of 4 bases is selected from TCTG, CATG, CCTG, CGTG, CAGA, CTTG, and TATG. In some embodiments, the insertion is an insertion of 9 bases. In some embodiments, the insertion of 9 bases is selected from CTCTTGCCC and CCCTGGAGA. In some embodiments, the mutation in the nucleophosmin (NPM1) gene includes a deletion of nucleotides 965-969 (GGAGG). In some embodiments, the subject further exhibits a mutation in the FLT3 gene. In some embodiments, the mutation in the FLT3 gene is an internal tandem duplication. In some embodiments, the subject further exhibits a mutation in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene.

[0047] In some embodiments, the mutation in the FLT3 gene is in the tyrosine kinase domain. In some embodiments, the mutations are in the nucleophosmin (NPM1) gene and the FMS-like tyrosine kinase-3 (FLT3) gene. In some embodiments, the mutations are in the nucleophosmin (NPM1) gene, the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, the isocitrate dehydrogenase 2 (IDH2) gene, and the FMS-like tyrosine kinase-3 (FLT3) gene. In some embodiments, the subject exhibits a mutation in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene.

[0048] In one aspect, the present disclosure provides a method of treating Ewing sarcoma, the method comprising a compound of formula (I-A),

[0049] [Chemical] or administering to a subject the pharmaceutically acceptable salt or prodrug thereof, H is selected from a carbocyclic ring and a 5- to 12-membered heterocyclic ring, each of which is optionally substituted with one or more R 5-12 ; 50 ; A is selected from a single bond, C 3-12 a carbocyclic ring, and a 3- to 12-membered heterocyclic ring; B is selected from C 3-12 a carbocyclic ring and a 3- to 12-membered heterocyclic ring; C is a 3- to 12-membered heterocyclic ring; L 1 , L 2 , and L 3 are each independently a single bond, -O-, -S-, -N(R 51 )-, -N(R 51 )CH2-, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R 51 )-, -C(O)N(R 51 )C(O)-, -C(O)N(R 51 )C(O)N(R 51 )-, -N(R 51 )C(O)-, -N(R 51 )C(O)N(R 51 )-, -N(R 51 )C(O)O-, -OC(O)N(R 51 )-, -C(NR 51 )-, -N(R 51 )C(NR 51 )-, -C(NR 51 )N(R 51 )-, -N(R 51 )C(NR 51 )N(R 51 )-, -S(O)2-, -OS(O)-, -S(O)O-, -S(O)-, -OS(O)2-, -S(O)2O-, -N(R 51 )S(O)2-, -S(O)2N(R 51 )-, -N(R 51 )S(O)-, -S(O)N(R 51)-, -N(R 51 )S(O)2N(R 51 )-, -N(R 51 )S(O)N(R 51 )-; alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, and heteroalkynylene, each independently selected, each of which is optionally substituted with one or more R 50 where L 1 , L 2 , or L 3 Two R 50 groups bonded to the same or different atoms can optionally combine to form a bridge or a ring; R A , R B , and R C are each independently selected each time they appear from R 50 , or two R A groups, two R B groups, or two R C groups can optionally combine to form a bridge or a ring; m, n, and p are each independently an integer from 0 to 6; R 50 is selected each time it appears from the following: halogen, -NO2, -CN, -OR 52 , -SR 52 , -N(R 52 )2, -NR 53 R 54 , -S(=O)R 52 , -S(=O)2R 52 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 )2, -NR 52 S(=O)2NR 53 R 54 , -C(O)R 52 , -C(O)OR 52 , -OC(O)R52 、 -OC(O)OR 52 、 -OC(O)N(R 52 )2, -OC(O)NR 53 R 54 、 -NR 52 C(O)R 52 、 -NR 52 C(O)OR 52 、 -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 、 -C(O)N(R 52 )2, -C(O)NR 53 R 54 、 -P(O)(OR 52 )2, -P(O)(R 52 )2, -P(O)(OR 52 )(R 52 )、 -P(O)(NR 52 )(R 52 )、 -NR 52 P(O)(R 52 )、 -P(O)(NR 52 )(OR 52 )、 -P(O)(NR 52 )2, =O, =S, =N(R 52 ); C 1-10 alkyl, C 2-10 alkenyl, and C 2-10 alkynyl, each of which is independently halogen, -NO2, -CN, -OR 52 、 -SR 52 、 -N(R 52 )2, -NR 53 R 54 、 -S(=O)R 52 、 -S(=O)2R 52 、 -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 、 -NR 52 S(=O)2R 52 、 -NR 52 S(=O)2N(R 52 )2, -NR 52 S(=O)2NR 53 R 54 、 -C(O)R52 , -C(O)OR 52 , -OC(O)R 52 , -OC(O)OR 52 , -OC(O)N(R 52 )2, -OC(O)NR 53 R 54 , -NR 52 C(O)R 52 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 , -C(O)N(R 52 )2, -C(O)NR 53 R 54 , -P(O)(OR 52 )2, -P(O)(R 52 )2, -P(O)(OR 52 )(R 52 ), -P(O)(NR 52 )(R 52 ), -NR 52 P(O)(R 52 ), -P(O)(NR 52 )(OR 52 ), -P(O)(NR 52 )2, =O, =S, =N(R 52 ), C 3-12 a carbon ring, and one or more substituents selected from 3- to 12-membered heterocyclic rings, optionally substituted each time it appears, C 1-10 alkyl, C 2-10 alkenyl, and C 2-10 alkynyl; and, C 3-12 a carbon ring and a 3- to 12-membered heterocyclic ring, wherein each C 50 in R 3-12 the carbon ring and the 3- to 12-membered heterocyclic ring are independently halogen, -NO2, -CN, -OR 52 , -SR 52 , -N(R 52 )2, -NR 53 R 54 , -S(=O)R 52 , -S(=O)2R 52 , -S(=O)2N(R52 ) 2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 ) 2, -NR 52 S(=O)2NR 53 R 54 , -C(O)R 52 , -C(O)OR 52 , -OC(O)R 52 , -OC(O)OR 52 , -OC(O)N(R 52 ) 2, -OC(O)NR 53 R 54 , -NR 52 C(O)R 52 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 ) 2, -NR 52 C(O)NR 53 R 54 , -C(O)N(R 52 ) 2, -C(O)NR 53 R 54 , -P(O)(OR 52 ) 2, -P(O)(R 52 ) 2, -P(O)(OR 52 )(R 52 , -P(O)(NR 52 )(R 52 , -NR 52 P(O)(R 52 , -P(O)(NR 52 )(OR 52 ), -P(O)(NR 52 ) 2, =O, =S, =N(R 52 ), C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, and, C 2-6 alkynyl optionally substituted with one or more substituents selected from 3-12 carbocyclic ring and 3-membered - 12-membered heterocyclic ring; R 51 is, each time it appears, selected from the following: hydrogen, -C(O)R52 , -C(O)OR 52 , -C(O)N(R 52 )2, -C(O)NR 53 R 54 ; C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is independently halogen, -NO2, -CN, -OR 52 , -SR 52 , -N(R 52 )2, -NR 53 R 54 , -S(=O)R 52 , -S(=O)2R 52 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 )2, -NR 52 S(=O)2NR 53 R 54 , -C(O)R 52 , -C(O)OR 52 , -OC(O)R 52 , -OC(O)OR 52 , -OC(O)N(R 52 )2, -OC(O)NR 53 R 54 , -NR 52 C(O)R 52 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 , -C(O)N(R 52 )2, -C(O)NR 53 R 54 , -P(O)(OR 52 )2, -P(O)(R 52 )2, -P(O)(OR 52 )(R 52 ), -P(O)(NR 52 )(R52 )、 -NR 52 P(O)(R 52 )、 -P(O)(NR 52 )(OR 52 )、 -P(O)(NR 52 )2、 =O、 =S、 =N(R 52 )、 C 3-12 carbon ring, and one or more substituents selected from 3 - 12 membered heterocyclic rings, optionally substituted each time it appears, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl; and, C 3-12 a carbon ring and a 3 - 12 membered heterocyclic ring, where each C 51 in R 3-12 the carbon ring and the 3 - 12 membered heterocyclic ring are independently halogen, -NO2, -CN, -OR 52 、 -SR 52 、 -N(R 52 )2、 -NR 53 R 54 、 -S(=O)R 52 、 -S(=O)2R 52 、 -S(=O)2N(R 52 )2、 -S(=O)2NR 53 R 54 、 -NR 52 S(=O)2R 52 、 -NR 52 S(=O)2N(R 52 )2、 -NR 52 S(=O)2NR 53 R 54 、 -C(O)R 52 、 -C(O)OR 52 、 -OC(O)R 52 、 -OC(O)OR 52 、 -OC(O)N(R 52 )2、 -OC(O)NR 53 R 54 、 -NR 52 C(O)R 52 、 -NR 52 C(O)OR 52 、 -NR 52 C(O)N(R 52 )2、 -NR 52 C(O)NR 53 R54 , -C(O)N(R 52 )2, -C(O)NR 53 R 54 , -P(O)(OR 52 )2, -P(O)(R 52 )2, -P(O)(OR 52 )(R 52 ), -P(O)(NR 52 )(R 52 ), -NR 52 P(O)(R 52 ), -P(O)(NR 52 )(OR 52 ), -P(O)(NR 52 )2, =O, =S, =N(R 52 ), C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, and, C 2-6 alkynyl, optionally substituted with one or more substituents selected from C 3-12 carbocyclic ring and 3- to 12-membered heterocyclic ring; R 52 is, each time it appears, hydrogen; and, C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, 1- to 6-membered heteroalkyl, C 3-12 carbocyclic ring, and 3- to 12-membered heterocyclic ring, each of which is optionally substituted with halogen, -CN, -NO2, -NH2, -NHCH3, -NHCH2CH3, =O, -OH, -OCH3, -OCH2CH3, C 3-12 carbocyclic ring, or 3- to 6-membered heterocyclic ring; R 53 and R 54 together with the nitrogen atom to which they are attached form a heterocyclic ring optionally substituted with one or more R 50 ; R 57 is selected from the following: halogen, -NO2, -CN, -SR 52 , -NR 53 R 54 , -S(=O)R 52 , -S(=O)2R 58 , -S(=O)2N(R 52) 2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 )2, -NR 52 S(=O)2NR 53 R 54 , -C(O)OR 52 , -OC(O)R 52 , -OC(O)OR 52 , -OC(O)N(R 52 )2, -OC(O)NR 53 R 54 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 , -C(O)NH(C 1-6 alkyl), -C(O)NR 53 R 54 , -P(O)(OR 52 )2, -P(O)(R 52 )2, -P(O)(OR 52 )(R 52 ), -P(O)(NR 52 )(R 52 ), -NR 52 P(O)(R 52 ), -P(O)(NR 52 )(OR 52 ), -P(O)(NR 52 )2, =S, =N(R 52 ); and, C 1-10 alkyl, C 2-10 alkenyl, and C 2-10 alkynyl, each of which is independently, -NO2, -CN, -SR 52 , -N(R 52 )2, -NR 53 R 54 , -S(=O)R 52 , -S(=O)2R 52 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 )2, -NR 52 S(=O)2NR 53 R 54 , -C(O)R 52 , -C(O)OR 52 , -OC(O)R 52 , -OC(O)OR 52 , -OC(O)N(R 52 )2, -OC(O)NR 53 R 54 , -NR 52 C(O)R 52 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 , -P(O)(OR 52 )2, -P(O)(R 52 )2, -P(O)(OR 52 )(R 52 ), -P(O)(NR 52 )(R 52 ), -NR 52 P(O)(R 52 ), -P(O)(NR 52 )(OR 52 ), -P(O)(NR 52 )2, =S, and, =N(R 52 ) selected from one or more substituents, and substituted each time it appears, C 1-10 alkyl, C 2-10 alkenyl, and C 2-10 alkynyl; R 58 is hydrogen; and, C 1-20 alkyl, C 3-20 alkenyl, C 2-20 alkynyl, 1-6 membered heteroalkyl, C 3-12A carbon ring and a heterocyclic ring having 3 to 12 members, each of which is halogen, -CN, -NO2, -NH2, -NHCH3, -NHCH2CH3, =O, -OH, -OCH3, -OCH2CH3, C 3-12 optionally substituted by a carbon ring or a heterocyclic ring having 3 to 6 members; Here, for the compound or salt of formula (I-A), when C is azetidinylene, piperidinylene, or piperazinylene, and R 57 is -S(=O)2R 58 , -S(=O)2N(R 52 )2, or -NR 52 S(=O)2R 52 : p is an integer from 1 to 6; and / or, L 3 is substituted with one or more R 50 , where L 3 is not -CH2CH(OH)-.

[0050] In one aspect, the present disclosure provides a method for treating Ewing's sarcoma, the method including administering to a subject in need thereof a compound of formula (I-B),

[0051]

Chemical formula

[0052] In some embodiments, R C is -C(O)R 52 , -S(=O)R 52 , -S(=O)2R 52 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , =O, C 1-3 alkyl, and C 1-3 haloalkyl, or two R C groups attached to different atoms are joined together to form a C 1-3 bridge.

[0053] In one aspect, the present disclosure provides a method of treating Ewing's sarcoma, the method comprising administering to a subject a compound of formula (II),

[0054] [Chemical formula] or a pharmaceutically acceptable salt or prodrug thereof, wherein H is selected from C 5-12 carbocyclic rings and 5- to 12-membered heterocyclic rings, each of which is optionally substituted with one or more R 50 ; A is selected from a single bond, C 3-12 carbocyclic rings, and 3- to 12-membered heterocyclic rings; B is selected from C 3-12 carbocyclic rings and 3- to 12-membered heterocyclic rings; L 1 , L 2 , and L 3 are each independently a single bond, -O-, -S-, -N(R 51 )-, -N(R 51 )CH2-, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R 51 )-, -C(O)N(R 51)C(O)-, -C(O)N(R 51 )C(O)N(R 51 )-, -N(R 51 )C(O)-, -N(R 51 )C(O)N(R 51 )-, -N(R 51 )C(O)O-, -OC(O)N(R 51 )-, -C(NR 51 )-, -N(R 51 )C(NR 51 )-, -C(NR 51 )N(R 51 )-, -N(R 51 )C(NR 51 )N(R 51 )-, -S(O)2-, -OS(O)-, -S(O)O-, -S(O)-, -OS(O)2-, -S(O)2O-, -N(R 51 )S(O)2-, -S(O)2N(R 51 )-, -N(R 51 )S(O)-, -S(O)N(R 51 )-, -N(R 51 )S(O)2N(R 51 )-, -N(R 51 )S(O)N(R 51 )-; selected from alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, and heteroalkynylene, each of which is optionally substituted with one or more R 50 ; R A , R B , and R C are each independently selected from R 50 each time it appears, or two R A groups or two R B groups bonded to the same atom or different atoms can optionally combine to form a bridge or a ring; m and n are each independently an integer from 0 to 6, W 1 is C 50 alkylene optionally substituted with one or more R 1-4 ; W 2 is a single bond; and, one or more R50 C optionally substituted with 1-4 selected from alkylene; W 3 is absent; and one or more R 50 C optionally substituted with 1-4 selected from alkylene; R 50 is each time it appears selected from: halogen, -NO2, -CN, -OR 52 , -SR 52 , -N(R 52 )2, -NR 53 R 54 , -S(=O)R 52 , -S(=O)2R 52 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 )2, -NR 52 S(=O)2NR 53 R 54 , -C(O)R 52 , -C(O)OR 52 , -OC(O)R 52 , -OC(O)OR 52 , -OC(O)N(R 52 )2, -OC(O)NR 53 R 54 , -NR 52 C(O)R 52 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 , -C(O)N(R 52 )2, -C(O)NR 53 R 54 , -P(O)(OR 52 )2, -P(O)(R 52 )2, =O, =S, =N(R 52 ); C 1-10Alkyl, C 2-10 Alkenyl, and C 2-10 Alkynyl, each of which is independently halogen, -NO2, -CN, -OR 52 , -SR 52 , -N(R 52 )2, -NR 53 R 54 , -S(=O)R 52 , -S(=O)2R 52 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 )2, -NR 52 S(=O)2NR 53 R 54 , -C(O)R 52 , -C(O)OR 52 , -OC(O)R 52 , -OC(O)OR 52 , -OC(O)N(R 52 )2, -OC(O)NR 53 R 54 , -NR 52 C(O)R 52 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 , -C(O)N(R 52 )2, -C(O)NR 53 R 54 , -P(O)(OR 52 )2, -P(O)(R 52 )2, =O, =S, =N(R 52 ), C 3-12 A carbon ring, and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time it appears, C 1-10 Alkyl, C 2-10 Alkenyl, and C 2-10 Alkynyl; and, C 3-12A carbon ring and a 3- to 12-membered heterocyclic ring, where R 50 each C in 3-12 The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO2, -CN, -OR 52 , -SR 52 , -N(R 52 )2, -NR 53 R 54 , -S(=O)R 52 , -S(=O)2R 52 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 )2, -NR 52 S(=O)2NR 53 R 54 , -C(O)R 52 , -C(O)OR 52 , -OC(O)R 52 , -OC(O)OR 52 , -OC(O)N(R 52 )2, -OC(O)NR 53 R 54 , -NR 52 C(O)R 52 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 , -C(O)N(R 52 )2, -C(O)NR 53 R 54 , -P(O)(OR 52 )2, -P(O)(R 52 )2, =O, =S, =N(R 52 ), C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, and C 2-6 alkynyl, optionally substituted with one or more substituents selected from 3-12 a carbon ring and a 3- to 12-membered heterocyclic ring; R51 is selected from the following each time it appears: hydrogen, -C(O)R 52 , -C(O)OR 52 , -C(O)N(R 52 )2, -C(O)NR 53 R 54 ; C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is independently halogen, -NO2, -CN, -OR 52 , -SR 52 , -N(R 52 )2, -NR 53 R 54 , -S(=O)R 52 , -S(=O)2R 52 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 )2, -NR 52 S(=O)2NR 53 R 54 , -C(O)R 52 , -C(O)OR 52 , -OC(O)R 52 , -OC(O)OR 52 , -OC(O)N(R 52 )2, -OC(O)NR 53 R 54 , -NR 52 C(O)R 52 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 , -C(O)N(R 52 )2, -C(O)NR 53 R 54 , -P(O)(OR 52 )2, -P(O)(R 52 )2, =O, =S, =N(R52 )), C 3-12 A carbon ring and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time they appear, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl; and, C 3-12 A carbon ring and a 3- to 12-membered heterocycle, where each C in R 51 The carbon ring and the 3- to 12-membered heterocycle are each independently halogen, -NO2, -CN, -OR 3-12 , -SR 52 , -N(R 52 )2, -NR 52 )2, -NR 53 R 54 , -S(=O)R 52 , -S(=O)2R 52 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 )2, -NR 52 S(=O)2NR 53 R 54 , -C(O)R 52 , -C(O)OR 52 , -OC(O)R 52 , -OC(O)OR 52 , -OC(O)N(R 52 )2, -OC(O)NR 53 R 54 , -NR 52 C(O)R 52 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 , -C(O)N(R 52 )2, -C(O)NR 53 R 54 , -P(O)(OR 52 )2, -P(O)(R 52)2, =O, =S, =N(R 52 ), C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, and, C 2-6 alkynyl, optionally substituted with one or more substituents selected from C 3-12 carbocyclic ring and 3 - to 12 - membered heterocyclic ring; R 52 is, each time it appears, hydrogen; and, C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, 2 - to 6 - membered heteroalkyl, C 3-12 carbocyclic ring, and 3 - to 12 - membered heterocyclic ring, each of which is halogen, -CN, -NO2, -NH2, -NHCH3, -NHCH2CH3, =O, -OH, -OCH3, -OCH2CH3, C 3-12 carbocyclic ring, or 3 - to 6 - membered heterocyclic ring, optionally substituted; and, R 53 and R 54 together with the nitrogen atom to which they are attached form a heterocyclic ring optionally substituted with one or more R 50 wherein, for the compound or salt of formula (II), when W 3 is absent: W 1 is C1 alkylene, W 2 is a single bond, and L 3 is not a single bond; W 1 is C 2-4 alkylene, W 2 is a single bond; or, W 1 and W 2 are each C1 alkylene, and L 3 is not a single bond, where C1 alkylene is each independently optionally substituted with one or more R 50 In one aspect, the present disclosure provides a method for treating Ewing's sarcoma, the method comprising a compound of formula (III),

[0055]

[0056] ​ [Chemistry] or comprises administering to a subject the pharmaceutically acceptable salt or prodrug thereof, H is selected from a carbocyclic ring and a 3- to 12-membered heterocyclic ring, each of which is optionally substituted with one or more R 3-12 ; 50 and is optionally substituted with; A is

[0057] [Chemistry] and is; Z 1 , Z 2 , Z 3 , and Z 4 each independently is selected from -C(R A1 )(R A2 )-, -C(R A1 )(R A2 )-C(R A1 )(R A2 )-, -C(O)-, and -C(R A1 )(R A2 )-C(O)-, and only one of Z 1 , Z 2 , Z 3 , and Z 4 is -C(O)- or -C(R A1 )(R A2 )-C(O)-; B is selected from a single bond, a C 3-12 carbocyclic ring, and a 3- to 12-membered heterocyclic ring; C is selected from a single bond, a C 3-12 carbocyclic ring, and a 3- to 12-membered heterocyclic ring; L 1 , L 2 , and L 3 each independently is a single bond, -O-, -S-, -N(R 51 )-, -N(R 51 )CH2-, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R 51 )-, -C(O)N(R 51 )C(O)-, -C(O)N(R51 )C(O)N(R 51 )-, -N(R 51 )C(O)-, -N(R 51 )C(O)N(R 51 )-, -N(R 51 )C(O)O-, -OC(O)N(R 51 )-, -C(NR 51 )-, -N(R 51 )C(NR 51 )-, -C(NR 51 )N(R 51 )-, -N(R 51 )C(NR 51 )N(R 51 )-, -S(O)2-, -OS(O)-, -S(O)O-, -S(O)-, -OS(O)2-, -S(O)2O-, -N(R 51 )S(O)2-, -S(O)2N(R 51 )-, -N(R 51 )S(O)-, -S(O)N(R 51 )-, -N(R 51 )S(O)2N(R 51 )-, -N(R 51 )S(O)N(R 51 )-; independently selected from alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, and heteroalkynylene, each of which is optionally substituted with one or more R 50 where L 1 , L 2 , or L 3 Two R 50 groups bonded to the same or different atoms of any one of can optionally combine to form a bridge or a ring; R B is independently selected each time it appears from R 50 or two R B groups bonded to the same or different atoms can optionally combine to form a bridge or a ring; R C is independently selected each time it appears from hydrogen and R 50 or two R CThe groups are integrated and can optionally form a bridge or a ring; R A1 and R A2 are each independently selected from hydrogen and R 50 each time they appear; n is an integer from 0 to 6, p is an integer from 1 to 6; and / or, R 50 is each time it appears selected from the following: halogen, -NO2, -CN, -OR 52 , -SR 52 , -N(R 52 )2, -NR 53 R 54 , -S(=O)R 52 , -S(=O)2R 52 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 )2, -NR 52 S(=O)2NR 53 R 54 , -C(O)R 52 , -C(O)OR 52 , -OC(O)R 52 , -OC(O)OR 52 , -OC(O)N(R 52 )2, -OC(O)NR 53 R 54 , -NR 52 C(O)R 52 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 , -C(O)N(R 52 )2, -C(O)NR 53 R 54 , -P(O)(OR 52 )2, -P(O)(R 52 )2, -P(O)(OR 52)(R 52 )、-P(O)(NR 52 )(R 52 )、-NR 52 P(O)(R 52 )、-P(O)(NR 52 )(OR 52 )、-P(O)(NR 52 )2、=O、=S、=N(R 52 ); C 1-10 alkyl, C 2-10 alkenyl, and C 2-10 alkynyl, each of which is independently halogen, -NO2, -CN, -OR 52 , -SR 52 , -N(R 52 )2, -NR 53 R 54 , -S(=O)R 52 , -S(=O)2R 52 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 )2, -NR 52 S(=O)2NR 53 R 54 , -C(O)R 52 , -C(O)OR 52 , -OC(O)R 52 , -OC(O)OR 52 , -OC(O)N(R 52 )2, -OC(O)NR 53 R 54 , -NR 52 C(O)R 52 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 , -C(O)N(R 52 )2, -C(O)NR 53 R 54 , -P(O)(OR 52)2, -P(O)(R 52 )2, -P(O)(OR 52 )(R 52 )、-P(O)(NR 52 )(R 52 )、-NR 52 P(O)(R 52 )、-P(O)(NR 52 )(OR 52 )、-P(O)(NR 52 )2, =O, =S, =N(R 52 )、C 3-12 A carbon ring and one or more substituents selected from 3- to 12-membered heterocyclic rings, optionally substituted each time it appears, C 1-10 Alkyl, C 2-10 Alkenyl, and C 2-10 Alkynyl; and, C 3-12 A carbon ring and a 3- to 12-membered heterocyclic ring, where each C 50 In R 3-12 The carbon ring and the 3- to 12-membered heterocyclic ring are independently halogen, -NO2, -CN, -OR 52 , -SR 52 , -N(R 52 )2, -NR 53 R 54 , -S(=O)R 52 , -S(=O)2R 52 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 )2, -NR 52 S(=O)2NR 53 R 54 , -C(O)R 52 , -C(O)OR 52 , -OC(O)R 52 , -OC(O)OR 52 , -OC(O)N(R 52 )2, -OC(O)NR 53 R 54 , -NR 52 C(O)R 52 , -NR 52 C(O)OR52 、 -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 、 -C(O)N(R 52 )2, -C(O)NR 53 R 54 、 -P(O)(OR 52 )2, -P(O)(R 52 )2, -P(O)(OR 52 )(R 52 )、 -P(O)(NR 52 )(R 52 ), -NR 52 P(O)(R 52 ), -P(O)(NR 52 )(OR 52 ), -P(O)(NR 52 )2, =O, =S, =N(R 52 ), C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, and, C 2-6 alkynyl optionally substituted with one or more substituents selected from 3-12 carbocyclic and 3 - to 12 - membered heterocyclic rings; R 51 is, each time it appears, selected from the following: hydrogen, -C(O)R 52 , -C(O)OR 52 , -C(O)N(R 52 )2, -C(O)NR 53 R 54 ; C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, each of which is independently halogen, -NO2, -CN, -OR 52 , -SR 52 , -N(R 52 )2, -NR 53 R 54 , -S(=O)R 52 , -S(=O)2R 52 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 )2, -NR 52 S(=O)2NR 53 R 54 , -C(O)R 52 , -C(O)OR 52 , -OC(O)R 52 , -OC(O)OR 52 , -OC(O)N(R 52 )2, -OC(O)NR 53 R 54 , -NR 52 C(O)R 52 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 , -C(O)N(R 52 )2, -C(O)NR 53 R 54 , -P(O)(OR 52 )2, -P(O)(R 52 )2, -P(O)(OR 52 )(R 52 ), -P(O)(NR 52 )(R 52 ), -NR 52 P(O)(R 52 ), -P(O)(NR 52 )(OR 52 ), -P(O)(NR 52 )2, =O, =S, =N(R 52 ), C 3-12 A carbon ring and one or more substituents selected from 3- to 12-membered heterocyclic rings, optionally substituted each time they appear, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl; and, C 3-12 A carbon ring and a 3- to 12-membered heterocyclic ring, where each C in R 51 Each C in 3-12The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO2, -CN, -OR 52 , -SR 52 , -N(R 52 )2, -NR 53 R 54 , -S(=O)R 52 , -S(=O)2R 52 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 )2, -NR 52 S(=O)2NR 53 R 54 , -C(O)R 52 , -C(O)OR 52 , -OC(O)R 52 , -OC(O)OR 52 , -OC(O)N(R 52 )2, -OC(O)NR 53 R 54 , -NR 52 C(O)R 52 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 , -C(O)N(R 52 )2, -C(O)NR 53 R 54 , -P(O)(OR 52 )2, -P(O)(R 52 )2, -P(O)(OR 52 )(R 52 ), -P(O)(NR 52 )(R 52 ), -NR 52 P(O)(R 52 ), -P(O)(NR 52 )(OR 52 ), -P(O)(NR 52 )2, =O, =S, =N(R 52 ), C 1-6 alkyl, C 1-6Haloalkyl, C 2-6 Alkenyl, and, C 2-6 Optionally substituted with one or more substituents selected from alkynyl, C 3-12 Carbocyclic ring and 3- to 12-membered heterocyclic ring; R 52 Is, each time it appears, hydrogen; and, C 1-20 Alkyl, C 2-20 Alkenyl, C 2-20 Alkynyl, 1- to 6-membered heteroalkyl, C 3-12 Carbocyclic ring, and a 3- to 12-membered heterocyclic ring selected from, each of which is halogen, -CN, -NO2, -NH2, -NHCH3, -NHCH2CH3, =O, -OH, -OCH3, -OCH2CH3, C 3-12 Optionally substituted by a carbocyclic ring, or a 3- to 6-membered heterocyclic ring; and, R 53 And R 54 Together with the nitrogen atom to which they are attached, form a heterocyclic ring optionally substituted with one or more R 50 s.

[0058] In one aspect, the present disclosure provides a method for treating Ewing's sarcoma, the method comprising administering to a subject a compound of formula (IV),

[0059]

Chemical formula

[0060]

Chemical formula

[0061] In one aspect, the present disclosure provides a method for treating Ewing's sarcoma, the method comprising administering to a subject a compound of formula (VI),

[0062]

Chemical formula

[0063]

Chemical formula

[0064] In some embodiments, the subject exhibits an EWSR1-FLI1 gene fusion, an EWSR1-ERG gene fusion, or an EWSR1-FEV gene fusion. In some embodiments, the subject exhibits a FUS-NCATc2 gene fusion, a CIC-FOXO4 gene fusion, or an ETV6-NTRK3 gene fusion. In some embodiments, the subject exhibits a mutation in the STAG2 gene, a mutation in the TP53 gene, or a CDKN2A deletion.

[0065] In some embodiments, for the compound of formula (I-A) or formula (I-B), C is a 5- to 12-membered heterocyclic ring, and the heterocyclic ring contains at least one nitrogen atom. In some embodiments, the heterocyclic ring is saturated. In some embodiments, the heterocyclic ring is selected from piperidinyl and piperazinyl. In some embodiments, C is selected from the following:

[0066]

Chemical formula

[0067]

Chemical formula

[0068] In some embodiments, for the compound of formula (I-A), formula (I-B), formula (II), or formula (III), H is a 5- to 12-membered heterocyclic ring optionally substituted with one or more R 50 ; A is a 3- to 12-membered heterocyclic ring; and B is a 3- to 12-membered heterocyclic ring.

[0069] In some embodiments, for the compound of formula (I-A), formula (I-B), formula (II), or formula (III), H is a 5- to 12-membered bicyclic heterocyclic ring optionally substituted with one or more R 50 . In some embodiments, H is thienopyrimidinyl optionally substituted with one or more R 50 .

[0070] In some embodiments, for the compounds of formula (I-A), formula (I-B), formula (II), or formula (III), H is

[0071]

Chemical formula

[0072] In some embodiments, for the compounds of formula (I-A), formula (I-B), or formula (II), A is a 5- to 8-membered heterocycle. In some embodiments, A is a 6-membered monocyclic heterocycle. In some embodiments, the heterocycle contains at least one nitrogen atom. In some embodiments, A is selected from piperidinylene and piperazinylene. In some embodiments, A is

[0073]

Chemical formula

[0074] In some embodiments, for the compounds of formula (I-A), formula (I-B), formula (II), formula (III), or formula (VI), A is a 7- to 12-membered spirocyclic heterocycle or a C7-12 spirocyclic carbocycle. In some embodiments, A is a 7- to 12-membered heterocyclic heterocycle such as a 7- to 10-membered spirocyclic heterocycle. In some embodiments, A is

[0075]

Chemical formula

[0076]

Chemical formula

[0077] In some embodiments, for the compounds of formula (I-A), formula (I-B), formula (II), formula (III), or formula (VI), B is a 6- to 12-membered bicyclic heterocycle. In some embodiments, the heterocycle contains at least one nitrogen atom. In some embodiments, B is indolylene. In some embodiments, B is optionally substituted with one or more R B ;

[0078]

Chemical formula

[0079] In some embodiments, for the compounds of formula (I-A), formula (I-B), or formula (II), H is one or more R 50 substituted thienopyrimidinyl; A is selected from piperidinylene and piperazinylene; and B is indolylene.

[0080] In some embodiments, for the compounds of formula (I-A), formula (I-B), or formula (II), H is substituted with -CH2CF3.

[0081] In some embodiments, for the compounds of formula (I-A), formula (I-B), or formula (II), m is 0. In some embodiments, for the compounds of formula (I-A), formula (I-B), formula (II), formula (III), or formula (VI), n is an integer from 1 to 3.

[0082] In some embodiments, for the compounds of formula (I-A), formula (I-B), formula (II), formula (III), or formula (VI), L 1 contains less than 10 atoms. In some embodiments, L 1 is -N(R 51 ).

[0083] In some embodiments, for the compounds of formula (I-A), formula (I-B), formula (II), formula (III), or formula (VI), L 2 contains less than 10 atoms. In some embodiments, L 2 is C 50 alkylene optionally substituted with one or more R 1-4 . In some embodiments, L 2 is selected from -CH2-, -N(R 51 ), -N(R 51 )CH2-, -N(R 51 )C(O)-, and -N(R 51 )S(O)2-.

[0084] In some embodiments, for a compound of formula (I-A), formula (I-B), formula (II), or formula (III), L 3 contains fewer than 20 atoms. In some embodiments, L 3 is C 50 alkylene optionally substituted with one or more R 1-6 . In some embodiments, L 3 is C 50 alkylene optionally substituted with one or more R 1-4 . In some embodiments, L 3 is -CH2-. In some embodiments, L 3 is C2 alkylene substituted with at least one C 1-3 alkyl or C 1-3 haloalkyl and optionally further substituted with one or more R 50 . In some embodiments, L 3 is substituted with =O, C 1-6 alkyl, C 1-6 haloalkyl, C 1-3 alkyl(cyclopropyl), C 1-3 alkyl(NR 52 C(O)R 52 ) or -O(C 1-6 alkyl). In some embodiments, L 3 is substituted with -CH3. In some embodiments, L 3 is

[0085]

Chem.

[0086]

Chem.

[0087] In some embodiments, for a compound of formula (I-A), formula (I-B), or formula (II), H is thienopyrimidinyl optionally substituted with one or more R 50 ; A is a 3- to 12-membered heterocyclic ring; B is a 6- to 12-membered bicyclic heterocyclic ring; m is an integer from 0 to 3; and n is an integer from 1 to 3.

[0088] In some embodiments, for a compound of formula (I-A), H is thienopyrimidinyl optionally substituted with one or more R 50 ; A is selected from piperidinylene and piperazinylene; B is indolylene; L 1 and L 2 are each independently selected from -O-, -S-, -NH-, or -CH2-; L 3 is a single bond, -O-, -S-, -N(R 51 ), -N(R 51 )CH2-, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R 51 ), -C(O)N(R 51 )C(O)-, -C(O)N(R 51 )C(O)N(R 51 ), -N(R 51 )C(O)-, -N(R 51 )C(O)N(R 51 ), -N(R 51 )C(O)O-, -OC(O)N(R 51 ), -C(NR 51 ), -N(R 51 )C(NR 51 ), -C(NR 51 )N(R 51 ), -N(R 51 )C(NR 51 )N(R 51 ), -S(O)2-, -OS(O)-, -S(O)O-, -S(O)-, -OS(O)2-, -S(O)2O-, -N(R 51 )S(O)2-, -S(O)2N(R 51)-, -N(R 51 )S(O)-, -S(O)N(R 51 )-, -N(R 51 )S(O)2N(R 51 )-, -N(R 51 )S(O)N(R 51 )-; independently selected from alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, and heteroalkynylene, each of which is optionally substituted with one or more R 50 and two R 3 groups bonded to the same or different atoms of L 50 can optionally form a ring together; R A , R B , and R C are each independently selected each time they appear from R 50 or two R A groups, two R B groups or two R C groups can optionally form a ring together; m is an integer from 0 to 3; n is an integer from 1 to 3; p is an integer from 0 to 6; R 57 is selected from the following: -S(=O)R 52 , -S(=O)2R 58 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 )2, -NR 52 S(=O)2NR 53 R 54 , -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 , -C(O)NH(C 1-6(alkyl), -C(O)NR 53 R 54 , -P(O)(OR 52 )2, -P(O)(R 52 )2, -P(O)(OR 52 )(R 52 ), -P(O)(NR 52 )(R 52 ), -NR 52 P(O)(R 52 ), -P(O)(NR 52 )(OR 52 ), -P(O)(NR 52 )2; and, C 1-10 alkyl, C 2-10 alkenyl, and C 2-10 alkynyl, each of which is independently -S(=O)R 52 , -S(=O)2R 58 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 ), -NR 52 S(=O)2NR 53 R 54 , -NR 52 C(O)N(R 52 ), -NR 52 C(O)NR 53 R 54 , -C(O)NH(C 1-6 alkyl), -C(O)NR 53 R 54 , -P(O)(OR 52 )2, and, -P(O)(R 52 )2, -P(O)(OR 52 )(R 52 ), -P(O)(NR 52 )(R 52 ), -NR 52 P(O)(R 52 ), -P(O)(NR 52 )(OR 52 ), -P(O)(NR 52 )2, each time it appears, C selected from1-10 Alkyl, C 2-10 Alkenyl, and C 2-10 Alkynyl; R 58 is hydrogen; and C 1-20 Alkyl, C 3-20 Alkenyl, C 2-20 Alkynyl, 1- to 6-membered heteroalkyl, C 3-12 carbocyclic, and 3- to 12-membered heterocyclic, each of which is optionally substituted by halogen, -CN, -NO2, -NH2, -NHCH3, -NHCH2CH3, =O, -OH, -OCH3, -OCH2CH3, C 3-12 carbocyclic, or 3- to 6-membered heterocyclic.

[0089] In some embodiments, for the compounds of formula (I-B), H is thienopyrimidinyl optionally substituted with one or more R 50 ; A is selected from piperidinylene and piperazinylene; B is indolylene; L 1 and L 2 are each independently selected from -O-, -S-, -NH-, or -CH2-; L 3 is C 1-6 alkylene, C 2-6 alkenylene, and C 2-6 alkynylene, each of which is substituted with one or more R 56 and optionally further substituted with one or more R 50 ; R A , R B , and R C are each independently selected each time they occur from R 50 , or two R A groups, two R B groups, or two R C groups attached to the same or different atoms may combine together to optionally form a bridge or a ring; m is an integer from 0 to 3; n is an integer from 1 to 3; p is an integer from 0 to 6; R 56 is, each time it appears, -OR 59 , =O, C 1-10 alkyl, C 2-10 alkenyl, and C 2-10 alkynyl selected from, R 56 each C in 1-10 alkyl, C 2-10 alkenyl, and C 2-10 alkynyl is independently halogen, -NO2, -CN, -OR 59 , -SR 52 , -N(R 52 )2, -NR 53 R 54 , -S(=O)R 52 , -S(=O)2R 52 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 )2, -NR 52 S(=O)2NR 53 R 54 , -C(O)R 52 , -C(O)OR 52 , -OC(O)R 52 , -OC(O)OR 52 , -OC(O)N(R 52 )2, -OC(O)NR 53 R 54 , -NR 52 C(O)R 52 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 , -C(O)N(R 52 )2, -C(O)NR 53 R 54 , -P(O)(OR 52 )2, -P(O)(R52 ) 2, -P(O)(OR 52 )(R 52 )、-P(O)(NR 52 )(R 52 )、-NR 52 P(O)(R 52 )、-P(O)(NR 52 )(OR 52 )、-P(O)(NR 52 )2、=O、=S、=N(R 52 )、C 3-12 a carbon ring, and one or more substituents selected from 3- to 12-membered heterocyclic rings, optionally substituted each time it appears, R 56 each C 3-12 in the carbon ring and 3- to 12-membered heterocyclic rings is independently halogen, -NO2, -CN, -OR 52 、-SR 52 、-N(R 52 )2、-NR 53 R 54 、-S(=O)R 52 、-S(=O)2R 52 、-S(=O)2N(R 52 )2、-S(=O)2NR 53 R 54 、-NR 52 S(=O)2R 52 、-NR 52 S(=O)2N(R 52 )2、-NR 52 S(=O)2NR 53 R 54 、-C(O)R 52 、-C(O)OR 52 、-OC(O)R 52 、-OC(O)OR 52 、-OC(O)N(R 52 )2、-OC(O)NR 53 R 54 、-NR 52 C(O)R 52 、-NR 52 C(O)OR 52 、-NR 52 C(O)N(R 52 )2、-NR 52 C(O)NR 53 R 54 、-C(O)N(R52 ) 2, -C(O)NR 53 R 54 , -P(O)(OR 52 )2, -P(O)(R 52 )2, -P(O)(OR 52 )(R 52 ), -P(O)(NR 52 )(R 52 ), -NR 52 P(O)(R 52 ), -P(O)(NR 52 )(OR 52 ), -P(O)(NR 52 )2, =O, =S, =N(R 52 ), C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, and C 2-6 alkynyl, optionally substituted with one or more substituents selected from and, where R 56 optionally forms a single bond to ring C; and R 59 is independently selected each time it occurs from C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, 1-6 membered heteroalkyl, C 3-12 carbocyclic ring, and 3-12 membered heterocyclic ring, each of which is optionally substituted with halogen, -CN, -NO2, -NH2, -NHCH3, -NHCH2CH3, =O, -OH, -OCH3, -OCH2CH3, C 3-12 carbocyclic ring, or 3-6 membered heterocyclic ring.

[0090] In some embodiments, for the compounds of formula (I-A), R 57 is selected from -S(=O)2R 58 , -S(=O)2N(R 52 )2, and -S(=O)2NR 53 R 54 . In some embodiments, R 57 is selected from -S(=O)2CH3 and -S(=O)2NHCH3.

[0091] In some embodiments, for the compound of formula (I-A), C is -S(=O)2R 58 , -S(=O)2N(R 52 )2, or -S(=O)2NR 53 R 54 substituted.

[0092] In some embodiments, for the compounds of formula (I-A), formula (I-B), formula (II), or formula (III), H is

[0093]

Chem.

[0094] In some embodiments, for the compounds of formula (I-A), formula (I-B), formula (II), or formula (III), L 3 is

[0095]

Chem.

[0096] In some embodiments, for formula (I-A), formula (I-B), formula (II), formula (III), or formula (VI), the compound is provided as a substantially pure stereoisomer. In some embodiments, the stereoisomer is provided with an enantiomeric excess of at least 90%. In some embodiments, for formula (I-A), formula (I-B), formula (II), formula (III), formula (IV), or formula (VI), the compound is isotopically enriched. In some embodiments, for the compound of formula (I-A) or formula (I-B), the compound is selected from Table 1. In some embodiments, with respect to the compound of formula (II), the compound is in some embodiments, for the compound of formula (III), the compound is selected from Table 3, Table 5, or Table 7. In some embodiments, with respect to the compound of formula (IV), the compound is selected from Table 4. In some embodiments, with respect to the compound of formula (IV), the compound is selected from Table 4.

[0097] In some embodiments, for the compound of formula (II), W 1 , W 2 , and W 3 are each independently selected from C 1-4 alkylene, where C 1-4 alkylene are each optionally substituted with one or more R 50 . In some embodiments, W 1 , W 2 , and W 3 are each C1 alkylene. In some embodiments, W 1 and W 2 are each C1 alkylene and W 3 is absent.

[0098] In some embodiments, for the compound of formula (II), R C is -N(R 52 )2, -NR 53 R 54 , -NR 52 S(=O)2R 52 , -C(O)R 52 , -C(O)OR 52 , -NR52 C(O)R 52 、 -NR 52 C(O)OR 52 、 -NR 52 C(O)N(R 52 )2、 -NR 52 C(O)NR 53 R 54 、 -C(O)N(R 52 )2、 and -C(O)NR 53 R 54 is selected from.

[0099] In some embodiments, the methods described herein further comprise reducing the expression of a target gene. In some embodiments, the target gene is selected from Hoxa5, Hoxa7, Hoxa9, Hoxa10, Hoxb2, Hoxb3, Hoxb4, Hoxb5, Hoxb8, Hoxd10, Hoxd11, Hoxd13, DLX2, PBX3, Meis1, Mir196b, Flt3, and Bahcc1. In some embodiments, the target gene is Hoxa9, DLX2, PBX3, or Meis1. In some embodiments, the methods described herein comprise administering a second therapeutic agent. In some embodiments, the second therapeutic agent is a DOT1L inhibitor. In some embodiments, the second therapeutic agent is an FLT3 inhibitor. In some embodiments, the FLT3 inhibitor is romidepsin. In some embodiments, the FLT3 inhibitor is midostaurin. In some embodiments, the subject is human. In some embodiments, the methods described herein further comprise obtaining a nucleic acid sample from the subject. In some embodiments, the nucleic acid sample comprises a nucleic acid selected from genomic DNA, cDNA, circulating tumor DNA, cell-free DNA, RNA, and mRNA. In some embodiments, the methods described herein further comprise obtaining a biological sample from the subject. In some embodiments, the biological sample is a tissue sample. In some embodiments, the tissue sample is fixed, paraffin-embedded, fresh, or frozen. In some embodiments, the tissue sample is derived from a fine needle, core, or other type of biopsy. In some embodiments, the biological sample is whole blood or plasma. In some embodiments, the methods described herein further comprise performing nucleic acid analysis on the nucleic acid sample. In some embodiments, the nucleic acid analysis comprises PCR, sequencing, hybridization, microarray, SNP, cell-free nucleic acid analysis, or whole genome sequencing.In some embodiments, the subject was tested for the presence of a nucleoporin 98 (NUP98) gene fusion, a mutation in the nucleophosmin (NPM1) gene, a mutation in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, or mixed lineage leukemia (MLL) gene amplification. In some embodiments, the methods described herein further comprise testing the subject for the presence of a nucleoporin 98 (NUP98) gene fusion, a mutation in the nucleophosmin (NPM1) gene, a mutation in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, or mixed lineage leukemia (MLL) gene amplification.

[0100] In some embodiments, the subject was tested for the presence of nucleoporin 98 (NUP98) gene fusions, mutations in the nucleophosmin (NPM1) gene, mutations in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, mutations in the FMS-like tyrosine kinase-3 (FLT3) gene, mutations in the isocitrate dehydrogenase 1 (IDH1) gene, mutations in the isocitrate dehydrogenase 2 (IDH2) gene, or mixed lineage leukemia (MLL) gene amplification. In some embodiments, the methods described herein further comprise testing the subject for the presence of nucleoporin 98 (NUP98) gene fusions, mutations in the nucleophosmin (NPM1) gene, mutations in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, mutations in the FMS-like tyrosine kinase-3 (FLT3) gene, mutations in the isocitrate dehydrogenase 1 (IDH1) gene, mutations in the isocitrate dehydrogenase 2 (IDH2) gene, or mixed lineage leukemia (MLL) gene amplification. In some embodiments, the subject was tested for the presence of MLL rearrangement, partial tandem duplication of MLL, or increased MEIS1 expression level. In some embodiments, the methods described herein further comprise testing the subject for the presence of MLL rearrangement, partial tandem duplication of MLL, or increased MEIS1 expression level. Incorporation by reference

[0101] All publications, patents, or patent applications mentioned herein are hereby incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually incorporated by reference.

Brief Description of the Drawings

[0102] The novel features of the invention are particularly set forth in the appended claims. A better understanding of the features and advantages of the invention will be obtained by reference to the following detailed description that illustrates embodiments in which the principles of the invention are utilized and to the following appended drawings.

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6A

Figure 6B

Figure 6C

Figure 7A

Figure 7B

Figure 7C

Figure 8A

Figure 8B

Figure 9A

Figure 9B

Figure 9C

Figure 9D

Figure 9E

Figure 10

Figure 11

Figure 12

Figure 13

Modes for Carrying Out the Invention

[0103] The present invention provides compositions and methods useful for treating hematological malignancies and Ewing sarcoma. In one aspect, the present invention provides a method for treating hematological malignancies such as acute myeloid leukemia in a subject presenting with a nucleoporin 98 (NUP98) gene fusion, a mutation in the nucleophosmin (NPM1) gene, a mutation in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, a mutation in the FMS-like tyrosine kinase-3 (FLT3) gene, a mutation in the isocitrate dehydrogenase 1 (IDH1) gene, a mutation in the isocitrate dehydrogenase 2 (IDH2) gene, or a mixed-lineage leukemia (MLL) gene amplification. In one aspect, the present invention provides a method for treating hematological malignancies such as acute myeloid leukemia or acute lymphoblastic leukemia in a subject presenting with MLL rearrangement, optionally, the subject further presents with an elevated MEIS1 expression level. In some embodiments, the subject presents with a partial tandem duplication of MLL (MLL-PTD). The subject methods generally include administering a menin inhibitor to a subject in need thereof. In some embodiments, the menin inhibitor administered for treating hematological malignancies is a compound of formula (I-A) or a compound of formula (I-B). In some embodiments, the menin inhibitor administered for treating hematological malignancies is a compound of formula (II). In some embodiments, the menin inhibitor administered for treating hematological malignancies is a compound of formula (III). In some embodiments, the menin inhibitor administered for treating hematological malignancies is a compound of formula (IV). In some embodiments, the menin inhibitor administered for treating hematological malignancies is a compound of formula (VI).

[0104] In another aspect, the present invention provides a method of treating Ewing's sarcoma by administering a menin inhibitor to a subject in need thereof. In some embodiments, the menin inhibitor administered to treat Ewing's sarcoma is a compound of formula (I-A) or a compound of formula (I-B). In some embodiments, the menin inhibitor administered to treat Ewing's sarcoma is a compound of formula (II). In some embodiments, the menin inhibitor administered to treat Ewing's sarcoma is a compound of formula (III). In some embodiments, the menin inhibitor administered to treat Ewing's sarcoma is a compound of formula (IV). In some embodiments, the menin inhibitor administered to treat Ewing's sarcoma is a compound of formula (VI).

[0105] In some embodiments, the subject being treated is tested for the presence of genetic abnormalities or mutations. Optionally, the subject is tested for the presence of a nucleoporin 98 (NUP98) gene fusion, a mutation in the nucleophosmin (NPM1) gene, a mutation in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, a mutation in the FMS-like tyrosine kinase-3 (FLT3) gene, a mutation in the isocitrate dehydrogenase 1 (IDH1) gene, a mutation in the isocitrate dehydrogenase 2 (IDH2) gene, or an amplification of the mixed lineage leukemia (MLL) gene. Optionally, the subject is tested for an increase in MLL MEIS1 expression, MLL rearrangement, or partial tandem duplication. A wide variety of nucleic acid samples and assays are available for such testing. The nucleic acid sample may be obtained from the subject. Optionally, the nucleic acid sample comprises a nucleic acid selected from genomic DNA, cDNA, circulating tumor DNA, cell-free DNA, RNA, and mRNA. A biological sample may be obtained from the subject. Optionally, the biological sample is a tissue sample (e.g., a fixed, paraffin-embedded, fresh, or frozen tissue sample). The tissue sample is derived from a fine needle, core, or other type of biopsy. Optionally, the biological sample is whole blood or plasma.

[0106] In some embodiments, nucleic acid analysis may be performed on a biological sample containing nucleic acids. Non-limiting examples of nucleic acid analysis include PCR, sequencing, hybridization, microarray, SNP, cell-free nucleic acid analysis, and whole genome sequencing.

[0107] The subject may exhibit a nucleoporin 98 (NUP98) gene fusion. In some cases, the nucleoporin 98 (NUP98) gene fusion is a gene fusion of NUP98 and a homeodomain partner gene. In some cases, the nucleoporin 98 (NUP98) gene fusion is a gene fusion of NUP98 and a non-homeodomain partner gene. In some cases, the nucleoporin 98 (NUP98) gene fusion is a gene fusion of NUP98 and a partner gene selected from HOXA9, HOXA11, HOXA13, HOXC11, HOXC13, HOXD11, HOXD13, PMX1, PMX2, HHEX, PHF23, JARID1A, NSD1, NSD3, MLL, SETBP1, LEDGF, CCDC28, HMGB3, IQCG, RAP1GDS1, ADD3, DDX10, TOP1, TOP2B, LNP1, RARG, ANKRD28, and POU1F1.

[0108] The subject may exhibit a mutation in the nucleophosmin (NPM1) gene. In some cases, the mutation in the nucleophosmin (NPM1) gene is a mutation in exon 12 of the NPM1 gene. In some cases, the mutation in the nucleophosmin (NPM1) gene is a frameshift mutation. In some cases, the mutation in the nucleophosmin (NPM1) gene includes an insertion of 2-9 bases, such as an insertion of 4 bases (e.g., TCTG, CATG, CCTG, CGTG, CAGA, CTTG, and TATG). In some cases, the insertion is an insertion of 9 bases (e.g., CTCTTGCCC and CCCTGGAGA). In some cases, the mutation in the nucleophosmin (NPM1) gene includes a deletion of nucleotides 965-969 (GGAGG).

[0109] Subjects may exhibit mutations in the FLT3 gene. In some embodiments, the mutation in the FLT3 gene is an internal tandem duplication (FLT3-ITD). In some cases, the mutation in the FLT3 gene is an in-frame internal tandem duplication mutation of the nucleotide sequence within exon 14. The size of the FLT3-ITD mutation may vary from 3 to over 400 bp. In some cases, the FLT3-ITD mutation is close to residues 590-600 of the FLT3 amino acid sequence. The FLT3-ITD mutation may be located in exon 14, exon 15, and / or the intron between exons 14 and 15. Subjects may contain both a partial tandem duplication of the MLL gene and the FLT3-ITD mutation. Subjects may exhibit FLT3 activating mutations. In some cases, the mutation in the FLT3 gene is a point mutation involving the tyrosine kinase domain. In some cases, the mutation in the FLT3 gene is a point mutation at aspartate 835 or isoleucine 836.

[0110] Subjects may exhibit mutations in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene. In some cases, the mutation in the DNMT3A gene is a mutation at R882. In some cases, the mutation in the DNMT3A gene is not a mutation at R882. In some cases, the mutation in the DNMT3A gene is a frameshift deletion, missense mutation, nonsense mutation, splice site substitution, splice site deletion, or whole gene deletion.

[0111] The subject may have a mutation in the isocitrate dehydrogenase 1 (IDH1) gene or the isocitrate dehydrogenase 2 (IDH2) gene. In some cases, the mutation in the isocitrate dehydrogenase 1 (IDH1) gene is a heterozygous point mutation in codon 132. In some cases, the mutation in the isocitrate dehydrogenase 2 (IDH2) gene is a heterozygous point mutation in codon 172 or 140. In some embodiments, the mutation in the isocitrate dehydrogenase 2 (IDH2) gene is R140Q.

[0112] The subject may have one or more of an NPM1 mutation, an FLT3 mutation, an IDH1 mutation, an IDH2 mutation, and a DNMT3A mutation. In some cases, the subject has an NPM1 mutation, an FLT3 mutation, an IDH2 mutation, and a DNMT3A mutation. In some cases, the subject has an NPM1 mutation, an IDH1 mutation, an FLT3 mutation, and a DNMT3A mutation. In some cases, the subject has an NPM1 mutation, an FLT3 mutation, and a DNMT3A mutation. In some cases, the subject has an NPM1 mutation, an FLT3 mutation, and an IDH1 mutation. In some cases, the subject has an NPM1 mutation, an FLT3 mutation, and an IDH2 mutation. In some cases, the subject has an NPM1 mutation, a DNMT3A mutation, and an IDH1 mutation. In some cases, the subject has an NPM1 mutation, a DNMT3A mutation, and an IDH2 mutation. In some cases, the subject has an NPM1 mutation and an FLT3 mutation.

[0113] The subject may have a mixed lineage leukemia (MLL) gene amplification. The subject may have a mixed lineage leukemia (MLL) gene rearrangement. The subject may have an 11q23 rearrangement. The subject may have a partial tandem duplication of MLL.

[0114] The subject may exhibit an EWSR1-FLI1 gene fusion, an EWSR1-ERG gene fusion, or an EWSR1-FEV gene fusion. In some embodiments, the subject may exhibit a FUS-NCATc2 gene fusion, a CIC-FOXO4 gene fusion, or an ETV6-NTRK3 gene fusion. In some embodiments, the subject may exhibit a mutation in the STAG2 gene, a mutation in the TP53 gene, or a CDKN2A deletion.

[0115] The subject has a myeloid ectopic viral integration site 1 homolog (MEIS1) expression level (MEIS1 high) may exhibit an increase. As used herein, "expression" refers to the process by which a polynucleotide is transcribed into mRNA and / or the process by which the transcribed mRNA (also referred to as the "transcript") is subsequently translated into a peptide, polypeptide, or protein. The transcript and the encoded polypeptide are collectively referred to as the "gene product". When the polynucleotide is derived from genomic DNA, expression may include splicing of the mRNA in eukaryotic cells. The level of expression (alternatively, "expression level") of the MEIS1 gene can be determined, for example, by determining the levels of MEIS1 polynucleotide, polypeptide, and / or gene product. "Differentially expressed" or "differential expression" as applied to a nucleotide sequence or polypeptide sequence of a subject refers to the differential production of mRNA transcribed and / or translated from the nucleotide sequence or the protein product encoded by the nucleotide sequence. A differentially expressed sequence may be overexpressed or underexpressed compared to the expression level of a reference sample (i.e., the reference level). As used herein, an increase in expression level refers to an increase in expression, i.e., at least usually 1.25-fold, alternatively at least 1.5-fold, alternatively at least 2-fold, alternatively at least 3-fold, alternatively at least 4-fold, alternatively at least 10-fold of the expression detected in the reference sample. As used herein, underexpression refers to a decrease in expression, which is usually at least 1.25-fold, alternatively at least 1.5-fold, alternatively at least 2-fold, alternatively at least 3-fold, alternatively at least 4-fold, alternatively at least 10-fold less than that detected in the reference sample. Underexpression includes the absence of expression of a particular sequence as evidenced by the absence of detectable expression in the test subject compared to the reference sample.

[0116] The present disclosure provides compounds for modulating the interaction of menin with proteins such as MLL1, MLL2, and MLL fusion oncoproteins. In certain embodiments, the present disclosure provides compounds and methods for inhibiting the interaction of menin with its upstream or downstream signaling molecules including, but not limited to, MLL1, MLL2, and MLL fusion oncoproteins. The compounds of the present disclosure may be used in methods for the treatment of a variety of cancers and other diseases associated with one or more of MLL1, MLL2, MLL fusion proteins, and menin, such as hematological malignancies and Ewing sarcoma. In some cases, the hematological malignancies include NUP98 gene fusions, mutations in the nucleophosmin (NPM1) gene, mutations in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, mutations in the FMS-like tyrosine kinase-3 (FLT3) gene, mutations in the isocitrate dehydrogenase 1 (IDH1) gene, mutations in the isocitrate dehydrogenase 2 (IDH2) gene, and / or mixed-lineage leukemia (MLL) gene amplifications. In certain embodiments, the compounds of the present disclosure interact non-covalently with menin and inhibit the interaction of menin with MLL. In certain embodiments, the compounds of the present disclosure covalently bind to menin and inhibit the interaction of menin with MLL.

[0117] In some aspects, the present disclosure provides a compound or a salt thereof that selectively binds to the menin protein and / or modulates the interaction of menin with an MLL protein (e.g., MLL1, MLL2, or an MLL fusion protein). In certain embodiments, the compound modulates the menin protein by binding to or interacting with one or more amino acids and / or one or more metal ions. Certain compounds may occupy the pockets of F9 and / or P13 of menin. The binding of the compounds disclosed herein may interfere with downstream signaling of menin or MLL (e.g., MLL1, MLL2, or an MLL fusion protein).

[0118] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0119] "Nucleoporin 98 (NUP98) gene fusion" refers to a gene encoding a protein that is an N-terminal fragment of NUP98 fused to a partner protein. "Nucleoporin 98 (NUP98) fusion protein" refers to a protein having an N-terminal fragment of NUP98 that is fused to a partner protein. Non-limiting examples of partner proteins include HOXA9, HOXA11, HOXA13, HOXC11, HOXC13, HOXD11, HOXD13, PMX1, PMX2, HHEX, PHF23, JARID1A, NSD1, NSD3, MLL, SETBP1, LEDGF, CCDC28, HMGB3, IQCG, RAP1GDS1, ADD3, DDX10, TOP1, TOP2B, LNP1, RARG, ANKRD28, and POU1F1. The NUP98 fusion protein may be generated through the joining of the gene encoding NUP98 and the gene encoding the partner protein that generates the fusion gene. Translation of this fusion gene may result in one or more polypeptides having functional properties derived from each of the original proteins.

[0120] The term "MLL fusion protein" refers to a protein having an N-terminal fragment of MLL that is fused to a partner protein. Non-limiting examples of partner proteins include 11q23, 11q23.3, 11q24, 1p13.1, 1p32 (EPS15), 21q22, 9p13.3, 9p22 (MLLT3 / AF9), ABI1, ABI2, ACACA, ACTN4, AFF1 / AF4, AFF3 / LAF4, AFF4 / AF5, AKAP13, AP2A2, ARHGEF12, ARHGEF17, BCL9L, BTBD18, BUD13, C2CD3, CASC5, CASP8AP2, CBL, CEP164, CEP170B, CREBBP, DCP1A, DCPS, EEFSEC / SELB, ELL, EPS15, FLNA, FNBP1, FOXO3, GAS7, GMPS, KIAA1524, LAMC3, LOC100131626, MAML2, ME2, MLLT1 / ENL, MLLT10 / AF10, MLLT11 / AF1Q, MLLT3 / AF9, MLLT4 / AF6, MLLT6 / AF17, MYH11, MYO1F, NA, NEBL, NRIP3, PDS5A, PICALM, PRPF19, PTD, RUNDC3B, SEPT11, SEPT2, SEPT5, SEPT6, SEPT9, SMAP1, TET1, TNRC18, TOP3A, VAV1, and Xq26.3 (CT45A2). The MLL fusion protein may also be generated through the binding of a gene encoding the MLL protein and a gene encoding a partner protein that generates a fusion gene. Translation of this fusion gene may result in one or more polypeptides having functional properties derived from each of the original proteins.

[0121] The term "C x-y " or "C x -C y ", when used in combination with a chemical moiety such as alkyl, alkynyl, or alkenyl, means a group containing from x to y carbons in the chain. For example, the term "C x-y alkyl" refers to a substituted or unsubstituted saturated hydrocarbon group containing straight-chain alkyl and branched-chain alkyl groups containing from x to y carbons in the chain. "C x-y"Alkenyl" and "C" x-y "Alkynyl" refers to a substituted or unsubstituted straight-chain or branched-chain unsaturated hydrocarbon group each containing at least one double or triple bond. Unless specifically defined otherwise herein, C x-y alkyl, C x-y alkenyl, or C x-y alkynyl is optionally substituted by one or more substituents such as the substituents described herein.

[0122] "Carbocyclic ring" refers to a saturated, unsaturated, or aromatic ring in which each atom of the ring is a carbon atom. The carbocyclic ring can include 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 6- to 12-membered bridged rings. The rings of the bicyclic carbocyclic ring can each be selected from a saturated ring, an unsaturated ring, and an aromatic ring. In some embodiments, the carbocyclic ring is aryl. In some embodiments, the carbocyclic ring is cycloalkyl. In some embodiments, the carbocyclic ring is cycloalkenyl. In a typical embodiment, an aromatic ring (e.g., phenyl) may be fused to a saturated or unsaturated ring, such as cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated bicyclic rings, unsaturated bicyclic rings, and aromatic bicyclic rings is included in the definition of carbocyclic as long as the valences permit. Typical carbocyclic rings include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. Unless specifically defined otherwise herein, the carbocyclic ring is optionally substituted by one or more substituents such as the substituents described herein.

[0123] "Heterocyclic ring" refers to a saturated ring, unsaturated ring, or aromatic ring containing one or more heteroatoms. Typical heteroatoms include atoms of N, O, Si, P, B, and S. The heterocyclic ring can include 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 6- to 12-membered bridged rings. The rings of the bicyclic heterocyclic ring can each be selected from a saturated ring, unsaturated ring, and aromatic ring. The heterocyclic ring may be bonded to the remainder of the molecule via any atom of the heterocyclic ring, such as a carbon atom or nitrogen atom of the heterocyclic ring, as permitted by the valence. In some embodiments, the heterocyclic ring is heteroaryl. In some embodiments, the heterocyclic ring is heterocycloalkyl. In a typical embodiment, the heterocyclic ring (e.g., pyridyl) may be fused to a saturated or unsaturated ring, such as cyclohexane, cyclopentane, or cyclohexene.

[0124] "Heteroaryl" refers to a 3- to 12-membered aromatic ring containing at least one heteroatom, where each heteroatom can be independently selected from N, O, and S. As used herein, a heteroaryl ring may be selected from monocyclic or bicyclic, and fused or bridged ring systems, where at least one of the rings in the ring system is aromatic, i.e., contains a cyclic delocalized (4n + 2)π-electron system according to Hückel's theory. The heteroatoms in heteroaryl can be optionally oxidized. One or more nitrogen atoms, if present, can be optionally quaternized. Heteroaryl may be attached to the remainder of the molecule through any atom of the heteroaryl, such as a carbon atom or nitrogen atom of the heteroaryl, as valence permits. Examples of heteroaryl include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzindolyl, 1,3-benzodioxolyl, benzofuranyl, benzoxazolyl, benz[d]thiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, benzo[b][1,4]oxazinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl, benzo[3,2-d]pyrimidinyl, benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, cyclopenta[d]pyrimidinyl, 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, 5,6-dihydrobenzo[h]quinazolinyl, 5,6-dihydrobenzo[h]cinnolinyl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-pyridazinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furanonyl, furo[3,2-c]pyridinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyrimidinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyridazinyl, 5,6,7,8,9,10-Hexahydrocycloocta[d]pyridinyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, 5,8-methano-5,6,7,8-tetrahydroquinazolinyl, naphthyridinyl, 1,6-naphthyridinonyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 5,6,6a,7,8,9,10,10a-octahydrobenzo[h]quinazolinyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyrazolo[3,4-d]pyrimidinyl, pyridinyl, pyrido[3,2-d]pyrimidinyl, pyrido[3,4-d]pyrimidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, 5,6,7,8-tetrahydroquinazolinyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, 6,7,8,9-tetrahydro-5H-cyclohepta[4,5]thieno[2,3-d]pyrimidinyl, 5,6,7,8-tetrahydropyrido[4,5-c]pyridazinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, thieno[2,3-c]purinyl, and thiophenyl (i.e., thienyl). Unless specifically defined otherwise herein, the term “heteroaryl” means including heteroaryl as defined above, optionally substituted by one or more substituents such as those described herein.,

[0125] The compounds of the present disclosure include crystalline and amorphous forms of these compounds, pharmaceutically acceptable salts of the above compounds having the same type of activity, and active metabolites, for example, in addition to polymorphs, pseudopolymorphs, solvates, hydrates, non-solvated polymorphs (including anhydrates), stereopolymorphs, and amorphous forms of the above compounds, combinations thereof are also included.,

[0126] The compounds disclosed in this specification may exhibit their natural isotope abundances, or one or more of the atoms may be artificially enriched with a specific isotope having an atomic mass or mass number that is different from the atomic mass or mass number that is predominantly found in nature but has the same atomic number. All isotopic variations of the compounds of the present disclosure, whether radioactive or not, are included within the scope of this disclosure. For example, hydrogen has three naturally occurring isotopes, shown as 1 H (protium), 2 H (deuterium), and 3 H (tritium). Protium is the most abundant hydrogen isotope in nature. Enrichment of deuterium can provide certain therapeutic advantages, such as increased half-life and / or exposure in vivo, or can provide compounds useful for investigating in vivo pathways of drug excretion and metabolism. Isotopically enriched compounds can be prepared by conventional techniques well known to those skilled in the art.

[0127] "Isomers" are different compounds that have the same molecular formula. "Stereoisomers" are isomers that differ only in the way the atoms are spatially arranged. Enantiomers are pairs of stereoisomers that are mirror images of each other and cannot be superimposed. A 1:1 mixture of a pair of enantiomers is a "racemic" mixture. The term "(±)" is used to denote a racemic mixture when appropriate. "Diastereoisomers" or "diastereomers" are stereoisomers that have at least two asymmetric atoms but are not mirror images of each other. Absolute stereochemistry is assigned according to the Cahn-Ingold-Prelog R-S system. When a compound is a pure enantiomer, the stereochemistry at each chiral carbon can be specified as either R or S. A resolved compound of unknown absolute configuration can be designated as (+) or (-) depending on the direction (dextrorotatory or levorotatory) in which it rotates plane-polarized light at the wavelength of the sodium D line. The specific compounds described herein contain one or more asymmetric centers and can therefore give rise to enantiomers, diastereomers, and other stereoisomeric forms, and the asymmetric centers can be defined as (R)- or (S)- with respect to absolute stereochemistry. The chemical entities, pharmaceutical compositions, and methods of the present case are meant to include all such possible stereoisomers, including racemic mixtures, optically pure forms, mixtures of diastereomers, and intermediate mixtures. Optically active (R)- and (S)-isomers can be prepared using chiral synthons or chiral reagents or can be separated using conventional techniques. The optical activity of a compound can be analyzed via appropriate methods including, but not limited to, chiral chromatography and polarimetry, and the degree of preponderance of one stereoisomer over the other isomers can be determined.

[0128] Chemical entities having a carbon-carbon double bond or a carbon-nitrogen double bond can exist in the Z-form or the E-form (or, the cis-form or the trans-form). Further, some chemical entities can exist in various tautomeric forms. Unless otherwise specified, the chemical entities described herein are likewise intended to include all Z-, E-, and tautomeric forms.

[0129] The term "substituted" refers to a moiety having a substituent that replaces hydrogen on one or more carbon or heteroatoms of a structure. "Substitution" or "substituted with" is such that the substitution follows the allowed valences of the substituted atom and the substituents, and implicitly includes the condition that a stable compound is brought about that does not spontaneously undergo deformations such as rearrangement, cyclization, removal, etc. as a result of the substitution. As used herein, the term "substituted" is considered to include all acceptable substituents of an organic compound. In a wide variety of embodiments, acceptable substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of an organic compound. Acceptable substituents can be one or more and the same or different for a suitable organic compound. For the purposes of the present disclosure, a heteroatom such as nitrogen can be provided with a hydrogen substituent and / or any acceptable substituent of an organic compound described herein that satisfies the valence of the heteroatom. Substituents can include any of the substituents described herein, for example, halogen, hydroxyl, carbonyl (carboxyl, alkoxycarbonyl, formyl, or acyl), thiocarbonyl (such as thioester, thioacetate, or thioformate), alkoxyl, phosphoryl, phosphate, phosphonate, phosphinate, amino, amide, amidine, imine, cyanono nitro, azide, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamide, sulfonyl, heterocyclyl, aralkyl, carbocycle, heterocycle, cycloalkyl, heterocycloalkyl, aromatic moiety, and heteroaromatic moiety. In some embodiments, substituents can be any of the substituents described herein, for example: halogen, hydroxy, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=N-H), oximo (=N-OH), hydrazino (=N-NH2), -R b -OR a , -R b -OC(O)-R a , -R b -OC(O)-OR a , -R b -OC(O)-N(R a )2, -Rb -N(R a )2, -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N(R a )2, -R b -O-R c -C(O)N(R a )2, -R b -N(R a )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (t is 1 or 2), -R b -S(O) t R a (t is 1 or 2), -R b -S(O) t OR a (t is 1 or 2), and -R b -S(O) t N(R a )2 (t is 1 or 2); and including alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, and heteroarylalkyl, any of which may be alkyl, alkenyl, alkynyl, halogen, hydroxy, haloalkyl, haloalkenyl, haloalkynyl, oxo(=O), thioxo(=S), cyano(-CN), nitro(-NO2), imino(=N-H), oxime(=N-OH), hydrazine(=N-NH2), -R b -OR a , -R b -OC(O)-R a , -R b -OC(O)-OR a , -R b -OC(O)-N(R a )2, -R b -N(R a) 2. -R b -C(O)R a 、-R b -C(O)OR a 、-R b -C(O)N(R a )2、-R b -O-R c -C(O)N(R a )2、-R b -N(R a )C(O)OR a 、-R b -N(R a )C(O)R a 、-R b -N(R a )S(O) t R a (t is 1 or 2), -R b -S(O) t R a (t is 1 or 2), -R b -S(O) t OR a (t is 1 or 2), and -R b -S(O) t N(R a )2 (t is 1 or 2) is optionally substituted; where R a is each independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl, and R a is each, valence permitting, alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo(=O), thioxo(=S), cyano(-CN), nitro(-NO2), imino(=N-H), oxime(=N-OH), hydrazine(=N-NH2), -R b -OR a 、-R b -OC(O)-R a 、-R b -OC(O)-OR a 、-R b -OC(O)-N(R a )2、-R b -N(R a) 2. -R b -C(O)R a . -R b -C(O)OR a . -R b -C(O)N(R a ) 2. -R b -O-R c -C(O)N(R a ) 2. -R b -N(R a )C(O)OR a . -R b -N(R a )C(O)R a . -R b -N(R a )S(O) t R a (t is 1 or 2), -R b -S(O) t R a (t is 1 or 2), -R b -S(O) t OR a (t is 1 or 2), and -R b -S(O) t N(R a ) 2 (t is 1 or 2) may be optionally substituted; and, herein, R B are each independently selected from a direct bond, or a chain of linear or branched alkylene, alkenylene, or alkynylene, and R C are each a chain of linear or branched alkylene, alkenylene, or alkynylene.

[0130] It is understood by those skilled in the art that substituents may themselves be substituted where appropriate. Unless specifically stated as "unsubstituted", references to chemical moieties in this specification are understood to include substituted variants. For example, references to a "heteroaryl" group or moiety implicitly include both substituted and unsubstituted variants.

[0131] When substituents are specified by their conventional chemical formulas and written from left to right, these equally include chemically identical substituents resulting from writing the structure from right to left. For example, -CH2O- is equal to -OCH2-.

[0132] The term "salt" or "pharmaceutically acceptable salt" refers to salts derived from various organic and inorganic counterions well-known in the art. Pharmaceutically acceptable acid addition salts can be formed with inorganic acids and organic acids. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. Pharmaceutically acceptable salt addition salts can be formed with inorganic bases and organic bases. Inorganic bases from which salts can be derived include, for example, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, and other similar ones. Organic bases from which salts can be derived include, for example, substituted amines including primary amines, secondary amines, and tertiary amines, naturally occurring substituted amines, cyclic amines, basic ion exchange resins, etc., specifically including isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine. In some embodiments, the pharmaceutically acceptable base addition salts are selected from ammonium, potassium, sodium, calcium, and magnesium salts.

[0133] The term "effective amount" or "therapeutically effective amount" refers to an amount of a compound described herein sufficient to affect the intended use, including, but not limited to, treatment of a disease as defined below. A therapeutically effective amount will vary depending on the intended treatment application (in vivo), or the subject and the state of the disease being treated, e.g., the subject's weight and age, the severity of the disease state, the method of administration, etc., which can be readily determined by one of ordinary skill in the art. This term also applies to the dosage that induces a specific response in target cells, e.g., a decrease in platelet adhesion and / or cell migration. The specific dosage will vary depending on the particular compound selected, the dosing regimen that follows, whether it is administered in combination with other compounds, the timing of administration, the tissue to which it is administered, and the physical delivery system by which it is carried.

[0134] As used herein, "treatment" or "treating" refers to a method for obtaining a beneficial or desired result, including, but not limited to, therapeutic and / or prophylactic benefits, with respect to a disease, disorder, or medical condition. By therapeutic benefit is meant eradication or amelioration of the underlying disease being treated. Similarly, a therapeutic benefit can be achieved by eradication or remission of one or more of the physiological symptoms associated with the underlying disorder such that improvement is observed in the subject, even though the subject may still be affected by the underlying disorder. In certain embodiments, with respect to prophylactic benefits, the composition is administered to a subject at risk of developing a particular disease or to a subject reporting one or more physiological symptoms of a disease, even though a diagnosis of the disease has not been made.

[0135] "Therapeutic effect" as the term is used herein encompasses the therapeutic and / or prophylactic benefits as described above. Prophylactic effects include delaying or eliminating the appearance of a disease or illness, delaying or eliminating the onset of symptoms of a disease or illness, delaying, halting, or reversing the progression of a disease or illness, or any combination thereof.

[0136] The terms "co - administered", "administered in combination with", and their grammatical equivalents encompass the administration of two or more agents to an animal, including a human, such that the agents and / or their metabolites are present in the subject simultaneously. Co - administration includes simultaneous administration in separate compositions, administration at different times in separate compositions, or administration in a composition in which both agents are present.

[0137] The terms "antagonist" and "inhibitor" are used interchangeably and refer to a compound having the ability to inhibit the biological function (e.g., activity, expression, binding, protein - protein interaction) of a target protein (e.g., menin, MLL1, MLL2, and / or MLL fusion protein). Thus, the terms "antagonist" and "inhibitor" are defined in relation to the biological role of the target protein. Preferred antagonists herein specifically interact (e.g., bind) with the target, but compounds that inhibit the biological activity of the target protein by interacting with other members of the signaling pathway of which the target protein is a member are also specifically included within this definition. Preferred biological activities inhibited by antagonists are related to tumor progression, growth, or expansion.

[0138] The term "agonist", as used herein, refers to a compound having the ability to initiate or enhance the biological function of a target protein, whether or not by inhibition of the activity or expression of the target protein. Thus, the term "agonist" is defined in relation to the biological role of the target polypeptide. Preferred agonists herein specifically interact (e.g., bind) with the target, but compounds that initiate or enhance the biological activity of the target polypeptide by interacting with other members of the signaling pathway of which the target polypeptide is a member are also specifically included within this definition.

[0139] "Signal transduction" refers to the process by which a stimulatory or inhibitory signal is transmitted to and within a cell to induce an intracellular response. A modulator of a signal transduction pathway refers to a compound that modulates the activity of one or more cellular proteins mapped to the same specific signal transduction pathway. A modulator can increase (agonist) or suppress (antagonist) the activity of a signal transduction molecule.

[0140] "Anticancer agent", "antineoplastic agent", or "chemotherapeutic agent" refers to any agent useful for the treatment of tumor diseases. One type of anticancer agent includes chemotherapeutic agents. "Chemotherapy" refers to the administration of one or more chemotherapeutic agents and / or other agents to a subject by various methods including intravenous, oral, intramuscular, intraperitoneal, intravesical, subcutaneous, transdermal, buccal, or inhalation, or in the form of a suppository.

[0141] "Subject" refers to an animal such as a mammal (e.g., human). The methods described herein can be useful for both human therapy and veterinary applications. In some embodiments, the subject is a mammal, and in some embodiments, the subject is a human. "Mammal" includes both humans and non-domestic animals such as wild animals, as well as domestic animals such as experimental animals and household pets (e.g., cats, dogs, pigs, cattle, sheep, goats, horses, rabbits).

[0142] The term "prodrug" is intended to encompass compounds that are convertible, under physiological conditions or by solvolysis, into the biologically active compounds described herein (e.g., compounds of formula (I-A), formula (I-B), formula (II), formula (III), formula (IV), or formula (VI)). Thus, the term "prodrug" refers to a precursor of a pharmaceutically acceptable biologically active compound. In some embodiments, a prodrug is inactive when administered to a subject but is converted in vitro to the active compound, e.g., by hydrolysis. Prodrug compounds often provide advantages of solubility, tissue compatibility, or delayed release in mammalian organisms (see, e.g., Bundgard, H., Design of Prodrugs (1985), pp. 7-9, 21-24 (Elsevier, Amsterdam); Higuchi, T., et al., "Pro-drugs as Novel Delivery Systems," (1987) A.C.S. Symposium Series, Vol. 14; and Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press), each of which is hereby incorporated by reference in its entirety. The term "prodrug" is meant to include any covalently attached carrier that releases the active compound in vivo when such prodrug is administered to a mammalian subject. Prodrugs of the active compounds are typically prepared by modifying the functional groups present in the active compounds in such a way that the modifying moiety is cleaved to the parent active compound, either by conventional manipulation or in vivo, as described herein. Prodrugs include compounds in which a hydroxy, amino, or mercapto group is bonded to any group that, when the prodrug of the active compound is administered to a mammalian subject, is cleaved to form a free hydroxy, free amino, or free mercapto group, respectively.Examples of prodrugs include, but are not limited to, derivatives of acetate, formate, and benzoate of hydroxy functional groups, or derivatives of acetamide, formamide, and benzamide of amine functional groups in the active compound, and the like.

[0143] The term "in vivo" refers to events occurring in the body of a subject.

[0144] The term "in vitro" refers to events occurring outside the body of a subject. For example, an in vitro assay includes any assay performed outside the subject. An in vitro assay includes cell-based assays in which living or dead cells are utilized. An in vitro assay also includes cell-free assays in which intact cells are not utilized.

[0145] "Optional" or "optionally" means that the event or circumstance described later may or may not occur, and this description includes examples of when the event or circumstance occurs and examples of when it does not occur. For example, "optionally substituted aryl" means that the aryl group may or may not be substituted, and this description includes both substituted aryl groups and aryl groups having no substitution.

[0146] "Pharmaceutically acceptable carrier, diluent, or excipient" includes, but is not limited to, any adjuvant, carrier, excipient, glidant, sweetening agent, diluent, preservative, dye, coloring agent, flavoring agent, surfactant, wetting agent, dispersing agent, suspending agent, stabilizer, isotonic agent, solvent, or emulsifying agent that is approved by the US Food and Drug Administration as acceptable for use in humans or domestic animals.

[0147] The present disclosure provides compounds for modulating the interaction of menin with proteins such as MLL1, MLL2, and MLL fusion oncoproteins. In certain embodiments, the present disclosure provides compounds and methods for inhibiting the interaction of menin with signaling molecules upstream or downstream thereof, including but not limited to MLL1, MLL2, and MLL fusion oncoproteins. The compounds of the present disclosure may be used in methods for the treatment of a variety of cancers and other diseases associated with one or more of MLL1, MLL2, MLL fusion proteins, and menin, such as hematological malignancies and Ewing's sarcoma. In certain embodiments, the compounds of the present disclosure covalently bind to menin and inhibit the interaction of menin with MLL. In certain embodiments, the compounds of the present disclosure non-covalently interact with menin and inhibit the interaction of menin with MLL.

[0148] In some aspects, the present disclosure provides compounds or salts that selectively bind to the menin protein and / or modulate the interaction of menin with an MLL protein (e.g., MLL1, MLL2, or an MLL fusion protein). In certain embodiments, the compound modulates the menin protein by binding to and / or interacting with one or more amino acids and / or one or more metal ions. Certain compounds may occupy the pockets of F9 and / or P13 of menin. The binding of the compounds disclosed herein may interfere with downstream signaling of menin or MLL (e.g., MLL1, MLL2, or an MLL fusion protein).

[0149] In certain aspects, the present disclosure provides a compound of formula (I-A),

[0150]

Chemical formula

[0151] In certain embodiments, the compound of formula (I-A) may be represented by:

[0152]

Chemical formula

[0153]

Chemical formula

[0154]

Chem.

[0155]

Chem.

[0156]

Chem.

[0157]

Chem.

[0158]

Chem.

[0159]

Chem.

[0160]

Chemical formula

[0161]

Chemical formula

[0162] In one aspect, the compound of formula (I-A) may be represented by:

[0163]

Chemical formula

[0164] [Chem.] In some embodiments, R 2 is selected from R 50 In some embodiments, R 2 is hydrogen, halogen, -OH, -OR 52 , -NH2, -N(R 52 )2, -CN, C 1-3 alkyl, C 1-3 alkyl OR 52 , C 1-3 alkyl-N(R 52 )2, C 1-3 haloalkyl, C 2-3 alkenyl, and C 2-3 alkynyl. In some embodiments, R 2 is -OH, -OR 52 , -NH2, -N(R 52 )2, -CN, and C 1-2 alkyl, etc., R 2 is halogen, -OH, -OR 52 , -NH2, -N(R 52 )2, -CN, C 1-3 alkyl, -CH2OH, -CH2OR 52 , -CH2NH2, -CH2N(R 52 )2, C 1-3 alkyl-N(R 52 )2, C 1-3 haloalkyl, C 2-3 alkenyl, and C 2-3 alkynyl. Optionally, R 2 is selected from -NH2, -CH3, -OCH3, -CH2OH, and -NHCH3. In some embodiments, R B is halogen, -CN, -OR 52 , -N(R 52 )2, -NR 53 R 54 , -C(O)R 52 , -C(O)OR 52, -OC(O)R 52 , -NR 52 C(O)R 52 , -C(O)N(R 52 )2, -C(O)NR 53 R 54 , =O, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, optionally substituted C 1-10 alkyl, optionally substituted C 2-10 alkenyl, and optionally substituted C 2-10 alkynyl are selected from. In some embodiments, R B is halogen, -CN, -OR 52 , -N(R 52 )2, -NR 53 R 54 , and C 1-2 alkyl, etc. selected from. R B is halogen, -CN, -OR 52 , -N(R 52 )2, -NR 53 R 54 , C 1-3 alkyl, and optionally substituted C 1-3 alkyl are selected from. In some embodiments, L 3 is C 1-6 alkylene, C 2-6 alkenylene, and C 2-6 alkynylene are selected from, each of which is substituted with one or more R 50 . In some embodiments, L 3 is C 50 alkylene optionally substituted with one or more R 1-6 . In some embodiments, L 3 is C 1-3 alkylene substituted with at least one C 1-3 alkyl or C 50 haloalkyl, and optionally further substituted with one or more R 3 . In some embodiments, L 1-6 is =O, C 1-6 alkyl, C 1-3 haloalkyl, C (cyclopropyl)alkyl, C1-3 alkyl(NR 52 C(O)R 52 ) or -O(C 1-6 alkyl). In some embodiments, L 3 is substituted with -CH3. In some embodiments, L 3 is

[0165]

Chemical formula

[0166]

Chemical formula

[0167]

Chemical formula

[0168]

Chemical formula

[0169]

Chemical formula

[0170] [Chemical formula] selected from, where R 57 is -S(=O)R 52 -S(=O)2R 52 -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 -NR 52 S(=O)2R 52 ; and, -S(=O)R 52 -S(=O)2R 52 -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 and -NR 52 S(=O)2R 52 substituted with one or more substituents selected from C 1-10 alkyl is selected. In some embodiments, R 57 is selected from -S(=O)CH3, -S(=O)2CH3, -S(=O)2NH2, -NHS(=O)2CH3, and -S(=O)2NHCH3, etc., R 57 is -S(=O)R 52 -S(=O)2R 58 -S(=O)2N(R 52 )2, and -NR 52 S(=O)2R 52 selected from. In some embodiments, C is

[0171] [Chemical formula] selected from. In some embodiments, R C is -N(R 52 )2, -NR 53 R 54 -NR 52 S(=O)2R 52 -C(O)R 52 -C(O)OR 52 -NR 52 C(O)R 52, -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 , -C(O)N(R 52 )2, and -C(O)NR 53 R 54 is selected from. In some embodiments, R C is, -N(R 52 )2, -NR 53 R 54 , -NR 52 S(=O)2R 52 , -C(O)R 52 , -C(O)OR 52 , -NR 52 C(O)R 52 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 , -C(O)N(R 52 )2, -C(O)NR 53 R 54 , C 1-6 alkyl, and -N(R 52 )2, -NR 53 R 54 , -NR 52 S(=O)2R 52 , -C(O)R 52 , -C(O)OR 52 , -NR 52 C(O)R 52 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 , -C(O)N(R 52 )2, or -C(O)NR 53 R 54 substituted C 1-6 alkyl is selected from. In some embodiments, C is

[0172]

Chem.

[0173] In one aspect, the compound of formula (I-A) may be represented by:

[0174]

Chem.

[0175]

Chem.

[0176] In one aspect, the compound of formula (I-A) may be represented by:

[0177]

Chemical formula

[0178]

Chemical formula

[0179] In certain aspects, the disclosure relates to a compound of formula (I-B),

[0180]

Chemical formula

[0181] In certain embodiments, the compound of formula (I-B) may be represented by:

[0182]

Chemical formula

[0183]

Chemical formula

[0184]

Chemical formula

[0185]

Chemical formula

[0186]

Chemical formula

[0187]

Chemical formula

[0188]

Chemical formula

[0189]

Chemical formula

[0190]

Chemical formula

[0191]

Chemical formula

[0192] In certain embodiments, the compound of formula (I-B) may be represented by:

[0193]

Chemical formula

[0194]

Chemical formula

[0195]

Chemical formula

[0196]

Chemical formula

[0197]

Chemical formula

[0198]

Chemical formula

[0199]

Chem.

[0200]

Chem.

[0201]

Chem.

[0202]

Chemical formula

[0203] In certain embodiments, the compound of formula (I-B) may be represented by:

[0204]

Chemical formula

[0205]

Chemical formula

[0206] In one aspect, the compound of formula (I-B) may be represented by:

[0207]

Chemical formula

[0208]

Chemical formula

[0209] In certain aspects, the present disclosure provides a compound of formula (II):

[0210]

Chemical formula

[0211] In certain embodiments, the compound of formula (II) may be represented by:

[0212]

Chemical formula

[0213]

Chemical formula

[0214]

Chemical formula

[0215] In certain embodiments, the compound of formula (II) may be represented by:

[0216]

Chemical formula

[0217]

Chemical formula

[0218]

Chemical formula

[0219] In certain embodiments, the compound of formula (II) may be represented by:

[0220]

Chemical formula

[0221]

Chemical formula

[0222] In certain embodiments, the present disclosure provides a compound of formula (III):

[0223] [Chemical formula] or a pharmaceutically acceptable salt or prodrug thereof, wherein H is selected from carbocycles and 3- to 12-membered heterocycles, each of which is optionally substituted with one or more R 3-12 ; 50 A is ;

[0224] [Chemical formula] ; Z 1 , Z 2 , Z 3 , and Z 4 are each independently selected from -C(R A1 )(R A2 )-, -C(R A1 )(R A2 )-C(R A1 )(R A2 )-, -C(O)-, and -C(R A1 )(R A2 )-C(O)-, provided that only one of Z 1 , Z 2 , Z 3 , and Z 4 is -C(O)- or -C(R A1 )(R A2 )-C(O)-; B is selected from a single bond, C 3-12 carbocycles, and 3- to 12-membered heterocycles; C is selected from a single bond, C 3-12 carbocycles, and 3- to 12-membered heterocycles; L 1 , L 2 , and L 3 are each independently a single bond, -O-, -S-, -N(R 51 )-, -N(R 51)CH2-, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R 51 )-, -C(O)N(R 51 )C(O)-, -C(O)N(R 51 )C(O)N(R 51 )-, -N(R 51 )C(O)-, -N(R 51 )C(O)N(R 51 )-, -N(R 51 )C(O)O-, -OC(O)N(R 51 )-, -C(NR 51 )-, -N(R 51 )C(NR 51 )-, -C(NR 51 )N(R 51 )-, -N(R 51 )C(NR 51 )N(R 51 )-, -S(O)2-, -OS(O)-, -S(O)O-, -S(O)-, -OS(O)2-, -S(O)2O-, -N(R 51 )S(O)2-, -S(O)2N(R 51 )-, -N(R 51 )S(O)-, -S(O)N(R 51 )-, -N(R 51 )S(O)2N(R 51 )-, -N(R 51 )S(O)N(R 51 )-; independently selected from alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, and heteroalkynylene, each of which is optionally substituted with one or more R 50 where L 1 , L 2 , or L 3 Two R 50 groups bonded to the same or different atoms of any one of can optionally combine to form a bridge or a ring; R B is independently selected each time it appears from R 50 , or two R B groups bonded to the same or different atoms can optionally combine to form a bridge or a ring; RC is hydrogen and R 50 are each independently selected each time they appear, or two R C groups attached to the same or different atoms can optionally form a bridge or a ring; R A1 and R A2 are each independently selected from hydrogen and R 50 each time they appear; n is an integer from 0 to 6, p is an integer from 1 to 6; and / or, R 50 is selected each time it appears from the following: halogen, -NO2, -CN, -OR 52 -SR 52 -N(R 52 )2, -NR 53 R 54 -S(=O)R 52 -S(=O)2R 52 -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 -NR 52 S(=O)2R 52 -NR 52 S(=O)2N(R 52 )2, -NR 52 S(=O)2NR 53 R 54 -C(O)R 52 -C(O)OR 52 -OC(O)R 52 -OC(O)OR 52 -OC(O)N(R 52 )2, -OC(O)NR 53 R 54 -NR 52 C(O)R 52 -NR 52 C(O)OR 52 -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 -C(O)N(R 52 )2, -C(O)NR53 R 54 、 -P(O)(OR 52 )2, -P(O)(R 52 )2, -P(O)(OR 52 )(R 52 )、 -P(O)(NR 52 )(R 52 )、 -NR 52 P(O)(R 52 )、 -P(O)(NR 52 )(OR 52 )、 -P(O)(NR 52 )2、 =O、 =S、 =N(R 52 ); C 1-10 alkyl, C 2-10 alkenyl, and C 2-10 alkynyl, each of which is independently halogen, -NO2, -CN, -OR 52 , -SR 52 , -N(R 52 )2, -NR 53 R 54 , -S(=O)R 52 , -S(=O)2R 52 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 )2, -NR 52 S(=O)2NR 53 R 54 , -C(O)R 52 , -C(O)OR 52 , -OC(O)R 52 , -OC(O)OR 52 , -OC(O)N(R 52 )2, -OC(O)NR 53 R 54 , -NR 52 C(O)R 52 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R54 , -C(O)N(R 52 )2, -C(O)NR 53 R 54 , -P(O)(OR 52 )2, -P(O)(R 52 )2, -P(O)(OR 52 )(R 52 ), -P(O)(NR 52 )(R 52 ), -NR 52 P(O)(R 52 ), -P(O)(NR 52 )(OR 52 ), -P(O)(NR 52 )2, =O, =S, =N(R 52 ), C 3-12 a carbon ring, and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time it appears, C 1-10 alkyl, C 2-10 alkenyl, and C 2-10 alkynyl; and, C 3-12 a carbon ring and a 3- to 12-membered heterocycle, wherein each C 50 in R 3-12 the carbon ring and the 3- to 12-membered heterocycle are independently halogen, -NO2, -CN, -OR 52 , -SR 52 , -N(R 52 )2, -NR 53 R 54 , -S(=O)R 52 , -S(=O)2R 52 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 ), -NR 52 S(=O)2NR 53 R 54 , -C(O)R 52 , -C(O)OR 52 , -OC(O)R 52 , -OC(O)OR 52 , -OC(O)N(R 52)2, -OC(O)NR 53 R 54 , -NR 52 C(O)R 52 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 ), -NR 52 C(O)NR 53 R 54 , -C(O)N(R 52 ), -C(O)NR 53 R 54 , -P(O)(OR 52 ), -P(O)(R 52 ), -P(O)(OR 52 )(R 52 ), -P(O)(NR 52 )(R 52 , -NR 52 P(O)(R 52 ), -P(O)(NR 52 )(OR 52 ), -P(O)(NR 52 ), =O, =S, =N(R 52 ), C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, and, C 2-6 alkynyl optionally substituted with one or more substituents selected from 3-12 carbocycles and 3-membered - 12-membered heterocycles; R 51 is, each time it appears, selected from: hydrogen, -C(O)R 52 , -C(O)OR 52 , -C(O)N(R 52 ), -C(O)NR 53 R 54 ; C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, wherein each of these is independently halogen, -NO2, -CN, -OR 52 , -SR 52 , -N(R 52 ), -NR 53 R 54, -S(=O)R 52 , -S(=O)₂R 52 , -S(=O)₂N(R 52 )₂, -S(=O)₂NR 53 R 54 , -NR 52 S(=O)₂R 52 , -NR 52 S(=O)₂N(R 52 )₂, -NR 52 S(=O)₂NR 53 R 54 , -C(O)R 52 , -C(O)OR 52 , -OC(O)R 52 , -OC(O)OR 52 , -OC(O)N(R 52 )₂, -OC(O)NR 53 R 54 , -NR 52 C(O)R 52 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 )₂, -NR 52 C(O)NR 53 R 54 , -C(O)N(R 52 )₂, -C(O)NR 53 R 54 , -P(O)(OR 52 )₂, -P(O)(R 52 )₂, -P(O)(OR 52 )(R 52 ), -P(O)(NR 52 )(R 52 ), -NR 52 P(O)(R 52 ), -P(O)(NR 52 )(OR 52 ), -P(O)(NR 52 )₂, =O, =S, =N(R 52 ), C 3-12 A carbon ring, and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time it appears, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl; and, C3-12 A carbon ring and a 3- to 12-membered heterocyclic ring, where R 51 each C in 3-12 The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO2, -CN, -OR 52 , -SR 52 , -N(R 52 )2, -NR 53 R 54 , -S(=O)R 52 , -S(=O)2R 52 , -S(=O)2N(R 52 )2, -S(=O)2NR 53 R 54 , -NR 52 S(=O)2R 52 , -NR 52 S(=O)2N(R 52 )2, -NR 52 S(=O)2NR 53 R 54 , -C(O)R 52 , -C(O)OR 52 , -OC(O)R 52 , -OC(O)OR 52 , -OC(O)N(R 52 )2, -OC(O)NR 53 R 54 , -NR 52 C(O)R 52 , -NR 52 C(O)OR 52 , -NR 52 C(O)N(R 52 )2, -NR 52 C(O)NR 53 R 54 , -C(O)N(R 52 )2, -C(O)NR 53 R 54 , -P(O)(OR 52 )2, -P(O)(R 52 )2, -P(O)(OR 52 )(R 52 ), -P(O)(NR 52 )(R 52 ), -NR 52 P(O)(R 52 ), -P(O)(NR 52 )(OR 52 ), -P(O)(NR52 ) 2, =O, =S, =N(R 52 ), C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, and, C 2-6 alkynyl, optionally substituted with one or more substituents selected from C 3-12 carbocyclic ring and 3 - to 12 - membered heterocyclic ring; R 52 is, each time it appears, hydrogen; and, C 1-20 alkyl, C 2-20 alkenyl, C 2-20 alkynyl, 1 - to 6 - membered heteroalkyl, C 3-12 carbocyclic ring, and 3 - to 12 - membered heterocyclic ring, each of which is halogen, -CN, -NO2, -NH2, -NHCH3, -NHCH2CH3, =O, -OH, -OCH3, -OCH2CH3, C 3-12 carbocyclic ring, or 3 - to 6 - membered heterocyclic ring, optionally substituted; and, R 53 and R 54 together with the nitrogen atom to which they are attached form a heterocyclic ring optionally substituted with one or more R 50 .

[0225] In certain embodiments, the compound of formula (III) may be represented by:

[0226]

Chemical formula

[0227]

Chemical formula

[0228] In some embodiments, for the compound of formula (III), A is selected from:

[0229]

Chem.

[0230] or a pharmaceutically acceptable salt or prodrug thereof,

[0231]

Chem.

[0232]

Chem.

[0233] In some embodiments, for the compound of formula (IV), G a is piperidinyl. In some embodiments, the compound of chemical formula (IV) is represented by:

[0234]

Chemical formula

[0235] In some embodiments, for the compound of formula (IV), R 3a and R 3b are independently selected from hydrogen and halo. In some embodiments, X a and Y a do not form a chemical bond and X a is hydrogen. In some embodiments, R4a is hydrogen; and is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclo, heteroaryl, aralkyl, (heterocyclo)alkyl, and (heteroaryl)alkyl, each of which is optionally substituted with one or more substituents selected from R 50 selected therefrom. In some embodiments, R 4a is a heterocyclo substituted with R 50 .

[0236] In certain embodiments, the present disclosure provides a compound of formula (VI):

[0237]

Chemical formula

[0238]

Chemical formula

[0239] In certain embodiments, the compound of formula (VI) may be represented by:

[0240]

Chemical formula

[0241]

Chemical formula

[0242]

Chemical formula

[0243]

Chemical formula

[0244]

Chemical formula

[0245]

Chemical formula

[0246] [Chemical formula] such as

[0247] [Chemical formula] and H2 is

[0248] [Chemical formula] one or more Rs such as H2 optionally further substituted with

[0249] [Chemical formula] is

[0250] In some embodiments, for the compounds of formula (VI), A is

[0251] [Chemical formula] selected from

[0252] Any combination of the groups described above for the various variables is contemplated herein. Throughout this specification, the groups and their substituents can be chosen to provide stable moieties and compounds.

[0253] The chemical substances described herein for use in the subject method can be synthesized according to one or more of the exemplary schemes herein and / or techniques known in the art. The substances used herein are either commercially available or are prepared by synthetic methods generally known in the art. These schemes are not limited to the compounds listed in the examples or by any particular substituents, which are utilized for illustrative purposes. Although various steps are described and depicted in Scheme 1 and Examples 1-11, in some cases the steps may be carried out in an order different from that shown in Scheme 1 and Examples 1-11. Various modifications to these synthetic reaction schemes can be made and will be suggested to those skilled in the art who refer to the present disclosure, which may be included in this application. The reference numerals or R groups in each scheme do not necessarily correspond to the reference numerals or R groups in the claims or other schemes or tables herein.

[0254] Unless otherwise specified, the reactions described herein generally occur at atmospheric pressure within a temperature range of -10°C to 200°C. Further, unless otherwise specified, the reaction times and conditions are intended to be approximate reaction times and conditions. For example, the reaction occurs at approximately atmospheric pressure within a temperature range of about -10°C to about 110°C over a period of about 1 hour to about 24 hours; The remaining reactions are run for approximately 16 hours on average overnight.

[0255] Generally, the compounds of the present disclosure for use in the subject method, including compounds of formulas (I-A), (I-B), (II), (III), and (VI), may be prepared by the following reaction schemes:

[0256]

Chemical formula

[0257] In some embodiments, the compounds of Formula 1-7 can be prepared according to Scheme 1. For example, methanesulfonyl chloride can be added to a solution of alcohol 1-1 and triethylamine to obtain mesylate 1-2. By adding mesylate 1-2 to a solution of Cs2CO3 and amine 1-3, the compound of Formula 1-4 can be provided. The coupling of 1-4 to amine 1-5 can proceed according to methods known in the art to afford the compound of Formula 1-6. The addition of TFA can reveal the free amine that can be optionally reacted with R 57 -LG (where LG is a suitable leaving group) to produce the compound of Formula 1-7.

[0258] In some embodiments, the compounds of the present disclosure used in the subject methods, e.g., compounds of the formulas provided in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, or Table 7, are synthesized according to one of the general routes outlined in Scheme 1, Example 1-11, or by methods known in the art. In some embodiments, exemplary compounds used in the subject methods may include, but are not limited to, compounds selected from Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, or Table 7 or salts thereof.

[0259] [Table 1-1]

[0260] [Table 1-2]

[0261] [Table 1-3]

[0262] [Table 1-4]

[0263]

Table 1-5

[0264]

Table 1-6

[0265]

Table 1-7

[0266]

Table 1-8

[0267]

Table 1-9

[0268]

Table 1-10

[0269]

Table 1-11

[0270]

Table 1-12

[0271]

Table 1-13

[0272]

Table 1-14

[0273]

Table 1-15

[0274]

Table 1-16

[0275]

Table 1-17

[0276]

Table 1-18

[0277]

Table 2-1

[0278]

Table 2-2

[0279]

Table 2-3

[0280]

Table 3-1

[0281]

Table 3-2

[0282]

Table 3-3

[0283]

Table 3-4

[0284]

Table 3-5

[0285]

Table 3-6

[0286]

Table 3-7

[0287]

Table 3-8

[0288]

Table 3-9

[0289]

Table 3-10

[0290]

Table 4-1

[0291]

Table 4-2

[0292]

Table 4-3

[0293]

Table 4-4

[0294]

Table 4-5

[0295]

Table 4-6

[0296]

Table 4-7

[0297]

Table 4-8

[0298]

Table 4-9

[0299]

Table 4-10

[0300]

Table 4-11

[0301]

Table 4-12

[0302]

Table 4-13

[0303]

Table 4-14

[0304]

Table 4-15

[0305]

Table 4-16

[0306]

Table 4-17

[0307]

Table 4-18

[0308]

Table 4-19

[0309]

Table 4-20

[0310]

Table 4-21

[0311]

Table 4-22

[0312]

Table 4-23

[0313]

Table 4-24

[0314]

Table 4-25

[0315]

Table 4-26

[0316]

Table 4-27

[0317]

Table 4-28

[0318]

Table 5-1

[0319]

Table 5-2

[0320]

Table 5-3

[0321]

Table 5-4

[0322]

Table 5-5

[0323]

Table 5-6

[0324]

Table 5-7

[0325]

Table 5-8

[0326]

Table 5-9

[0327]

Table 5-10

[0328]

Table 5-11

[0329]

Table 5-12

[0330]

Table 5-13

[0331]

Table 6-1

[0332]

Table 6-2

[0333]

Table 6-3

[0334]

Table 6-4

[0335]

Table 6-5

[0336]

Table 6-6

[0337]

Table 6-7

[0338]

Table 6-8

[0339]

Table 6-9

[0340]

Table 6-10

[0341]

Table 6-11

[0342]

Table 6-12

[0343]

Table 6-13

[0344]

Table 6-14

[0345]

Table 6-15

[0346]

Table 6-16

[0347]

Table 6-17

[0348]

Table 6-18

[0349]

Table 6-19

[0350]

Table 6-20

[0351]

Table 7-1

[0352]

Table 7-2

[0353]

Table 7-3

[0354]

Table 7-4

[0355]

Table 7-5

[0356]

Table 7-6

[0357]

Table 7-7

[0358]

Table 7-8

[0359]

Table 7-9

[0360]

Table 7-10

[0361] Pharmaceutical composition

[0362] The compositions and methods of the present disclosure may be utilized to treat an individual. In certain embodiments, the individual is a mammal, such as a human or a non-human mammal. When administered to an animal such as a human, the composition or compound is preferably administered as a pharmaceutical composition comprising, for example, a compound or salt of formula (I-A), formula (I-B), formula (II), formula (III), formula (IV), or formula (VI) and a pharmaceutically acceptable carrier.

[0363] In some embodiments, the pharmaceutical composition is formulated for oral administration. In other embodiments, the pharmaceutical composition is formulated for injection. In further embodiments, the pharmaceutical composition comprises a compound as disclosed herein and an additional therapeutic agent (e.g., an anti-cancer agent). Non-limiting examples of such therapeutic agents are described herein below.

[0364] Suitable routes of administration include, but are not limited to, oral administration, intravenous administration, rectal administration, aerosol administration, parenteral administration, ophthalmic administration, pulmonary administration, transmucosal administration, transdermal administration, intravaginal administration, otic administration, nasal administration, and topical administration. In addition, by way of example only, parenteral delivery includes intrathecal, direct intraventricular, intraperitoneal, intralymphatic, and intranasal injections, as well as intramuscular, subcutaneous, intravenous, and intramedullary injections.

[0365] In certain embodiments, a composition of a compound or salt of formula (I-A), formula (I-B), formula (II), formula (III), formula (IV) or formula (VI) is often in a depot formulation or a sustained release formulation and is administered locally, for example, by directly injecting the compound into an organ rather than systemically. In certain embodiments, the long-acting formulation is administered by implantation (e.g., subcutaneously or intramuscularly) or intramuscular injection. Further, in other embodiments, a compound or salt of formula (I-A), formula (I-B), formula (II), formula (III), formula (IV) or formula (VI) is delivered in a targeted drug delivery system, for example, in liposomes coated with an organ-specific antibody. In such embodiments, the liposomes target and are selectively taken up by the organ. In still other embodiments, the composition is provided in the form of an immediate release formulation, a sustained release formulation, or an intermediate release formulation. In still other embodiments, the composition is administered locally.

[0366] Compounds of formula (I-A), formula (I-B), formula (II), formula (III), formula (IV) or formula (VI), or pharmaceutically acceptable salts thereof, may be effective over a wide dosage range. For example, in the treatment of adult humans, dosages of 0.01 to 1000 mg per day, 0.5 to 100 mg per day, 1 to 50 mg per day, and 5 to 40 mg per day are examples of dosages that may be used in some embodiments. The exact dosage depends on the route of administration, the form in which the compound is administered, the subject being treated, the body weight of the subject being treated, and the choice and experience of the attending physician.

[0367] In some embodiments, the compounds or salts of formula (I-A), formula (I-B), formula (II), formula (III), formula (IV) or formula (VI) are administered as a single dose. Typically, such administration is by injection, for example intravenous injection, to rapidly introduce the age...

Claims

**Claim 1** A method for treating acute myeloid leukemia in a subject presenting with a nucleoporin 98 (NUP98) gene fusion, a mutation in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, or a mixed lineage leukemia (MLL) gene amplification, comprising: administering a menin inhibitor to a subject in need thereof, the method. **Claim 2** A method for treating a subject having acute myeloid leukemia or acute lymphoblastic leukemia, comprising: (a) screening the subject for the presence of an MLL rearrangement, a partial tandem duplication of MLL, or an elevated MEIS1 expression level; and (b) administering a menin inhibitor to the subject if one or more of an MLL rearrangement, a partial tandem duplication of MLL, or an elevated MEIS1 expression level is detected, the method. **Claim 3** The method according to claim 1, wherein the subject presents with a nucleoporin 98 (NUP98) gene fusion. **Claim 4** The method according to claim 3, wherein the nucleoporin 98 (NUP98) gene fusion is a gene fusion of NUP98 and a homeodomain partner gene. **Claim 5** The method according to claim 3, wherein the nucleoporin 98 (NUP98) gene fusion is a gene fusion of NUP98 and a non-homeodomain partner gene. **Claim 6** The method according to claim 3, wherein the nucleoporin 98 (NUP98) gene fusion is a gene fusion of NUP98 and a partner gene selected from HOXA9, HOXA11, HOXA13, HOXC11, HOXC13, HOXD11, HOXD13, PMX1, PMX2, HHEX, PHF23, JARID1A, NSD1, NSD3, MLL, SETBP1, LEDGF, CCDC28, HMGB3, IQCg, RAP1GDS1, ADD3, DDX10, TOP1, TOP2B, LNP1, RARG, ANKRD28, and POU1F1. **Claim 7** The method according to claim 1, wherein the subject presents with a mutation in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene. **Claim 8** The method according to claim 7, wherein the mutation in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene is a mutation at R882. **Claim 9** The method according to claim 7, wherein the mutation in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene is not the mutation at R882.

10. The method according to claim 7, wherein the mutation in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene is a frameshift deletion, a missense mutation, a nonsense mutation, a splice site substitution, a splice site deletion, or a whole gene deletion.

11. The method according to claim 1, wherein the subject exhibits amplification of the mixed-lineage leukemia (MLL) gene.

12. The menin inhibitor is a compound of formula (I-A): 【Chemical 1】 or a pharmaceutically acceptable salt or prodrug thereof, H is C ５－１２ selected from a carbocyclic ring and a 5- to 12-membered heterocyclic ring, each of which is optionally substituted with one or more R ５０ ; A is selected from a single bond, C ３－１２ a carbocyclic ring, and a 3- to 12-membered heterocyclic ring; B is C ３－１２ selected from a carbocyclic ring and a 3- to 12-membered heterocyclic ring; C is a 3- to 12-membered heterocyclic ring; L １ 、 L ２ 、 and L ３ are each independently a single bond, -O-, -S-, -N(R ５１ ), -N(R ５１ ), -CH ２ -, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -N(R ５１ ), -C(O)-, -N(R ５１ ), -C(O)N(R ５１ ), -N(R ５１ ), -C(O)O-, -OC(O)N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -C(NR ５１ ), -C(NR ５１ ), -N(R ５１ ), -N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -S(O) ２ -, -OS(O)-, -S(O)O-, -S(O)-, -OS(O) ２ -, -S(O) ２ O-, -N(R ５１ ), -S(O) ２ -, -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)-, -S(O)N(R ５１ ), -N(R ５１ ), -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)N(R ５１ ); independently selected from alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, and heteroalkynylene, each of which is optionally substituted with one or more R ５０ , where L １ , L ２ , or L ３ Two Rs bonded to any one of the same or different atoms can be combined to optionally form a bridge or a ring; ５０ The groups can combine to optionally form a bridge or a ring; R Ａ 、R Ｂ 、and R Ｃ are each independently selected each time they appear from R ５０ , or two R Ａ groups, two R Ｂ groups, or two R Ｃ groups can combine together to optionally form a bridge or a ring; m, n, and p are each independently an integer from 0 to 6; R ５０ is selected from the following each time it appears: Halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ NR ２ R ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ S(=O) ５２ NR ２ R ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(OR ５２ )(R ２ ), -P(O)(NR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ); C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl, each of which is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ NR ２ R ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ S(=O) ５２ NR ２ R ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ a carbon ring, and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time it appears, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where R ５０ each C in ３－１２ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from ３－１２ carbocycles and 3 - to 12 - membered heterocycles; R ５１ is selected from the following each time it appears: hydrogen, -C(O)R ５２ , -C(O)OR ５２ , -C(O)N(R ５２ ), ２ , -C(O)NR ５３ R ５４ ; C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl, wherein each of these is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ a carbon ring, and one or more substituents selected from 3- to 12-membered heterocyclic rings, optionally substituted each time it appears, C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where R ５１ each C in ３－１２ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from ３－１２ carbocyclic rings and 3- to 12-membered heterocyclic rings; R ５２ is, each time it appears, hydrogen; and C １－２０ alkyl, C ２－２０ alkenyl, C ２－２０ alkynyl, 1-6 membered heteroalkyl, C ３－１２ carbocycle, and 3-12 membered heterocycle, each of which is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocycle, or 3-6 membered heterocycle; R ５３ and R ５４ together with the nitrogen atom to which they are attached form a heterocyclic ring optionally substituted with one or more R ５０ ; R ５７ is selected from the following: Halogen, -NO ２ , -CN, -SR ５２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５８ , -S(=O) ２ , -S(=O) ５２ N(R ２ ), -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ , -NR ５２ N(R ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)NH(C １－６ alkyl), -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ 、 = S, = N(R ５２ ); and, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl, each of which is independently, -NO ２ , -CN, -SR ５２ , -N(R ５２ ), ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), ２ , -NR ５２ C(O)NR ５３ R ５４ , -P(O)(OR ５２ ), ２ , -P(O)(R ５２ ), ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =S, and =N(R ５２ ), one or more substituents selected from, and substituted each time it appears, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl; R ５８ is hydrogen; and C １－２０ alkyl, C ３－２０ alkenyl, C ２－２０ alkynyl, 1- to 6-membered heteroalkyl, C ３－１２ carbocyclic, and 3- to 12-membered heterocyclic, each of which is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocyclic, or 3- to 6-membered heterocyclic; wherein, for the compound or salt of formula (I-A), C is azetidinylene, piperidinylene, or piperazinylene, and R ５７ is, -S(=O) ２ R ５８ , -S(=O) ２ N(R ５２ ), ２ or -NR ５２ S(=O) ２ R ５２ when: p is an integer from 1 to 6; and / or L ３ is substituted by one or more Rs ５０ wherein L ３ is not -CH ２ CH(OH)- the method according to claim 1 or 2.

13. The menin inhibitor is a compound of formula (I-B): [Chemical Formula 2] or a pharmaceutically acceptable salt thereof, H is C ５－１２ selected from a carbocyclic ring and a 5- to 12-membered heterocyclic ring, each of which is optionally substituted with one or more R ５０ ; A, B, and C are each independently selected from a carbocyclic ring and a 3- to 12-membered heterocyclic ring; ３－１２ and are independently selected from a carbocyclic ring and a 3- to 12-membered heterocyclic ring; L １ and L ２ are each independently a single bond, -O-, -S-, -N(R ５１ ), -N(R ５１ ), -CH ２ -, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -N(R ５１ ), -C(O)-, -N(R ５１ ), -C(O)N(R ５１ ), -N(R ５１ ), -C(O)O-, -OC(O)N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -C(NR ５１ ), -C(NR ５１ ), -N(R ５１ ), -N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -S(O) ２ -, -OS(O)-, -S(O)O-, -S(O)-, -OS(O) ２ -, -S(O) ２ O-, -N(R ５１ ), -S(O) ２ -, -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)-, -S(O)N(R ５１ ), -N(R ５１ ), -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)N(R ５１ ); selected from alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, and heteroalkynylene, each of which is optionally substituted with one or more R ５０ ; L ３ is selected from alkylene, alkenylene, and alkynylene, each of which is substituted with one or more R ５６ and optionally further substituted with one or more R ５０ ; R Ａ 、R Ｂ 、and R Ｃ are each independently selected each time they appear from R ５０ or two R Ａ groups, two R Ｂ groups, or two R Ｃ groups can combine together to optionally form a bridge or a ring; m, n, and p are each independently an integer from 0 to 6; R ５０ is selected from the following each time it appears: Halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ NR ２ R ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ S(=O) ５２ NR ２ R ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(OR ５２ )(R ２ ), -P(O)(NR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ , =O, =S, =N(R ５２ ); C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl, each of which is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ a carbon ring, and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time it appears, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where R ５０ each C in ３－１２ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from C ３－１２ carbocyclic ring and 3-membered - 12-membered heterocyclic ring; R ５１ is selected from the following each time it appears: hydrogen, -C(O)R ５２ , -C(O)OR ５２ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ ; C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl, wherein each of these is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ carbon ring, and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time it appears, C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where R ５１ each C in ３－１２ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from ３－１２ carbocycles and 3-membered - 12-membered heterocycles; R ５２ is, each time it appears, hydrogen; and C １－２０ alkyl, C ２－２０ alkenyl, C ２－２０ alkynyl, 1-6 membered heteroalkyl, C ３－１２ carbocyclic, and 3-12 membered heterocyclic, each of which is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocyclic, or 3-6 membered heterocyclic; R ５３ and R ５４ together with the nitrogen atom to which they are attached form a heterocyclic ring optionally substituted with one or more ５０ R; R ５６ appears each time as -NO ２ 、-OR ５９ 、-SR ５２ 、-NR ５３ R ５４ 、-S(=O)R ５２ 、-S(=O) ２ R ５２ 、-S(=O) ２ N(R ５２ ) ２ 、-S(=O) ２ NR ５３ R ５４ 、-NR ５２ S(=O) ２ R ５２ 、-NR ５２ S(=O) ２ N(R ５２ ) ２ 、-NR ５２ S(=O) ２ NR ５３ R ５４ 、-C(O)R ５２ 、-C(O)OR ５２ 、-OC(O)R ５２ 、-OC(O)OR ５２ 、-OC(O)N(R ５２ ) ２ 、-OC(O)NR ５３ R ５４ 、-NR ５２ C(O)R ５２ 、-NR ５２ C(O)OR ５２ 、-NR ５２ C(O)N(R ５２ ) ２ 、-NR ５２ C(O)NR ５３ R ５４ 、-C(O)N(R ５２ ) ２ 、-C(O)NR ５３ R ５４ 、-P(O)(OR ５２ ) ２ 、-P(O)(R ５２ ) ２ 、-P(O)(OR ５２ )(R ５２ )、-P(O)(NR ５２ )(R ５２ )、-NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ), =O, =S, =N(R ２ ), C ５２ alkyl, C １－１０ alkenyl, C ２－１０ alkynyl, C ２－１０ carbon ring, and 3-membered - 12-membered heterocyclic ring, selected from ３－１２ ​ R ５６ Each C in １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl is independently halogen, -NO ２ , -CN, -OR ５９ , -SR ５２ , -N(R ５２ ), -NR ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ , -NR ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ５２ ​) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C ３－１２ a carbon ring, and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time it appears, R ５６ each C in ３－１２ The carbocyclic ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ NR ２ R ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ S(=O) ５２ NR ２ R ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(OR ５２ ), (R ５２ ), -P(O)(NR ５２ ), (R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ ), (OR ５２ ), -P(O)(NR ５２ ), ( ２ ), =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and C ２－６ alkynyl, optionally substituted with one or more substituents selected from ２－６ Furthermore, here, R ５６ optionally forms a single bond to the ring C; and, R ５９ is independently selected, each time it appears, from C １－２０ alkyl, C ２－２０ alkenyl, C ２－２０ alkynyl, 1-6 membered heteroalkyl, C ３－１２ carbocyclic, and 3-12 membered heterocyclic, and each of them is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocyclic, or 3-6 membered heterocyclic; Here, for the compound or salt of formula (I-B), when R ５６ is -CH ３ , L ３ is not further substituted with -OH, -NH ２ , or -CN, the method according to claim 1 or 2.

14. R Ｃ is -C(O)R ５２ ,-S(=O)R ５２ ,-S(=O) ２ R ５２ ,-S(=O) ２ N(R ５２ ), ２ ,-S(=O) ２ NR ５３ R ５４ ,-NR ５２ S(=O) ２ R ５２ ,=O,C １－３ alkyl, and C １－３ haloalkyl, or two R Ｃ groups attached to different atoms are taken together to form a C １－３ bridge, the method according to claim 12 or 13.

15. The menin inhibitor is a compound of formula (II): [Chemical Formula 3] or a pharmaceutically acceptable salt or prodrug thereof, H is C ５－１２ selected from a carbocyclic ring and a 5- to 12-membered heterocyclic ring, each of which is optionally substituted with one or more R ５０ ; A is selected from a single bond, a C ３－１２ carbocyclic ring, and a 3- to 12-membered heterocyclic ring; B is C ３－１２ selected from a carbocyclic ring and a 3- to 12-membered heterocyclic ring; L １ 、L ２ 、and L ３ are each independently a single bond, -O-, -S-, -N(R ５１ ), -N(R ５１ ), -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R ２ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -C(NR ５１ ), -C(NR ５１ ), -N(R ５１ ), -N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -S(O) ２ -, -OS(O)-, -S(O)O-, -S(O)-, -OS(O) ２ -, -S(O) ２ O-, -N(R ５１ ), -S(O) ２ -, -S(O) ２ N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -S(O)N(R ５１ ), -N(R ２ ), -S(O) ５１ N(R ５１ ), -N(R ５１ ), -S(O)N(R ５０ ); selected from alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, and heteroalkynylene, each of which is optionally substituted with one or more R R Ａ 、 R Ｂ 、 and R Ｃ are each independently selected from R ５０ each time they appear, or two R Ａ groups or two R Ｂ groups attached to the same or different atoms can optionally combine to form a bridge or a ring; m and n are each independently an integer from 0 to 6, W １ is alkylene optionally substituted with one or more R ５０ and is C １－４ ; W ２ is a single bond; and C optionally substituted with one or more R ５０ selected from alkylene optionally substituted with １－４ one or more R; W ３ is absent; and one or more Rs ５０ optionally substituted C １－４ selected from alkylene; R ５０ is selected from the following each time it appears: halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ NR ２ R ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ S(=O) ５２ NR ２ R ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(R ２ , =O, =S, =N(R ５２ ); C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl, each of which is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ２ , =O, =S, =N(R ５２ ), C ３－１２ One or more substituents selected from a carbon ring and a 3- to 12-membered heterocyclic ring, optionally substituted each time it appears, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where R ５０ each C in ３－１２ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and C ２－６ alkynyl, optionally substituted with one or more substituents selected from C ３－１２ carbocyclic ring and 3-membered - 12-membered heterocyclic ring; R ５１ is selected from the following each time it appears: hydrogen, -C(O)R ５２ , -C(O)OR ５２ , -C(O)N(R ５２ ), ２ , -C(O)NR ５３ R ５４ ; C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl, each of which is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ 、 =O, =S, =N(R ５２ ), C ３－１２ One or more substituents selected from a carbon ring and a 3- to 12-membered heterocyclic ring, optionally substituted each time it appears, C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where R ５１ each C in ３－１２ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and C ２－６ alkynyl, optionally substituted with one or more substituents selected from C ３－１２ carbocyclic ring and 3-membered - 12-membered heterocyclic ring; R ５２ appears each time as hydrogen; and C １－２０ alkyl, C ２－２０ alkenyl, C ２－２０ alkynyl, 2- to 6-membered heteroalkyl, C ３－１２ carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocycle, or 3- to 6-membered heterocycle; and, R ５３ and R ５４ together with the nitrogen atom to which they are attached form a heterocyclic ring optionally substituted with one or more R ５０ wherein, for the compound or salt of formula (II), when W ３ is absent: W １ is C １ alkylene, and W ２ is a single bond, and L ３ is not a single bond; W １ is C ２－４ alkylene, and W ２ is a single bond; Alternatively, W １ and W ２ are each C １ alkylene, L ３ is not a single bond, where C １ alkylene is each independently optionally substituted with one or more R ５０ The method according to claim 1 or 2.

16. The menin inhibitor is a compound of formula (III): [Chemical Formula 4] or a pharmaceutically acceptable salt or prodrug thereof, H is C ３－１２ selected from a carbocyclic ring and a 3- to 12-membered heterocyclic ring, each of which is optionally substituted with one or more R ５０ ; A is 【Chemical Formula 5】 ; Z １ , Z ２ , Z ３ , and Z ４ each of which is independently selected from -C(R Ａ１ )(R Ａ２ ), -C(R Ａ１ )(R Ａ２ )-C(R Ａ１ )(R Ａ２ ), -C(O)-, and -C(R Ａ１ )(R Ａ２ )-C(O)-, and only one of Z １ , Z ２ , Z ３ , and Z ４ is -C(O)- or -C(R Ａ１ )(R Ａ２ )-C(O)-; B is a single bond, C ３－１２ is selected from a carbon ring and a 3- to 12-membered heterocyclic ring; C is selected from a single bond, a C ３－１２ carbocyclic ring, and a 3- to 12-membered heterocyclic ring; L １ 、L ２ 、and L ３ are each independently a single bond, -O-, -S-, -N(R ５１ ), -N(R ５１ ), -CH ２ -, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -N(R ５１ ), -C(O)-, -N(R ５１ ), -C(O)N(R ５１ ), -N(R ５１ ), -C(O)O-, -OC(O)N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -C(NR ５１ ), -C(NR ５１ ), -N(R ５１ ), -N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -S(O) ２ -, -OS(O)-, -S(O)O-, -S(O)-, -OS(O) ２ -, -S(O) ２ O-, -N(R ５１ ), -S(O) ２ -, -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)-, -S(O)N(R ５１ ), -N(R ５１ ), -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)N(R ５１ ); independently selected from alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, and heteroalkynylene, each of which is optionally substituted with one or more R ５０ , where L １ , L ２ , or L ３ Two Rs bonded to any one same or different atom can be combined together to optionally form a bridge or a ring; ５０ The groups can be combined together to optionally form a bridge or a ring; R Ｂ is R ５０ either independently selected each time it appears from R Ｂ or two R groups bonded to the same atom or different atoms can together optionally form a bridge or a ring; R Ｃ is independently selected each time it appears from hydrogen and R ５０ or two R groups bonded to the same or different atoms may combine together to optionally form a bridge or a ring; Ｃ ​ R Ａ１ and R Ａ２ are each independently selected from hydrogen and R ５０ each time they appear; n is an integer from 0 to 6, p is an integer from 1 to 6; and / or R ５０ is selected from the following each time it appears: Halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ NR ２ R ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ S(=O) ５２ NR ２ R ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(OR ５２ )(R ２ ), -P(O)(NR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ , =O, =S, =N(R ５２ ); C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl, each of which is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ carbon ring, and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time it appears, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where R ５０ each C in ３－１２ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from C ３－１２ carbocycles and 3-membered - 12-membered heterocycles; R ５１ is selected from the following each time it appears: hydrogen, -C(O)R ５２ , -C(O)OR ５２ , -C(O)N(R ５２ ), ２ , -C(O)NR ５３ R ５４ ; C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl, wherein each of these is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ a carbon ring, and one or more substituents selected from 3- to 12-membered heterocyclic rings, optionally substituted each time it appears, C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where each C in R ５１ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ３－１２ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ , -S(=O) ５２ N(R ２ ), -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ , -NR ５２ S(=O) ２ , -NR ５２ S(=O) ２ , -NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from ３－１２ carbocyclic rings and 3 - to 12 - membered heterocyclic rings; R ５２ is, each time it appears, hydrogen; and C １－２０ alkyl, C ２－２０ alkenyl, C ２－２０ alkynyl, 1-6 membered heteroalkyl, C ３－１２ carbocycle, and 3-12 membered heterocycle, each of which is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocycle, or 3-6 membered heterocycle; and, R ５３ and R ５４ together with the nitrogen atom to which they are attached form a heterocyclic ring optionally substituted with one or more R ５０ The method according to claim 1 or 2, wherein:

17. The menin inhibitor is a compound of formula (IV): [Chemical Formula 6] or a pharmaceutically acceptable salt or prodrug thereof, 【Chemical Formula 7】 is a fused thienyl or fused phenyl group; G ａ is selected from a carbon ring and a 3- to 12-membered heterocyclic ring, each of which is substituted with -E ３－１２ -R １ and optionally further substituted with one or more Rs ４ａ ; ５０ ​ R ２ａ is selected from hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocycle, optionally substituted heteroaryl, and aralkyl; R ３ａ and R ３ｂ are each independently selected from hydrogen, alkyl, halo, hydroxy, cyano, amino, alkylamino, dialkylamino, haloalkyl, alkoxy, and haloalkoxy; X ａ -Y ａ is selected from -N(R ５２ ), -C(=O)-, -C(=O)-O-, -C(=O)-N(R ５２ ), -CH ２ N(R ５２ ), -CH ２ -, -C(=O)N(R ５２ ), -CH ２ -, -CH ２ CH ２ -N(R ５２ ), -CH ２ N(R ５２ ), -C(=O)-, and -CH ２ OCH ２ -; Alternatively, X ａ and Y ａ do not form a chemical bond, where: X ａ is selected from hydrogen, alkyl, halo, hydroxy, cyano, amino, alkylamino, dialkylamino, haloalkyl, alkoxy, and haloalkoxy; and Y ａ is selected from cyano, hydroxy, and -CH ２ R ５０ ; and E １ is absent, -C(=O)-, -C(=O)N(R ５２ ), -[C(R １４ａ )) ２ , １－５ O-, -[C(R １４ａ )) ２ , １－５ NR ５２ -, -[C(R １４ａ )) ２ , １－５ -, -CH ２ (=O)-, and, -S(=O) ２ - is selected from; R ４ａ is selected from hydrogen, alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocycle, optionally substituted heteroaryl, aralkyl, (heterocycle)alkyl, and (heteroaryl)alkyl; R １４ａ is selected from hydrogen and alkyl; R ５０ is selected from the following each time it appears: Halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ N(R ２ R ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ S(=O) ５２ N(R ２ R ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(OR ５２ )(R ２ ), -P(O)(NR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ); C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl, wherein each of these is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ NR ２ R ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ S(=O) ５２ NR ２ R ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ a carbon ring, and one or more substituents selected from 3- to 12-membered heterocyclic rings, optionally substituted each time it appears, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where each C in R ５０ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ３－１２ , -CN, -OR ２ , -SR ５２ , -N(R ５２ ), -NR ５２ R ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ , -NR ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ , -P(O)(OR ５４ ), -P(O)(R ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from ３－１２ carbocyclic rings and 3- to 12-membered heterocyclic rings; R ５２ is, each time it appears, hydrogen; and, C １－２０ alkyl, C ２－２０ alkenyl, C ２－２０ alkynyl, 1-6 membered heteroalkyl, C ３－１２ carbocycle, and 3-12 membered heterocycle, each of which is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocycle, or 3-6 membered heterocycle; and, R ５３ and R ５４ together with the nitrogen atom to which they are attached form a heterocyclic ring optionally substituted with one or more R ５０ groups, the method according to claim 1 or 2.

18. The menin inhibitor is a compound of formula (VI): 【Chemical 8】 or a pharmaceutically acceptable salt or prodrug thereof, H ２ is selected from a C ３－１２ carbocyclic ring and a 3- to 12-membered heterocyclic ring; H is C ３－１２ selected from a carbocyclic ring and a 3- to 12-membered heterocyclic ring, each of which is optionally substituted with one or more Rs ５０ ; A is 【Chemical Formula 9】 ; Z １ 、Z ２ 、Z ３ 、and Z ４ each independently is selected from -C(R Ａ１ )(R Ａ２ )-, -C(R Ａ１ )(R Ａ２ )-C(R Ａ１ )(R Ａ２ )-, -O-, -C(R Ａ１ )(R Ａ２ )-O-, -C(R Ａ１ )(R Ａ２ )-N(R ５１ )-, -C(O)-, -C(R Ａ１ )(R Ａ２ )-C(O)-, and -N=C(NH ２ )-; Z １ , Z ２ , Z ３ , and Z ４ only one of which is —O—, —C(R Ａ１ )(R Ａ２ )—O—, —C(R Ａ１ )(R Ａ２ )—N(R ５１ )—, —C(O)—, —C(R Ａ１ )(R Ａ２ )—C(O)—, or —N═C(NH ２ )—; Z ５ and Z ６ is independently selected from -C(R Ａ３ )- and -N-; B is a single bond, C ３－１２ is selected from a carbon ring and a 3- to 12-membered heterocyclic ring; L １ 、L ２ 、and L ４ are each independently a single bond, -O-, -S-, -N(R ５１ ), -N(R ５１ ), -CH ２ -, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -C(O)N(R ５１ ), -N(R ５１ ), -C(O)O-, -OC(O)N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -C(NR ５１ ), -C(NR ５１ ), -N(R ５１ ), -N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -S(O) ２ -, -OS(O)-, -S(O)O-, -S(O)-, -OS(O) ２ -, -S(O) ２ O-, -N(R ５１ ), -S(O) ２ -, -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)-, -S(O)N(R ５１ ), -N(R ５１ ), -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)N(R ５１ ); independently selected from alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, and heteroalkynylene, Each of these is optionally replaced with one or more R ５０ and is optionally substituted with Here, L １ , L ２ , or L ４ Two R ５０ groups bonded to the same atom or different atoms of any one of them can be combined to optionally form a bridge or a ring; R Ｂ is independently selected each time it appears from hydrogen and R ５０ or two R groups bonded to the same or different atoms can combine together to optionally form a bridge or a ring; Ｂ ​ R Ｈ２ is independently selected each time it appears from R ５０ or two R groups bonded to the same atom or different atoms may combine together to optionally form a bridge or a ring; Ｈ２ ​ R Ａ１ 、 R Ａ２ 、 and R Ａ３ are each independently selected from hydrogen and R ５０ each time they appear; n is an integer from 0 to 6, r is an integer from 1 to 6; R ５０ is selected from the following each time it appears: Halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ N(R ２ ), -S(=O) ５３ NR ５４ R, -NR ５２ S(=O) ２ R, -NR ５２ S(=O) ５２ N(R ２ ), -NR ５２ S(=O) ２ NR ５２ R, -C(O)R ２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ５２ R, -NR ２ C(O)R, -NR ５３ C(O)OR, -NR ５４ C(O)N(R ５２ ), -NR ５２ C(O)NR ５２ R, -C(O)N(R ５２ ), -C(O)NR ５２ R, -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(OR ５２ )(R ５３ ), -P(O)(NR ５４ )(R ５２ ), -P(O)(OR ２ )(R ５３ ), -P(O)(R ５４ ), -P(O)(OR ５２ )(R ２ ), -P(O)(NR ５２ )(R ２ ), -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ); C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl, each of which is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ a carbon ring, and one or more substituents selected from 3- to 12-membered heterocyclic rings, optionally substituted each time it appears, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where each C in R ５０ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ３－１２ , -CN, -OR ２ , -SR ５２ , -N(R ５２ ), -NR ５２ R ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ , -NR ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ , -P(O)(OR ５４ ), -P(O)(R ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from ３－１２ carbocycles and 3-membered - 12-membered heterocycles; R ５１ is selected from the following each time it appears: hydrogen, -C(O)R ５２ , -C(O)OR ５２ , -C(O)N(R ５２ ), ２ , -C(O)NR ５３ R ５４ ; C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl, each of which is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ a carbon ring, and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time it appears, C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where each C in R ５１ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ３－１２ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from C ３－１２ carbocyclic ring and 3-membered - 12-membered heterocyclic ring; R ５２ is, each time it appears, hydrogen; and C １－２０ alkyl, C ２－２０ alkenyl, C ２－２０ alkynyl, 1-6 membered heteroalkyl, C ３－１２ carbocycle, and 3-12 membered heterocycle, each of which is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocycle, or 3-6 membered heterocycle; and R ５３ and R ５４ together with the nitrogen atom to which they are attached form a heterocyclic ring optionally substituted with one or more R ５０ The method according to claim 1 or 2, wherein

19. A method for treating a hematologic malignancy in a subject having a mutation in the nucleophosmin (NPM1) gene, DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, FMS-like tyrosine kinase-3 (FLT3) gene, isocitrate dehydrogenase 1 (IDH1) gene, isocitrate dehydrogenase 2 (IDH2) gene, or a combination thereof, comprising: The method comprises administering to a subject in need thereof a compound of formula (I-A), 【Chemical Formula 10】 or a pharmaceutically acceptable salt or prodrug thereof, H is C ５－１２ selected from a carbocyclic ring and a 5- to 12-membered heterocyclic ring, each of which is optionally substituted with one or more R ５０ ; A is selected from a single bond, a C ３－１２ carbocyclic ring, and a 3- to 12-membered heterocyclic ring; B is C ３－１２ selected from a carbocyclic ring and a 3- to 12-membered heterocyclic ring; C is a 3- to 12-membered heterocyclic ring; L １ 、 L ２ 、 and L ３ are each independently a single bond, -O-, -S-, -N(R ５１ ), -N(R ５１ ), -N(R ２ ), -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -C(NR ５１ ), -C(NR ５１ ), -N(R ５１ ), -N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -S(O) ２ ), -OS(O)-, -S(O)O-, -S(O)-, -OS(O) ２ ), -S(O) ２ O-, -N(R ５１ ), -S(O) ２ N(R ２ ), -N(R ５１ ), -N(R ５１ ), -S(O)N(R ５１ ), -N(R ５１ ), -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)N(R ５１ ); independently selected from alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, and heteroalkynylene, each of which is optionally substituted with one or more R ５０ , where L １ , L ２ , or L ３ Two Rs bonded to any one of the same or different atoms can combine together to optionally form a bridge or a ring; ５０ The groups can combine together to optionally form a bridge or a ring; R Ａ 、 R Ｂ 、 and R Ｃ are each independently selected each time they appear from R ５０ , or two R Ａ groups, two R Ｂ groups, or two R Ｃ groups can combine together to optionally form a bridge or a ring; m, n, and p are each independently an integer from 0 to 6; R ５０ is selected from the following each time it appears: Halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ NR ２ R ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ S(=O) ５２ NR ２ R ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(OR ５２ )(R ２ ), -P(O)(NR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ); C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl, wherein each of these is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ carbon ring, and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time it appears, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where R ５０ each C in ３－１２ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from ３－１２ carbocycles and 3-membered - 12-membered heterocycles; R ５１ is selected from the following each time it appears: hydrogen, -C(O)R ５２ , -C(O)OR ５２ , -C(O)N(R ５２ ), ２ , -C(O)NR ５３ R ５４ ; C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl, wherein each of these is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ a carbon ring, and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time it appears, C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where each C in R ５１ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ３－１２ , -CN, -OR ２ , -SR ５２ , -N(R ５２ ), -NR ５２ R ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ , -NR ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ , -P(O)(OR ５４ ), -P(O)(R ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from ３－１２ carbocyclic rings and 3- to 12-membered heterocyclic rings; R ５２ is, each time it appears, hydrogen; and C １－２０ alkyl, C ２－２０ alkenyl, C ２－２０ alkynyl, 1- to 6-membered heteroalkyl, C ３－１２ carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocycle, or 3- to 6-membered heterocycle; R ５３ and R ５４ together with the nitrogen atom to which they are attached form a heterocyclic ring optionally substituted with one or more R ５０ ; R ５７ is selected from the following: Halogen, -NO ２ , -CN, -SR ５２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５８ , -S(=O) ２ , -S(=O) ５２ N(R ２ ), -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ , -NR ５２ S(=O) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ R ５４ , -C(O)NH(C １－６ alkyl), -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(OR ５２ )(R ２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ 、 = S, = N(R ５２ ); and C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl, each of which is independently, -NO ２ , -CN, -SR ５２ , -N(R ５２ ), ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), ２ , -NR ５２ C(O)NR ５３ R ５４ , -P(O)(OR ５２ ), ２ , -P(O)(R ５２ ), ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =S, and =N(R ５２ ), one or more substituents selected from, and substituted each time they appear, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl; R ５８ is hydrogen; and C １－２０ alkyl, C ３－２０ alkenyl, C ２－２０ alkynyl, 1- to 6-membered heteroalkyl, C ３－１２ carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocycle, or 3- to 6-membered heterocycle; wherein, for the compound or salt of formula (I-A), C is azetidinylene, piperidinylene, or piperazinylene, and R ５７ is -S(=O) ２ R ５８ , -S(=O) ２ N(R ５２ ), ２ or -NR ５２ S(=O) ２ R ５２ when: p is an integer from 1 to 6; and / or L ３ is substituted by one or more Rs ５０ wherein L ３ is not -CH ２ CH(OH)-, a method.

20. A method for treating a hematologic malignancy in a subject having a mutation in the nucleophosmin (NPM1) gene, DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, FMS-like tyrosine kinase-3 (FLT3) gene, isocitrate dehydrogenase 1 (IDH1) gene, isocitrate dehydrogenase 2 (IDH2) gene, or a combination thereof, comprising: The method comprises administering to a subject in need thereof a compound of formula (I-B), 【Chemical 11】 or a pharmaceutically acceptable salt thereof, H is C ５－１２ selected from a carbocyclic ring and a 5- to 12-membered heterocyclic ring, each of which is optionally substituted with one or more R ５０ ; A, B, and C are each independently selected from a carbocyclic ring and a 3- to 12-membered heterocyclic ring; ３－１２ and are independently selected from a carbocyclic ring and a 3- to 12-membered heterocyclic ring; L １ and L ２ each independently is a single bond, -O-, -S-, -N(R ５１ ), -N(R ５１ ),CH ２ -, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R ５１ ), -C(O)N(R ５１ ),C(O)-, -C(O)N(R ５１ ),C(O)N(R ５１ ), -N(R ５１ ),C(O)-, -N(R ５１ ),C(O)N(R ５１ ), -N(R ５１ ),C(O)O-, -OC(O)N(R ５１ ), -C(NR ５１ ), -N(R ５１ ),C(NR ５１ ), -C(NR ５１ ),N(R ５１ ), -N(R ５１ ),C(NR ５１ ),N(R ５１ ), -S(O) ２ -, -OS(O)-, -S(O)O-, -S(O)-, -OS(O) ２ -, -S(O) ２ O-, -N(R ５１ ),S(O) ２ -, -S(O) ２ N(R ５１ ), -N(R ５１ ),S(O)-, -S(O)N(R ５１ ), -N(R ５１ ),S(O) ２ N(R ５１ ), -N(R ５１ ),S(O)N(R ５１ ), -; selected from alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, and heteroalkynylene, each of which is optionally substituted with one or more R ５０ ; L ３ is selected from alkylene, alkenylene, and alkynylene, each of which is substituted with one or more R ５６ and optionally further substituted with one or more R ５０ ; R Ａ 、 R Ｂ 、 and R Ｃ are each independently selected each time they appear from R ５０ , or two R Ａ groups, two R Ｂ groups, or two R Ｃ groups can combine to optionally form a bridge or a ring; m, n, and p are each independently an integer from 0 to 6; R ５０ is selected from the following each time it appears: Halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ N(R ２ R ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ S(=O) ５２ N(R ２ R ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(OR ５２ )(R ２ ), -P(O)(NR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ); C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl, each of which is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ a carbon ring, and one or more substituents selected from 3- to 12-membered heterocyclic rings, optionally substituted each time it appears, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where each C in R ５０ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ３－１２ , -CN, -OR ２ , -SR ５２ , -N(R ５２ ), -NR ５２ R ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ , -NR ５４ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ５２ C(O)NR ２ R ５２ , -C(O)N(R ５３ ), -C(O)NR ５４ R ５２ , -P(O)(OR ２ ), -P(O)(R ５３ ５４ ), -P(O)(OR ５２ ), -P(O)(R ２ ５２ ​​) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from C ３－１２ carbocyclic ring and 3-membered - 12-membered heterocyclic ring; R ５１ is selected from the following each time it appears: hydrogen, -C(O)R ５２ , -C(O)OR ５２ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ ; C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl, wherein each of these is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ carbon ring, and one or more substituents selected from 3- to 12-membered heterocyclic rings, optionally substituted each time it appears, C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where each C in R ５１ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ３－１２ , -CN, -OR ２ , -SR ５２ , -N(R ５２ ), -NR ５２ R ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ NR ２ R ５３ , -NR ５４ S(=O) ５２ R ２ , -NR ５２ S(=O) ５２ N(R ２ ), -NR ５２ S(=O) ２ NR ５２ R ２ , -C(O)R ５３ , -C(O)OR ５４ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ５２ R ５２ , -NR ２ C(O)R ５３ , -NR ５４ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ５２ C(O)NR ５２ R ２ , -C(O)N(R ５２ ), -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(OR ５３ ), -P(O)(R ５４ ), -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(OR ５２ ), -P(O)(R ２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from C ３－１２ carbocyclic ring and 3-membered - 12-membered heterocyclic ring; R ５２ is, each time it appears, hydrogen; and C １－２０ alkyl, C ２－２０ alkenyl, C ２－２０ alkynyl, 1-6 membered heteroalkyl, C ３－１２ carbocycle, and 3-12 membered heterocycle, each of which is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocycle, or 3-6 membered heterocycle; R ５３ and R ５４ together with the nitrogen atom to which they are attached form a heterocyclic ring optionally substituted with one or more R ５０ ; R ５６ appears each time as -NO ２ 、-OR ５９ 、-SR ５２ 、-NR ５３ R ５４ 、-S(=O)R ５２ 、-S(=O) ２ R ５２ 、-S(=O) ２ N(R ５２ ) ２ 、-S(=O) ２ NR ５３ R ５４ 、-NR ５２ S(=O) ２ R ５２ 、-NR ５２ S(=O) ２ N(R ５２ ) ２ 、-NR ５２ S(=O) ２ NR ５３ R ５４ 、-C(O)R ５２ 、-C(O)OR ５２ 、-OC(O)R ５２ 、-OC(O)OR ５２ 、-OC(O)N(R ５２ ) ２ 、-OC(O)NR ５３ R ５４ 、-NR ５２ C(O)R ５２ 、-NR ５２ C(O)OR ５２ 、-NR ５２ C(O)N(R ５２ ) ２ 、-NR ５２ C(O)NR ５３ R ５４ 、-C(O)N(R ５２ ) ２ 、-C(O)NR ５３ R ５４ 、-P(O)(OR ５２ ) ２ 、-P(O)(R ５２ ) ２ 、-P(O)(OR ５２ )(R ５２ )、-P(O)(NR ５２ )(R ５２ 、-NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ), ２ =O, =S, =N(R ５２ ), C １－１０ alkyl, C ２－１０ alkenyl, C ２－１０ alkynyl, C ３－１２ selected from carbocycles, and 3-membered to 12-membered heterocycles, R ５６ Each C in １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl is independently halogen, -NO ２ , -CN, -OR ５９ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ NR ２ R ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ S(=O) ５２ NR ２ R ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ５２ ​) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C ３－１２ a carbon ring, and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time it appears, R ５６ each C in ３－１２ The carbocyclic ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ ), (R ５２ ), -P(O)(NR ５２ ), (R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ), ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and C ２－６ alkynyl, optionally substituted with one or more substituents selected from Furthermore, here, R ５６ optionally forms a single bond to ring C; and, R ５９ is independently selected, each time it appears, from C １－２０ alkyl, C ２－２０ alkenyl, C ２－２０ alkynyl, 1-6 membered heteroalkyl, C ３－１２ carbocyclic, and 3-12 membered heterocyclic, and each of them is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocyclic, or 3-6 membered heterocyclic; Here, for the compound or salt of formula (I-B), when R ５６ is -CH ３ , L ３ is a method that is not further substituted by -OH, -NH ２ , or -CN.

21. R Ｃ is -C(O)R ５２ 、-S(=O)R ５２ 、-S(=O) ２ R ５２ 、-S(=O) ２ N(R ５２ ) ２ 、-S(=O) ２ NR ５３ R ５４ 、-NR ５２ S(=O) ２ R ５２ 、=O、C １－３ alkyl, and C １－３ haloalkyl, or two R Ｃ groups attached to different atoms may combine to form a C １－３ bridge, the method according to claim 19 or 20.

22. A method for treating a hematologic malignancy in a subject having a mutation in the nucleophosmin (NPM1) gene, DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, FMS-like tyrosine kinase-3 (FLT3) gene, isocitrate dehydrogenase 1 (IDH1) gene, isocitrate dehydrogenase 2 (IDH2) gene, or a combination thereof, comprising: The method comprises administering to a subject in need thereof a compound of formula (II), 【Chemical 12】 or a pharmaceutically acceptable salt or prodrug thereof, H is C ５－１２ selected from a carbocyclic ring and a 5- to 12-membered heterocyclic ring, each of which is optionally substituted with one or more R ５０ ; A is selected from a single bond, a C ３－１２ carbocyclic ring, and a 3- to 12-membered heterocyclic ring; B is C ３－１２ selected from a carbocyclic ring and a 3- to 12-membered heterocyclic ring; L １ 、L ２ 、and L ３ are each independently a single bond, -O-, -S-, -N(R ５１ ), -N(R ５１ ), -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R ２ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -C(O)-, -N(R ５１ ), -C(O)N(R ５１ ), -N(R ５１ ), -C(O)O-, -OC(O)N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -C(NR ５１ ), -C(NR ５１ ), -N(R ５１ ), -N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -S(O) ２ -, -OS(O)-, -S(O)O-, -S(O)-, -OS(O) ２ -, -S(O) ２ O-, -N(R ５１ ), -S(O) ２ -, -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)-, -S(O)N(R ５１ ), -N(R ５１ ), -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)N(R ５１ ); alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, and heteroalkynylene, each of which is optionally substituted with one or more R ５０ ; R Ａ 、 R Ｂ 、 and R Ｃ are each independently selected from R ５０ each time it appears, or two R Ａ groups or two R Ｂ groups attached to the same or different atoms may combine together to optionally form a bridge or a ring; m and n are each independently an integer from 0 to 6, W １ is alkylene optionally substituted with one or more R ５０ and is C １－４ alkylene; W ２ is a single bond; and C optionally substituted with one or more R ５０ selected from alkylene １－４ and optionally substituted with one or more R; W ３ is absent; and one or more R ５０ optionally substituted C １－４ selected from alkylene; R ５０ is selected from the following each time it appears: Halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ NR ２ R ５３ , -NR ５４ S(=O) ５２ R ２ , -NR ５２ S(=O) ５２ N(R ２ ), -NR ５２ S(=O) ２ NR ５２ R ２ , -C(O)R ５３ , -C(O)OR ５４ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ５２ R ５２ , -NR ２ C(O)R ５３ , -NR ５４ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ５２ C(O)NR ５２ R ５２ , -C(O)N(R ２ ), -C(O)NR ５２ R ５３ , -P(O)(OR ５４ ), -P(O)(R ５２ ), =O, =S, =N(R ２ ), -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), =O, =S, =N(R ５２ ); ２ , =O, =S, =N(R ５２ ); C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl, wherein each of these is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ 、 =O, =S, =N(R ５２ ), C ３－１２ One or more substituents selected from a carbon ring and a 3- to 12-membered heterocyclic ring, optionally substituted each time it appears, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where R ５０ each C in ３－１２ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and C ２－６ alkynyl, optionally substituted with one or more substituents selected from C ３－１２ a carbocyclic ring and a 3-membered to 12-membered heterocyclic ring; R ５１ is selected from the following each time it appears: hydrogen, -C(O)R ５２ , -C(O)OR ５２ , -C(O)N(R ５２ ), ２ , -C(O)NR ５３ R ５４ ; C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl, wherein each of these is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ NR ２ R ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ S(=O) ５２ NR ２ R ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ) ２ 、 =O, =S, =N(R ５２ ), C ３－１２ One or more substituents selected from a carbon ring and a 3- to 12-membered heterocyclic ring, optionally substituted each time it appears, C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where each C in R ５１ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ３－１２ , -CN, -OR ２ , -SR ５２ , -N(R ５２ ), -NR ５２ R ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ , -NR ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ , -P(O)(OR ５４ ), -P(O)(R ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and C ２－６ alkynyl, optionally substituted with one or more substituents selected from C ３－１２ carbocyclic ring and 3- to 12-membered heterocyclic ring; R ５２ is, each time it appears, hydrogen; and, C １－２０ alkyl, C ２－２０ alkenyl, C ２－２０ alkynyl, 2- to 6-membered heteroalkyl, C ３－１２ carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocycle, or 3- to 6-membered heterocycle; and, R ５３ and R ５４ together with the nitrogen atom to which they are attached form a heterocyclic ring optionally substituted with one or more R ５０ wherein, for the compound or salt of formula (II), when W ３ is absent: W １ is C １ alkylene, and W ２ is a single bond, and L ３ is not a single bond; W １ is C ２－４ alkylene, and W ２ is a single bond; or, W １ and W ２ are each C １ alkylene, and L ３ is not a single bond, where C １ alkylene is each independently optionally substituted with one or more R ５０ s, a method.

23. A method for treating a hematological malignancy in a subject having a mutation in the nucleophosmin (NPM1) gene, DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, FMS-like tyrosine kinase-3 (FLT3) gene, isocitrate dehydrogenase 1 (IDH1) gene, isocitrate dehydrogenase 2 (IDH2) gene, or a combination thereof, comprising: said method comprising administering to a subject in need thereof a compound of formula (III), 【Chemical Formula 13】 or a pharmaceutically acceptable salt or prodrug thereof, H is C ３－１２ selected from a carbocyclic ring and a 3- to 12-membered heterocyclic ring, each of which is optionally substituted with one or more R ５０ ; A is 【Chemical 14】 wherein; Z １ 、Z ２ 、Z ３ 、and Z ４ each of which is independently selected from -C(R Ａ１ )(R Ａ２ ), -C(R Ａ１ )(R Ａ２ )-C(R Ａ１ )(R Ａ２ )-, -C(O)-, and -C(R Ａ１ )(R Ａ２ )-C(O)-; and only one of Z １ 、Z ２ 、Z ３ 、and Z ４ is -C(O)- or -C(R Ａ１ )(R Ａ２ )-C(O)-; B is a single bond, C ３－１２ is selected from a carbon ring, and a 3- to 12-membered heterocyclic ring; C is selected from a single bond, C ３－１２ a carbocyclic ring, and a 3- to 12-membered heterocyclic ring; L １ 、 L ２ 、 and L ３ are each independently a single bond, -O-, -S-, -N(R ５１ ), -N(R ５１ ), -CH ２ -, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -N(R ５１ ), -C(O)-, -N(R ５１ ), -C(O)N(R ５１ ), -N(R ５１ ), -C(O)O-, -OC(O)N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -C(NR ５１ ), -C(NR ５１ ), -N(R ５１ ), -N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -S(O) ２ -, -OS(O)-, -S(O)O-, -S(O)-, -OS(O) ２ -, -S(O) ２ O-, -N(R ５１ ), -S(O) ２ N(R ２ ), -N(R ５１ ), -S(O)-, -S(O)N(R ５１ ), -N(R ５１ ), -S(O) ５１ N(R ２ ), -N(R ５１ ), -S(O)N(R ５１ ), -N(R ５１ ), -S(O)N(R ５０ ); independently selected from alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, and heteroalkynylene, each of which is optionally substituted with one or more R １ , L ２ , or L ３ Two Rs bonded to any one of the same or different atoms can combine together to optionally form a bridge or a ring; ５０ The groups can combine together to optionally form a bridge or a ring; R Ｂ is selected independently each time it appears from R ５０ or two R groups bonded to the same atom or different atoms can combine together to optionally form a bridge or a ring; Ｂ ​ R Ｃ is independently selected each time it appears from hydrogen and R ５０ or two R groups bonded to the same atom or different atoms can combine together to optionally form a bridge or a ring; Ｃ ​ R Ａ１ and R Ａ２ are each independently selected from hydrogen and R ５０ each time they appear; n is an integer from 0 to 6, p is an integer from 1 to 6; and / or, R ５０ is selected from the following each time it appears: Halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ N(R ２ ), -NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ S(=O) ５２ N(R ２ ), -NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(OR ５２ )(R ２ ), -P(O)(NR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ); C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl, each of which is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ a carbon ring, and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time it appears, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where R ５０ each C in ３－１２ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from ３－１２ carbocyclic rings and 3 - to 12 - membered heterocyclic rings; R ５１ is selected from the following each time it appears: hydrogen, -C(O)R ５２ , -C(O)OR ５２ , -C(O)N(R ５２ ), ２ , -C(O)NR ５３ R ５４ ; C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl, each of which is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ , -S(=O)R ５４ , -S(=O) ５２ R ２ , -S(=O) ５２ N(R ２ ), -S(=O) ５２ NR ２ R ２ , -NR ５３ S(=O) ５４ R ５２ , -NR ２ S(=O) ５２ N(R ５２ ), -NR ２ S(=O) ５２ NR ２ R ５２ , -NR ２ S(=O) ５３ NR ５４ R ５２ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ２ ), -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ , -C(O)N(R ５４ ), -C(O)NR ５２ R ２ , -P(O)(OR ５３ ), -P(O)(R ５４ ), -P(O)(R ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ , -P(O)(NR ５２ )(R ５２ , -NR ５２ P(O)(R ５２ , -P(O)(NR ５２ )(OR ５２ , -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ carbon ring, and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time it appears, C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where each C in R ５１ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ３－１２ , -CN, -OR ２ , -SR ５２ , -N(R ５２ ), -NR ５２ R ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ NR ２ R ５３ , -NR ５４ S(=O) ５２ R ２ , -NR ５２ S(=O) ５２ N(R ２ ), -NR ５２ S(=O) ２ NR ５２ R ２ , -C(O)R ５３ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ , -NR ５４ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ５２ C(O)NR ２ R ５２ , -C(O)N(R ５３ ), -C(O)NR ５４ R ５２ , -P(O)(OR ２ ), -P(O)(R ５３ ), -P(O)(OR ５４ ), -P(O)(R ５２ ), -P(O)(OR ２ ), -P(O)(R ５２ ), -P(O)(OR ２ ), -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ )( ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from C ３－１２ carbocyclic rings and 3- to 12-membered heterocyclic rings; R ５２ is, each time it appears, hydrogen; and C １－２０ alkyl, C ２－２０ alkenyl, C ２－２０ alkynyl, 1-6 membered heteroalkyl, C ３－１２ carbocycle, and 3-12 membered heterocycle, each of which is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocycle, or 3-6 membered heterocycle; and R ５３ and R ５４ together with the nitrogen atom to which they are attached form a heterocyclic ring optionally substituted with one or more R ５０ groups, a method.

24. A method for treating a hematological malignancy in a subject having a mutation in the nucleophosmin (NPM1) gene, DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, FMS-like tyrosine kinase-3 (FLT3) gene, isocitrate dehydrogenase 1 (IDH1) gene, isocitrate dehydrogenase 2 (IDH2) gene, or a combination thereof, comprising: said method comprising administering to a subject in need thereof a compound of formula (IV), 【Chemical Formula 15】 or a pharmaceutically acceptable salt or prodrug thereof, 【Chemical 16】 is a fused thienyl or fused phenyl group; G ａ is selected from a C ３－１２ carbocyclic ring and a 3- to 12-membered heterocyclic ring, each of which is substituted with -E １ -R ４ａ and optionally further substituted with one or more R ５０ ; R ２ａ is selected from hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocycle, optionally substituted heteroaryl, and aralkyl; R ３ａ and R ３ｂ are each independently selected from hydrogen, alkyl, halo, hydroxy, cyano, amino, alkylamino, dialkylamino, haloalkyl, alkoxy, and haloalkoxy; X ａ -Y ａ is selected from -N(R ５２ ), -C(=O)-, -C(=O)-O-, -C(=O)-N(R ５２ ), -CH ２ N(R ５２ ), -CH ２ -, -C(=O)N(R ５２ ), -CH ２ -, -CH ２ CH ２ -N(R ５２ ), -CH ２ N(R ５２ ), -C(=O)-, and -CH ２ OCH ２ -; Alternatively, X ａ and Y ａ do not form a chemical bond, where: X ａ is selected from hydrogen, alkyl, halo, hydroxy, cyano, amino, alkylamino, dialkylamino, haloalkyl, alkoxy, and haloalkoxy; and, Y ａ is selected from cyano, hydroxy, and -CH ２ R ５０ ; and E １ is absent, selected from -C(=O)-, -C(=O)N(R ５２ ), -[C(R １４ａ ) ２ , -[C(R １－５ ) １４ａ ) ２ , -[C(R １－５ ) ５２ ) １４ａ ) ２ , -[C(R １－５ ) ２ =O)-, and -S(=O) ２ -; R ４ａ is selected from hydrogen, alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocycle, optionally substituted heteroaryl, aralkyl, (heterocycle)alkyl, and (heteroaryl)alkyl; R １４ａ is selected from hydrogen and alkyl; R ５０ is selected from the following each time it appears: Halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ NR ２ R ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ S(=O) ５２ NR ２ R ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(OR ５２ )(R ２ ), -P(O)(NR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ); C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl, each of which is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ５２ ), -P(O)(R ２ ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ carbon ring, and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time it appears, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl; and, C ３－１２ Carbocycles and 3- to 12-membered heterocycles, R ５０ Each C in ３－１２ The carbocycle and the 3- to 12-membered heterocycle are independently selected from halogen, —NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N (R ５２ ) ２ , -S(=O) ２ N.R. ５３ R ５４ , -NR ５２ S (=O) ２ R ５２ , -NR ５２ S (=O) ２ N (R ５２ ) ２ , -NR ５２ S (=O) ２ N.R. ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from ３－１２ carbocycles and 3-membered - 12-membered heterocycles; R ５２ is, each time it appears, hydrogen; and C １－２０ alkyl, C ２－２０ alkenyl, C ２－２０ alkynyl, 1-6 membered heteroalkyl, C ３－１２ carbocycle, and 3-12 membered heterocycle, each of which is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocycle, or 3-6 membered heterocycle; and R ５３ and R ５４ together with the nitrogen atom to which they are attached form a heterocyclic ring optionally substituted with one or more R ５０ groups, method.

25. A method for treating a hematological malignancy in a subject having a mutation in the nucleophosmin (NPM1) gene, DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, FMS-like tyrosine kinase-3 (FLT3) gene, isocitrate dehydrogenase 1 (IDH1) gene, isocitrate dehydrogenase 2 (IDH2) gene, or a combination thereof, comprising: said method comprising administering to a subject in need thereof a compound of formula (VI), 【Chemical 17】 or a pharmaceutically acceptable salt or prodrug thereof, H ２ is selected from a C ３－１２ carbocyclic ring and a 3- to 12-membered heterocyclic ring; H is C ３－１２ selected from a carbocyclic ring and a 3- to 12-membered heterocyclic ring, each of which is optionally substituted with one or more R ５０ ; A is 【Chemical 18】 wherein; Z １ 、Z ２ 、Z ３ 、and Z ４ each independently is selected from -C(R Ａ１ )(R Ａ２ )-, -C(R Ａ１ )(R Ａ２ )-C(R Ａ１ )(R Ａ２ )-, -O-, -C(R Ａ１ )(R Ａ２ )-O-, -C(R Ａ１ )(R Ａ２ )-N(R ５１ )-, -C(O)-, -C(R Ａ１ )(R Ａ２ )-C(O)-, and -N=C(NH ２ )-; only one of Z １ , Z ２ , Z ３ , and Z ４ is -O-, -C(R Ａ１ )(R Ａ２ )-O-, -C(R Ａ１ )(R Ａ２ )-N(R ５１ )-, -C(O)-, -C(R Ａ１ )(R Ａ２ )-C(O)-, or -N=C(NH ２ )-; Z ５ and Z ６ is independently selected from -C(R Ａ３ )- and -N-; B is a single bond, C ３－１２ is selected from a carbon ring and a 3- to 12-membered heterocyclic ring; L １ 、 L ２ 、 and L ４ are each independently a single bond, -O-, -S-, -N(R ５１ ), -N(R ５１ ), -N(R ２ ), -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -C(NR ５１ ), -C(NR ５１ ), -N(R ５１ ), -N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -S(O) ２ -, -OS(O)-, -S(O)O-, -S(O)-, -OS(O) ２ -, -S(O) ２ O-, -N(R ５１ ), -S(O) ２ -, -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)-, -S(O)N(R ５１ ), -N(R ５１ ), -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)N(R ５１ ); independently selected from alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, and heteroalkynylene, each of which is optionally substituted with one or more R ５０ , where L １ , L ２ , or L ４ Two Rs bonded to any one of the same or different atoms can be combined to optionally form a bridge or a ring; ５０ The groups can be combined to optionally form a bridge or a ring; R Ｂ is independently selected each time it appears from hydrogen and R ５０ or two R groups bonded to the same or different atoms may combine together to optionally form a bridge or a ring; Ｂ ​ R Ｈ２ is R ５０ independently selected each time it appears from R, or two R groups bonded to the same or different atoms may combine together to optionally form a bridge or a ring; Ｈ２ ​ R Ａ１ 、R Ａ２ 、and R Ａ３ are each independently selected from hydrogen and R ５０ each time they appear; n is an integer from 0 to 6, r is an integer from 1 to 6; R ５０ is selected from the following each time it appears: Halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ , -S(=O)R ５４ , -S(=O) ５２ R ２ , -S(=O) ５２ N(R ２ ), -S(=O) ５２ NR ２ R ２ , -NR ５３ S(=O) ５４ R ５２ , -NR ２ S(=O) ５２ N(R ５２ ), -NR ２ S(=O) ５２ NR ２ R ５２ , -NR ２ S(=O) ５３ NR ５４ R ５２ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ , -NR ５４ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ５２ C(O)NR ２ R ５２ , -C(O)N(R ５３ ), -C(O)NR ５４ R ５２ , -P(O)(OR ２ ), -P(O)(R ５３ ), -P(O)(OR ５４ )(R ５２ ), -P(O)(NR ２ )(R ５２ ), -P(O)(OR ２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -P(O)(NR ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ); C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl, each of which is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ , -NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ a carbon ring, and one or more substituents selected from 3- to 12-membered heterocyclic rings, optionally substituted each time it appears, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where each C in R ５０ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ３－１２ , -CN, -OR ２ , -SR ５２ , -N(R ５２ ), -NR ５２ R ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from ３－１２ a carbocyclic ring and a 3-membered - 12-membered heterocyclic ring; R ５１ is selected from the following each time it appears: hydrogen, -C(O)R ５２ , -C(O)OR ５２ , -C(O)N(R ５２ ), ２ , -C(O)NR ５３ R ５４ ; C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl, wherein each of these is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ a carbon ring, and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time it appears, C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where each C ５１ in R ３－１２ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from C ３－１２ carbocyclic ring and 3-membered - 12-membered heterocyclic ring; R ５２ is, each time it appears, hydrogen; and C １－２０ alkyl, C ２－２０ alkenyl, C ２－２０ alkynyl, 1-6 membered heteroalkyl, C ３－１２ carbocycle, and 3-12 membered heterocycle, each of which is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocycle, or 3-6 membered heterocycle; and R ５３ and R ５４ together with the nitrogen atom to which they are attached form a heterocyclic ring optionally substituted with one or more R ５０ groups, method.

26. The hematological malignancy is selected from malignant lymphoma, leukemia, mature B-cell neoplasm, mature T-cell and natural killer (NK) cell neoplasm, precursor lymphoid neoplasm, Hodgkin lymphoma (HL), plasmacytoma, mast cell tumor, histiocytic and accessory lymphoid cell neoplasm, immunoproliferative disease, myeloid leukemia, and myelodysplastic syndrome (MDS), and is the method according to any one of claims 19 - 25.

27. The hematological malignancy is selected from acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, non-Hodgkin lymphoma, multiple myeloma, mixed-lineage leukemia, and myelodysplastic syndrome, and is the method according to any one of claims 19 - 26.

28. The hematological malignancy is acute myeloid leukemia, and is the method according to claim 27.

29. The recurrence of the hematological malignancy is prevented, and is the method according to any one of claims 19 - 28.

30. The subject exhibits a mutation in the nucleophosmin (NPM1) gene, and is the method according to any one of claims 19 - 29.

31. The mutation in the nucleophosmin (NPM1) gene is a mutation in exon 12 of the NPM1 gene, and is the method according to claim 30.

32. The mutation in the nucleophosmin (NPM1) gene is a frameshift mutation, and is the method according to claim 30.

33. The mutation in the nucleophosmin (NPM1) gene includes an insertion of 2 to 9 bases, and is the method according to claim 30.

34. The insertion is an insertion of 4 bases, and is the method according to claim 33.

35. The insertion of 4 bases is selected from TCTG, CATG, CCTG, CGTG, CAGA, CTTG, and TATG, and is the method according to claim 34.

36. The insertion is an insertion of 9 bases, and is the method according to claim 33.

37. The insertion of 9 bases is selected from CTCTTGCCC and CCCCTGGAGA, and is the method according to claim 36.

38. The mutation in the nucleophosmin (NPM1) gene includes a deletion of nucleotides 965 - 969 (GGAGG), and is the method according to claim 30.

39. The subject exhibits a mutation in the FLT3 gene, and is the method according to any one of claims 19 - 38.

40. The mutation in the FLT3 gene is an internal tandem duplication, and is the method according to claim 39.

41. The method according to claim 39, wherein the mutation in the FLT3 gene is in the tyrosine kinase domain.

42. The method according to any one of claims 19 - 41, wherein the mutation is in the nucleophosmin (NPM1) gene and the FMS-like tyrosine kinase-3 (FLT3) gene.

43. The method according to any one of claims 19 - 42, wherein the mutation is in the nucleophosmin (NPM1) gene, DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, isocitrate dehydrogenase 2 (IDH2) gene, and FMS-like tyrosine kinase-3 (FLT3) gene.

44. The method according to any one of claims 19 - 41, wherein the subject exhibits a mutation in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene.

45. A method of treating Ewing's sarcoma, wherein the method comprises administering to a subject in need thereof a compound of formula (I-A), 【Chemical Formula 19】 or a pharmaceutically acceptable salt or prodrug thereof, H is C ５－１２ selected from a carbocyclic ring and a 5- to 12-membered heterocyclic ring, each of which is optionally substituted with one or more R ５０ ; A is selected from a single bond, a C ３－１２ carbocyclic ring, and a 3- to 12-membered heterocyclic ring; B is C ３－１２ selected from a carbocyclic ring and a 3- to 12-membered heterocyclic ring; C is a 3 - 12 membered heterocyclic ring; L １ 、 L ２ 、 and L ３ are each independently a single bond, -O-, -S-, -N(R ５１ ), -N(R ５１ ), -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R ２ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -OC(O)N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -C(NR ５１ ), -C(NR ５１ ), -N(R ５１ ), -N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -S(O) ２ -, -OS(O)-, -S(O)O-, -S(O)-, -OS(O) ２ -, -S(O) ２ O-, -N(R ５１ ), -S(O) ２ -, -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)-, -S(O)N(R ５１ ), -N(R ５１ ), -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)N(R ５１ ); independently selected from alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, and heteroalkynylene, each of which is optionally substituted with one or more R ５０ , where L １ , L ２ , or L ３ Two Rs bonded to any one same atom or different atoms can be combined together to optionally form a bridge or a ring; ５０ The groups can be combined together to optionally form a bridge or a ring; R Ａ 、 R Ｂ 、 and R Ｃ are each independently selected each time they appear from R ５０ , or two R Ａ groups, two R Ｂ groups, or two R Ｃ groups can combine together to optionally form a bridge or a ring; m, n, and p are each independently an integer from 0 to 6; R ５０ is selected from the following each time it appears: Halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ N(R ２ ), -S(=O) ５３ NR ５４ R ５２ , -NR ２ S(=O)R ５２ , -NR ５２ S(=O)N(R ２ ), -NR ５２ S(=O)N(R ２ ), -NR ５２ S(=O)NR ２ R ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(OR ５２ )(R ２ ), -P(O)(NR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ); C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl, each of which is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ , -P(O)(NR ５２ )(R ５２ , -NR ５２ P(O)(R ５２ , -P(O)(NR ５２ )(OR ５２ , -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ arbon ring, and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time it appears, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where R ５０ each C in ３－１２ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from C ３－１２ carbocycles and 3-membered - 12-membered heterocycles; R ５１ is selected from the following each time it appears: hydrogen, -C(O)R ５２ , -C(O)OR ５２ , -C(O)N(R ５２ ), ２ , -C(O)NR ５３ R ５４ ; C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl, each of which is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ a carbon ring, and one or more substituents selected from 3- to 12-membered heterocyclic rings, optionally substituted each time it appears, C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where R ５１ each C in ３－１２ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from ３－１２ carbocyclic rings and 3-membered - 12-membered heterocyclic rings; R ５２ is, each time it appears, hydrogen; and C １－２０ alkyl, C ２－２０ alkenyl, C ２－２０ alkynyl, 1- to 6-membered heteroalkyl, C ３－１２ carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocycle, or 3- to 6-membered heterocycle; R ５３ and R ５４ together with the nitrogen atom to which they are attached form a heterocyclic ring optionally substituted with one or more R ５０ ; R ５７ is selected from the following: Halogen, -NO ２ , -CN, -SR ５２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５８ , -S(=O) ２ , -S(=O) ５２ N(R ２ ), -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ , -NR ５２ S(=O) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ R ５４ , -C(O)NH(C １－６ alkyl), -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(OR ５２ )(R ２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =S, =N(R ５２ ); and C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl, wherein each of these is independently, -NO ２ , -CN, -SR ５２ , -N(R ５２ ), ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), ２ , -NR ５２ C(O)NR ５３ R ５４ , -P(O)(OR ５２ ), ２ , -P(O)(R ５２ ), ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =S, and =N(R ５２ ), one or more substituents selected from the group consisting of, each occurrence being substituted, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl; R ５８ is hydrogen; and C １－２０ alkyl, C ３－２０ alkenyl, C ２－２０ alkynyl, 1-6 membered heteroalkyl, C ３－１２ carbocycle, and 3-12 membered heterocycle, each of which is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocycle, or 3-6 membered heterocycle; wherein, for the compound or salt of formula (I-A), C is azetidinylene, piperidinylene, or piperazinylene, and R ５７ is, -S(=O) ２ R ５８ , -S(=O) ２ N(R ５２ ), ２ or -NR ５２ S(=O) ２ R ５２ when: p is an integer from 1 to 6; and / or L ３ is substituted by one or more R ５０ wherein L ３ is not -CH ２ CH(OH)-, a method.

46. A method of treating Ewing's sarcoma, wherein the method comprises administering to a subject in need thereof a compound of formula (I-B), 【Chemical 20】 or a pharmaceutically acceptable salt thereof, H is C ５－１２ selected from a carbocyclic ring and a 5- to 12-membered heterocyclic ring, each of which is optionally substituted with one or more R ５０ ; A, B, and C are each independently selected from a carbocyclic ring and a 3- to 12-membered heterocyclic ring; ３－１２ and are independently selected from a carbocyclic ring and a 3- to 12-membered heterocyclic ring; L １ and L ２ each independently is a single bond, -O-, -S-, -N(R ５１ ), -N(R ５１ ), -CH ２ -, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -N(R ５１ ), -OC(O)N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -C(NR ５１ ), -C(NR ５１ ), -N(R ５１ ), -N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -S(O) ２ -, -OS(O)-, -S(O)O-, -S(O)-, -OS(O) ２ -, -S(O) ２ O-, -N(R ５１ ), -S(O) ２ -, -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)N(R ５１ ), -N(R ５１ ), -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)N(R ５１ ); selected from alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, and heteroalkynylene, each of which is optionally substituted with one or more R ５０ ; L ３ is selected from alkylene, alkenylene, and alkynylene, each of which is substituted with one or more R ５６ and optionally further substituted with one or more R ５０ ; R Ａ 、 R Ｂ 、 and R Ｃ are each independently selected each time they appear from R ５０ , or two R Ａ groups, two R Ｂ groups, or two R Ｃ groups can combine together to optionally form a bridge or a ring; m, n, and p are each independently an integer from 0 to 6; R ５０ is selected from the following each time it appears: Halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ N(R ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ S(=O) ５２ NR ２ R ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(OR ５２ )(R ２ ), -P(O)(NR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ); C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl, wherein each of these is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ carbon ring, and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time it appears, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where R ５０ each C in ３－１２ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from ３－１２ carbocycles and 3- to 12-membered heterocycles; R ５１ is selected from the following each time it appears: hydrogen, -C(O)R ５２ , -C(O)OR ５２ , -C(O)N(R ５２ ), ２ , -C(O)NR ５３ R ５４ ; C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl, each of which is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ , =O, =S, =N(R ５２ ), C ３－１２ arbon ring, and one or more substituents selected from 3- to 12-membered heterocyclic rings, optionally substituted each time it appears, C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where each C in R ５１ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ３－１２ , -CN, -OR ２ , -SR ５２ , -N(R ５２ ), -NR ５２ R ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ )( ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from C ３－１２ carbocyclic ring and 3-membered - 12-membered heterocyclic ring; R ５２ is, each time it appears, hydrogen; and C １－２０ alkyl, C ２－２０ alkenyl, C ２－２０ alkynyl, 1-6 membered heteroalkyl, C ３－１２ carbocycle, and 3-12 membered heterocycle, each of which is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocycle, or 3-6 membered heterocycle; R ５３ and R ５４ together with the nitrogen atom to which they are attached form a heterocyclic ring optionally substituted with one or more R ５０ ; R ５６ each time it appears, -NO ２ 、-OR ５９ 、-SR ５２ 、-NR ５３ R ５４ 、-S(=O)R ５２ 、-S(=O) ２ R ５２ 、-S(=O) ２ N(R ５２ ) ２ 、-S(=O) ２ NR ５３ R ５４ 、-NR ５２ S(=O) ２ R ５２ 、-NR ５２ S(=O) ２ N(R ５２ ) ２ 、-NR ５２ S(=O) ２ NR ５３ R ５４ 、-C(O)R ５２ 、-C(O)OR ５２ 、-OC(O)R ５２ 、-OC(O)OR ５２ 、-OC(O)N(R ５２ ) ２ 、-OC(O)NR ５３ R ５４ 、-NR ５２ C(O)R ５２ 、-NR ５２ C(O)OR ５２ 、-NR ５２ C(O)N(R ５２ ) ２ 、-NR ５２ C(O)NR ５３ R ５４ 、-C(O)N(R ５２ ) ２ 、-C(O)NR ５３ R ５４ 、-P(O)(OR ５２ ) ２ 、-P(O)(R ５２ ) ２ 、-P(O)(OR ５２ )(R ５２ )、-P(O)(NR ５２ )(R ５２ )、-NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ), ２ =O, =S, =N(R ５２ ), C １－１０ alkyl, C ２－１０ alkenyl, C ２－１０ alkynyl, C ３－１２ selected from carbocyclic rings and 3- to 12-membered heterocyclic rings, R ５６ each C in １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl is independently halogen, -NO ２ , -CN, -OR ５９ , -SR ５２ , -N(R ５２ ), -NR ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ５２ ​) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C ３－１２ a carbon ring, and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time it appears, R ５６ each C in ３－１２ The carbocyclic ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from Furthermore, here, R ５６ optionally forms a single bond to the ring C; and, R ５９ is independently selected, each time it appears, from C １－２０ alkyl, C ２－２０ alkenyl, C ２－２０ alkynyl, 1-6 membered heteroalkyl, C ３－１２ carbocyclic, and 3-12 membered heterocyclic rings, and each of them is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocyclic, or 3-6 membered heterocyclic ring; Here, for the compound or salt of formula (I-B), when R ５６ is -CH ３ , L ３ is a method that is not further substituted by -OH, -NH ２ , or -CN.

47. R Ｃ is -C(O)R ５２ ,-S(=O)R ５２ ,-S(=O) ２ R ５２ ,-S(=O) ２ N(R ５２ ) ２ ,-S(=O) ２ NR ５３ R ５４ ,-NR ５２ S(=O) ２ R ５２ ,=O,C １－３ alkyl, and C １－３ haloalkyl, or two R Ｃ groups bonded to different atoms are taken together to form a C １－３ bridge, the method according to claim 46.

48. A method of treating Ewing's sarcoma, wherein the method comprises administering to a subject in need thereof a compound of formula (II), 【Chemical 21】 or a pharmaceutically acceptable salt or prodrug thereof, H is C ５－１２ selected from a carbocyclic ring and a 5- to 12-membered heterocyclic ring, each of which is optionally substituted with one or more R ５０ ; A is selected from a single bond, a C ３－１２ carbocyclic ring, and a 3- to 12-membered heterocyclic ring; B is C ３－１２ selected from a carbocyclic ring and a 3- to 12-membered heterocyclic ring; L １ 、 L ２ 、 and L ３ are each independently a single bond, -O-, -S-, -N(R ５１ ), -N(R ５１ ), CH ２ -, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R ５１ ), -C(O)N(R ５１ ), C(O)-, -C(O)N(R ５１ ), C(O)N(R ５１ ), -N(R ５１ ), C(O)-, -N(R ５１ ), C(O)N(R ５１ ), -N(R ５１ ), C(O)O-, -OC(O)N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), C(NR ５１ ), -C(NR ５１ ), N(R ５１ ), -N(R ５１ ), C(NR ５１ ), N(R ５１ ), -S(O) ２ -, -OS(O)-, -S(O)O-, -S(O)-, -OS(O) ２ -, -S(O) ２ O-, -N(R ５１ ), S(O) ２ -, -S(O) ２ N(R ５１ ), -N(R ５１ ), S(O)-, -S(O)N(R ５１ ), -N(R ５１ ), S(O) ２ N(R ５１ ), -N(R ５１ ), S(O)N(R ５１ ), -; selected from alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, and heteroalkynylene, each of which is optionally substituted with one or more R ５０ ; R Ａ 、 R Ｂ 、 and R Ｃ are each independently selected from R ５０ each time it appears, or two R Ａ groups or two R Ｂ groups attached to the same or different atoms can optionally combine to form a bridge or a ring; m and n are each independently an integer from 0 to 6, W １ is alkylene optionally substituted with one or more R ５０ and is C １－４ substituted with; W ２ is a single bond; and C ５０ optionally substituted with one or more R １－４ selected from alkylene; W ３ is absent; and one or more R ５０ optionally substituted C １－４ selected from alkylene; R ５０ is selected from the following each time it appears: Halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ N(R ２ ), -S(=O) ５３ NR ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ S(=O) ５２ NR ２ R ５３ ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ５２ ), -P(O)(R ２ ５２ ), =O, =S, =N(R ５２ );​​​​ C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl, each of which is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , =O, =S, =N(R ５２ ), C ３－１２ One or more substituents selected from a carbon ring and a 3- to 12-membered heterocyclic ring, optionally substituted each time it appears, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where R ５０ each C in ３－１２ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from, C ３－１２ a carbocyclic ring and a 3- to 12-membered heterocyclic ring; R ５１ is selected from the following each time it appears: hydrogen, -C(O)R ５２ , -C(O)OR ５２ , -C(O)N(R ５２ ), ２ , -C(O)NR ５３ R ５４ ; C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl, each of which is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ 、 =O, =S, =N(R ５２ ), C ３－１２ One or more substituents selected from a carbon ring and a 3- to 12-membered heterocyclic ring, optionally substituted each time it appears, C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where each C in R ５１ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ３－１２ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from, C ３－１２ a carbocyclic ring and a 3-membered - 12-membered heterocyclic ring; R ５２ each time it appears, hydrogen; and C １－２０ alkyl, C ２－２０ alkenyl, C ２－２０ alkynyl, 2- to 6-membered heteroalkyl, C ３－１２ a carbocycle, and a 3- to 12-membered heterocycle, each of which is selected from halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ a carbocycle, or a 3- to 6-membered heterocycle, optionally substituted therewith; and, R ５３ and R ５４ together with the nitrogen atom to which they are attached form a heterocyclic ring optionally substituted with one or more R ５０ wherein, for the compound or salt of formula (II), when W ３ is absent: W １ is C １ alkylene, and W ２ is a single bond, and L ３ is not a single bond; W １ is C ２－４ alkylene, and W ２ is a single bond; alternatively, W １ and W ２ are each C １ alkylene, and L ３ is not a single bond, where C １ alkylene is each independently optionally substituted with one or more R ５０ . A method

49. A method of treating Ewing's sarcoma, wherein the method comprises administering to a subject in need thereof a compound of formula (III), 【Chemical 22】 or a pharmaceutically acceptable salt or prodrug thereof, H is C ３－１２ selected from a carbocyclic ring and a 3- to 12-membered heterocyclic ring, each of which is optionally substituted with one or more R ５０ ; A is, 【Chemical 23】 ; Z １ 、Z ２ 、Z ３ 、and Z ４ each is independently selected from -C(R Ａ１ )(R Ａ２ ), -C(R Ａ１ )(R Ａ２ )-C(R Ａ１ )(R Ａ２ ), -C(O)-, and -C(R Ａ１ )(R Ａ２ )-C(O)-, and only one of Z １ , Z ２ , Z ３ , and Z ４ is -C(O)- or -C(R Ａ１ )(R Ａ２ )-C(O)-; B is a single bond, C ３－１２ is selected from a carbon ring, and a 3- to 12-membered heterocyclic ring; C is selected from a single bond, C ３－１２ a carbocyclic ring, and a 3- to 12-membered heterocyclic ring; L １ 、 L ２ 、 and L ３ are each independently a single bond, -O-, -S-, -N(R ５１ ), -N(R ５１ ), -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R ２ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -C(NR ５１ ), -C(NR ５１ ), -N(R ５１ ), -N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -S(O) ２ ), -OS(O)-, -S(O)O-, -S(O)-, -OS(O) ２ ), -S(O) ２ O-, -N(R ５１ ), -S(O) ２ ), -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)-, -S(O)N(R ５１ ), -N(R ５１ ), -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)N(R ５１ ); independently selected from alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, and heteroalkynylene, each of which is optionally substituted with one or more R ５０ ; where L １ , L ２ , or L ３ Two Rs bonded to any one of the same or different atoms may combine together to optionally form a bridge or a ring; ５０ ​ R Ｂ is selected independently each time it appears from R ５０ or two R groups bonded to the same atom or different atoms can be taken together to optionally form a bridge or a ring; Ｂ ​ R Ｃ is independently selected each time it appears from hydrogen and R ５０ or two R groups bonded to the same or different atoms may combine together to optionally form a bridge or a ring; Ｃ ​ R Ａ１ and R Ａ２ are each independently selected from hydrogen and R ５０ each time they appear; n is an integer from 0 to 6, p is an integer from 1 to 6; and / or R ５０ is selected from the following each time it appears: Halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ NR ２ R ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ S(=O) ５２ NR ２ R ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(OR ５２ )(R ２ ), -P(O)(NR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ); C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl, wherein each of these is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ a carbon ring, and one or more substituents selected from 3- to 12-membered heterocyclic rings, optionally substituted each time it appears, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where each C in R ５０ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ３－１２ , -CN, -OR ２ , -SR ５２ , -N(R ５２ ), -NR ５２ R ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ )([[]]END) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from C ３－１２ carbocyclic ring and 3-membered - 12-membered heterocyclic ring; R ５１ is selected from the following each time it appears: hydrogen, -C(O)R ５２ , -C(O)OR ５２ , -C(O)N(R ５２ ), ２ , -C(O)NR ５３ R ５４ ; C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl, each of which is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ NR ２ R ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ S(=O) ５２ NR ２ R ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), -P(O)(OR ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ a carbon ring, and one or more substituents selected from 3- to 12-membered heterocyclic rings, optionally substituted each time it appears, C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where R ５１ each C in ３－１２ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from C ３－１２ carbocyclic ring and 3-membered - 12-membered heterocyclic ring; R ５２ is, each time it appears, hydrogen; and C １－２０ alkyl, C ２－２０ alkenyl, C ２－２０ alkynyl, 1-6 membered heteroalkyl, C ３－１２ carbocycle, and 3-12 membered heterocycle, each of which is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocycle, or 3-6 membered heterocycle; and R ５３ and R ５４ together with the nitrogen atom to which they are attached form a heterocyclic ring optionally substituted with one or more R ５０ groups, method.

50. A method of treating Ewing's sarcoma, wherein the method comprises administering to a subject in need thereof a compound of formula (IV), 【Chemical 24】 or administering to a subject in need thereof the pharmaceutically acceptable salt or prodrug thereof, 【Chemical 25】 is a fused thienyl or fused phenyl group; G ａ is selected from a C ３－１２ carbocyclic ring and a 3- to 12-membered heterocyclic ring, each of which is substituted with -E １ -R ４ａ and optionally further substituted with one or more R ５０ ; R ２ａ is selected from hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocycle, optionally substituted heteroaryl, and aralkyl; R ３ａ and R ３ｂ are each independently selected from hydrogen, alkyl, halo, hydroxy, cyano, amino, alkylamino, dialkylamino, haloalkyl, alkoxy, and haloalkoxy; X ａ -Y ａ is selected from -N(R ５２ ), -C(=O)-, -C(=O)-O-, -C(=O)-N(R ５２ ), -CH ２ N(R ５２ ), -CH ２ -, -C(=O)N(R ５２ ), -CH ２ -, -CH ２ CH ２ -N(R ５２ ), -CH ２ N(R ５２ ), -C(=O)-, and -CH ２ OCH ２ -; Alternatively, X ａ and Y ａ do not form a chemical bond, where: X ａ is selected from hydrogen, alkyl, halo, hydroxy, cyano, amino, alkylamino, dialkylamino, haloalkyl, alkoxy, and haloalkoxy; and Y ａ is cyano, hydroxy, and -CH ２ R ５０ selected from; E １ is absent, selected from -C(=O)-, -C(=O)N(R ５２ ), -[C(R １４ａ ) ２ , １－５ O-, -[C(R １４ａ ) ２ , １－５ NR ５２ -, -[C(R １４ａ ) ２ , １－５ -, -CH ２ (=O)-, and -S(=O) ２ -; R ４ａ is selected from hydrogen, alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocycle, optionally substituted heteroaryl, aralkyl, (heterocycle)alkyl, and (heteroaryl)alkyl; R １４ａ is selected from hydrogen and alkyl; R ５０ is selected from the following each time it appears: Halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ NR ２ R ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ S(=O) ５２ NR ２ R ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ C(O)NR ５２ R ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(OR ５２ )(R ２ ), -P(O)(NR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ); C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl, wherein each of these is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ R ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ ), -P(O)(R ５２ ), ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ carbon ring, and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time it appears, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where each C in R ５０ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ３－１２ , -CN, -OR ２ , -SR ５２ , -N(R ５２ ), -NR ５２ R ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ , -NR ５４ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ５２ C(O)NR ２ R ５２ , -C(O)N(R ５３ ), -C(O)NR ５４ R ５２ , -P(O)(OR ２ ), -P(O)(R ５３ , -P(O)(OR ５４ ), -P(O)(R ５２ ), -P(O)(OR ２ ), -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from ３－１２ carbocycles and 3 - to 12 - membered heterocycles; R ５２ is, each time it appears, hydrogen; and C １－２０ alkyl, C ２－２０ alkenyl, C ２－２０ alkynyl, 1-6 membered heteroalkyl, C ３－１２ carbocycle, and 3-12 membered heterocycle, each of which is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocycle, or 3-6 membered heterocycle; and R ５３ and R ５４ together with the nitrogen atom to which they are attached form a heterocyclic ring optionally substituted with one or more R ５０ groups, a method.

51. A method of treating Ewing's sarcoma, said method comprising administering to a subject in need thereof a compound of formula (VI), 【Chemical 26】 or administering to a subject in need thereof the pharmaceutically acceptable salt or prodrug thereof, H ２ is selected from a C ３－１２ carbocyclic ring and a 3- to 12-membered heterocyclic ring; H is C ３－１２ selected from a carbocyclic ring and a 3- to 12-membered heterocyclic ring, each of which is optionally substituted with one or more R ５０ ; A is 【Chemical 27】 ; Z １ 、Z ２ 、Z ３ 、and Z ４ each independently is selected from -C(R Ａ１ )(R Ａ２ ), -C(R Ａ１ )(R Ａ２ )-C(R Ａ１ )(R Ａ２ ), -O-, -C(R Ａ１ )(R Ａ２ )-O-, -C(R Ａ１ )(R Ａ２ )-N(R ５１ ), -C(O)-, -C(R Ａ１ )(R Ａ２ )-C(O)-, and -N=C(NH ２ ); only one of Z １ , Z ２ , Z ３ , and Z ４ is -O-, -C(R Ａ１ )(R Ａ２ )-O-, -C(R Ａ１ )(R Ａ２ )-N(R ５１ ), -C(O)-, -C(R Ａ１ )(R Ａ２ )-C(O)-, or -N=C(NH ２ ); Z ５ and Z ６ is independently selected from -C(R Ａ３ )- and -N-; B is a single bond, C ３－１２ is selected from a carbon ring, and a 3- to 12-membered heterocyclic ring; L １ 、 L ２ 、 and L ４ are each independently a single bond, -O-, -S-, -N(R ５１ ), -N(R ５１ ), -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R ２ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -C(NR ５１ ), -C(NR ５１ ), -N(R ５１ ), -N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -S(O) ２ ), -OS(O)-, -S(O)O-, -S(O)-, -OS(O) ２ ), -S(O) ２ O-, -N(R ５１ ), -S(O) ２ ), -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)-, -S(O)N(R ５１ ), -N(R ５１ ), -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)N(R ５１ ); independently selected from alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, and heteroalkynylene, each of which is optionally substituted with one or more R ５０ , where L １ , L ２ , or L ４ Two Rs bonded to any one of the same or different atoms may combine together to optionally form a bridge or a ring; ５０ ​ R Ｂ is independently selected each time it appears from hydrogen and R ５０ or two R groups bonded to the same atom or different atoms can combine together to optionally form a bridge or a ring; Ｂ ​ R Ｈ２ is selected independently each time it appears from R ５０ or two R Ｈ２ groups bonded to the same or different atoms may combine together to optionally form a bridge or a ring; R Ａ１ 、 R Ａ２ 、 and R Ａ３ are each independently selected from hydrogen and R ５０ each time they appear; n is an integer from 0 to 6, r is an integer from 1 to 6; R ５０ is selected from the following each time it appears: Halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ), -NR ２ R ５３ , -S(=O)R ５４ , -S(=O) ５２ R ２ , -S(=O) ５２ N(R ２ ), -S(=O) ５２ NR ２ R ２ , -NR ５３ S(=O)R ５４ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ５２ S(=O) ２ NR ５２ R ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ R ５３ , -NR ５４ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ５２ C(O)NR ２ R ５２ , -C(O)N(R ５３ ), -C(O)NR ５４ R ５２ , -P(O)(OR ２ ), -P(O)(R ５３ ), -P(O)(OR ５４ )(R ５２ ), -P(O)(NR ２ )(R ５２ ), -P(O)(OR ２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -P(O)(NR ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ , =O, =S, =N(R ５２ ); C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl, each of which is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ a carbon ring, and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time it appears, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where R ５０ each C in ３－１２ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from ３－１２ carbocycles and 3-membered - 12-membered heterocycles; R ５１ is selected from the following each time it appears: hydrogen, -C(O)R ５２ , -C(O)OR ５２ , -C(O)N(R ５２ ), ２ , -C(O)NR ５３ R ５４ ; C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl, each of which is independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ); ２ =O, =S, =N(R ５２ ), C ３－１２ a carbon ring, and one or more substituents selected from 3- to 12-membered heterocycles, optionally substituted each time it appears, C １－６ alkyl, C ２－６ alkenyl, and C ２－６ alkynyl; and, C ３－１２ A carbon ring and a 3- to 12-membered heterocyclic ring, where R ５１ each C in ３－１２ The carbon ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and, C ２－６ alkynyl, optionally substituted with one or more substituents selected from C ３－１２ carbocyclic ring and 3-membered - 12-membered heterocyclic ring; R ５２ is, each time it appears, hydrogen; and C １－２０ alkyl, C ２－２０ alkenyl, C ２－２０ alkynyl, 1-6 membered heteroalkyl, C ３－１２ carbocycle, and 3-12 membered heterocycle, each of which is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocycle, or 3-6 membered heterocycle; and, R ５３ and R ５４ together with the nitrogen atom to which they are attached form a heterocyclic ring optionally substituted with one or more R ５０ groups, a method.

52. The method according to any one of claims 45 - 51, wherein the subject exhibits an EWSR1-FLI1 gene fusion, an EWSR1-ERG gene fusion, or an EWSR1-FEV gene fusion.

53. The method according to any one of claims 45 - 51, wherein the subject exhibits a FUS-NCATc2 gene fusion, a CIC-FOXO4 gene fusion, or an ETV6-NTRK3 gene fusion.

54. The method according to any one of claims 45 - 51, wherein the subject exhibits a mutation in the STAG2 gene, a mutation in the TP53 gene, or a CDKN2A deletion.

55. C is a 5 - to 12-membered heterocyclic ring, the heterocyclic ring containing at least one nitrogen atom, the method according to any one of claims 12 - 14, 19 - 21, and 45 - 47.

56. The method according to claim 55, wherein the heterocyclic ring is saturated.

57. The method according to claim 56, wherein the heterocyclic ring is selected from piperidinyl and piperazinyl.

58. C is 【Chemical 28】 selected from, the method according to claim 12, 19, or 45.

59. R ５７ is -S(=O)R ５２ , -S(=O) ２ R ５８ , -S(=O) ２ , -S(=O) ５２ N(R ２ ), and -NR ５２ S(=O) ２ R ５２ The method according to any one of claims 12, 19, 45, and 58, selected from

60. C is 【Chemical 29】 selected from, Here, R ５７ is -S(=O)R ５２ -, -S(=O) ２ R ５２ -, -S(=O) ２ N(R ５２ ), ２ -, -S(=O) ２ NR ５３ R ５４ -, -NR ５２ S(=O) ２ R ５２ ; and, -S(=O)R ５２ -, -S(=O) ２ R ５２ -, -S(=O) ２ N(R ５２ ), ２ -, -S(=O) ２ NR ５３ R ５４ , and -NR ５２ S(=O) ２ R ５２ substituted with one or more substituents selected from １－１０ C alkyl selected, the method according to claim 13, 20, or 46

61. R ５７ is -S(=O)R ５２ 、-S(=O) ２ R ５２ 、-S(=O) ２ 、-S(=O) ５２ N(R ２ ), and -NR ５２ S(=O) ２ R ５２ The method according to claim 60, selected from

62. R ５７ is -S(=O)CH ３ , -S(=O) ２ CH ３ , -S(=O) ２ NH ２ , -NH S(=O) ２ CH ３ , and -S(=O) ２ NHCH ３ The method according to any one of claims 12, 19, 45, and 58 - 61, selected from

63. R Ｃ is C １－３ alkyl and C １－３ haloalkyl selected from any one of claims 12-14, 19-21, 45-47, and 55-62.

64. H is a 5- to 12-membered bicyclic heterocyclic ring optionally substituted with one or more Rs ５０ and is optionally substituted with ５０ ; A is a 3 - to 12-membered heterocyclic ring; and B is a 3 - to 12-membered heterocyclic ring, the method according to any one of claims 12 - 15, 19 - 22, 26 - 48, or 52 - 63.

65. H is one or more Rs ５０ The method according to any one of claims 12-16, 18-23, 25-49, or 51-64, which is a 6- to 12-membered bicyclic heterocyclic ring optionally substituted with

66. H is one or more Rs ５０ The method according to claim 65, wherein it is thienopyrimidinyl optionally substituted with

67. H is 【Chemical 30】 ; X １ and X ２ are each independently selected from CR ２ and N; X ３ and X ４ are each independently selected from C and N; Y １ and Y ２ are each independently selected from CR ３ , N, NR ４ , O, and S; R １ , R ２ , and R ３ are each independently selected from hydrogen and R ５０ each time it appears; and R ４ is R ５１ The method according to claim 65, selected from

68. X ３ and X ４ are each C, the method according to claim 67.

69. X １ is CR ２ wherein R ２ is selected from hydrogen, halogen, -OH, -OR ５２ , -NH ２ , -N(R ５２ ), ２ , -CN, C １－３ alkyl, -CH ２ OH, -CH ２ OR ５２ , -CH ２ NH ２ , -CH ２ N(R ５２ ), ２ , C １－３ alkyl-N(R ５２ ), ２ , C １－３ haloalkyl, C ２－３ alkenyl, and C ２－３ alkynyl, the method according to claim 67 or 68.

70. X １ is CR ２ wherein R ２ is hydrogen, halogen, -OH, -OR ５２ , -NH ２ , -N(R ５２ ), ２ , -CN, C １－３ alkyl, C １－３ alkyl-N(R ５２ ), ２ C １－３ haloalkyl, C ２－３ alkenyl, and C ２－３ alkynyl, the method according to claim 69.

71. X ２ The method according to any one of claims 67 - 70, wherein X is N.

72. Y ２ is CR ３ where R ３ is selected from hydrogen, halogen, -OH, -N(R ５２ ) ２ , -CN, -C(O)OR ５２ , C １－３ alkyl, and C １－３ haloalkyl, the method according to any one of claims 67 - 71.

73. R １ is C １－３ a haloalkyl, the method according to any one of claims 67 - 72.

74. A is a 5 - to 8-membered heterocyclic ring, the method according to any one of claims 12 - 15, 19 - 22, 26 - 48, or 52 - 63.

75. The method according to claim 74, wherein A is a 6-membered monocyclic heterocyclic ring.

76. The method according to claim 74 or 75, wherein the heterocyclic ring contains at least one nitrogen atom.

77. The method according to claim 76, wherein A is selected from piperidinylene and piperazinylene.

78. A is 【Chemical 31】 The method according to claim 77.

79. A is 【Chemical 32】 ; Z １ 、Z ２ 、Z ３ 、and, Z ４ each of which is independently selected from -C(R Ａ１ )(R Ａ２ ), -C(R Ａ１ )(R Ａ２ )-C(R Ａ１ )(R Ａ２ ), -C(O)-, and, -C(R Ａ１ )(R Ａ２ )-C(O)-, and only one of Z １ , Z ２ , Z ３ , and Z ４ is -C(O)- or -C(R Ａ１ )(R Ａ２ )-C(O)-; R Ａ１ and R Ａ２ are each independently selected each time they appear from hydrogen and R ５０ by the method according to any one of claims 12 - 74.

80. R Ａ１ and R Ａ２ are each independently hydrogen, halo, C １－４ alkyl, C １－４ alkoxy, C １－４ haloalkyl, C １－４ haloalkoxy, -CN, -NO ２ , and, OH, each time they appear, are selected from the method according to claim 79.

81. A is 【Chemical 33】 The method according to claim 79 or 80, selected from

82. The method according to any one of claims 12-16, 18-23, 25-49, or 51-81, wherein B is a 6- to 12-membered bicyclic heterocycle.

83. The method according to claim 82, wherein the heterocycle contains at least one nitrogen atom.

84. The method according to claim 83, wherein B is indolylene.

85. B is one or more Rs Ｂ optionally replaced by 【Chemical 34】 The method according to claim 84.

86. H is thienopyrimidinyl substituted by one or more Rs ５０ ; and A is selected from piperidinylene and piperazinylene; and B is indolylene. The method according to claim 64.

87. H is -CH ２ CF ３ The method according to any one of claims 12-16, 18-23, 25-49, or 51-86, which is substituted with

88. The method according to any one of claims 12-16, 19-23, 26-49, or 52-87, wherein m is 0.

89. The method according to any one of claims 12-16, 18-23, 25-49, or 51-88, wherein n is an integer from 1 to 3.

90. L １ is the method according to any one of claims 12-16, 18-23, 25-49, or 51-89, which contains atoms less than 10.

91. L １ is -N(R ５１ )-, the method according to any one of claims 12-16, 18-23, 25-49, or 51-90.

92. L ２ is the method according to any one of claims 12-16, 18-23, 25-49, or 51-91, comprising atoms less than 10.

93. L ２ is C optionally substituted with one or more R ５０ and is alkylene, the method according to any one of claims 12 - 16, 18 - 23, 25 - 49, or 51 - 92. １－４ ​

94. L ２ is selected from -CH ２ -, -N(R ５１ ), -N(R ５１ ), -CH ２ -, -N(R ５１ ), -N(R ５１ )(C=O)-, and -N(R ２ ), and is the method according to any one of claims 12-16, 18-23, 25-49, or 51-92.

95. L ３ is the method according to any one of claims 12-16, 19-23, 26-49, or 52-94, comprising atoms less than 20.

96. L ３ is C optionally substituted with one or more R ５０ and is an alkylene, the method according to any one of claims 12 - 16, 19 - 23, 26 - 49, or 52 - 95. １－６ ​

97. L ３ is C optionally substituted with one or more R ５０ alkylene, the method according to any one of claims 12 - 16, 19 - 23, 26 - 49, or 52 - 96. １－４ ​

98. L ３ is - CH ２ - and is the method according to any one of claims 12 - 16, 19 - 23, 26 - 49, or 52 - 97.

99. L ３ is a C2 alkylene substituted with at least one C １－３ alkyl or C １－３ haloalkyl and optionally further substituted with one or more R ５０ The method according to claim 96, which is

100. L ３ is =O, C １－６ alkyl, C １－６ haloalkyl, C １－３ alkyl(cyclopropyl), C １－３ alkyl(NR ５２ C(O)R ５２ ), or -O(C １－６ alkyl) substituted, the method according to any one of claims 12 - 16, 19 - 23, 26 - 49, or 52 - 99.

101. L ３ is - CH ３ The method according to claim 100, which is substituted with

102. L ３ is 【Chemical 35】 The method according to any one of claims 12-16, 19-23, 26-49, or 52-96, selected from

103. R ５０ The method according to claim 102, wherein R is methyl.

104. L ３ is 【Chemical 36】 The method according to any one of claims 12-16, 19-23, 26-49, or 52-96, selected from

105. R ５６ The method according to claim 104, wherein R is methyl.

106. H is thienopyrimidinyl optionally substituted with one or more R ５０ and; A is a 3- to 12-membered heterocycle; B is a 6- to 12-membered bicyclic heterocycle; m is an integer from 0 to 3; n is an integer from 1 to 3. The method according to any one of claims 12-15, 19-22, 26-48, or 52-63.

107. H is thienopyrimidinyl optionally substituted with one or more Rs ５０ and; A is selected from piperidinylene and piperazinylene; B is indolylene; L １ and L ２ are each independently selected from -O-, -S-, -NH-, or -CH ２ -; L ３ is independently selected from a single bond, -O-, -S-, -N(R ５１ ), -N(R ５１ ), -CH ２ -, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -C(O)N(R ５１ ), -N(R ５１ ), -C(O)-, -N(R ５１ ), -C(O)N(R ５１ ), -N(R ５１ ), -C(O)O-, -OC(O)N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -C(NR ５１ ), -C(NR ５１ ), -N(R ５１ ), -N(R ５１ ), -C(NR ５１ ), -N(R ５１ ), -S(O) ２ -, -OS(O)-, -S(O)O-, -S(O)-, -OS(O) ２ -, -S(O) ２ O-, -N(R ５１ ), -S(O) ２ -, -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)-, -S(O)N(R ５１ ), -N(R ５１ ), -S(O) ２ N(R ５１ ), -N(R ５１ ), -S(O)N(R ５１ ); and is independently selected from alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, and heteroalkynylene, each of which is optionally substituted with one or more R ５０ ; provided that two R ３ groups bonded to the same atom and different atoms of L ５０ can combine together to optionally form a ring; R Ａ 、 R Ｂ 、 and R Ｃ are each independently selected each time they appear from R ５０ or two R Ａ groups, two R Ｂ groups or two R Ｃ groups can combine together to optionally form a ring; m is an integer from 0 to 3; n is an integer from 1 to 3; p is an integer from 0 to 6; R ５７ is selected from the following: -S(=O)R ５２ 、-S(=O) ２ R ５８ 、-S(=O) ２ N(R ５２ ) ２ 、-S(=O) ２ NR ５３ R ５４ 、-NR ５２ S(=O) ２ R ５２ 、-NR ５２ S(=O) ２ N(R ５２ ) ２ 、-NR ５２ S(=O) ２ NR ５３ R ５４ 、-NR ５２ C(O)N(R ５２ ) ２ 、-NR ５２ C(O)NR ５３ R ５４ 、-C(O)NH(C １－６ alkyl), -C(O)NR ５３ R ５４ 、-P(O)(OR ５２ ) ２ 、-P(O)(R ５２ ) ２ 、-P(O)(OR ５２ )(R ５２ )、-P(O)(NR ５２ )(R ５２ )、-NR ５２ P(O)(R ５２ )、-P(O)(NR ５２ )(OR ５２ )、-P(O)(NR ５２ ) ２ ; and, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl, each of which is independently —S(═O)R ５２ , —S(═O) ２ R ５８ , —S(═O) ２ N(R ５２ ), —S(═O) ２ , —S(═O) ２ NR ５３ R ５４ , —NR ５２ S(═O) ２ R ５２ , —NR ５２ S(═O) ２ N(R ５２ ), —NR ２ , —NR ５２ S(═O) ２ NR ５３ R ５４ , —NR ５２ C(O)N(R ５２ ), —NR ２ , —NR ５２ C(O)NR ５３ R ５４ , —C(O)NH(C １－６ alkyl), —C(O)NR ５３ R ５４ , —P(O)(OR ５２ ), and —P(O)(R ２ ), —P(O)(OR ５２ )(R ２ ), —P(O)(NR ５２ )(R ５２ ), —NR ５２ P(O)(R ５２ ), —P(O)(NR ５２ )(OR ５２ ), —P(O)(NR ５２ )(OR ５２ ), —P(O)(NR ５２ ), ２ each time it appears, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl; R ５８ is hydrogen; and C １－２０ alkyl, C ３－２０ alkenyl, C ２－２０ alkynyl, 1-6 membered heteroalkyl, C ３－１２ carbocyclic, and 3-12 membered heterocyclic, each of which is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocyclic, or 3-6 membered heterocyclic, the method according to claim 12, 19, or 45.

108. H is thienopyrimidinyl optionally substituted with one or more Rs ５０ and is; A is selected from piperidinylene and piperazinylene; B is indolylene; L １ and L ２ are each independently selected from -O-, -S-, -NH-, or -CH ２ -; L ３ is selected from C １－６ alkylene, C ２－６ alkenylene, and C ２－６ alkynylene, each of which is substituted with one or more R ５６ and optionally further substituted with one or more R ５０ ; R Ａ 、 R Ｂ 、 and R Ｃ are each independently selected each time they appear from R ５０ , or two R Ａ groups, two R Ｂ groups, or two R Ｃ groups can combine to optionally form a bridge or a ring; m is an integer from 0 to 3; n is an integer from 1 to 3; p is an integer from 0 to 6; R ５６ appears each time as -OR ５９ , =O, C １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ selected from alkynyl, R ５６ each C in １－１０ alkyl, C ２－１０ alkenyl, and C ２－１０ alkynyl is independently halogen, -NO ２ , -CN, -OR ５９ , -SR ５２ , -N(R ５２ ), -NR ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ), -S(=O) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ), -NR ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ), -OC(O)NR ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ), -NR ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ), -C(O)NR ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ), -P(O)(R ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ )(R ５２ ), -P(O)(NR ５２ )(R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ) ２ , =O, =S, =N(R ５２ ), C ３－１２ a carbon ring, and one or more substituents selected from 3- to 12-membered heterocyclic rings, optionally substituted each time it appears, R ５６ each C in ３－１２ The carbocyclic ring and the 3- to 12-membered heterocyclic ring are each independently halogen, -NO ２ , -CN, -OR ５２ , -SR ５２ , -N(R ５２ ) ２ , -NR ５３ R ５４ , -S(=O)R ５２ , -S(=O) ２ R ５２ , -S(=O) ２ N(R ５２ ) ２ , -S(=O) ２ NR ５３ R ５４ , -NR ５２ S(=O) ２ R ５２ , -NR ５２ S(=O) ２ N(R ５２ ) ２ , -NR ５２ S(=O) ２ NR ５３ R ５４ , -C(O)R ５２ , -C(O)OR ５２ , -OC(O)R ５２ , -OC(O)OR ５２ , -OC(O)N(R ５２ ) ２ , -OC(O)NR ５３ R ５４ , -NR ５２ C(O)R ５２ , -NR ５２ C(O)OR ５２ , -NR ５２ C(O)N(R ５２ ) ２ , -NR ５２ C(O)NR ５３ R ５４ , -C(O)N(R ５２ ) ２ , -C(O)NR ５３ R ５４ , -P(O)(OR ５２ ) ２ , -P(O)(R ５２ ) ２ , -P(O)(OR ５２ ), (R ５２ ), -P(O)(NR ５２ ), (R ５２ ), -NR ５２ P(O)(R ５２ ), -P(O)(NR ５２ )(OR ５２ ), -P(O)(NR ５２ ), ２ =O, =S, =N(R ５２ ), C １－６ alkyl, C １－６ haloalkyl, C ２－６ alkenyl, and C ２－６ alkynyl, optionally substituted with one or more substituents selected from Furthermore, here, R ５６ optionally forms a single bond to ring C; and R ５９ is independently selected each time it occurs from C １－２０ alkyl, C ２－２０ alkenyl, C ２－２０ alkynyl, 1-6 membered heteroalkyl, C ３－１２ carbocyclic, and 3-12 membered heterocyclic, each of which is optionally substituted by halogen, -CN, -NO ２ , -NH ２ , -NHCH ３ , -NHCH ２ CH ３ , =O, -OH, -OCH ３ , -OCH ２ CH ３ , C ３－１２ carbocyclic, or 3-6 membered heterocyclic, the method according to claim 13, 20, or 46.

109. R ５７ is —S(=O) ２ R ５８ , —S(=O) ２ N(R ５２ ) ２ , and —S(=O) ２ NR ５３ R ５４ The method according to claim 107, selected from

110. R ５７ is - S(=O) ２ CH ３ and - S(=O) ２ NHCH ３ The method according to claim 109, selected from

111. C is -S(=O) ２ R ５８ 、 -S(=O) ２ N(R ５２ ) ２ 、 or -S(=O) ２ NR ５３ R ５４ The method according to claim 108, wherein it is substituted by

112. H is 【Chemical 37】 and R ２ is hydrogen, halogen, —OH, —OR ５２ , —NH ２ , —N(R ５２ ), ２ , —CN, C １－３ alkyl, C １－３ alkyl-OR ５２ , C １－３ alkyl-N(R ５２ ), ２ , C １－３ haloalkyl, C ２－３ alkenyl, and C ２－３ alkynyl, the method according to any one of claims 106-111.

113. R ２ is -NH ２ , -CH ３ , and -NHCH ３ The method according to claim 112, selected from.

114. L ３ is 【Chemical 38】 The method according to any one of claims 106 - 113, selected from

115. The method according to any one of claims 12 - 114, wherein the compound is provided as a substantially pure stereoisomer.

116. The method according to claim 115, wherein the stereoisomer is provided with an enantiomeric excess of at least 90%.

117. The method according to any one of claims 12 - 116, wherein the compound is isotopically enriched.

118. The method according to claim 12, 19, or 45, wherein the compound is selected from Table 1.

119. The method according to claim 13, 20, or 46, wherein the compound is selected from Table 1.

120. W １ 、 W ２ 、 and W ３ are each independently selected from C １－４ alkylene, where C １－４ alkylene are each optionally substituted with one or more R ５０ The method according to claim 15, 22, or 48.

121. W １ 、 W ２ 、 and W ３ are each C １ alkylene, the method according to claim 120.

122. W １ and W ２ are each C １ alkylene, and W ３ is absent, the method according to claim 15, 22, or 48.

123. R Ｃ is —N(R ５２ ), —NR ２ R ５３ R ５４ —NR ５２ S(=O) ２ R ５２ —C(O)R ５２ —C(O)OR ５２ —NR ５２ C(O)R ５２ —NR ５２ C(O)OR ５２ —NR ５２ C(O)N(R ５２ ) ２ —NR ５２ C(O)NR ５３ R ５４ —, —C(O)N(R ５２ ) ２ and —C(O)NR ５３ R ５４ selected from, the method according to any one of claims 15, 22, 48, and 119 - 122

124. The method according to claim 15, 22, or 48, wherein the compound is selected from Table 2.

125. The method according to claim 16, 23, or 49, wherein the compound is selected from Table 3, Table 5, or Table 7.

126. The method according to claim 17, 24, or 50, wherein the compound is selected from Table 4.

127. The method according to claim 18, 25, or 51, wherein the compound is selected from Table 6.

128. The method according to any one of claims 1 - 127, further comprising the step of reducing the expression of a target gene.

129. The method according to claim 128, wherein the target gene is selected from Hoxa5, Hoxa7, Hoxa9, Hoxa10, Hoxb2, Hoxb3, Hoxb4, Hoxb5, Hoxb8, Hoxd10, Hoxd11, Hoxd13, DLX2, PBX3, Meis1, Mir196b, Flt3, and Bahcc1.

130. The method according to claim 128, wherein the target gene is Hoxa9, DLX2, PBX3, or Meis1.

131. The method according to any one of claims 1 - 130, further comprising the step of administering a second therapeutic agent.

132. The method according to claim 131, wherein the second therapeutic agent is a DOT1L inhibitor.

133. The method according to claim 131, wherein the second therapeutic agent is an Flt3 inhibitor.

134. The method according to claim 133, wherein the Flt3 inhibitor is quizartinib.

135. The method according to claim 133, wherein the Flt3 inhibitor is midostaurin.

136. The method according to any one of claims 1-135, wherein the subject is a human.

137. The method according to any one of claims 1-136, further comprising the step of obtaining a nucleic acid sample from the subject.

138. The method according to claim 137, wherein the nucleic acid sample comprises a nucleic acid selected from genomic DNA, cDNA, circulating tumor DNA, cell-free DNA, RNA, and mRNA.

139. The method according to any one of claims 1-138, further comprising the step of obtaining a biological sample from the subject.

140. The method according to claim 139, wherein the biological sample is a tissue sample.

141. The method according to claim 140, wherein the tissue sample is fixed, paraffin-embedded, fresh, or frozen.

142. The method according to claim 140, wherein the tissue sample is derived from a fine needle, core, or other type of biopsy.

143. The method according to claim 139, wherein the biological sample is whole blood or plasma.

144. The method according to claim 137, further comprising the step of performing nucleic acid analysis on the nucleic acid sample.

145. The method according to claim 144, wherein the nucleic acid analysis comprises PCR, sequencing, hybridization, microarray, SNP, cell-free nucleic acid analysis, or whole genome sequencing.

146. The method according to any one of claims 1-145, wherein the subject has been tested for the presence of nucleoporin 98 (NUP98) gene fusion, mutation in the nucleophosmin (NPM1) gene, mutation in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, mutation in the FMS-like tyrosine kinase-3 (FLT3) gene, mutation in the isocitrate dehydrogenase 1 (IDH1) gene, mutation in the isocitrate dehydrogenase 2 (IDH2) gene, or mixed lineage leukemia (MLL) gene amplification.

147. The method according to any one of claims 1-146, further comprising the step of testing a subject for the presence of a nucleoporin 98 (NUP98) gene fusion, a mutation in the nucleophosmin (NPM1) gene, a mutation in the DNA (cytosine-5)-methyltransferase 3A (DNMT3A) gene, a mutation in the FMS-like tyrosine kinase-3 (FLT3) gene, a mutation in the isocitrate dehydrogenase 1 (IDH1) gene, a mutation in the isocitrate dehydrogenase 2 (IDH2) gene, or amplification of the mixed lineage leukemia (MLL) gene.

148. The method according to any one of claims 1-147, wherein the subject is tested for the presence of an MLL rearrangement, a partial tandem duplication of MLL, or an increased level of MEIS1 expression.

149. The method according to any one of claims 1-148, further comprising the step of testing a subject for the presence of an MLL rearrangement, a partial tandem duplication of MLL, or an increased level of MEIS1 expression.

Images