AMINE-SUBSTITUTED HETEROCYCLIC COMPOUNDS AS EHMT2 INHIBITORS, SALTS THEREOF, AND METHODS OF SYNTHESIS THEREOF
The present disclosure relates to amine-substituted heterocyclic compounds. The present disclosure also relates to pharmaceutical compositions containing these compounds and methods of treating a disorder (e.g., cancer) by administering an amine-substituted heterocyclic compound disclosed herein or a pharmaceutical composition thereof to subjects in need thereof. The present disclosure also relates to the use of such compounds for research or other non-therapeutic purposes.
1 . A compound being selected from
tautomers thereof, pharmaceutically acceptable salts thereof, and pharmaceutically acceptable salts of the tautomers.
2 . The compound of claim 1 , being selected from:
Compound No.
Structure
1
1R
1S
2
3
4
4R
4S
5
5R
5S
6
7
tautomers thereof, pharmaceutically acceptable salts thereof, and pharmaceutically acceptable salts of the tautomers.
3 . The compound of claim 1 or claim 2 , being
(Compound 1), a tautomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of the tautomer.
4 . The compound of any one of the preceding claims, being
a tautomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of the tautomer.
5 . The compound of any one of the preceding claims, being Compound 1R, a tautomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of the tautomer.
6 . The compound of any one of the preceding claims, being Compound 1R.
7 . The compound of any one of the preceding claims, being a crystalline form of Compound 1R.
8 . The compound of any one of the preceding claims, being a pharmaceutical salt of Compound 1R.
9 . The compound of any one of the preceding claims, being a hydrochloride salt of Compound 1R.
10 . The compound of any one of the preceding claims, being a crystalline form of a hydrochloride salt of Compound 1R.
11 . The compound of claim 1 or claim 2 , being
a tautomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of the tautomer.
12 . The compound of any one of the preceding claims, being Compound 2.
13 . The compound of any one of the preceding claims, being a crystalline form of Compound 2.
14 . The compound of any one of the preceding claims, being a pharmaceutical salt of Compound 2.
15 . The compound of any one of the preceding claims, being a hydrochloride salt of Compound 2.
16 . The compound of any one of the preceding claims, being a crystalline form of a hydrochloride salt of Compound 2.
17 . The compound of claim 1 or claim 3 , being
a tautomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of the tautomer.
18 . The compound of any one of the preceding claims, being Compound 3.
19 . The compound of any one of the preceding claims, being a crystalline form of Compound 3.
20 . The compound of any one of the preceding claims, being a pharmaceutical salt of Compound 3.
21 . The compound of any one of the preceding claims, being a hydrochloride salt of Compound 3.
22 . The compound of any one of the preceding claims, being a crystalline form of a hydrochloride salt of Compound 3.
23 . The compound of any one of the preceding claims, being a sulfate salt of Compound 3.
24 . The compound of any one of the preceding claims, being a crystalline form of a sulfate salt of Compound 3.
25 . The compound of any one of the preceding claims, being a glycolate salt of Compound 3.
26 . The compound of any one of the preceding claims, being a crystalline form of a glycolate salt of Compound 3.
27 . The compound of any one of the preceding claims, being a succinate salt of Compound 3.
28 . The compound of any one of the preceding claims, being a crystalline form of a succinate salt of Compound 3.
29 . The compound of claim 1 or claim 2 , being
a tautomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of the tautomer.
30 . The compound of any one of the preceding claims, being
a tautomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of the tautomer.
31 . The compound of any one of the preceding claims, being Compound 4R.
32 . The compound of any one of the preceding claims, being a crystalline form of Compound 4R.
33 . The compound of any one of the preceding claims, being a pharmaceutical salt of Compound 4R.
34 . The compound of any one of the preceding claims, being a hydrochloride salt of Compound 4R.
35 . The compound of any one of the preceding claims, being a crystalline form of a hydrochloride salt of Compound 4R.
36 . The compound of any one of the preceding claims, being a succinate salt of Compound 4R.
37 . The compound of any one of the preceding claims, being a crystalline form of a succinate salt of Compound 4R.
38 . The compound of claim 1 or claim 2 , being
a tautomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of the tautomer.
39 . The compound of any one of the preceding claims, being
a tautomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of the tautomer.
40 . The compound of any one of the preceding claims, being Compound 5R.
41 . The compound of any one of the preceding claims, being a crystalline form of Compound 5R.
42 . The compound of any one of the preceding claims, being a pharmaceutical salt of Compound 5R.
43 . The compound of any one of the preceding claims, being a sulfate salt of Compound 5R.
44 . The compound of any one of the preceding claims, being a crystalline form of a sulfate salt of Compound 5R.
45 . The compound of any one of the preceding claims, being a glycolate salt of Compound 5R.
46 . The compound of any one of the preceding claims, being a crystalline form of a glycolate salt of Compound 5R.
47 . The compound of any one of the preceding claims, being a fumarate salt of Compound 5R.
48 . The compound of any one of the preceding claims, being a crystalline form of a fumarate salt of Compound 5R.
49 . The compound of any one of the preceding claims, being a hippurate salt of Compound 5R.
50 . The compound of any one of the preceding claims, being a crystalline form of a hippurate salt of Compound 5R.
51 . The compound of any one of the preceding claims, being an adipate salt of Compound 5R.
52 . The compound of any one of the preceding claims, being a crystalline form of an adipate salt of Compound 5R.
53 . The compound of any one of the preceding claims, being a gentisate salt of Compound 5R.
54 . The compound of any one of the preceding claims, being a crystalline form of a gentisate salt of Compound 5R.
55 . The compound of any one of the preceding claims, being a benzoate salt of Compound 5R.
56 . The compound of any one of the preceding claims, being a crystalline form of a benzoate salt of Compound 5R.
57 . The compound of claim 1 or claim 2 , being
a tautomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of the tautomer.
58 . The compound of any one of the preceding claims, being a pharmaceutical salt of Compound 6.
59 . The compound of any one of the preceding claims, being a hydrochloride salt of Compound 6.
60 . The compound of any one of the preceding claims, being a crystalline form of a hydrochloride salt of Compound 6.
61 . The compound of any one of the preceding claims, being a glycolate salt of Compound 6.
62 . The compound of any one of the preceding claims, being a crystalline form of a glycolate salt of Compound 6.
63 . The compound of any one of the preceding claims, being an adipate salt of Compound 6.
64 . The compound of any one of the preceding claims, being a crystalline form of an adipate salt of Compound 6.
65 . The compound of claim 1 or claim 2 , being
a tautomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of the tautomer.
66 . The compound of any one of the preceding claims, being a pharmaceutical salt of Compound 7.
67 . The compound of any one of the preceding claims, being a hydrochloride salt of Compound 7.
68 . The compound of any one of the preceding claims, being a crystalline form of a hydrochloride salt of Compound 7.
69 . The compound of any one of the preceding claims, being an oxalate salt of Compound 7.
70 . The compound of any one of the preceding claims, being a crystalline form of an oxalate salt of Compound 7.
71 . The compound of any one of the preceding claims, being a sulfate salt of Compound 7.
72 . The compound of any one of the preceding claims, being a crystalline form of a sulfate salt of Compound 7.
73 . The compound of any one of the preceding claims, being a phosphate salt of Compound 7.
74 . The compound of any one of the preceding claims, being a crystalline form of a phosphate salt of Compound 7.
75 . The compound of any one of the preceding claims, being a fumarate salt of Compound 7.
76 . The compound of any one of the preceding claims, being a crystalline form of a fumarate salt of Compound 7.
77 . A pharmaceutical composition comprising the compound of any one of the preceding claims and a pharmaceutically acceptable carrier.
78 . A method of inhibiting one or both of EHMT1 and EHMT2, the method comprising administering to a subject in need thereof a therapeutically effective amount of the compound of any one of the preceding claims.
79 . The method of claim 49 , wherein the subject has an EHMT-mediated disorder.
80 . The method of claim 49 , wherein the subject has a blood disorder.
81 . The method of claim 49 , wherein the subject has a cancer.
82 . A method of preventing or treating a blood disorder, the method comprising administering to a subject in need thereof a therapeutically effective amount of the compound of any one of the preceding claims.
83 . The method of claim 54 , wherein the blood disorder is sickle cell anemia or R-thalassemia.
84 . The method of claim 54 , wherein the blood disorder is a hematological cancer.
85 . A method of preventing or treating a cancer, the method comprising administering to a subject in need thereof a therapeutically effective amount of the compound of any one of the preceding claims.
86 . The method of claim 56 , wherein the cancer is lymphoma, leukemia, melanoma, breast cancer, ovarian cancer, hepatocellular carcinoma, prostate carcinoma, lung cancer, brain cancer, or hematological cancer.
87 . The method of claim 56 , wherein the cancer is melanoma.
88 . The method of claim 57 , wherein the hematological cancer is acute myeloid leukemia (AML) or chronic lymphocytic leukemia (CLL).
89 . The method of claim 57 , wherein the lymphoma is diffuse large B-cell lymphoma, follicular lymphoma, Burkitt's lymphoma or Non-Hodgkin's Lymphoma.
90 . The method of claim 56 , wherein the cancer is chronic myelogenous leukemia (CML), acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), mixed lineage leukemia (MLL), or myelodysplastic syndromes (MDS).
91 . The compound of any one of the preceding claims for use in inhibiting one or both of EHMT1 and EHMT2 in a subject in need thereof.
92 . The compound of any one of the preceding claims for use in preventing or treating an EHMT-mediated disorder in a subject in need thereof.
93 . The compound of any one of the preceding claims for use in preventing or treating a blood disorder in a subject in need thereof.
94 . The compound of any one of the preceding claims for use in preventing or treating a cancer in a subject in need thereof.
95 . Use of the compound of any one of the preceding claims in the manufacture of a medicament for inhibiting one or both of EHMT1 and EHMT2 in a subject in need thereof.
96 . Use of the compound of any one of the preceding claims in the manufacture of a medicament for preventing or treating an EHMT-mediated disorder in a subject in need thereof.
97 . Use of the compound of any one of the preceding claims in the manufacture of a medicament for preventing or treating a blood disorder in a subject in need thereof.
98 . Use of the compound of any one of the preceding claims in the manufacture of a medicament for preventing or treating a cancer in a subject in need thereof.