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 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 crystalline form of a compound being selected from:
or a tautomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of the tautomer thereof.
2 . The crystalline form of claim 1 , wherein the compound is:
or a tautomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of the tautomer thereof.
3 . The crystalline form of claim 2 , wherein the crystalline form is the free base, sulfate salt, glycolate salt, fumarate salt, hippurate salt, adipate salt, gentisate salt, benzoate salt.
4 . The free base of claim 3 , having at least one peak selected from 12.8±0.2, 13.4±0.2, 14.6±0.2, 17.6±0.2, 20.9±0.2, and 23.9±0.2° 2θ;
at least one peak selected from 10.2±0.2, 12.5±0.2, 14.0±0.2, 17.8±0.2, 18.8±0.2, 19.3±0.2, and 24.6±0.2° 2θ; or
at least one peak selected from 8.5±0.2, 12.9±0.2, 13.6±0.2, 15.4±0.2, 16.0±0.2, 18.1±0.2, 21.3±0.2, 21.6±0.2, 22.9±0.2, and 24.8±0.2° 2θ using Cu Kα radiation.
5 . The sulfate salt of claim 3 , having at least one peak selected from 6.8±0.2, 8.7±0.2, 14.0±0.2, 16.4±0.2, 23.5±0.2, 25.3±0.2, and 26.5±0.2° 2θ using Cu Kα radiation.
6 . The glycolate salt of claim 3 , having at least one peak selected from 6.5±0.2, 14.1±0.2, 17.8±0.2, 18.9±0.2, 24.7±0.2, 25.7±0.2, and 26.5±0.2° 2θ using Cu Kα radiation.
7 . The fumarate salt of claim 3 , having at least one peak selected from 5.9±0.2, 7.7±0.2, 11.3±0.2, 11.9±0.2, 15.4±0.2, 18.4±0.2, 25.8±0.2, and 26.5±0.2° 2θ using Cu Kα radiation.
8 . The hippurate salt of claim 3 , having at least one peak selected from 6.5±0.2, 9.7±0.2, 11.0±0.2, 13.0±0.2, 19.4±0.2, 23.6±0.2, and 26.1±0.2° 2θ using Cu Kα radiation.
9 . The adipate salt of claim 3 , having at least one peak selected from 10.7±0.2, 13.1±0.2, 17.8±0.2, 18.8±0.2, 21.6±0.2, 22.9±0.2, 24.6±0.2, and 25.5±0.2° 2θ using Cu Kα radiation.
10 . The gentisate salt of claim 3 , having at least one peak selected from 5.3±0.2, 7.7±0.2, 8.8±0.2, 9.3±0.2, 15.0±0.2, 16.2±0.2, 17.2±0.2, 21.2±0.2, and 25.3±0.2° 2θ; or
at least one peak selected from 6.0±0.2, 9.1±0.2, 15.0±0.2, 17.7±0.2, 18.4±0.2, 20.7±0.2, 23.8±0.2, 25.8±0.2, and 26.6±0.2° 2θ using Cu Kα radiation.
11 . The benzoate salt of claim 3 , having at least one peak selected from 5.2±0.2, 9.7±0.2, 15.5±0.2, 18.3±0.2, 19.0±0.2, 21.3±0.2, 22.9±0.2, 23.7±0.2, and 26.9±0.2° 2θ;
at least one peak selected from 7.9±0.2, 10.1±0.2, 11.7±0.2, 17.2±0.2, 24.4±0.2, and 25.1±0.2° 2θ;
at least one peak selected from 5.5±0.2, 11.1±0.2, 14.3±0.2, 15.9±0.2, 16.7±0.2, 17.0±0.2, 17.5±0.2, 19.1±0.2, 24.4±0.2, and 24.9±0.2° 2θ;
at least one peak selected from 5.5±0.2, 5.7±0.2, 6.2±0.2, 12.6±0.2, 15.4±0.2, and 25.1±0.2° 2θ; or
at least one peak selected from 6.1±0.2, 12.3±0.2, 16.3±0.2, 18.3±0.2, 21.2±0.2, 22.2±0.2, 23.1±0.2, 24.4±0.2, and 26.3±0.2° 2θ using Cu Kα radiation.
12 . The crystalline form of claim 1 , wherein the compound is:
or a tautomer thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of the tautomer thereof.
13 . The crystalline form of claim 12 , wherein the compound is the hydrochloride salt, oxalate salt, sulfate salt, phosphate salt, or fumarate salt.
14 . The hydrochloride salt of claim 13 , having at least one peak selected from 6.8±0.2, 9.4±0.2, 12.1±0.2, 14.5±0.2, 15.0±0.2, 18.7±0.2, 24.2±0.2, 25.1±0.2, 25.6±0.2, and 26.8±0.2° 2θ; or
at least one peak selected from 5.9±0.2, 8.3±0.2, 10.0±0.2, 11.7±0.2, 21.9±0.2, 25.1±0.2, and 26.9±0.2° 2θ using Cu Kα radiation.
15 . The oxalate salt of claim 13 , having at least one peak selected from 4.5±0.2, 8.7±0.2, 9.1±0.2, 9.7±0.2, 13.8±0.2, 24.9±0.2, and 25.4±0.2° 2θ using Cu Kα radiation.
16 . The sulfate salt of claim 13 , having at least one peak selected from 13.1±0.2, 15.8±0.2, 17.9±0.2, 18.0±0.2, 18.9±0.2, 19.2±0.2, 19.7±0.2, 23.8±0.2, 25.1±0.2, 25.7±0.2, and 26.4±0.2° 2θ using Cu Kα radiation.
17 . The phosphate salt of claim 13 , having at least one peak selected from 3.8±0.2, 14.4±0.2, 15.3±0.2, 16.8±0.2, 24.1±0.2, and 25.0±0.2° 2θ using Cu Kα radiation.
18 . The fumarate salt of claim 13 , having at least one peak selected from 8.2±0.2, 9.0±0.2, 11.6±0.2, 14.4±0.2, 16.6±0.2, 20.7±0.2, 21.1±0.2, 22.2±0.2, and 24.5±0.2° 2θ;
at least one peak selected from 4.4±0.2, 7.5±0.2, 9.0±0.2, 11.7±0.2, 14.5±0.2, 16.7±0.2, 21.3±0.2, 22.2±0.2, 24.7±0.2, and 25.9±0.2° 2θ; or
at least one peak selected from 9.7±0.2, 12.2±0.2, 12.8±0.2, 13.6±0.2, 14.0±0.2, 22.5±0.2, 24.4±0.2, and 24.9±0.2° 2θ using Cu Kα radiation.
19 . A pharmaceutical composition comprising the crystalline form of claim 1 and a pharmaceutically acceptable carrier.
20 . A method of treating a blood disorder or cancer, the method comprising administering to a subject in need thereof a crystalline form of claim 1 .