Cycloalkane-1,3-diamine derivative
The present invention provides a compound or a pharmaceutically acceptable salt thereof having an inhibitory action on the interaction between menin and an MLL protein. The compound represented by the formula (1) or a pharmaceutically acceptable salt thereof. wherein, in the formula (1), the dotted circle, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , Ring Q 1 , W, m and n are each as defined in the description.
1. A compound which is (1R,2S,4R)-4-({[4-(5,6-dimethoxypyridazin-3-yl)phenyl]methyl}amino)-2-{methyl[6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl]amino}cyclopentan-1-ol or a pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 , which is (1R,2S,4R)-4-({[4-(5,6-dimethoxypyridazin-3-yl)phenyl]methyl}amino)-2-{methyl[6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl]amino}cyclopentan-1-ol succinate.
3. The compound according to claim 1 , which is represented by the formula.
4. The compound according to claim 1 , which is benzenesulfonate, maleate, fumarate, or hydrochloride of (1R,2S,4R)-4-({[4-(5,6-dimethoxypyridazin-3-yl)phenyl]methyl}amino)-2-{methyl[6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl]amino}cyclopentan-1-ol.
5. A crystal of the compound according to claim 2 , wherein the compound is (1R,2S,4R)-4-({[4-(5,6-dimethoxypyridazin-3-yl)phenyl]methyl}amino)-2-{methyl[6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl]amino}cyclopentan-1-ol succinate, having at least five peaks at diffraction angles (2θ) selected from 4.66±0.2, 7.02±0.2, 14.10±0.2, 16.68±0.2, 17.46±0.2, 18.68±0.2, 21.34±0.2, 24.52±0.2, 25.54±0.2 and 28.22±0.2 in a powder X-ray diffraction diagram obtained through irradiation with copper Kα line (λ=1.54 angstroms).
6. A crystal of the compound according to claim 4 , wherein the compound is (1R,2S,4R)-4-({[4-(5,6-dimethoxypyridazin-3-yl)phenyl]methyl}amino)-2-{methyl[6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl]amino}cyclopentan-1-ol maleate, having at least five peaks at diffraction angles (2θ) selected from 4.64±0.2, 7.02±0.2, 7.46±0.2, 11.14±0.2, 14.04±0.2, 16.76±0.2, 18.54±0.2, 19.76±0.2, 21.26±0.2 and 22.62±0.2 in a powder X-ray diffraction diagram obtained through irradiation with copper Kα line (λ=1.54 angstroms).
7. A pharmaceutical composition comprising the compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
8. The pharmaceutical composition according to claim 7 , wherein the pharmaceutically acceptable salt is selected from the group consisting of succinate, benzenesulfonate, maleate, fumarate, and hydrochloride.
9. A pharmaceutical composition comprising the compound according to claim 2 and a pharmaceutically acceptable carrier.
10. A pharmaceutical composition comprising the crystal according to claim 5 and a pharmaceutically acceptable carrier.
11. The pharmaceutical composition according to claim 9 further comprising one drug selected from the group consisting of Venetoclax, Azacitidine, and Cytarabine.
12. A method for the treatment of acute myelogenous leukemia (AML) or acute lymphocytic leukemia (ALL), the method comprising administering to a subject in need thereof a therapeutically effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt thereof.
13. The method according to claim 12 , wherein the pharmaceutically acceptable salt is selected from the group consisting of succinate, benzenesulfonate, maleate, fumarate, and hydrochloride.
14. The method according to claim 12 , wherein the pharmaceutically acceptable salt is succinate.
15. The method according to claim 12 , wherein the disease is acute lymphocytic leukemia (ALL).
16. The method according to claim 12 , wherein the disease is acute myelogenous leukemia (AML).
17. The method according to claim 12 , wherein the disease is acute myelogenous leukemia (AML) with NPM1 mutation.