Cyclopropylamines as LSD1 inhibitors
The present invention is directed to cyclopropylamine derivatives which are LSD1 inhibitors useful in the treatment of diseases such as cancer.
1. A method of treating cancer, wherein said cancer is selected from myelodysplasia syndrome, acute myelogenous leukemia, undifferentiated small cell lung cancer, Ewing's sarcoma, and primary myelofibrosis, comprising administering to a patient a therapeutically effective amount of a compound selected from:
1-{[4-(methoxymethyl)-4-({[(1R,2 S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclopentanecarboxylic acid,
1-{[4-(methoxymethyl)-4-({[(1R,2 S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid,
1-{[4-({[(1R,2S)-2-(4-fluorophenyl)cyclopropyl]amino}methyl)-4-(methoxymethyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid, and
1-{[4-(ethoxymethyl)-4-({[(1R,2S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid,
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the cancer is myelodysplasia syndrome.
3. The method of claim 1 , wherein the cancer is acute myelogenous leukemia.
4. The method of claim 1 , wherein the cancer is Ewing's sarcoma.
5. The method of claim 1 , wherein the cancer is undifferentiated small cell lung cancer.
6. The method of claim 1 , wherein the cancer is primary myelofibrosis.
7. The method of claim 1 , wherein the compound is 1-{[4-(methoxymethyl)-4-({[(1R,2 S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclopentanecarboxylic acid, or a pharmaceutically acceptable salt thereof.
8. The method of claim 1 , wherein the compound is 1-{[4-(methoxymethyl)-4-({[(1R,2 S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid, or a pharmaceutically acceptable salt thereof.
9. The method of claim 1 , wherein the compound is 1-{[4-({[(1R,2 S)-2-(4-fluorophenyl)cyclopropyl]amino}methyl)-4-(methoxymethyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid, or a pharmaceutically acceptable salt thereof.
10. The method of claim 1 , wherein the compound is 1-{[4-(ethoxymethyl)-4-({[(1R,2 S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid, or a pharmaceutically acceptable salt thereof.