Cyclopropaneamine compound
The present invention provides a compound having a lysine-specific demethylase 1 inhibitory action, and useful as a medicament such as a prophylactic or therapeutic agent for cancer, and central nervous system diseases, and the like. The present invention relates to a compound represented by the formula wherein A is a hydrocarbon group or heterocyclic group optionally having substituent(s); R is H, a hydrocarbon group or heterocyclic group optionally having substituent(s); A and R are optionally bonded to each other to form a ring optionally having substituent(s); Q 1 , Q 2 , Q 3 and Q 4 are each a hydrogen atom or a substituent; Q 1 and Q 2 , and Q 3 and Q 4 , are each optionally bonded to each other to form a ring optionally having substituent(s); X is H, an acyclic hydrocarbon group or saturated cyclic group optionally having substituent(s); Y 1 , Y 2 and Y 3 are each H, a hydrocarbon group or heterocyclic group optionally having substituent(s); X and Y 1 , and Y 1 and Y 2 , are each optionally bonded to each other to form a ring optionally having substituent(s); and Z 1 , Z 2 and Z 3 are each H or a substituent, or a salt thereof.
1. N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}phenyl)biphenyl-4-carboxamide or a salt thereof.
2. N-(4-{trans-2-[(1-methylpiperidin-4-yl)amino]cyclopropyl}phenyl)-3-(trifluoromethy)benzamide or a salt thereof.
3. N-(4-{trans-2-[(cyclopropylmethy)amino]cyclopropyl}phenyl)-1H-pyrazole-4-carboxamide or a salt thereof.
4. A compound selected from the group consisting of
(1) N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}-2-methylphenyl)benzamide,
(2) N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}phenyl)-3-(trifluoromethoxy)benzamide,
(3) N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}phenyl)benzamide,
(4) N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}phenyl)-cyclohexanecarboxamide,
(5) N-(4-{trans-2-[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)amino]cyclopropyl}phenyl)-3-(trifluoromethyl)benzamide,
(6) N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}phenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamide,
(7) N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}phenyl)-1,5-dimethyl-1H-pyrazole-3-carboxamide,
(8) N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}phenyl)-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide,
(9) N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}phenyl)-1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide, and
(10) N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}phenyl)-1-methyl-1H-pyrazole-4-carboxamide,
or a salt thereof.
5. A medicament comprising: an effective amount of the compound according to claim 4 or a salt thereof; and a pharmaceutically acceptable carrier.
6. The medicament according to claim 5 , which is a therapeutic agent for cancer.
7. The medicament according to claim 5 , which is an LSD1 inhibitor.
8. The medicament according to claim 5 , which is a therapeutic agent for schizophrenia, Alzheimer's disease, Parkinson's disease or Huntington's chorea.
9. A method for a treatment of schizophrenia, Alzheimer's disease, Parkinson's disease or Huntington's chorea, comprising administering an effective amount of the compound according to claim 4 or a salt thereof to a mammal in need thereof.
10. A method of inhibiting LSD1, comprising administering an effective amount of the compound according to claim 4 or a salt thereof to a mammal.
11. A method for a treatment of cancer, comprising administering an effective amount of the compound according to claim 4 or a salt thereof to a mammal in need thereof.
12. The compound according to claim 4 , which is N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}-2-methylphenyl)benzamide or a salt thereof.
13. The compound according to claim 4 , which is N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}phenyl)-3 -(trifluoromethoxy)benzamide or a salt thereof.
14. The compound according to claim 4 which is N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}phenyl)benzamide or a salt thereof.
15. The compound according to claim 4 , which is N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}phenyl)cyclohexanecarboxamide or a salt thereof.
16. The compound according to claim 4 , which is N-(4-{trans-2-[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)amino]cyclopropyl}phenyl)-3-(trifluoromethyl)benzamide or a salt thereof.
17. The compound according to claim 4 , which is N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}phenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamide or a salt thereof.
18. The compound according to claim 4 , which is N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}phenyl)-1,5-dimethyl-1H-pyrazole-3-carboxamide or a salt thereof.
19. The compound according to claim 4 , which is N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}phenyl)-1-methyl-3 -(trifluoromethyl)-1H-pyrazole-4-carboxamide or a salt thereof.
20. The compound according to claim 4 , which is N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}phenyl)-1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide or a salt thereof.
21. The compound according to claim 4 , which is N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}phenyl)-1-methyl-1H-pyrazole-4-carboxamide or a salt thereof.