1,3-benzodioxole derivative
The present invention provides a compound having a particular chemical structure or a pharmacologically acceptable salt thereof which has an excellent inhibitory effect on EZH1 and/or EZH2 activity. The present invention provides a compound having a 1,3-benzodioxole structure represented by the general formula (I) or a pharmacologically acceptable salt thereof, or a pharmaceutical composition comprising the compound (wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and V in the formula (I) are each as defined in the present specification).
1. A compound represented by the formula (I) or a pharmacologically acceptable salt thereof:
wherein
R 1 represents a hydrogen atom, a halogen atom, or a C 1 -C 6 alkyl group optionally having 1 to 3 halogen atoms,
V represents a single bond,
R 2 represents a hydrogen atom, a C 1 -C 6 alkyl group, or a C 3 -C 6 cycloalkyl group wherein the C 1 -C 6 alkyl group, or a C 3 -C 6 cycloalkyl group optionally has a substituent group of —NR 20 R 21 , wherein R 20 and R 21 each independently represent a hydrogen atom, a formyl group, or a C 1 -C 6 alkyl group,
R 3 represents a C 1 -C 6 alkyl group,
R 4 represents a halogen atom or a C 1 -C 6 alkyl group optionally having 1 to 3 halogen atoms,
R 5 represents a C 1 -C 6 alkyl group or a C 1 -C 6 alkoxy group,
R 6 represents a C 1 -C 6 alkyl group.
2. The compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein R 1 represents a halogen atom.
3. The compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein R 1 represents a chloro group.
4. The compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein R 2 represents a C 3 -C 6 cycloalkyl group and the C 3 -C 6 cycloalkyl group has a substituent group of —NR 20 R 21 , wherein R 20 and R 21 each independently represent a hydrogen atom, a formyl group, or a C 1 -C 6 alkyl group.
5. The compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein R 3 represents a methyl group.
6. Any one compound selected from the following group or a pharmacologically acceptable salt thereof:
7-bromo-2-[trans-4-(dimethylamino)cyclohexyl]-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-2,4-dimethyl-1,3-benzodioxole-5-carboxamide,
(2R)-7-bromo-2-[trans-4-(dimethylamino)cyclohexyl]-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-2,4-dimethyl-1,3-benzodioxole-5-carboxamide,
7-chloro-2-[trans-4-(dimethylamino)cyclohexyl]-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-2,4-dimethyl-1,3-benzodioxole-5-carboxamide,
(2R)-7-chloro-2-[trans-4-(dimethylamino)cyclohexyl]-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-2,4-dimethyl-1,3-benzodioxole-5-carboxamide,
2-[trans-4-(dimethylamino)cyclohexyl]-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-2,4,7-trimethyl-1,3-benzodioxole-5-carboxamide,
(2S)-2-[trans-4-(dimethylamino)cyclohexyl]-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-2,4,7-trimethyl-1,3-benzodioxole-5-carboxamide,
4,7-dichloro-2-[trans-4-(dimethylamino)cyclohexyl]-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-2-methyl-1,3-benzodioxole-5-carboxamide,
2-[trans-4-(dimethylamino)cyclohexyl]-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-2,4-dimethyl-1,3-benzodioxole-5-carboxamide, and
2-[trans-4-(dimethylamino)cyclohexyl]-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-ethyl-2,4-dimethyl-1,3-benzodioxole-5-carboxamide.
7. A pharmaceutical composition comprising a compound according to claim 1 or a pharmacologically acceptable salt thereof as an active ingredient.
8. The compound according to claim 1 , wherein the compound is (2R)-7-chloro-2-[trans-4-(dimethylamino)cyclohexyl]-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-2,4-dimethyl-1,3-benzodioxole-5-carboxamide or a pharmacologically acceptable salt thereof.
9. The compound according to claim 1 , wherein the compound is (2R)-7-chloro-2-[trans-4-(dimethylamino)cyclohexyl]-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-2,4-dimethyl-1,3-benzodioxole-5-carboxamide p-toluenesulfonate.