Heterocyclic compound
The present invention provide a heterocyclic compound having a HDAC inhibitory action, and useful for the treatment of autoimmune diseases and/or inflammatory diseases, graft versus host disease, cancers, central nervous diseases including neurodegenerative diseases, Charcot-Marie-Tooth disease and the like, and a medicament comprising the compound. The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.
1. A compound represented by the formula:
wherein
X is CH or N,
R 1 is an optionally substituted C 6-14 aromatic hydrocarbon ring or an optionally substituted 5- to 6-membered monocyclic aromatic heterocycle;
R 2 and R 3 are independently a hydrogen atom, an optionally substituted C 1-6 alkyl group or an optionally substituted carbamoyl group; and
R 4 and R 5 are independently a hydrogen atom or an optionally substituted C 1-6 alkyl group,
or a salt thereof.
2. The compound or salt according to claim 1 , wherein
R 1 is a C 6-14 aromatic hydrocarbon ring or a 5- to 6-membered monocyclic aromatic heterocycle, each of which is optionally substituted by 1 to 3 substituents selected from
(a) a halogen atom,
(b) a cyano group,
(c) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from
(i) a mono- or di-C 1-6 alkyl-carbamoyl group, and
(ii) a halogen atom,
(d) a C 1-6 alkoxy group optionally substituted by 1 to 3 substituents selected from
(i) a halogen atom, and
(ii) a 3- to 14-membered non-aromatic heterocyclic group,
(e) a C 6-14 aryloxy group,
(f) a C 1-6 alkylsulfonyl group,
(g) a (C 1-6 alkyl)(C 1-6 alkylsulfonyl)amino group,
(h) a mono- or di-C 1-6 alkyl-carbamoyl group,
(i) a C 6-14 aryl group, and
(j) a 3- to 14-membered non-aromatic heterocyclic group optionally substituted by 1 to 3 oxo groups;
R 2 and R 3 are independently
(1) a hydrogen atom,
(2) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from
(a) a C 1-6 alkoxy group,
(b) a mono- or di-C 1-6 alkyl-carbamoyl group, and
(c) a 3- to 14-membered non-aromatic heterocyclic group optionally substituted by 1 to 3 oxo groups, or
(3) a mono- or di-C 1-6 alkyl-carbamoyl group; and
R 4 and R 5 are independently a hydrogen atom or a C 1-6 alkyl group.
3. The compound or salt according to claim 1 , wherein
R 1 is benzene or a 5- to 6-membered monocyclic aromatic heterocycle, each of which is optionally substituted by 1 to 3 C 1-6 alkoxy groups;
R 2 and R 3 are independently a hydrogen atom or a C 1-6 alkyl group; and
R 4 and R 5 are both hydrogen atoms.
4. The compound or salt according to claim 1 , wherein
R 1 is benzene;
R 2 and R 3 are independently a hydrogen atom or a C 1-6 alkyl group; and
R 4 and R 5 are both hydrogen atoms.
5. 6-Benzyl-3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one, or a salt thereof.
6. 2-Benzyl-6-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)isoindolin-1-one, or a salt thereof.
7. 2-((1S)-1-Phenylethyl)-6-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)isoindolin-1-one, or a salt thereof.
8. A medicament comprising the compound or salt according to claim 1 .
9. The medicament according to claim 8 , which is a histone deacetylase inhibitor.
10. The medicament according to claim 8 , which is an agent for the prophylaxis or treatment of neurodegenerative diseases.
11. The compound or salt according to claim 1 for use in the prophylaxis or treatment of neurodegenerative diseases.
12. A method of inhibiting histone deacetylase in a mammal, which comprises administering an effective amount of the compound or salt according to claim 1 to the mammal.
13. A method for the prophylaxis or treatment of neurodegenerative diseases in a mammal, which comprises administering an effective amount of the compound or salt according to claim 1 to the mammal.