Heterocyclic compound
The present invention provides a heterocyclic compound having a HDAC inhibitory action, and useful for the treatment of inflammatory 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 (I):
wherein
Ring A is an optionally further substituted 5- or 6-membered aromatic ring,
Ring B is an optionally further substituted nitrogen-containing heterocycle, and
R 1 , R 2 and R 3 are independently a hydrogen atom or a substituent,
or a salt thereof.
2. The compound or salt according to claim 1 , wherein
R 1 is a hydrogen atom;
R 2 is
(1) an optionally substituted C 1-6 alkyl group,
(2) an optionally substituted C 3-10 cycloalkyl group,
(3) an optionally substituted C 6-14 aryl group,
(4) an optionally substituted C 7-16 aralkyl group,
(5) an optionally substituted 5- to 14-membered aromatic heterocyclic group,
(6) an optionally substituted 3- to 14-membered non-aromatic heterocyclic group,
(7) an optionally substituted mono- or di-C 6-14 arylamino group, or
(8) an optionally substituted C 1-6 alkoxy group; and
R 3 is a hydrogen atom.
3. The compound or salt according to claim 1 , wherein
Ring A is a benzene ring or a pyridine ring;
Ring B is a morpholine ring or a piperidine ring;
R 1 is a hydrogen atom;
R 2 is
(1) a C 1-6 alkyl group optionally substituted by 1 to 3 of 5- to 14-membered aromatic heterocyclic groups,
(2) a C 3-10 cycloalkyl group,
(3) a C 6-14 aryl group optionally substituted by 1 to 3 substituents selected from
(a) a halogen atom,
(b) a hydroxy group,
(c) a cyano group,
(d) an optionally halogenated C 1-6 alkyl group,
(e) a C 1-6 alkoxy group,
(f) a C 6-14 aryl group,
(g) a carbamoyl group, and
(h) a mono- or di-C 1-6 alkylamino group,
(4) a C 7-16 aralkyl group,
(5) a 5- to 14-membered aromatic heterocyclic group optionally substituted by 1 to 3 substituents selected from
(a) a hydroxy group, and
(b) an optionally halogenated C 1-6 alkyl group,
(6) a 3- to 14-membered non-aromatic heterocyclic group optionally substituted by 1 to 3
substituents selected from
(a) a C 1-6 alkyl group, and
(b) a C 1-6 alkyl-carbonyl group,
(7) a mono- or di-C 6-14 arylamino group, or
(8) a C 1-6 alkoxy group; and
R 3 is a hydrogen atom.
4. The compound or salt according to claim 1 , wherein Ring B is an optionally further substituted morpholine ring.
5. The compound or salt according to claim 1 , wherein
Ring A is a benzene ring or a pyridine ring;
Ring B is a morpholine ring;
R 1 is a hydrogen atom;
R 2 is
(1) a phenyl group, or
(2) a pyrazolyl group optionally substituted by 1 to 3 C 1-6 alkyl groups; and
R 3 is a hydrogen atom.
6. 3-((Benzoylamino)methyl)-N-(4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)morpholine-4-carboxamide, or a salt thereof.
7. (3R)-3-((((1-Methyl-1H-pyrazol-5-yl)carbonyl)amino)methyl)-N-(4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)morpholine-4-carboxamide, or a salt thereof.
8. 3-((Benzoylamino)methyl)-N-(5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-yl)morpholine-4-carboxamide, or a salt thereof.
9. A medicament comprising the compound or salt according to claim 1 .
10. 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.
11. A method for the treatment of HDAC-associated inflammatory diseases in a mammal, which comprises administering an effective amount of the compound or salt according to claim 1 to the mammal.