Heterocyclic compound
Provided is a compound having a melanin-concentrating hormone receptor antagonistic action and is useful as an agent for the prophylaxis or treatment of obesity and the like. 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 formula (I):
wherein ring Ar is an aromatic ring optionally further substituted;
L 1 is O, S(O) m1 , NR 3A or CR 3B R 3C ;
L 2 is O, S(O) m2 , NR 4A or CR 4B R 4C ;
(excluding the combination of L 1 being other than CR 3B R 3C and L 2 being other than CR 4B R 4C )
m1 and m2 are each independently an integer of 0 to 2;
R 3A and R 4A are each independently a hydrogen atom or an optionally substituted hydrocarbon group;
R 3B , R 3C , R 4B and R 4C are each independently a hydrogen atom or a substituent;
when L 1 is CR 3B R 3C and ring Ar has substituent(s), R 3B and the substituent are optionally bonded to each other to form an optionally substituted ring;
X 1 , X 2 and X 3 are each independently CR 5 or N;
R 5 is a hydrogen atom, a halogen atom, a cyano group, an optionally substituted C 1-6 alkyl group, an optionally substituted C 1-6 alkoxy group or an optionally substituted C 3-10 cycloalkyl group;
R 1 is an optionally substituted C 1-6 alkyl group or an optionally substituted cyclic group;
R 2 is a halogen atom, an optionally substituted C 1-6 alkyl group or an optionally substituted cyclic group;
Y 1 , Y 2 and Y 3 are each independently CR 6 or N; and
R 6 is a hydrogen atom, a halogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 1-6 alkoxy group or an optionally substituted C 3-10 cycloalkyl group, or a salt thereof.
2. The compound according to claim 1 , wherein ring Ar is a C 6-14 aromatic hydrocarbon ring or a 5- to 10-membered aromatic heterocycle, each of which is optionally further substituted by 1 to 3 substituents selected from the group consisting of:
(a) a halogen atom,
(b) a C 1-6 alkyl group optionally substituted by 1 to 3 halogen atoms,
(c) a C 1-6 alkoxy group optionally substituted by 1 to 3 halogen atoms, and
(d) a pentafluorosulfanyl group,
or a salt thereof.
3. The compound according to claim 1 , wherein L 1 is CH 2 ; and L 2 is O, or a salt thereof.
4. The compound according to claim 1 , wherein X 1 , X 2 and X 3 are CH, or a salt thereof.
5. The compound according to claim 1 , wherein R 1 is a C 1-6 alkyl group or a C 3-10 cycloalkyl group, or a salt thereof.
6. The compound according to claim 1 , wherein R 2 is a C 1-6 alkyl group, or a salt thereof.
7. The compound according to claim 1 , wherein Y 1 , Y 2 and Y 3 are CH, or a salt thereof.
8. The compound according to claim 1 , wherein ring Ar is a C 6-14 aromatic hydrocarbon ring or a 5- to 10-membered aromatic heterocycle, each of which is optionally further substituted by 1 to 3 substituents selected from the group consisting of:
(a) a halogen atom,
(b) a C 1-6 alkyl group optionally substituted by 1 to 3 halogen atoms,
(c) a C 1-6 alkoxy group optionally substituted by 1 to 3 halogen atoms, and
(d) a pentafluorosulfanyl group,
L 1 is CH 2 ,
L 2 is O,
X 1 , X 2 and X 3 are CH,
R 1 is a C 1-6 alkyl group or a C 3-10 cycloalkyl group,
R 2 is a C 1-6 alkyl group, and
Y 1 , Y 2 and Y 3 are CH, or a salt thereof.
9. 4-[(4-Chlorobenzyl)oxy]-1-(2,3-dimethyl-2H-indazol-5-yl)pyridin-2(1H)-one or a salt thereof.
10. 1-(2-Cyclopropyl-3-methyl-2H-indazol-5-yl)-4-{[5-(trifluoromethyl)thiophen-3-yl]methoxy}pyridin-2(1H)-one or a salt thereof.
11. 1-(2-Cyclopropyl-3-methyl-2H-indazol-5-yl)-4-{[2-(trifluoromethyl)-1,3-thiazol-4-yl]methoxy}pyridin-2(1H)-one or a salt thereof.
12. A pharmaceutical composition comprising the compound according to claim 1 , or a salt thereof, and a pharmacologically acceptable carrier.
13. The pharmaceutical composition according to claim 12 , which is a melanin-concentrating hormone receptor antagonist.
14. The pharmaceutical composition according to claim 12 , which is an anorexigenic agent.
15. The pharmaceutical composition according to claim 12 , which is a prophylactic or therapeutic agent for obesity.
16. A method of preventing or treating obesity in a mammal, comprising administering an effective amount of the compound according to claim 1 or a salt thereof to the mammal.
17. A method of antagonizing a melanin-concentrating hormone receptor in a mammal, comprising administering an effective amount of the compound according to claim 1 or a salt thereof to the mammal.
18. A method of suppressing food intake in a mammal, comprising administering an effective amount of the compound according to claim 1 or a salt thereof to the mammal.
19. The compound according to claim 1 or a salt thereof for use in the prophylaxis or treatment of obesity.
20. The compound according to claim 1 or a salt thereof for use in the suppression of food intake.