Substituted pyrrolidine compound and use thereof

1. A compound represented by the formula (I):

wherein

X 1 , X 2 , X 3 and X 4 are each independently a nitrogen atom, or CR a ;

Y is an oxygen atom, NR b , or CR c R d ;

R 1 is an optionally substituted C 1-6 alkyl group, an optionally substituted hydrocarbon ring group, or an optionally substituted heterocyclic group bonded on the carbon atom;

R 2 is a hydrogen atom, or an optionally substituted C 1-6 alkyl group;

R 3 is an optionally substituted C 1-6 alkyl group, or an optionally substituted cyclic group;

Ring A is an optionally further substituted pyrrolidine ring;

R a , R c and R d are each independently a hydrogen atom, a halogen atom, an optionally substituted C 1-6 alkyl group, or an optionally substituted C 1-6 alkoxy group; and

R b is 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

X 1 is a nitrogen atom, or CR a wherein R a is a hydrogen atom, a halogen atom or a C 1-6 alkyl group;

X 2 is a nitrogen atom, or CR a wherein R a is a hydrogen atom, a halogen atom or a C 1-6 alkyl group;

X 3 is a nitrogen atom, or CR a wherein R a is a hydrogen atom, a halogen atom or a C 1-6 alkyl group;

X 4 is a nitrogen atom, or CR a wherein R a is a hydrogen atom or a halogen atom;

Y is

(1) an oxygen atom,

(2) NR b wherein R b is

(a) a hydrogen atom, or

(b) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from

(i) a C 1-6 alkoxy group, and

(ii) a mono- or di-C 1-6 alkyl-carbamoyl group, or

(3) CH 2 ;

R 1 is

(1) a C 1-6 alkyl group,

(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 C 1-6 alkoxy group,

(c) a C 6-14 aryl group optionally substituted by 1 to 3 mono- or di-C 1-6 alkyl-carbamoyl groups, and

(d) a pyrrolidyl group, a piperidyl group, a morpholinyl group and a 1-oxa-8-azaspiro[5.5]undecyl group, each optionally substituted by 1 to 3 substituents selected from

(i) an oxo group,

(ii) a C 1-6 alkyl-carbonyl group,

(iii) a mono- or di-C 1-6 alkylamino group,

(iv) a pyridyl group, and

(v) a pyrrolidylcarbonyl group,

(4) a thienyl group or a pyridyl group, each optionally substituted by 1 to 3 substituents selected from

(a) a halogen atom,

(b) a C 1-6 alkoxy group, and

(c) a mono- or di-C 1-6 alkyl-carbamoyl group, or

(5) a tetrahydropyranyl group, a piperidyl-3-yl group or an isoindolin-5-yl group, each optionally substituted by 1 to 3 C 1-6 alkyl-carbonyl groups;

R 2 is a hydrogen atom, or a C 1-6 alkyl group optionally substituted by 1 to 3 halogen atoms;

R 3 is

(1) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from a C 6-14 aryl group optionally substituted by 1 to 3 C 1-6 alkoxy groups,

(2) a C 6-14 aryl group optionally substituted by 1 to 3 substituents selected from

(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,

(d) a mono- or di-C 1-6 alkylamino group,

(e) a C 1-6 alkylsulfanyl group, and

(f) a morpholinyl group,

(3) a pyrazolyl group, a thienyl group or a pyridyl group, each optionally substituted by 1 to 3 substituents selected from

(a) a halogen atom,

(b) a C 1-6 alkyl group optionally substituted by 1 to 3 halogen atoms, and

(c) a C 6-14 aryl group,

(4) a tetrahydropyranyl group or a dihydrobenzofuryl group, or

(5) a C 3-10 cycloalkyl group optionally substituted by 1 to 3 C 6-14 aryl groups; and

Ring A is a pyrrolidine ring optionally further substituted by 1 to 3 substituents selected from

(a) a halogen atom,

(b) a hydroxy group,

(c) a cyano group,

(d) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from

(i) a halogen atom, and

(ii) a C 1-6 alkoxy group,

(e) a C 1-6 alkoxy group optionally substituted by 1 to 3 halogen atoms,

(f) a mono- or di-C 1-6 alkyl-carbamoyl group,

(g) an amino group,

(h) a mono- or di-C 1-6 alkylamino group, and

(i) a C 1-6 alkyl-carbonylamino group.

3. The compound or salt according to claim 1 , wherein

X 1 is CR a wherein R a is a hydrogen atom, a halogen atom or a C 1-6 alkyl group;

X 2 is CH;

X 3 is a nitrogen atom, or CR a wherein R a is a hydrogen atom, a halogen atom or a C 1-6 alkyl group;

X 4 is a nitrogen atom or CH;

Y is an oxygen atom;

R 1 is

(1) a C 1-6 alkyl group,

(2) a phenyl group optionally substituted by 1 to 3 substituents selected from

(a) a halogen atom,

(b) a C 1-6 alkoxy group, and

(c) a phenyl group optionally substituted by 1 to 3 mono- or di-C 1-6 alkyl-carbamoyl groups, or

(3) a thienyl group optionally substituted by 1 to 3 halogen atoms;

R 2 is a hydrogen atom;

R 3 is

(1) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from a phenyl group optionally substituted by 1 to 3 C 1-6 alkoxy groups,

(2) a phenyl group optionally substituted by 1 to 3 substituents selected from

(a) a C 1-6 alkyl group, and

(b) a C 1-6 alkoxy group, or

(3) a pyrazolyl group optionally substituted by 1 to 3 substituents selected from a C 1-6 alkyl group optionally substituted by 1 to 3 halogen atoms; and

Ring A is a pyrrolidine ring optionally further substituted by one substituent selected from

(a) a halogen atom,

(b) a C 1-6 alkyl group, and

(c) a C 1-6 alkoxy group.

4. The compound or salt according to claim 1 , wherein

X 1 is CR a wherein Ra is a hydrogen atom or a halogen atom;

X 2 is CH;

X 3 is CH;

X 4 is CH;

Y is an oxygen atom;

R 1 is a phenyl group optionally substituted by 1 to 3 substituents selected from

(a) a C 1-6 alkoxy group, and

(b) a phenyl group optionally substituted by 1 to 3 mono- or di-C 1-6 alkyl-carbamoyl groups;

R 2 is a hydrogen atom;

R 3 is a phenyl group optionally substituted by 1 to 3 C 1-6 alkyl groups; and

Ring A is a pyrrolidine ring optionally further substituted by one C 1-6 alkoxy group.

5. The compound 3′-((3-(((3S)-1-(2,6-Dimethylbenzoyl)pyrrolidin-3-yl)oxy)phenyl)sulfamoyl)-4′-methoxy-N,N-dimethylbiphenyl-3-carboxamide or a salt thereof.

6. The compound N-(3-(((3R,4R)-1-(2,5-Dimethylbenzoyl)-4-methoxypyrrolidin-3-yl)oxy)phenyl)-2-methoxybenzenesulfonamide or a salt thereof.

7. The compound 3′-((3-(((3S)-1-(2,6-Dimethylbenzoyl)pyrrolidin-3-yl)oxy)-2-fluorophenyl)sulfamoyl)-4′-methoxy-N,N-dimethylbiphenyl-3-carboxamide 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 an orexin type 2 receptor agonist.

10. The medicament according to claim 8 , which is an agent for the treatment of narcolepsy.

11. The compound or salt according to claim 1 for use in the treatment of narcolepsy.

12. A method of activating an orexin type 2 receptor 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 treatment of narcolepsy in a mammal, which comprises administering an effective amount of the compound or salt according to claim 1 to the mammal.