Heterocyclic compound and application thereof
The present invention provides a heterocyclic compound having an orexin type 2 receptor agonist activity. A compound represented by the formula (I): wherein each symbol is as described in the specification, or a salt thereof has an orexin type 2 receptor agonist activity, and is useful as an agent for the prophylaxis or treatment of narcolepsy.
1. A compound represented by the formula (I):
wherein
R 1 is
(1) a mono- or di-C 1-6 alkyl-carbamoyl group, or
(2) a 3- to 6-membered monocyclic non-aromatic heterocyclic group;
R 2 is
(1) a C 1-6 alkyl-carbonyl group,
(2) a C 3-10 cycloalkyl-carbonyl group optionally substituted by 1 to 3 hydroxy groups,
(3) a 3- to 14-membered non-aromatic heterocyclylcarbonyl group,
(4) a C 1-6 alkoxy-carbonyl group, or
(5) a mono- or di-C 1-6 alkyl-carbamoyl group;
L 1 is an oxygen atom;
L 2 is a methylene group;
Ring A is
(1) a pyrrolidine ring having no additional substituent, or
(2) a piperidine ring having no additional substituent;
Ring B is
(1) a cyclohexane ring having no additional substituent, or
(2) a 6-membered monocyclic saturated heterocycle having no additional substituent; and
Ring C is
(1) a 6-membered monocyclic aromatic heterocycle optionally further substituted by 1 to 3 halogen atoms, or
(2) a benzene ring optionally further substituted by 1 to 3 halogen atoms, or a salt thereof.
2. The compound or salt according to claim 1 , wherein
R 1 is a 3- to 6-membered monocyclic non-aromatic heterocyclic group;
R 2 is
(1) a C 3-10 cycloalkyl-carbonyl group, or
(2) a C 1-6 alkoxy-carbonyl group;
L 1 is an oxygen atom;
L 2 is a methylene group;
Ring A is a piperidine ring having no additional substituent;
Ring B is a piperidine ring having no additional substituent; and
Ring C is a pyrimidine ring optionally further substituted by 1 to 3 halogen atoms.
3. The compound or salt according to claim 1 , wherein
R 1 is a tetrahydrofuryl group;
R 2 is
(1) a cyclobutylcarbonyl group, or
(2) a C 1-6 alkoxy-carbonyl group;
L 1 is an oxygen atom;
L 2 is a methylene group;
Ring A is a piperidine ring having no additional substituent;
Ring B is a piperidine ring having no additional substituent; and
Ring C is a pyrimidine ring optionally further substituted by 1 to 3 halogen atoms.
4. (2S)—N-[cis-1-(Cyclobutanecarbonyl)-2-({[1-(5-fluoropyrimidin-2-yl)piperidin-4-yl]oxy}methyl)piperidin-3-yl]oxolane-2-carboxamide, or a salt thereof.
5. Propan-2-yl cis-3-{[(2S)-oxolane-2-carbonyl]amino}-2-({[1-(pyrimidin-2-yl)piperidin-4-yl]oxy}methyl)piperidine-1-carboxylate, or a salt thereof.
6. Propan-2-yl cis-2-({[1-(5-fluoropyrimidin-2-yl)piperidin-4-yl]oxy}methyl)-3-{[(2S)-oxolane-2-carbonyl]amino}piperidine-1-carboxylate, or a salt thereof.
7. A medicament comprising the compound or salt according to claim 1 .
8. 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.
9. 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.
10. The medicament of claim 7 , further comprising a pharmacologically acceptable carrier.
11. A method for the treatment of idiopathic hypersomnia in a mammal, which comprises administering an effective amount of the compound or salt according to claim 1 to the mammal.