Heterocyclic compound and application thereof

Patent metadata

Field	Value
Publication number	US-11319286-B2
Application number	US-201816635408-A
Country	US
Kind code	B2
Filing date	Aug 2, 2018
Priority date	Aug 3, 2017
Publication date	May 3, 2022
Grant date	May 3, 2022

Abstract

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.

First claim

The invention claimed is:

1. A compound represented by the formula:

wherein
R 1 is selected from a C 1-6 alkoxy-carbonyl group, a C 1-6 alkyl-carbonyl group optionally substituted by 1 to 3 substituents selected from a halogen atom and a hydroxy group, a C 3-10 cycloalkyl-carbonyl group, a mono- or di-C 1-6 alkyl-carbamoyl group, a 3- to 8-membered non-aromatic heterocyclylcarbonyl group, and a hydrogen atom;
R 2 is C 3-6 cycloalkyl group or a 3- to 6-membered saturated monocyclic non-aromatic heterocyclic group, each optionally substituted by 1 to 3 substituents selected from a C 6-14 aryl group which is further optionally substituted by 1 to 3 substituents selected from a halogen atom, a cyano group, a C 1-6 alkyl group optionally substituted by 1 to 3 halogen atoms, a C 1-6 alkoxy group optionally substituted by 1 to 3 halogen atoms, and a hydroxy group, and a 5- to 6-membered aromatic heterocyclic group optionally substituted by 1 to 3 substituents selected from a halogen atom, a C 1-6 alkyl group, and a C 1-6 alkoxy group;
R 3 is a C 1-6 alkyl group, or a mono- or di-C 1-6 alkylamino group; and
Ring A is an azetidine ring or a pyrrolidine ring, each optionally further substituted with a halogen atom, a cyano group, a nitro group, a C 1-6 alkyl group, a hydroxy group, or a sulfanyl group,
or a salt thereof.

2. The compound or salt according to claim 1 , wherein
R 2 is
(1) a C 3-6 cycloalkyl group optionally substituted by a C 6-14 aryl group group(s) optionally substituted by 1 to 3 optionally halogenated C 1-6 alkyl groups, or
(2) a 3- to 6-membered saturated monocyclic non-aromatic heterocyclic group optionally substituted by 5- to 6-membered aromatic heterocyclic group(s) optionally substituted by 1 to 3 halogen atoms;

R 3 is a C 1-6 alkyl group; and
Ring A is a pyrrolidine ring.

3. The compound or salt according to claim 1 , wherein
R 1 is
(1) an azetidinylcarbonyl group,
(2) a cyclobutylcarbonyl group,
(3) a mono- or di-C 1-6 alkyl-carbamoyl group, or
(4) a C 1-6 alkoxy-carbonyl group;

R 2 is a C 3-6 cycloalkyl group substituted by one C 6-14 aryl group;
R 3 is a C 1-6 alkyl group; and
Ring A is a pyrrolidine ring.

4. The compound or salt according to claim 1 , wherein
R 1 is
(1) an azetidinylcarbonyl group,
(2) a cyclobutylcarbonyl group, or
(3) a mono- or di-C 1-6 alkyl-carbamoyl group;

R 2 is a C 3-6 cycloalkyl group substituted by one C 6-14 aryl group;
R 3 is a C 1-6 alkyl group; and
Ring A is a pyrrolidine ring.

5. N-(cis-1-(Azetidin-1-ylcarbonyl)-2-(((cis-4-phenylcyclohexyl)oxy)methyl)pyrrolidin-3-yl)methanesulfonamide, or a salt thereof.

6. N-(cis-1-(Cyclobutylcarbonyl)-2-(((cis-4-phenylcyclohexyl)oxy)methyl)pyrrolidin-3-yl)methanesulfonamide, or a salt thereof.

7. cis-N,N-Dimethyl-3-((methylsulfonyl)amino)-2-(((cis-4-phenylcyclohexyl)oxy)methyl)pyrrolidine-1-carboxamide, or a salt thereof.

8. A medicament comprising the compound or salt according to claim 1 .

9. 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.

10. 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.

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Fujimoto Tatsuhiko
• Rikimaru Kentaro
• Fukuda Koichiro
• Sugimoto Hiromichi
• Matsumoto Takahiro
• Kajita Yuichi
• Mikami Satoshi
• Miyanohana Yuhei
• Koike Tatsuki
• Daini Masaki
• Ogino Masaki
• Takeuchi Kohei
• Miyazaki Tohru
• Ito Yoshiteru
• Tokunaga Norihito
• Sugimoto Takahiro
• Oda Tsuneo
• Hoashi Yasutaka
• Hattori Yasushi
• Imamura Keisuke

Classifications

• C07D401/14

  containing three or more hetero rings · CPC title

• A61K31/40 Primary

  having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil · CPC title

• C07D403/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• A61K31/506

  not condensed and containing further heterocyclic rings · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title