NITROGEN-CONTAINING HETEROCYCLIC COMPOUND AND USE OF SAME

• US 20110178060A1
• Filed: 09/18/2009
• Published: 07/21/2011
• Est. Priority Date: 09/19/2008
• Status: Active Grant

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Takeda Pharmaceutical Company Limited
• Inventors: Sugiyama, Hideyuki, Kamei, Taku, Shirai, Junya, Maezaki, Hironobu
• Granted Patent: US 8,592,454 B2
• Time in Patent Office: Days
• US Class Current: 514/210.18
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 207/14 Nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 211/58 attached in position 4
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 403/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 405/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 409/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 409/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 413/08 : linked by a carbon chain containing alicyclic rings
• CPC Class Codes: C07D 413/14 : containing three or more hetero rings
• CPC Class Codes: C07D 417/08 : linked by a carbon chain containing alicyclic rings

Abstract

The present invention relates to a compound represented by the formula

• wherein ring A is a nitrogen-containing heterocycle;
• ring B is an aromatic ring optionally having substituent(s);
• ring D is an aromatic ring optionally having substituent(s);
• L is a group represented by the formula

• R², R³, R^4a and R^4b are each independently a hydrogen atom, an optionally halogenated C_1-6 alkyl group or an optionally halogenated C_3-6 cycloalkyl group, or R² and R³ are optionally bonded via an alkylene chain or an alkenylene chain, or R^4a and R^4b are optionally bonded via an alkylene chain or an alkenylene chain;
• R¹ is a hydrogen atom or a substituent;
• m and n are each independently an integer of 0 to 5;
• m+n is an integer of 2 to 5; and
• is a single bond or double bond, or a salt thereof; and the like. The compound has a superior tachykinin receptor antagonistic action, and is useful as an agent for the prophylaxis or treatment of various diseases such as lower urinary tract diseases, digestive tract diseases, central neurological disease and the like.

Claims

1. A compound represented by the formula

2. The compound according to claim 1, wherein ring A is a piperidine ring or a pyrrolidine ring.

3. The compound according to claim 1, wherein ring B is a phenyl group optionally having substituent(s) or a pyridyl group optionally having substituent(s).

4. The compound according to claim 1, wherein ring B is a phenyl group optionally having substituent(s) or a thienyl group optionally having substituent(s).

5. The compound according to claim 1, wherein ring D is a phenyl group optionally having substituent(s).

6. The compound according to claim 1, wherein R¹ is a hydrogen atom, a hydrocarbon group optionally having substituent(s), an acyl group, a heterocyclic group optionally having substituent(s), or a group represented by —

NR⁵R⁶ wherein R⁵ and R⁶ are each independently a hydrogen atom, a hydrocarbon group optionally having substituent(s) or an acyl group, or in combination shows an oxygen atom.

7. The compound according to claim 1, wherein R² is a hydrogen atom or a C_1-6 alkyl group.

8. The compound according to claim 1, wherein L is a group represented by the formula

9. The compound according to claim 1, wherein ring D is a 3,5-bis(trifluoromethyl)phenyl group or a 3,5-dichlorophenyl group.

10. Methyl 4-{[(3S,4R)-3-[{[3,5-bis(trifluoromethyl)phenyl](methyl)carbamoyl}(methyl)amino]-4-(4-fluorophenyl)pyrrolidin-1-yl]carbonyl}piperidine-1-carboxylate according to claim 1, or a salt thereof.

11. 1-[(3S,4R)-4-(4-chlorophenyl)-1-{[4-(methylsulfonyl)piperazin-1-yl]carbonyl}pyrrolidin-3-yl]-3-(3,5-dichlorophenyl)-1,3-dimethylurea according to claim 1, or a salt thereof.

12. 1-[3,5-Bis(trifluoromethyl)phenyl]-3-[(3S,4R)-4-(5-fluoropyridin-2-yl)-1-({trans-4-[5-(trifluoromethyl)-1H-tetrazol-1-yl]cyclohexyl}carbonyl)pyrrolidin-3-yl]-1,3-dimethylurea according to claim 1, or a salt thereof.

13. A prodrug of the compound according to claim 1.

14. A medicament comprising the compound according to claim 1 or a prodrug thereof.

15. The medicament according to claim 14, which is an NK1 receptor antagonist.

16. The medicament according to claim 15, which also has an NK2 receptor antagonistic action and/or an NK3 receptor antagonistic action.

17. The medicament according to claim 14, which is an NK2 receptor antagonist.

18. The medicament according to claim 17, which also has an NK1 receptor antagonistic action and/or an NK3 receptor antagonistic action.

19. The medicament according to claim 14, which is an agent for the prophylaxis or treatment of a lower urinary tract disease, a digestive tract disease or a central neurological disease.

20. The medicament according to claim 14, which is an agent for the prophylaxis or treatment of overactive bladder, irritable bowel syndrome, functional dyspepsia, inflammatory bowel disease, gastroesophageal reflux, vomiting, nausea, depression, anxiety neurosis, anxiety, pelvic organ pain or interstitial cystitis.

21. A method for the prophylaxis or treatment of a lower urinary tract disease, a digestive tract disease or a central neurological disease, comprising administering an effective amount of the compound according to claim 1 or a prodrug thereof to a mammal.

22. Use of the compound according to claim 1 or a prodrug thereof for the production of an agent for the prophylaxis or treatment of a lower urinary tract disease, a digestive tract disease or a central neurological disease.