Indole derivative or pharmaceutically acceptable salt thereof

• US 8,680,120 B2
• Filed: 07/26/2010
• Issued: 03/25/2014
• Est. Priority Date: 07/27/2009
• Status: Active Grant

• Current Assignee: Kissei Pharmaceutical Company Limited
• Original Assignee: Kissei Pharmaceutical Company Limited
• Inventors: Tatani, Kazuya, Kawamura, Naohiro, Kondo, Tatsuhiro, Kondo, Atsushi
• Primary Examiner(s): Otton, Alicia L
• Application Number:
  US13/387,266
• Publication Number:
  US 20120129890A1
• Time in Patent Office: 1,338 Days
• Field of Search: None
• US Class Current: 514/333
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• 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 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 209/08 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 209/10 with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 209/12 Radicals substituted by oxygen atoms
• 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 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 405/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• 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 409/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 413/14 : containing three or more hetero rings
• CPC Class Codes: C07D 417/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 417/14 : containing three or more hetero rings

Abstract

A compound (I) of the present invention, which has an EP₁ receptor antagonism:

• • [wherein A represents a benzene ring or the like; Y¹ represents a C_1-6 alkylene group; Y² represents a single bond or the like; R¹ represents a hydrogen atom, a C_1-6 alkyl group or the like; R² represents a phenyl group which may have a substituent, a 5-membered aromatic heterocyclic ring which may have a substituent, a 6-membered aromatic heterocyclic ring which may have a substituent or the like; R³ represents a halogen atom, a C_1-6 alkoxy group or the like; R⁴ represents a hydrogen atom or the like; and R⁵ represents a hydrogen atom or the like] or a pharmaceutically acceptable salt thereof is provided. Furthermore, the compound (I) of the present invention can be used as an agent for treating or preventing LUTS, in particular, various symptoms of OABs.

Claims

1. A compound represented by the general formula (I) or a pharmaceutically acceptable salt thereof:

2. The compound as claimed in claim 1 or a pharmaceutically acceptable salt thereof, wherein R² is a group selected from the group consisting of the following a) to d):

a) a branched C_3-6 alkyl group,

b) a C_3-6 cycloalkyl group,

c) a phenyl group, and

d) a 5-membered aromatic;

R⁴ is a hydrogen atom or a halogen atom; and

R⁵ is a hydrogen atom.

3. The compound as claimed in claim 1 or a pharmaceutically acceptable salt thereof, wherein R³ is a methoxy group.

4. The compound as claimed in claim 1 or a pharmaceutically acceptable salt thereof, wherein R³ is a fluorine atom.

5. The compound as claimed in claim 1 or a pharmaceutically acceptable salt thereof, wherein R² is an isopropyl group, an isobutyl group, a sec-butyl group or a 1-ethylpropyl group.

6. The compound as claimed in claim 1 or a pharmaceutically acceptable salt thereof, wherein R² is a phenyl group or a 5-membered aromatic heterocyclic group.

7. The compound as claimed in claim 6 or a pharmaceutically acceptable salt thereof, wherein R² is a phenyl group, a 3-thienyl group or a 3-furyl group.

8. The compound as claimed in claim 1 or a pharmaceutically acceptable salt thereof, wherein R² is a group selected from the group consisting of the following a) to c):

9. A pharmaceutical composition comprising the compound as claimed in claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

10. A method for treating lower urinary tract symptoms, selected from the group consisting of urinary urgency, increased daytime frequency, nocturia, urinary incontinence and bladder sensation, comprising administering an effective amount of the compound as claimed in claim 1 or a pharmaceutically acceptable salt thereof.