Quinolinone-carboxamide compounds as 5-HT;receptor agonists

• US 8,962,653 B2
• Filed: 10/01/2013
• Issued: 02/24/2015
• Est. Priority Date: 04/07/2004
• Status: Active Grant

• Current Assignee: Theravance Biopharma R&D IP, LLC (Theravance Biopharma, Inc.)
• Original Assignee: Theravance Biopharma R&D IP, LLC (Theravance Biopharma, Inc.)
• Inventors: Marquess, Daniel, Fatheree, Paul R., Turner, S. Derek, Long, Daniel D., Choi, Seok-Ki, Goldblum, Adam A., Genov, Daniel
• Primary Examiner(s): Rahmani, Niloofar
• Application Number:
  US14/043,585
• Publication Number:
  US 20140163063A1
• Time in Patent Office: 511 Days
• Field of Search: 514/304, 546/124, 546/126
• US Class Current: 514/304
• 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 1/10 Laxatives
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/28 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 Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 451/02 containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
• CPC Class Codes: C07D 451/04 with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system

Abstract

The invention provides novel quinolinone-carboxamide 5-HT₄ receptor agonist compounds. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with 5-HT₄ receptor activity, and processes and intermediates useful for preparing such compounds.

Claims

1. A compound of formula (II):

2. The compound of claim 1 wherein R⁵ is hydrogen, C_1-3alkyl, or —

CH₂-pyridyl; and

R⁶ is C_1-3alkyl.

3. The compound of claim 2 wherein R³ is hydrogen.

4. The compound of claim 2 wherein R⁴ is —

S(O)₂R⁶.

5. The compound of claim 2 wherein R⁵ is hydrogen or C_1-3alkyl.

6. The compound of claim 2 wherein

R³ is hydrogen;

R⁴ is —

S(O)₂R⁶;

R⁵ is hydrogen or methyl; and

R⁶ is methyl.

7. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

9. A method of treating a disorder of reduced motility of the gastrointestinal tract in a mammal, the method comprising administering to the mammal, a pharmaceutical composition comprising a pharmaceutically-acceptable carrier and a compound of claim 1.

10. The method of claim 9, wherein the disorder of reduced motility is chronic constipation, constipation-predominant irritable bowel syndrome, diabetic gastroparesis, drug-induced delayed transit, or functional dyspepsia.

11. A method of treating gastroparesis in a mammal, the method comprising administering to the mammal, a pharmaceutical composition comprising a pharmaceutically-acceptable carrier and a compound of claim 1.

8. A process for preparing a compound of formula (II′

),