Quinolinone-carboxamide compounds as 5-HT 4 receptor agonists

• US 8,309,575 B2
• Filed: 05/19/2010
• Issued: 11/13/2012
• Est. Priority Date: 04/07/2004
• Status: Active Grant

• Current Assignee: Theravance Biopharma R&D IP, LLC (Theravance Biopharma, Inc.)
• Original Assignee: Theravance, 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:
  US12/782,915
• Publication Number:
  US 20100285519A1
• Time in Patent Office: 909 Days
• Field of Search: 514/312
• US Class Current: 514/312
• 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
• CPC Class Codes: G01N 33/5088 of vertebrates

Abstract

The invention provides novel quinolinone-carboxamide 5-HT4 receptor agonist compounds of Formula (I). The invention also provides pharmaceutical compositions comprising such compounds, the use such compounds to treat diseases associated with 5-HT4 receptor activity, and processes and intermediates useful for preparing such compounds. Wherein; R¹ is hydrogen, halo, hydroxy, C_1-4 alkyl, or C_1-4 alkoxy; R² is C_3-4 alkyl, or C_3-6cycloalkyl; R³ is hydrogen or C_1-3 alkyl: R⁴ is S(O)₂R⁶ or C(O)R⁷; R⁵ is hydrogen, C_1-3alkyl, C_2-3 alkyl substituted with —OH or C_1-3 alkoxy, or —CH₂-pyrydyl; R⁶ is C_1-3 alkyl; or R⁵ and R⁶ taken together from C_3-4 alkylenyl; and R⁷ is hydrogen, C_1-3alkyl, or pyrydyl; or pharmaceutically-acceptable salt or solvate or stereoisomer thereof.

Claims

1. A method of studying the response of a biological system or sample comprising a 5-HT₄ receptor to a selective 5-HT₄ receptor agonist, the method comprising:

(a) contacting the biological system or sample with a compound of formula (I);

2. The method of claim 1 wherein in the compound of formula (I),

R⁵ is hydrogen, C_1-3alkyl, C_2-3alkyl substituted with —

OH or C_1-3alkoxy, or —

CH₂-pyridyl; and

R⁶ is C_1-3alkyl.

3. The method of claim 2 wherein in the compound of formula (I),

R¹ is hydrogen or halo;

and

R² is C_3-4alkyl.

4. The method of claim 1 wherein the biological system is a cell.

5. The method of claim 1 wherein determining the effect on the biological system or sample is determining the functional potency of the compound on the biological system or sample.