Quinolinone-carboxamide compounds as 5-HT4, receptor agonists
AssigneeTheravance, Inc.
InventorsDaniel Marquess, Paul R. Fatheree, S. Derek Turner, Daniel D. Long, Seok-Ki Choi, Adam A. Goldblum, Daniel Genov
Life of this patent
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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.
Claims20
1-23. (canceled)
A method of treating chronic constipation in a mammal, the method comprising administering to the mammal a compound of formula (I):
- wherein:
- R1 is hydrogen, halo, hydroxy, C1-4alkyl, or C1-4alkoxy;
- R2 is C3-4alkyl, or C3-6cycloalkyl;
- R3 is hydrogen or C1-3alkyl;
- R4 is —S(O)2R6 or —C(O)R7;
- R5 is hydrogen, C1-3alkyl, C2-3alkyl substituted with —OH or C1-3alkoxy, or —H2-pyridyl;
- R6 is C1-3alkyl;
- or, R5 and R6 taken together form C3-4alkylenyl;
- and
- R7 is hydrogen, C1-3alkyl, or pyridyl;
- or a pharmaceutically-acceptable salt or stereoisomer thereof.
A method of treating constipation-predominant irritable bowel syndrome in a mammal, the method comprising administering to the mammal a compound of formula (I):
- wherein:
- R1 is hydrogen, halo, hydroxy, C1-4alkyl, or C1-4alkoxy;
- R2 is C3-4alkyl, or C3-6cycloalkyl;
- R3 is hydrogen or C1-3alkyl;
- R4 is —S(O)2R6 or —C(O)R7;
- R5 is hydrogen, C1-3alkyl, C2-3alkyl substituted with —OH or C1-3alkoxy, or —CH2-pyridyl;
- R6 is C1-3alkyl;
- or, R5 and R6 taken together form C3-4alkylenyl;
- and
- R7 is hydrogen, C1-3alkyl, or pyridyl;
- or a pharmaceutically-acceptable salt or stereoisomer thereof.
A method of treating functional dyspepsia in a mammal, the method comprising administering to the mammal a compound of formula (I):
- wherein:
- R1 is hydrogen, halo, hydroxy, C1-4alkyl, or C1-4alkoxy;
- R2 is C3-4alkyl, or C3-6cycloalkyl;
- R3 is hydrogen or C1-3alkyl;
- R4 is —S(O)2R6 or —C(O)R7;
- R5 is hydrogen, C1-3alkyl, C2-3alkyl substituted with —OH or C1-3alkoxy, or —CH2-pyridyl;
- R6 is C1-3alkyl;
- or, R5 and R6 taken together form C3-4alkylenyl;
- and
- R7 is hydrogen, C1-3alkyl, or pyridyl;
- or a pharmaceutically-acceptable salt or stereoisomer thereof.
A method of treating gastroparesis in a mammal, the method comprising administering to the mammal a compound of formula (I):
- wherein:
- R1 is hydrogen, halo, hydroxy, C1-4alkyl, or C1-4alkoxy;
- R2 is C3-4alkyl, or C3-6cycloalkyl;
- R3 is hydrogen or C1-3alkyl;
- R4 is —S(O)2R6 or —C(O)R7;
- R5 is hydrogen, C1-3alkyl, C2-3alkyl substituted with —OH or C1-3alkoxy, or —CH2-pyridyl;
- R6 is C1-3alkyl;
- or, R5 and R6 taken together form C3-4alkylenyl;
- and
- R7 is hydrogen, C1-3alkyl, or pyridyl;
- or a pharmaceutically-acceptable salt or stereoisomer thereof.
A method of treating a mammal having a disease or medical condition mediated by treatment with a 5-HT4 receptor agonist, wherein the disease or medical condition is chronic constipation, constipation-predominant irritable bowel syndrome, functional dyspepsia, gastroparesis, gastroesophageal reflux disease, or drug-induced delayed transit, the method comprising administering to the mammal, a pharmaceutical composition comprising a pharmaceutically-acceptable carrier and a compound of formula (I):
- wherein:
- R1 is hydrogen, halo, hydroxy, C1-4alkyl, or C1-4alkoxy;
- R2 is C3-4alkyl, or C3-6cycloalkyl;
- R3 is hydrogen or C1-3alkyl;
- R4 is —S(O)2R6 or —(O)R7;
- R5 is hydrogen, C1-3alkyl, C2-3alkyl substituted with —H or C1-3alkoxy, or —CH2-pyridyl;
- R6 is C1-3alkyl;
- or, R5 and R6 taken together form C3-4alkylenyl;
- and
- R7 is hydrogen, C1-3alkyl, or pyridyl;
- or a pharmaceutically-acceptable salt or stereoisomer thereof.
Dependencies are inferred from the claim text.