Oxazolone and pyrrolidinone-substituted arylamides as p2x3 and p2x 2/3 antagonists

A compound of formula I:

• or a pharmaceutically acceptable salt thereof,
• wherein:
• R1 is:
• C1-6alkyl;
• or
• halo;
• R2 is:
• C1-6cycloalkyl;
• C1-6alkoxy-C1-6alkyl;
• hydroxy-C1-6alkyl;
• or
• heteroaryl-C1-6alkyl;
• R3 is:
• hydrogen;
• halo;
• C1-6alkyl;
• or
• C1-6alkoxy-carbonyl;
• R4 is:
• hydrogen;
• halo;
• C1-6alkyl;
• or R3 and R4 together with the atoms to which they are attached may form a fused 6-membered aromatic ring that optionally includes one or two nitrogens;
• or R3 and R4 together with the atom to which they are attached may form C3-6cycloalkyl;
• R5, R6 and R7 each independently is fluoro or hydrogen.
• X is:
• —CRa− wherein Ra is C1-6alkyl or halo;
• and
• Y is:
• —O—;
• —CHRb—;
• or —NRc—;
• wherein Rb and Rc each independently is hydrogen or C1-6alkyl.

The compound of claim 1, wherein said compound is selected from:

• 4′-Methyl-5-(2-oxo-pyrrolidin-1-yl)-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide;
• 4′-Methyl-5-(2-oxo-imidazolidin-1-yl)-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide;
• 4′-Methyl-5-(2-methyl-5-oxo-pyrrolidin-1-yl)-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide;
• (S)-1-[5-(2-Methoxy-1-methyl-ethylcarbamoyl)-4′-methyl-biphenyl-3-yl]-5-oxo-pyrrolidine-2-carboxylic acid methyl ester;
• 5-((R)-4-Isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid ((S)-2-hydroxy-1-methyl-ethyl)-amide;
• 5-((R)-4-Isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid (1-pyrazin-2-yl-ethyl)-amide;
• 5-((R)-4-Isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid (5-methyl-pyrazin-2-ylmethyl)-amide;
• 5-((R)-4-Isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid cyclopropylamide;
• 5-((S)-4-Isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid cyclopropylamide;
• 5-((S)-4-Isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid
• ((S)-2-hydroxy-1-methyl-ethyl)-amide;
• 5-((S)-4-Isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid (5-methyl-pyrazin-2-ylmethyl)-amide;
• 5-((S)-4-Isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid (1-pyrazin-2-yl-ethyl)-amide;
• 2′-Fluoro-5-((R)-4-isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid ((S)-2-hydroxy-1-methyl-ethyl)-amide;
• 2′-Fluoro-5-((R)-4-isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid (1-pyrazin-2-yl-ethyl)-amide;
• 2′-Fluoro-5-((R)-4-isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid (5-methyl-pyrazin-2-ylmethyl)-amide;
• 2′-Fluoro-5-((R)-4-isopropyl-2-oxo-oxazolidin-3-yl)-4′-methyl-biphenyl-3-carboxylic acid cyclopropylamide;
• 4′-Methyl-5-(2-oxo-benzooxazol-3-yl)-biphenyl-3-carboxylic acid (1-pyrazin-2-yl-ethyl)-amide;
• 4′-Methyl-5-(2-oxo-benzooxazol-3-yl)-biphenyl-3-carboxylic acid (5-methyl-pyrazin-2-ylmethyl)-amide;
• 4′-Methyl-5-(2-oxo-imidazolidin-1-yl)-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide;
• 4′-Methyl-5-(2-oxo-2,3-dihydro-indol-1-yl)-biphenyl-3-carboxylic acid (5-methyl-pyrazin-2-ylmethyl)-amide;
• 4′-Methyl-5-(2-oxo-2,3-dihydro-indol-1-yl)-biphenyl-3-carboxylic acid (1-pyrazin-2-yl-ethyl)-amide;
• and
• 4′-Methyl-5-(8-oxo-7,8-dihydro-purin-9-yl)-biphenyl-3-carboxylic acid ((S)-1-pyrazin-2-yl-ethyl)-amide.