Derivatives of 3-heteroarylisoxazol-5-carboxylic amide useful for the treatment of inter alia cystic fibrosis

A compound represented by:

• and pharmaceutically acceptable salts, stereoisomers, and prodrugs thereof, wherein;
• X3 is selected from the group consisting of O, S, and NRhh;
• pp is 1, 2, or 3;
• R22 is independently selected for each occurrence from the group consisting of hydrogen, halogen, and C1-4alkyl (optionally substituted by one, two or three halogens);
• R31 is selected from the group consisting of hydrogen, halogen, and C1-4alkyl;
• L1 is selected from the group consisting of C1-6alkylene, C3-6cycloalkylene, C3-6cycloalkylene-C1-4alkylene, C1-3alkylene-NRhh—S(O)w—, —C1-3alkylene-S(O)w—NRhh—, C3-6cycloalkylene-C0-2alkylene-S(O)w—NRhh, and C3-6cycloalkylene-C0-2alkylene NRhh—S(O)w—, wherein L1 may be optionally substituted by one, two or three substituents selected from the group consisting of halogen, hydroxyl, and C1-3alkyl (optionally substituted by one, two or three substituents each selected independently from Rff);
• R44 is selected from the group consisting of heterocycle and a 5-6 membered monocyclic or 8-10 membered bicyclic heteroaryl having one, two or three heteroatoms each selected from O, N, and S;
• wherein the heterocycle and the heteroaryl may be optionally substituted by one or two substituents each selected independently from Rgg;
• Rff is selected for each occurrence from group consisting of halogen, hydroxyl, C1-4alkyl, C1-4alkyoxy, C2-4alkenyl, C3-6cycloalkyl, —NR′R″, —NR′—S(O)w—C1-3alkyl, S(O)w—NR′R″, and —S(O)w—C1-3alkyl, where w is 0, 1, or 2, wherein C1-4alkyl, C1-4alkyoxy, C2-4alkenyl and C3-6cycloalkyl may be optionally substituted by one, two or three substituents each independently selected from the group consisting of halogen, hydroxyl, —NR′R″, —NR′—S(O)w—C1-3alkyl, S(O)w—NR′R″, and —S(O)w—C1-3alkyl;
• Rgg is selected for each occurrence from group consisting of halogen, hydroxyl, C1-6alkyl, C1-6alkyoxy, C2-6alkenyl, C3-6cycloalkyl, —NR′R″, —NR′—S(O)w—C1-3alkyl, S(O)w—NR′R″, —O—Si(R′″)3, and —S(O)w—C1-3alkyl, where w is 0, 1, or 2, wherein C1-6alkyl, C1-6alkyoxy, C2-6alkenyl and C3-6cycloalkyl may each be optionally substituted by one, two or three substituents each independently selected from the group consisting of halogen, C1-6alkyl, C1-6alkoxy, hydroxyl, C(O)OH, —C(O)OC1-6alkyl, —O—C3-6cycloalkyl, —O-heterocycle, —O-heteroaryl, —O— phenyl, —NR′R″, —NR′—S(O)w—C1-3alkyl, —O—Si(R′″)3, S(O)w—NR′R″, and —S(O)w—C1-3alkyl;
• w is 0, 1 or 2;
• Rhh is selected for each occurrence from the group consisting of H, C1-6alkyl, and C3-6cycloalkyl;
• R′ and R″ are selected for each occurrence from the group consisting of H, C1-6alkyl and C3-6cycloalkyl;
• and
• R′″ is selected for each occurrence from C1-6alkyl.