Compounds and compositions for the treatment of cystic fibrosis

A pharmaceutical composition comprising a compound of formula (Ia):

• or pharmaceutically acceptable salts, hydrates, solvates, clathrates, polymorphs, stereoisomers thereof wherein:
• R1 and R2 are independently selected from the group consisting of hydrogen, C1-4alkyl, hydroxyC1-4alkyl, and C1-6alkyl-O—C1-6alkyl;
• R3 is selected from the group consisting of C1-6alkyl, haloC1-6alkyl, OH, O—C1-6alkyl, C1-6alkyl-O—C1-6alkyl, CN, NO2 and halogen;
• R4 is independently selected from the group consisting of C1-6alkyl, haloC1-6alkyl and halogen;
• A is selected from the group consisting of S, SO, and SO2;
• B is selected from the group consisting of CRivRv, O, and NRii;
• C is selected from the group consisting of C1-6alkyl, haloC1-6alkyl, C3-6cycloalkyl optionally substituted with one or more R5, C3-6heterocycloalkyl optionally substituted with one or more R5, aryl optionally substituted with one or more R5, heteroaryl optionally substituted with one or more R5, C1-6alkyl-O—C1-6alkyl, C1-6alkyl-O-aryl, C1-6alkyl-O-heteroaryl, C1-6alkyl-O—C3-6heterocycloalkyl, aryl-O-aryl, and aryl-O-heteroaryl;
• R5 is selected from the group consisting of C1-6alkyl, haloC1-6alkyl, O—C1-6alkyl, C3-6cycloalkyl, C3-6heterocycloalkyl, aryl, heteroaryl, O-aryl, O-aryl-O—C1-6alkyl, O-heteroaryl, O—C3-6heterocycloalkyl, O-haloC1-6alkyl, OH, CN, NO2, SF6, halogen and COORi;
• n is an integer comprised from 0 to 2;
• m is an integer comprised from 0 to 2;
• Ri is independently selected from the group consisting of hydrogen and C1-6alkyl;
• Rii is independently selected from the group consisting of hydrogen and C1-6alkyl;
• Riv and Rv are independently selected from the group consisting of hydrogen, C1-6alkyl and hydroxyC1-6alkyl;
• and at least a pharmaceutically acceptable excipient.

A method for treating a disease or modulating protein or protein activities, the method comprising administering to a subject in need thereof a compound of formula (Ia)

• or pharmaceutically acceptable salts, hydrates, solvates, clathrates, polymorphs, stereoisomers thereof wherein:
• R1 and R2 are independently selected from the group consisting of hydrogen, C1-4alkyl, hydroxyC1-4alkyl, and C1-6alkyl-O—C1-6alkyl;
• R3 is selected from the group consisting of C1-6alkyl, haloC1-6alkyl, OH, O—C1-6alkyl, C1-6alkyl-O—C1-6alkyl, CN, NO2 and halogen;
• R4 is independently selected from the group consisting of C1-6alkyl, haloC1-6alkyl and halogen;
• A is selected from the group consisting of S, SO, and SO2;
• B is selected from the group consisting of CRivRv, O, and NRii;
• C is selected from the group consisting of C1-6alkyl, haloC1-6alkyl, C3-6cycloalky optionally substituted with one or more R5, C3-6heterocycloalkyl optionally substituted with one or more R5, aryl optionally substituted with one or more R5, heteroaryl optionally substituted with one or more R5, C1-6alkyl-O—C1-6alkyl, C1-6alkyl-O-aryl, C1-6alkyl-O-heteroaryl, C1-6alkyl-O-C3heterocycloalkyl, aryl-O-aryl, and aryl-O-heteroaryl;
• R5 is selected from the group consisting of C1-6alkyl, haloC1-6alkyl, O—C1-6alkyl, C3-6cycloalkyl, C3-6heterocycloalkyl, aryl, heteroaryl, O-aryl, O-aryl-O—C1-6alkyl, O-heteroaryl, O—C3-6heterocycloalkyl, O-haloC1-6alkyl, OH, CN, NO2, SF6, halogen and COORi;
• n is an integer comprised from 0 to 2;
• m is an integer comprised from 0 to 2;
• Ri is independently selected from the group consisting of hydrogen and C1-6alkyl;
• Rii is independently selected from the group consisting of hydrogen and C1-6alkyl;
• Riv and Rv are independently selected from the group consisting of hydrogen, C1-6alkyl and hydroxyC1-6alkyl.