Modulators of Cystic Fibrosis Transmembrane Conductance Regulator

A pharmaceutical composition comprising:

• A Compound of Formula I
• or pharmaceutically acceptable salts thereof, wherein:
• ring A is selected from:
• R1 is —CF3, —CN, or —C≡CCH2N(CH3)2;
• R2 is hydrogen, —CH3, —CF3, —OH, or —CH2OH;
• R3 is hydrogen, —CH3, —OCH3, or —CN;
• provided that both R2 and R3 are not simultaneously hydrogen;
• and
• one or both of the following:
• B. A Compound of Formula II
• or pharmaceutically acceptable salts thereof, wherein:
• T is —CH2—, —CH2CH2—, —CF2—, —C(CH3)2—, or —C(O)—;
• R1′ is H, C1-6 aliphatic, halo, CF3, CHF2, O(C1-6 aliphatic);
• and
• RD1 or RD2 is ZDR9
• wherein:
• ZD is a bond, CONH, SO2NH, SO2N(C1-6 alkyl), CH2NHSO2, CH2N(CH3)SO2, CH2NHCO, COO, SO2, or CO;
• and
• R9 is H, C1-6 aliphatic, or aryl;
• and/or
• C. A Compound of Formula III
• or pharmaceutically acceptable salts thereof, wherein:
• R is H, OH, OCH3 or two R taken together form —OCH2O— or —OCF2O—;
• R4 is H or alkyl;
• R5 is H or F;
• R6 is H or CN;
• R7 is H, —CH2CH(OH)CH2OH, —CH2CH2N+(CH3)3, or —CH2CH2OH;
• R8 is H, OH, —CH2CH(OH)CH2OH, —CH2OH, or R7 and R8 taken together form a five membered ring.