Pyrrolopyrimidines as CFTR potentiators

A pharmaceutical composition comprising a therapeutically effective amount of one or more of a compound of Formula I or a pharmaceutically acceptable salt thereof, one or more additional therapeutic agents, and a pharmaceutically acceptable carrier,

• wherein
• W is selected from the group consisting of phenyl, which is optionally fused with a five to six membered cycloalkyl or a five to six membered heterocycloalkyl comprising one, two, three, or four heteroatoms selected independently for each occurrence from the group consisting of N, O and S(O)n;
• a five to ten membered heteroaryl comprising one, two, three, or four heteroatoms selected independently for each occurrence from the group consisting of N, O and S(O)n;
• a four to seven membered heterocycloalkyl comprising one, two, three, or four heteroatoms selected independently for each occurrence from the group consisting of N, O and S(O)n;
• and
• C3-C7 cycloalkyl;
• wherein the phenyl, five to ten membered heteroaryl, four to seven membered heterocycloalkyl, and C3-C7 cycloalkyl are optionally substituted with one, two, three, four, or five R5;
• Y is a five membered heteroaryl comprising one, two, three, or four heteroatoms selected independently for each occurrence from the group consisting of N, O and S(O)n, wherein the five membered heteroaryl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, C1-C6alkyl, and C1-C6 haloalkyl;
• Z is selected from the group consisting of phenyl, C1-C6 alkyl, C3-C7 cycloalkyl, a five or six membered heteroaryl comprising one, two or three heteroatoms selected independently for each occurrence from the group consisting of N, O and S(O)n, and a four to seven membered heterocycloalkyl comprising one, two, or three heteroatoms selected independently for each occurrence from the group consisting of N, O and S(O)n;
• wherein the phenyl, C1-C6 alkyl, C3-C7 cycloalkyl, five or six membered heteroaryl, and four to seven membered heterocycloalkyl are each independently optionally substituted with one, two, three, four, or five R6;
• R1a and R1b are each independently selected from the group consisting of —H, —OH, halo, C1-C6 alkyl, C3-C7 cycloalkyl, and a four to seven membered heterocycloalkyl comprising one, two, or three heteroatoms each independently selected from the group consisting of N, O and S(O)n, wherein the C1-C6 alkyl group is optionally substituted with one, two, or three substituents each independently selected from the group consisting of halo, —OH, C1-C3 alkyoxy, C3-C7 cycloalkyl, and a four to seven membered heterocycloalkyl comprising one, two, or three heteroatoms each independently selected from the group consisting of N, O and S(O)n;
• and wherein each C3-C7 cycloalkyl and each four to seven membered heterocycloalkyl are optionally substituted with one, two or three substituents independently selected for each occurrence from the group consisting of —OH, halo, and C1-C6 alkyl;
• or R1a and R1b taken together with the carbon to which they are attached form a C3-C7 cycloalkyl or a four to seven membered heterocycloalkyl comprising one, two, or three heteroatoms each independently selected from the group consisting of N, O and S(O)n;
• and wherein the C3-C7 cycloalkyl and the four to seven membered heterocycloalkyl are each optionally substituted with one, two or three substituents each independently selected from the group consisting of —OH, halo, and C1-C6 alkyl;
• R2 is selected from the group consisting of —H, halo, —CN, C1-C6 alkyl and C1-C6 haloalkyl;
• R3 and R4 are independently selected for each occurrence from the group consisting of —H, C1-C6 alkyl and C1-C6 haloalkyl;
• R5 at each occurrence is independently selected from the group consisting of halo, —CN, C1-C6 alkyl, C1-C6haloalkyl, —OR7, —N(R7)2, —N(R7)C(O)R7, —SR7, oxo, C2-C7 alkoxyalkyl, —S(O)2 C1-C6 alkyl, —C(O)R7, and a five membered heteroaryl comprising one, two, three, or four heteroatoms selected independently for each occurrence from the group consisting of N, O and S(O)n, wherein the five membered heteroaryl is optionally substituted with one, two, or three substituents independently selected for each occurrence from the group consisting of halo, —CN, C1-C6 alkyl, C1-C6 haloalkyl, —OR7, —N(R7)2 and —SR7;
• R6 at each occurrence is independently selected from the group consisting of halo, C1-C6 alkyl and C1-C6 haloalkyl, —OR7, —N(R7)2 and —SR7;
• R7 is independently selected for each occurrence from the group consisting of —H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, and C1-C6 alkylC3-C7 cycloalkyl;
• and
• n at each occurrence is independently 0, 1, or 2, or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier.