Triazolopyridine compounds and methods for the treatment of cystic fibrosis

A compound of Formula II or IIA:

• or a pharmaceutically acceptable salt, ester or prodrug thereof;
• wherein represents a single or double bond;
• each n, m, p and q is independently selected from 0, 1, 2 and 3;
• Cy1 is selected from heteroaryl, substituted heteroaryl, heterocyclic and substituted heterocyclic;
• each R1, R2, and R3 is selected from hydrogen, halogen, alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aliphatic, substituted aliphatic, aryl and substituted aryl, —OR100, —NR100R101, —C(O)R100, —C(O)OR100, —C(O)NR100R101, —N(R100)C(O)R101, —S(O)2R100, —S(O)R100, —SR100, —S(O)2N(R100)R101, —CF3, —CN, —NO2, —N3;
• alternatively two R1 and R2 groups or two R3 groups or an R100 and an R101 group together with the atoms to which they are attached and any intervening atoms may form an additional optionally substituted, 3, 4, 5, 6 or 7 membered ring;
• each R5 and R6 is independently selected from hydrogen, halogen, alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aliphatic, substituted aliphatic, aryl and substituted aryl;
• alternatively, R5 and R6 groups together with the atoms to which they are attached and any intervening atoms may form an additional optionally substituted, 3, 4, 5, 6 or 7 membered ring;
• alternatively, two R1 groups or two R2 groups together may form an oxo, vinyl or substituted vinyl group;
• and,
• each R100 and R101 is selected from hydrogen, halogen, alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aliphatic, substituted aliphatic, aryl and substituted aryl.

A compound of Formula III or IIIA:

• or a pharmaceutically acceptable salt, ester or prodrug thereof;
• wherein represents a single or double bond;
• each n, m, p and q is independently selected from 0, 1, 2 and 3;
• r is 1, 2 or 3;
• Cy1 is selected from heteroaryl, substituted heteroaryl, heterocyclic and substituted heterocyclic;
• Cy2 is selected from aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, substituted heterocyclic, carbocyclic and substituted carbocyclic;
• L1 is a absent or a linker;
• preferably an alkyl or substituted alkyl, aryl or substituted aryl;
• each R1, R2, and R3 is selected from hydrogen, halogen, alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aliphatic, substituted aliphatic, aryl and substituted aryl, —OR100, —NR100R101, —C(O)R100, —C(O)OR100, —C(O)NR100R101, —N(R100)C(O)R101, —S(O)2R100, —S(O)R100, —SR100, —S(O)2N(R100)R101, —CF3, —CN, —NO2, —N3;
• alternatively two R1 and R2 groups or two R3 groups or an R100 and an Run group together with the atoms to which they are attached and any intervening atoms may form an additional optionally substituted, 3, 4, 5, 6 or 7 membered ring;
• alternatively, two R1 groups or two R2 groups together may form an oxo, vinyl or substituted vinyl group;
• R5 is selected from hydrogen, halogen, alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aliphatic, substituted aliphatic, aryl and substituted aryl;
• each R100 and R101 is selected from hydrogen, halogen, alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aliphatic, substituted aliphatic, aryl and substituted aryl.

A compound of Formula IV or IVA:

• or a pharmaceutically acceptable salt, ester or prodrug thereof;
• wherein represents a single or double bond;
• each n, m, p and q is independently selected from 0, 1, 2 and 3;
• r is 1, 2 or 3;
• Cy2 is selected from aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, substituted heterocyclic, carbocyclic and substituted carbocyclic;
• L1 is a absent or a linker;
• preferably an alkyl or substituted alkyl;
• aryl or substituted aryl
• each R1, R2, and R3 is selected from hydrogen, halogen, alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aliphatic, substituted aliphatic, aryl and substituted aryl, —OR100, —NR100R101, —C(O)R100, —C(O)OR100, —C(O)NR100R101, —N(R100)C(O)R101, —S(O)2R100, —S(O)R100, —SR100, —S(O)2N(R100)R101, —CF3, —CN, —NO2, —N3;
• alternatively two R1 and R2 groups or two R3 groups or an R100 and an R101 group together with the atoms to which they are attached and any intervening atoms may form an additional optionally substituted, 3, 4, 5, 6 or 7 membered ring;
• alternatively, two R1 groups or two R2 groups together may form an oxo, vinyl or substituted vinyl group;
• R5 is selected from hydrogen, halogen, alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aliphatic, substituted aliphatic, aryl and substituted aryl;
• and,
• each R100 and R101 is selected from hydrogen, halogen, alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aliphatic, substituted aliphatic, aryl and substituted aryl.

A compound of Formula V or VA:

• or a pharmaceutically acceptable salt, ester or prodrug thereof;
• wherein represents a single or double bond;
• each n, m, p and q is independently selected from 0, 1, 2 and 3;
• r is 1, 2 or 3;
• Cy2 is selected from aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, substituted heterocyclic, carbocyclic and substituted carbocyclic;
• L1 is a absent or a linker;
• preferably an alkyl or substituted alkyl, aryl or substituted aryl;
• each R2, and R3 is selected from hydrogen, halogen, alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aliphatic, substituted aliphatic, aryl and substituted aryl, —OR100, —NR100R101, —C(O)R100, —C(O)OR100, —C(O)NR100R101, —N(R100)C(O)R101, —S(O)2R100, —S(O)R100, —SR100, —S(O)2N(R100)R101, —CF3, —CN, —NO2, —N3;
• alternatively two R2 groups or two R3 groups or an R100 and an R101 group together with the atoms to which they are attached and any intervening atoms may form an additional optionally substituted, 3, 4, 5, 6 or 7 membered ring;
• alternatively, two R1 groups or two R2 groups together may form an oxo, vinyl or substituted vinyl group;
• R5 is selected from hydrogen, halogen, alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aliphatic, substituted aliphatic, aryl and substituted aryl;
• and,
• each R100 and R101 is selected from hydrogen, halogen, alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aliphatic, substituted aliphatic, aryl and substituted aryl.

A compound of Formula VI or VIA:

• or a pharmaceutically acceptable salt, ester or prodrug thereof;
• wherein represents a single or double bond;
• each m, p and r is independently selected from 0, 1, 2 and 3;
• L1 is a absent or a linker;
• preferably an alkyl or substituted alkyl, aryl or substituted aryl
• Cy2 is selected from aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, substituted heterocyclic, carbocyclic and substituted carbocyclic;
• each R1, R2, R3, and R7 is selected from hydrogen, halogen, alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aliphatic, substituted aliphatic, aryl and substituted aryl, —OR100, —NR100R101, —C(O)R100, —C(O)OR100, —C(O)NR100R101, —N(R100)C(O)R101, —S(O)2R100, —S(O)R100, —SR100, —S(O)2N(R100)R101, —CF3, —CN, —NO2, —N3;
• alternatively two R1 and R2 groups or two R3 groups, or two R7 groups or an R100 and an R101 group together with the atoms to which they are attached and any intervening atoms may form an additional optionally substituted, 3, 4, 5, 6 or 7 membered ring;
• alternatively, two R1 groups, or two R2 groups, or two R7 groups together may form an oxo, vinyl or substituted vinyl group;
• and,
• each R100 and R101 is selected from hydrogen, halogen, alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aliphatic, substituted aliphatic, aryl and substituted aryl.