ISOXAZOLE COMPOUNDS AND METHODS FOR THE TREATMENT OF CYSTIC FIBROSIS

摘要

The invention relates to a compound of Formula I and methods of treating cystic fibrosis comprising the step of administering a therapeutically effective amount of a compound of Formula I or II to a patient in need thereof:;

主权项

1. A compound of Formula I: or a pharmaceutically acceptable salt, ester of prodrug thereof; wherein, X is S or O; G1 is absent or selected from —C(O)N(R10)—, —C(S)N(R10)—, —N(R10)—, —C(O)O—, —C(O)—, —C(S)—, —N(R11)C(O)N(R10)—, —S—, —O—, —SO—, —S(O)2—, —S(O)2N(R10)—, —C(S)O— and —C(S)N(R10);
each R10 and R11 is independently selected from hydrogen, halogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aliphatic, substituted aliphatic, aryl, substituted aryl, heterocyclyl, substituted heterocyclyl, heteroaryl, or substituted heteroaryl; each G2 is absent or is selected from a bivalent aliphatic, substituted aliphatic, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aliphatic, substituted aliphatic, aryl, substituted aryl, heterocyclyl, substituted heterocyclyl, heteroaryl, and substituted heteroaryl; G3 is absent or is selected from —N(R10)C(O)—, —N(R10)C(S)—, —OC(O)—, —C(O)—, —C(S)—, —N(R11)C(O)—, —SO—, —S(O)2—, —N(R10)S(O)2—, —OC(S)— and —N(R10)C(S)—; R1 is selected from aryl, substituted aryl, heterocyclyl, substituted heterocyclyl, heteroaryl, and substituted heteroaryl; each R2 and R3 is independently selected from hydrogen, halogen, —OR10, —SR10, —NR10R11, —CF3, —CN, —NO2, —N3, —C(O)OR10, —C(O)R10, —C(O)NR10R11, —S(O)R10, —S(O)NR10, —S(O)2R10, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aliphatic, substituted aliphatic, aryl, substituted aryl, heterocyclyl, substituted heterocyclyl, heteroaryl and substituted heteroaryl; and, n is 0, 1, 2, 3, 4, 5 or 6.