SMALL MOLECULE BICYCLIC AND TRICYCLIC CFTR CORRECTORS

摘要

Novel CFTR corrector compounds that are effective in rescuing halide efflux, delF508-CFTR protein processing, and apical functional chloride ion transport in a cell are provided. Also provided are methods for treating protein folding disorders (e.g., cystic fibrosis). The methods include administering a CFTR corrector compound or pharmaceutically acceptable salt or prodrug thereof. Methods of rescuing halide efflux in a cell, correcting a processing defect of a delF508-CFTR protein in a cell, and correcting functional delF508-CFTR chloride channels in a cell are also provided.

主权项

1. A compound of the following formula: or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R1 is substituted or unsubstituted alkyl;R2 is hydrogen or methyl;R3 is hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted aryl;R4 and R5 are each independently selected from the group consisting of hydrogen and methyl; and is a single bond or a double bond.