Cyanoquinoline compounds having activity in correcting mutant-CFTR processing and increasing ion transport and uses thereof

摘要

The present disclosure provides pharmaceutical compositions, pharmaceutical preparations and methods for increasing activity of a mutant cystic fibrosis transmembrane conductance regulator protein (mutant-CFTR). The pharmaceutical compositions, pharmaceutical preparations and methods are useful for the study and treatment of disorders associated with mutant-CFTR, such as cystic fibrosis. The pharmaceutical compositions and pharmaceutical preparations may include one or more cyanoquinoline-containing compounds of the embodiments, or an analog or derivative thereof.

主权项

1. A pharmaceutical composition that comprises a compound of formula (I): or salts, solvates, and hydrates thereof, and stereoisomers thereof,wherein:
R1 and R2 are each independently selected from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkoxy, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, heterocyclyl, and substituted heterocyclyl; R3 is selected from alkyl, substituted alkyl, alkylamino, alkylarylamino, aryl, substituted aryl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, heterocyclyl, and substituted heterocyclyl; R4 is an alkyl or substituted alkyl; R5 is optional and, if present, is an alkyl or substituted alkyl; and Y is C or S, with the provisos that:
when Y is C, X is either O or S, and n is 1,when Y is S, X is O, and n is 2, andwherein if R3 is alkyl, then Y is S.