COMPOUNDS, COMPOSITIONS AND THEIR METHODS OF USE

Abstract

The present invention relates to compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein X1 and X2 are each -C(H)=, -C(R4)=, or -N=; L1 is a bond or -C(=O)-; L2 is an optionally substituted C4-8 alkylene chain, wherein 1-3 methylene units are optionally replaced with -O- or -N(H)-, and wherein L2 is optionally substituted with 1-4 halogen instances; M is =O or =N(H); W is selected from the group consisting of -N(H)-, among others; each R1 is independently selected from the group consisting of H, halogen, optionally substituted C1-5 alkyl, and optionally substituted -O-C1-8 alkyl, wherein the -O-C1-8 alkyl is optionally substituted with 1-3 halogen instances; Each R3 and R4 is H, halogen, or optionally a substituted C1-3 alkyl; m is selected from the group consisting of 1, 2, 3, 4, and 5; n is selected from the group consisting of 1, 2, 3, and 4; and p is 1 or 2.The compound is selected from: 6-[3-(3,3-dimethylbutoxy)phenyl]-2lambda6,5-dithia-3,20,25,26tetrazatetracyclo[19.3.1.14,7.08,13]hexacose-1(25),4(26),6,8,10,12,21,23-octaene 2,2-dioxide; 6-[3-(3,3-dimethylbutoxy)phenyl]-14-oxa-2lambda 6,5-dithia-3,20,25,26-tetrazatetracyclo[19.3.1.14,7.08,13]hexacose-1(25),4(26),6,8,10,12,21,23-octaene 2,2-dioxide; among others. The invention also relates to a pharmaceutical composition comprising the compound, together with one or more pharmaceutically acceptable excipients or carriers. The compound or pharmaceutical composition enables the treatment of deficient activity of the cystic fibrosis transmembrane conductance regulator (CFTR) in a cell, as well as a CFTR-mediated condition and / or disease, where the disease or condition is selected from cystic fibrosis, asthma, smoking-induced COPD, chronic bronchitis, among others.