Cystic fibrosis transmembrane conductance regulator (CFTR) modulators, pharmaceutical compositions, and uses thereof

Inventors

Sorscher, Eric • Fu, Haian • Davies, Huw • Hong, Jeong • Du, Yuhong • Rab, Andras • Manfredi, Candela • Yang, Xun • Ren, Zhi

Assignees

Emory University • Children's Healthcare of Atlanta

Abstract

This disclosure relates to compounds that are cystic fibrosis transmembrane conductance regulator (CFTR) modulators and pharmaceutical compositions containing the same. In certain embodiments, this disclosure relates to methods of managing a CFTR related disease or condition or respiratory distress comprising administering an effective amount of a CFTR modulator disclosed herein to a subject in need thereof.

Core Innovation

The disclosure provides CFTR-modulating compounds and compositions, including a specific chemical scaffold family and representative compounds such as 3-(2-bromo-5-methoxyphenyl)-6-isopropyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine and salts thereof. The compounds are positioned as CFTR modulators in a therapeutic framework for managing CFTR-related disease and respiratory distress associated with CFTR mutations.

The disclosure describes use with subjects having CFTR mutations, including W1282X, N1303K, F508del, and G551D. It further includes combination treatment contexts with known CFTR modulators, including ivacaftor, lumacaftor, tezacaftor, and elexacaftor, where some compounds are positioned as co-potentiators to enhance CFTR-mediated chloride transport.

The patent content also includes pharmaceutically acceptable excipients and pharmaceutical composition forms. It includes general scaffold definitions and disclosed chemical formulas I-IV with named exemplars, along with referenced SAR/functional testing and a general synthetic approach.

Claims Coverage

The independent claim covers one specific compound, 3-(2-bromo-5-methoxyphenyl)-6-isopropyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine, or a salt. Dependent claims extend coverage to therapeutic treating methods, pharmaceutical compositions, and combination or co-administration with named CFTR modulator drugs, with inventive features concentrated in the compound identity, the treating purpose, and the co-ingredient composition context.

Overall, the claim coverage is anchored on the defined triazolo-thiadiazine compound or salt, with dependent coverage that shifts from compound identity to treating cystic fibrosis or rhinosinusitis, pharmaceutical compositions using pharmaceutically acceptable carrier, adjuvant, and/or excipient, and combination contexts that include ivacaftor, lumacaftor, tezacaftor, and elexacaftor individually or in combinations.

Stated Advantages

Documented Applications