- Discovery of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid diamides that increase CFTR mediated chloride transport.
Discovery of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid diamides that increase CFTR mediated chloride transport.
Bioorganic & medicinal chemistry letters (2005-04-06)
Bradford H Hirth, Shuang Qiao, Lisa M Cuff, Brian M Cochran, Marko J Pregel, Jill S Gregory, Scott F Sneddon, John L Kane
PMID15808474
ABSTRACT
A series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid diamides that increase chloride transport in cells expressing mutant cystic fibrosis transmembrane conductance regulator (CFTR) protein has been identified from our compound library. Analoging efforts and the resulting structure-activity relationships uncovered are detailed. Compound potency was improved over 30-fold from the original lead, yielding several analogs with EC(50) values below 10nM in our cellular chloride transport assay.