Marivingt-Mounir, Cecile published the artcileSynthesis, SAR, Crystal Structure, and Biological Evaluation of Benzoquinoliziniums as Activators of Wild-Type and Mutant Cystic Fibrosis Transmembrane Conductance Regulator Channels, COA of Formula: C9H8Cl2O2, the main research area is benzoquinolizinium preparation cystic fibrosis transmembrane conductance regulator channel activation; benzoindoloquinolizinium preparation cystic fibrosis transmembrane conductance regulator channel activation.
Chloride channels play important roles in homeostasis and regulate cell volume, transepithelial transport, and elec. excitability. Despite recent progress made in the genetic and mol. aspect of chloride channels, their pharmacol. is still poorly understood. The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated epithelial chloride channel for which mutations cause cystic fibrosis. Here we have synthesized benzo[c]quinolizinium, e.g., I, and benzo[f]indolo[2,3-a]quinolizinium salts (MPB), e.g., II, and performed a SAR to identify the structural basis for activation of the CFTR chloride channel. Synthesized compounds were evaluated on wild-type CFTR and on CFTR having the glycine-to-aspartic acid missense mutation at codon 551 (G551D-CFTR), using a robot and cell-based assay. The presence of an hydroxyl group at position 6 of the benzo[c]quinolizinium skeleton associated with a chlorine atom at position 10 or 7 and an alkyl chain at position 5 determined the highest activity. The most potent product is 5-butyl-7-chloro-6-hydroxybenzo[c]quinolizinium chloride (I, MPB-104). I is 100 times more potent than the parent compound III (MPB-07).
Journal of Medicinal Chemistry published new progress about Chloride channels Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 35112-27-7 belongs to class chlorides-buliding-blocks, name is Ethyl 2,5-dichlorobenzoate, and the molecular formula is C9H8Cl2O2, COA of Formula: C9H8Cl2O2.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics