49609-11-2Relevant academic research and scientific papers
Phenyl ether- and aniline-containing 2-aminoquinolines as potent and selective inhibitors of neuronal nitric oxide synthase
Cinelli, Maris A.,Li, Huiying,Pensa, Anthony V.,Kang, Soosung,Roman, Linda J.,Martásek, Pavel,Poulos, Thomas L.,Silverman, Richard B.
, p. 8694 - 8712 (2015/11/25)
Excess nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) is implicated in neurodegenerative disorders. As a result, inhibition of nNOS and reduction of NO levels is desirable therapeutically, but many nNOS inhibitors are poorly bioavailable. Promising members of our previously reported 2-aminoquinoline class of nNOS inhibitors, although orally bioavailable and brain-penetrant, suffer from unfavorable off-target binding to other CNS receptors, and they resemble known promiscuous binders. Rearranged phenyl ether- and aniline-linked 2-aminoquinoline derivatives were therefore designed to (a) disrupt the promiscuous binding pharmacophore and diminish off-target interactions and (b) preserve potency, isoform selectivity, and cell permeability. A series of these compounds was synthesized and tested against purified nNOS, endothelial NOS (eNOS), and inducible NOS (iNOS) enzymes. One compound, 20, displayed high potency, selectivity, and good human nNOS inhibition, and retained some permeability in a Caco-2 assay. Most promisingly, CNS receptor counterscreening revealed that this rearranged scaffold significantly reduces off-target binding.
Synthesis of 5-, 6- and 7-substituted-2-aminoquinolines as SH3 domain ligands
Inglis, Steven,Jones, Rhiannon,Fritz, Daniel,Stojkoski, Cvetan,Booker, Grant,Pyke, Simon
, p. 2543 - 2557 (2007/10/03)
The Src homology 3 (SH3) domains are small protein-protein interaction domains that mediate a range of important biological processes and are considered valuable targets for the development of therapeutic agents. We have been developing 2-aminoquinolines
