1208102-86-6Relevant articles and documents
Isoxazole analogues bind the System xc- transporter: Structure-activity relationship and pharmacophore model
Patel, Sarjubhai A.,Rajale, Trideep,O'Brien, Erin,Burkhart, David J.,Nelson, Jared K.,Twamley, Brendan,Blumenfeld, Alex,Szabon-Watola, Monika I.,Gerdes, John M.,Bridges, Richard J.,Natale, Nicholas R.
supporting information; experimental part, p. 202 - 213 (2010/04/05)
Analogues of amino methylisoxazole propionic acid (AMPA), were prepared from a common intermediate 12, including lipophilic analogues using lateral metalation and electrophilic quenching, and were evaluated at System xc-. Both the 5-naphthylethyl-(16) and 5-naphthylmethoxymethyl-(17) analogues adopt an E-conformation in the solid state, yet while the former has robust binding at System xc-, the latter is virtually devoid of activity. The most potent analogues were amino acid naphthyl-ACPA 7g, and hydrazone carboxylic acid, 11e Y = Y′ = 3,5-(CF3)2, which both inhibited glutamate uptake by the System xc- transporter with comparable potency to the endogenous substrate cystine, whereas in contrast the closed isoxazolo[3,4-d] pyridazinones 13 have significantly lower activity. A preliminary pharmacophore model has been constructed to provide insight into the analogue structure-activity relationships.
