Bridged tetrahydroisoquinolines as selective NADPH oxidase 2 (Nox2) inhibitors

Abstract

(1<i>SR</i>,4<i>RS</i>)-3,3-Dimethyl-1,2,3,4-tetrahydro-1,4-(epiminomethano)naphthalenes were synthesized in 2-3 steps from commercially available materials and assessed for specificity and effectiveness across a range of Nox isoforms. The <i>N</i>-pentyl and <i>N</i>-methylenethiophene substituted analogs 11g and 11h emerged as selective Nox2 inhibitors with cellular IC₅₀ values of 20 and 32 μM, respectively.