Bridged tetrahydroisoquinolines as selective NADPH oxidase 2 (Nox2) inhibitors

  • Medchemcomm. 2013 Jul;4(7):1085-1092. doi: 10.1039/C3MD00061C.
Eugenia Cifuentes-Pagano  1 ,  Jaideep Saha  2 ,  Gábor Csányi  1 ,  Imad Al Ghouleh  1 ,  Sanghamitra Sahoo  1 ,  Andrés Rodríguez  1 ,  Peter Wipf  3 ,  Patrick J Pagano  4 ,  Erin M Skoda  5
Affiliations
  • 1. Vascular Medicine Institute, Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
  • 2. Vascular Medicine Institute, Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA ; Center for Chemical Methodologies and Library Development, Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15261, USA.
  • 3. Center for Chemical Methodologies and Library Development, Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15261, USA ; Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
  • 4. Vascular Medicine Institute, Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA ; [email protected].
  • 5. Center for Chemical Methodologies and Library Development, Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15261, USA ; [email protected].
PMID: 24466406 DOI: 10.1039/C3MD00061C
Abstract

(1SR,4RS)-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 N-pentyl and N-methylenethiophene substituted analogs 11g and 11h emerged as selective NOX2 inhibitors with cellular IC50 values of 20 and 32 μM, respectively.

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