2. Academic Validation
  3. Bridged tetrahydroisoquinolines as selective NADPH oxidase 2 (Nox2) inhibitors

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

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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