Bridged tetrahydroisoquinolines as selective NADPH oxidase 2 (Nox2) inhibitors.
(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. TheN-pentyl andN-methylenethiophene substituted analogs 11g and 11h emerged as selective Nox2 inhibitors with cellular IC50values of 20 and 32 μM, respectively.
Vascular Medicine Institute, Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Eugenia
E
Cifuentes-Pagano
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.
Jaideep
J
Saha
Vascular Medicine Institute, Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Gábor
G
Csányi
Vascular Medicine Institute, Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Imad Al
IA
Ghouleh
Vascular Medicine Institute, Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Sanghamitra
S
Sahoo
Vascular Medicine Institute, Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Andrés
A
Rodríguez
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.
Peter
P
Wipf
Vascular Medicine Institute, Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA ; pagano@pitt.edu.
Patrick J
PJ
Pagano
Center for Chemical Methodologies and Library Development, Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15261, USA ; emf53@pitt.edu.
Erin M
EM
Skoda