桥连四氢异喹啉类作为选择性NADPH氧化酶2（Nox2）抑制剂。
Bridged tetrahydroisoquinolines as selective NADPH oxidase 2 (Nox2) inhibitors.
作者信息
Cifuentes-Pagano Eugenia, Saha Jaideep, Csányi Gábor, Ghouleh Imad Al, Sahoo Sanghamitra, Rodríguez Andrés, Wipf Peter, Pagano Patrick J, Skoda Erin M
机构信息
Vascular Medicine Institute, Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
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.
出版信息
Medchemcomm. 2013 Jul;4(7):1085-1092. doi: 10.1039/C3MD00061C.
Abstract
(1,4)-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 -pentyl and -methylenethiophene substituted analogs 11g and 11h emerged as selective Nox2 inhibitors with cellular IC values of 20 and 32 μM, respectively.
摘要
（1,4）-3,3-二甲基-1,2,3,4-四氢-1,4-（环氧亚甲基）萘可由市售原料经2至3步合成，并针对一系列Nox亚型评估其特异性和有效性。戊基和亚甲基噻吩取代的类似物11g和11h成为选择性Nox2抑制剂，细胞IC值分别为20和32μM。
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2
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Chem Biol. 2012 Jun 22;19(6):752-63. doi: 10.1016/j.chembiol.2012.04.015.
3
Oxidative stress, Noxs, and hypertension: experimental evidence and clinical controversies.
Ann Med. 2012 Jun;44 Suppl 1:S2-16. doi: 10.3109/07853890.2011.653393.
4
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Cell Mol Life Sci. 2012 Jul;69(14):2315-25. doi: 10.1007/s00018-012-1009-2. Epub 2012 May 15.
5
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