Selective Acetamidine-Based Nitric Oxide Synthase Inhibitors: Synthesis, Docking, and Biological Studies

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• 作者：Cristina Maccallini ; Monica Montagnani ; Roberto Paciotti ; Alessandra Ammazzalorso ; Barbara De Filippis ; Mauro Di Matteo ; Sara Di Silvestre ; Marialuigia Fantacuzzi ; Letizia Giampietro ; Maria A. Potenza ; Nazzareno Re ; Assunta Pandolfi ; Rosa Amoroso
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2015
• 出版时间：June 11, 2015
• 年：2015
• 卷：6
• 期：6
• 页码：635-640
• 全文大小：336K
• ISSN：1948-5875

文摘

N-[(3-Aminomethyl)benzyl]acetamidine derivatives were synthesized and in vitro evaluated as inhibitors of the inducible isoform of nitric oxide synthase (iNOS). Because of the high potency of action and the excellent selectivity over the endothelial nitric oxide synthase (eNOS), compound 10 was ex vivo evaluated on isolated and perfused resistance arteries. The results confirm that compound 10 selectively inhibits the iNOS, without affecting the endothelial isoform. The outcome of the docking studies showed that the hydrophobic interaction is the driving force of the binding process, especially for iNOS, where the binding pocket is characterized by a significant lipophilic region.