2-Amino-3-(phenylsulfanyl)norbornane-2-carboxylate: An Appealing Scaffold for the Design of Rac1鈥揟iam1 Protein鈥揚rotein Interaction Inhibitors

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• 作者：Alessandro Ruffoni ; Nicola Ferri ; Sergio K. Bernini ; Chiara Ricci ; Alberto Corsini ; Irene Maffucci ; Francesca Clerici ; Alessandro Contini
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：April 10, 2014
• 年：2014
• 卷：57
• 期：7
• 页码：2953-2962
• 全文大小：551K
• 年卷期：v.57,no.7(April 10, 2014)
• ISSN：1520-4804

文摘

The use of the 2-amino-3-(phenylsulfanyl)norbornane-2-carboxylate scaffold has been exploited for the de novo design of potent Rac1 inhibitors acting as modulators of the protein鈥損rotein interaction between Rac1 and Tiam1. A series of compounds differing in regio- and stereochemistry has been prepared by way of a multistep synthesis based on cycloaddition reactions and Pd chemistry. Pharmacological analyses showed that all the prepared compounds were active and selective for Rac1, and the most effective compound 13 was capable of inhibiting smooth muscle cell migration. The synthesis of this derivative was successfully scaled up to 1 g.