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-protein 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 resulted capable to inhibit smooth muscle cell migration. The synthesis of this derivative was successfully scaled up to 1 gram.

2-Amino-3-(phenylsulfanyl)norbornane-2-carboxylate : an Appealing Scaffold for the Design of Rac1-Tiam1 Protein-Protein Interaction Inhibitors / A. Ruffoni, N. Ferri, S.K. Bernini, C. Ricci, A. Corsini, I. Maffucci, F. Clerici, A. Contini. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 57:7(2014), pp. 2953-2962. [10.1021/jm401924s]

2-Amino-3-(phenylsulfanyl)norbornane-2-carboxylate : an Appealing Scaffold for the Design of Rac1-Tiam1 Protein-Protein Interaction Inhibitors

A. Ruffoni;N. Ferri;C. Ricci;A. Corsini;I. Maffucci;F. Clerici;A. Contini
2014

Abstract

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-protein 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 resulted capable to inhibit smooth muscle cell migration. The synthesis of this derivative was successfully scaled up to 1 gram.
protein-Protein Interaction; rac1; tiam1; drug design; Rho GTPase; cardiovascular disease; palladium chemistry; norbornane
Settore CHIM/06 - Chimica Organica
Settore BIO/14 - Farmacologia
Settore CHIM/08 - Chimica Farmaceutica
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/235494
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