title: 2-Amino-3-(phenylsulfanyl)norbornane-2-carboxylate: an appealing scaffold for the design of Rac1-Tiam1 protein-protein interaction inhibitors.
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 was capable of inhibiting smooth muscle cell migration. The synthesis of this derivative was successfully scaled up to 1 g.
authors: Dipartimento di Scienze Farmaceutiche-Sezione di Chimica Generale e Organica "Alessandro Marchesini", Università degli Studi di Milano , Via Venezian 21, 20133 Milano, Italy.
authors: Alessandro
authors: A
authors: Ruffoni
authors: Nicola
authors: N
authors: Ferri
authors: Sergio K
authors: SK
authors: Bernini
authors: Chiara
authors: C
authors: Ricci
authors: Alberto
authors: A
authors: Corsini
authors: Irene
authors: I
authors: Maffucci
authors: Francesca
authors: F
authors: Clerici
authors: Alessandro
authors: A
authors: Contini
mesh_terms: D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004159:Diphenylamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D020662:Guanine Nucleotide Exchange Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D018715:Microscopy, Video; D008958:Models, Molecular; D015394:Molecular Structure; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D009636:Norbornanes / Q000737:chemistry / Q000494:pharmacology*; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D006571:Heterocyclic Compounds; D009636:Norbornanes; C107953:RAC1 protein, human; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C087334:TIAM1 protein, human; C000589310:ethyl 2-amino-6-(3-((4-aminophenyl)amino)phenyl)-3-(phenylsulfanyl)bicyclo(2.2.1)heptane-2-carboxylate; D004159:Diphenylamine; D020830:rac1 GTP-Binding Protein