Giorgio Bonanomi
GlaxoSmithKline
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Publication
Featured researches published by Giorgio Bonanomi.
Journal of Medicinal Chemistry | 2010
Fabrizio Micheli; Paolo Cavanni; Daniele Andreotti; Roberto Arban; Roberto Benedetti; Barbara Bertani; Michela Bettati; Letizia Bettelini; Giorgio Bonanomi; Simone Braggio; Renzo Carletti; Anna Checchia; Mauro Corsi; Elettra Fazzolari; Stefano Fontana; Carla Marchioro; Emilio Merlo-Pich; Michele Negri; Beatrice Oliosi; Emiliangelo Ratti; Kevin D. Read; Maja Roščić; Ilaria Sartori; Simone Spada; Giovanna Tedesco; Luca Tarsi; Silvia Terreni; Filippo Visentini; Alessandro Zocchi; Laura Zonzini
A pharmacophore model for triple reuptake inhibitors and the new class of 1-(aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes were recently reported. Further investigation in this area led to the identification of a new series of potent and selective triple reuptake inhibitors endowed with good developability characteristics. Excellent bioavailability and brain penetration are associated with this series of 6-(3,4-dichlorophenyl)-1-[(methyloxy)methyl]-3-azabicyclo[4.1.0]heptanes together with high in vitro potency and selectivity at SERT, NET, and DAT. In vivo microdialysis experiments in different animal models and receptor occupancy studies in rat confirmed that derivative 17 showed an appropriate profile to guarantee further progression of the compound.
Journal of Medicinal Chemistry | 2010
Fabrizio Micheli; Luca Arista; Giorgio Bonanomi; Frank E. Blaney; Simone Braggio; Anna Maria Capelli; Anna Checchia; Federica Damiani; Romano Di-Fabio; Stefano Fontana; Gabriella Gentile; Cristiana Griffante; Dieter Hamprecht; Carla Marchioro; Manolo Mugnaini; Jacqui Piner; Emiliangelo Ratti; Giovanna Tedesco; Luca Tarsi; Silvia Terreni; Angela Worby; Charles R. Ashby; Christian Heidbreder
The discovery of new highly potent and selective dopamine (DA) D(3) receptor antagonists has recently allowed the characterization of the DA D(3) receptor in a range of preclinical animal models of drug addiction. A novel series of 1,2,4-triazol-3-yl-azabicyclo[3.1.0]hexanes, members of which showed a high affinity and selectivity for the DA D(3) receptor and excellent pharmacokinetic profiles, is reported here. Members of a group of derivatives from this series showed good oral bioavailability and brain penetration and very high in vitro affinity and selectivity for the DA D(3) receptor, as well as high in vitro potency for antagonism at this receptor. Several members of this series also significantly attenuate the expression of conditioned place preference (CPP) to nicotine and cocaine.
Journal of Medicinal Chemistry | 2010
Fabrizio Micheli; Paolo Cavanni; Roberto Arban; Roberto Benedetti; Barbara Bertani; Michela Bettati; Letizia Bettelini; Giorgio Bonanomi; Simone Braggio; Anna Checchia; Silvia Davalli; Romano Di Fabio; Elettra Fazzolari; Stefano Fontana; Carla Marchioro; Doug Minick; Michele Negri; Beatrice Oliosi; Kevin D. Read; Ilaria Sartori; Giovanna Tedesco; Luca Tarsi; Silvia Terreni; Filippo Visentini; Alessandro Zocchi; Laura Zonzini
The discovery of new highly potent and selective triple reuptake inhibitors is reported. The new classes of 1-(aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes and 6-(aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes are described together with detailed SAR. Appropriate decoration of the scaffolds was achieved with the help of a triple reuptake inhibitor pharmacophore model detailed here. Selected derivatives showed good oral bioavailability (>30%) and brain penetration (B/B > 4) in rats associated with high in vitro potency and selectivity at SERT, NET, and DAT. Among these compounds, microdialysis and in vivo experiments confirm that derivative 15 has an appropriate developability profile to be considered for further progression.
Tetrahedron Letters | 1996
Roberto Camerini; Mauro Panunzio; Giorgio Bonanomi; Daniele Donati; Alcide Perboni
Abstract The azetidinone 14 , a key intermediate in the synthesis of novel tribactam antibiotics ( e.g. 2 ) was obtained via condensation of an ester enolate with a N -trimethylsilylimine.
Bioorganic & Medicinal Chemistry Letters | 2008
Fabrizio Micheli; Giorgio Bonanomi; Simone Braggio; Anna Maria Capelli; Paolo Celestini; Federica Damiani; Romano Di Fabio; Daniele Donati; Stefania Gagliardi; Gabriella Gentile; Dieter Hamprecht; Marcella Petrone; Stefano Radaelli; Giovanna Tedesco; Silvia Terreni; Angela Worby; Christian Heidbreder
The synthesis and SAR of a new series of potent and selective dopamine D(3) receptor antagonists is reported. The introduction of a tricyclic [h]-fused benzazepine moiety on the recently disclosed scaffold of 1,2,4-triazol-3-yl-thiopropyl-tetrahydrobenzazepines is reported. A full rat pharmacokinetic characterization is also reported.
ChemMedChem | 2010
Giorgio Bonanomi; Simone Braggio; Anna Maria Capelli; Anna Checchia; Romano Di Fabio; Carla Marchioro; Luca Tarsi; Giovanna Tedesco; Silvia Terreni; Angela Worby; Christian Heibreder; Fabrizio Micheli
Herein we report a detailed description of the structure–activity relationships for a novel series of “C‐linked” 1,2,4‐triazolylazabicyclo[3.1.0]hexanes. These derivatives are endowed with very high in vitro affinity and selectivity for the dopamine D3 receptor. An optimization with respect to undesired affinity toward the hERG potassium channel is also reported. Members of this compound series also show excellent in vitro and in vivo pharmacokinetic properties.
ChemMedChem | 2007
Roberto Arban; Roberto Benedetti; Giorgio Bonanomi; Anna-Maria Capelli; Emiliano Castiglioni; Stefania Contini; Fabio Degiorgis; Pina Di Felice; Daniele Donati; Elettra Fazzolari; Gabriella Gentile; Chiara Marchionni; Carla Marchioro; Flavia Messina; Fabrizio Micheli; Beatrice Oliosi; Francesca Pavone; Alessandra Pasquarello; Benedetta Perini; Marilisa Rinaldi; Fabio Maria Sabbatini; Giovanni Vitulli; Paola Zarantonello; Romano Di Fabio; Yves St-Denis
Two new classes of potent and selective CRF1 receptor antagonists are presented. Exploration of general templates 3 and 4 through modifications of the top amine and bottom phenyl substituents led to optimization of the in vitro affinity and pharmacokinetic profiles. The typical alkyl chains present in the top region of CRF1 antagonists were replaced by substituted heteroaryl moieties, leading to a dramatic improvement of the metabolic stability. This improvement was apparent when the compounds were dosed in vivo: several compounds exhibited low plasma clearance, good oral bioavailability, and high brain penetration. As a consequence of their outstanding pharmacokinetic profiles, these CRF1 antagonists, as exemplified by compound 4 fi (4‐(4‐bromo‐3‐methyl‐1H‐pyrazol‐1‐yl)‐7‐(2,4‐dichlorophenyl)‐2‐methyl‐6,7‐dihydro‐5H‐pyrrolo[2,3‐d]pyrimidine), produced a dose‐dependent “anxiolytic‐like” effect when administered orally, decreasing the vocalization of rat pups.
Bioorganic & Medicinal Chemistry Letters | 2008
Fabrizio Micheli; Giorgio Bonanomi; Simone Braggio; Anna Maria Capelli; Federica Damiani; Romano Di Fabio; Daniele Donati; Gabriella Gentile; Dieter Hamprecht; Ornella Perini; Marcella Petrone; Giovanna Tedesco; Silvia Terreni; Angela Worby; Christian Heidbreder
The synthesis and the SAR of a new series of potent and selective dopamine D(3) receptor antagonists is reported. The new scaffolds of the [g]-fused and the hetero-fused tricyclic benzazepine are here reported together with their pharmacokinetic profile.
Bioorganic & Medicinal Chemistry Letters | 2010
Fabrizio Micheli; Dieter Hamprecht; Giorgio Bonanomi; Romano Di Fabio; Daniele Donati; Gabriella Gentile; Christian Heidbreder; Adolfo Prandi; Luca Tarsi; Silvia Terreni
A new class of azabicyclo[3.1.0]benzenesulfonamides is presented as selective dopamine D3 antagonists together with SAR and selectivity data.
Journal of Medicinal Chemistry | 2007
Fabrizio Micheli; Giorgio Bonanomi; Frank E. Blaney; Simone Braggio; Anna Maria Capelli; Anna Checchia; Ornella Curcuruto; Federica Damiani; Romano Di Fabio; Daniele Donati; Gabriella Gentile; Andy Gribble; Dieter Hamprecht; Giovanna Tedesco; Silvia Terreni; Luca Tarsi; Andrew P. Lightfoot; Geoff Stemp; Gregor James Macdonald; Alex Smith; Michela Pecoraro; Marcella Petrone; Ornella Perini; Jacqui Piner; Tino Rossi; Angela Worby; Maria Pilla; Enzo Valerio; Cristiana Griffante; Manolo Mugnaini