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10 results on '"Dal Forno, Giovanna"'

1. Design and Synthesis of Novel Tricyclic Benzoxazines as Potent 5-HT1A/B/DReceptor Antagonists Leading to the Discovery of 6-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}-4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide (GSK588045)

Author

Bromidge, Steven M., Arban, Roberto, Bertani, Barbara, Bison, Silvia, Borriello, Manuela, Cavanni, Paolo, Dal Forno, Giovanna, Di-Fabio, Romano, Donati, Daniele, Fontana, Stefano, Gianotti, Massimo, Gordon, Laurie J., Granci, Enrica, Leslie, Colin P., Moccia, Luca, Pasquarello, Alessandra, Sartori, Ilaria, Sava, Anna, Watson, Jeannette M., Worby, Angela, Zonzini, Laura, and Zucchelli, Valeria

Abstract

Bioisoteric replacement of the metabolically labile N-methyl amide group of a series of benzoxazinones with small heterocyclic rings has led to novel series of fused tricyclic benzoxazines which are potent 5-HT1A/B/Dreceptor antagonists with and without concomitant human serotonin transporter (hSerT) activity. Optimizing against multiple parameters in parallel identified 6-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}-4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide (GSK588045) as a potent 5-HT1A/B/Dreceptor antagonist with a high degree of selectivity over human ether-à-go-go related gene (hERG) potassium channels, favorable pharmacokinetics, and excellent activity in vivo in rodent pharmacodynamic (PD) models. On the basis of its outstanding overall profile, this compound was progressed as a clinical candidate with the ultimate aim to assess its potential as a faster acting antidepressant/anxiolytic with reduced side-effect burden.

Published
2024
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2. Discovery Process and Characterization of Novel Carbohydrazide Derivatives as Potent and Selective GHSR1a Antagonists

Author

Sabbatini, Fabio Maria, primary, Di Fabio, Romano, additional, Corsi, Mauro, additional, Cavanni, Paolo, additional, Bromidge, Steve M., additional, St-Denis, Yves, additional, D'Adamo, Lucilla, additional, Contini, Stefania, additional, Rinaldi, Marilisa, additional, Guery, Sebastien, additional, Savoia, Chiara, additional, Mundi, Claudia, additional, Perini, Benedetta, additional, Carpenter, Andrew J., additional, Dal Forno, Giovanna, additional, Faggioni, Federico, additional, Tessari, Michela, additional, Pavone, Francesca, additional, Di Francesco, Carla, additional, Buson, Alberto, additional, Mattioli, Mario, additional, Perdona', Elisabetta, additional, and Melotto, Sergio, additional

Published
2010
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3. Design and Synthesis of Novel Tricyclic Benzoxazines as Potent 5-HT1A/B/D Receptor Antagonists Leading to the Discovery of 6-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}-4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide (GSK588045)

Author

Bromidge, Steven M., primary, Arban, Roberto, additional, Bertani, Barbara, additional, Bison, Silvia, additional, Borriello, Manuela, additional, Cavanni, Paolo, additional, Dal Forno, Giovanna, additional, Di-Fabio, Romano, additional, Donati, Daniele, additional, Fontana, Stefano, additional, Gianotti, Massimo, additional, Gordon, Laurie J., additional, Granci, Enrica, additional, Leslie, Colin P., additional, Moccia, Luca, additional, Pasquarello, Alessandra, additional, Sartori, Ilaria, additional, Sava, Anna, additional, Watson, Jeannette M., additional, Worby, Angela, additional, Zonzini, Laura, additional, and Zucchelli, Valeria, additional

Published
2010
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4. Enantiomerically pure tetrahydroquinoline derivatives as in vivo potent antagonists of the glycine binding site associated to the NMDA receptor

Author

Di Fabio, Romano, primary, Tranquillini, Elvira, additional, Bertani, Barbara, additional, Alvaro, Giuseppe, additional, Micheli, Fabrizio, additional, Sabbatini, Fabio, additional, Domenica Pizzi, Maria, additional, Pentassuglia, Giorgio, additional, Pasquarello, Alessandra, additional, Messeri, Tommaso, additional, Donati, Daniele, additional, Ratti, Emiliangelo, additional, Arban, Roberto, additional, Dal Forno, Giovanna, additional, Reggiani, Angelo, additional, and Barnaby, Robert J., additional

Published
2003
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5. Benzoazepine derivative as potent antagonists of the glycine binding site associated to the NMDA receptor

Author

Di Fabio, Romano, primary, Micheli, Fabrizio, additional, Baraldi, Davide, additional, Bertani, Barbara, additional, Conti, Nadia, additional, Dal Forno, Giovanna, additional, Feriani, Aldo, additional, Donati, Daniele, additional, Marchioro, Carla, additional, Messeri, Tommaso, additional, Missio, Andrea, additional, Pasquarello, Alessandra, additional, Pentassuglia, Giorgio, additional, Pizzi, Domenica A., additional, Provera, Stefano, additional, Quaglia, Anna M., additional, and Sabbatini, Fabio M., additional

Published
2003
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7. Design and Synthesis of Novel Tricyclic Benzoxazines as Potent 5-HT1A/B/D Receptor Antagonists Leading to the Discovery of 6-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}-4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide (GSK588045).

Author

Bromidge, Steven M., Arban, Roberto, Bertani, Barbara, Bison, Silvia, Borriello, Manuela, Cavanni, Paolo, Dal Forno, Giovanna, Di-Fabio, Romano, Donati, Daniele, Fontana, Stefano, Gianotti, Massimo, Gordon, Laurie J., Granci, Enrica, Leslie, Colin P., Moccia, Luca, Pasquarello, Alessandra, Sartori, Ilaria, Sava, Anna, Watson, Jeannette M., and Worby, Angela

Published
2010
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9. Novel carbazole derivatives as NPY Y1 antagonists.

Author

Leslie CP, Di Fabio R, Bonetti F, Borriello M, Braggio S, Dal Forno G, Donati D, Falchi A, Ghirlanda D, Giovannini R, Pavone F, Pecunioso A, Pentassuglia G, Pizzi DA, Rumboldt G, and Stasi L

Subjects
Animals, Biological Availability, Brain drug effects, Brain metabolism, CHO Cells, Carbazoles pharmacokinetics, Chemical Phenomena, Chemistry, Physical, Cricetinae, Cricetulus, Half-Life, Indicators and Reagents, Male, Rats, Rats, Sprague-Dawley, Structure-Activity Relationship, Carbazoles chemical synthesis, Carbazoles pharmacology, Receptors, Neuropeptide Y antagonists & inhibitors
Abstract

The synthesis of a series of carbazole derivatives and their SAR at the NPY Y1 receptor is described. Modulation of physicochemical properties by appropriate decoration led to the identification of a high-affinity NPY Y1 antagonist that shows high brain penetration and modest oral bioavailability.

Published
2007
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10. Benzoazepine derivative as potent antagonists of the glycine binding site associated to the NMDA receptor.

Author

Di Fabio R, Micheli F, Baraldi D, Bertani B, Conti N, Dal Forno G, Feriani A, Donati D, Marchioro C, Messeri T, Missio A, Pasquarello A, Pentassuglia G, Pizzi DA, Provera S, Quaglia AM, and Sabbatini FM

Subjects
Animals, Anticonvulsants chemistry, Anticonvulsants pharmacology, Arterial Occlusive Diseases complications, Azepines chemistry, Azepines pharmacology, Binding Sites, Brain Ischemia drug therapy, Brain Ischemia etiology, Male, Mice, Middle Cerebral Artery, Models, Molecular, Neuroprotective Agents chemistry, Neuroprotective Agents pharmacology, Rats, Rats, Sprague-Dawley, Structure-Activity Relationship, Anticonvulsants chemical synthesis, Azepines chemical synthesis, Neuroprotective Agents chemical synthesis, Receptors, Glycine antagonists & inhibitors, Receptors, N-Methyl-D-Aspartate antagonists & inhibitors
Abstract

A series of benzoazepine derivatives, bearing suitable substituents at the C-3 position, was designed and evaluated by superimposition with the pharmacophore model of the glycine binding site. To fully explore the SAR of this class of compounds and to allow the preparation of new different compounds at the C-3 position, appropriate synthetic routes were set up. The benzoazepines were evaluated in terms of in vitro affinity using [3H]glycine binding assay and in vivo potency by inhibition of convulsions induced by N-methyl-D-aspartate (NMDA) in mice. This further analysis confirmed the preliminary results previously reported and that compound 27 is the most promising compound (Ki=32 nM, ED(50)=0.09 mg/kg, i.v.) in this series. Significant neuroprotective effect was observed after both pre- and post-ischaemia administration in the MCAo model. In particular, after post-ischaemia administration, it was found to be still effective when the administration was delayed up to 6 h after occlusion of the middle cerebral artery.

Published
2003
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