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Your search keyword '"Alonso De Diego, Sergio A."' showing total 9 results
Start Over Author "Alonso De Diego, Sergio A." Journal journal of medicinal chemistry
9 results on '"Alonso De Diego, Sergio A."'

2. Discovery of 6,7-Dihydropyrazolo[1,5-a]pyrazin-4(5H)-one Derivatives as mGluR2Negative Allosteric Modulators with In VivoActivity in a Rodent’s Model of Cognition

Author

Alonso de Diego, Sergio A., Linares, María Lourdes, García Molina, Aránzazu, de Lucas, Ana Isabel, del Cerro, Alcira, Alonso, Jose Manuel, Ver Donck, Luc, Cid, Jose María, Trabanco, Andrés A., and Van Gool, Michiel

Abstract

Allosteric modulators of the metabotropic group II receptors, mGluR2and mGluR3, have been widely explored due to their ability to modulate cognitive and neurological functions in mood disorders, although none have been approved yet. In our search for new and selective mGluR2negative allosteric modulators (NAMs), series of 6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one derivatives were identified from our published series of 1,3,5-trisubstituted pyrazoles. SAR evolution of the initial hit resulted in 100-fold improvement in the mGluR2NAM potency and subsequent selection of compound 11based on its overall profile, including selectivity and ADMET properties. Further pharmacokinetic-pharmacodynamic (PK–PD) relationship built showed that compound 11occupied the mGluR2receptor in a dose-dependent manner. Additionally, the compound revealed in vivoactivity in V-maze as a model of cognition from a dose of 0.32 mg/kg. Compound 11was selected to be evaluated further.

Published
2024
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3. Correction to Optimization of 1,4-Oxazine β-Secretase 1 (BACE1) Inhibitors Toward a Clinical Candidate

Author

Gijsen, Harrie J. M., primary, Alonso de Diego, Sergio A., additional, De Cleyn, Michel, additional, García-Molina, Aránzazu, additional, Macdonald, Gregor J., additional, Martinez-Lamenca, Carolina, additional, Oehlrich, Daniel, additional, Prokopcova, Hana, additional, Rombouts, Frederik J. R., additional, Surkyn, Michel, additional, Trabanco, Andrés A., additional, Van Brandt, Sven, additional, Van den Bossche, Dries, additional, Van Gool, Michiel, additional, Austin, Nigel, additional, Borghys, Herman, additional, Dhuyvetter, Deborah, additional, Urmaliya, Vijay, additional, Teisman, Ard, additional, and Moechars, Diederik, additional

Published
2018
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4. Optimization of 1,4-Oxazine β-Secretase 1 (BACE1) Inhibitors Toward a Clinical Candidate

Author

Gijsen, Harrie J. M., primary, Alonso de Diego, Sergio A., additional, De Cleyn, Michel, additional, García-Molina, Aránzazu, additional, Macdonald, Gregor J., additional, Martínez-Lamenca, Carolina, additional, Oehlrich, Daniel, additional, Prokopcova, Hana, additional, Rombouts, Frederik J. R., additional, Surkyn, Michel, additional, Trabanco, Andrés A., additional, Van Brandt, Sven, additional, Van den Bossche, Dries, additional, Van Gool, Michiel, additional, Austin, Nigel, additional, Borghys, Herman, additional, Dhuyvetter, Deborah, additional, and Moechars, Diederik, additional

Published
2018
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5. 1,4-Oxazine β-Secretase 1 (BACE1) Inhibitors: From Hit Generation to Orally Bioavailable Brain Penetrant Leads

Author

Rombouts, Frederik J. R., primary, Tresadern, Gary, additional, Delgado, Oscar, additional, Martínez-Lamenca, Carolina, additional, Van Gool, Michiel, additional, García-Molina, Aránzazu, additional, Alonso de Diego, Sergio A., additional, Oehlrich, Daniel, additional, Prokopcova, Hana, additional, Alonso, José Manuel, additional, Austin, Nigel, additional, Borghys, Herman, additional, Van Brandt, Sven, additional, Surkyn, Michel, additional, De Cleyn, Michel, additional, Vos, Ann, additional, Alexander, Richard, additional, Macdonald, Gregor, additional, Moechars, Dieder, additional, Gijsen, Harrie, additional, and Trabanco, Andrés A., additional

Published
2015
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6. Identification of a Novel Orally Bioavailable Phosphodiesterase 10A (PDE10A) Inhibitor with Efficacy in Animal Models of Schizophrenia.

Author

Bartolomé-Nebreda, José Manuel, primary, Alonso de Diego, Sergio A., additional, Artola, Marta, additional, Delgado, Francisca, additional, Delgado, Óscar, additional, Martín-Martín, María Luz, additional, Martínez-Viturro, Carlos M., additional, Pena, Miguel Ángel, additional, Tong, Han Min, additional, Van Gool, Michiel, additional, Alonso, José Manuel, additional, Fontana, Alberto, additional, Macdonald, Gregor J., additional, Megens, Anton, additional, Langlois, Xavier, additional, Somers, Marijke, additional, Vanhoof, Greet, additional, and Conde-Ceide, Susana, additional

Published
2015
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7. Imidazo[1,2-a]pyridines: Orally Active Positive Allosteric Modulators of the Metabotropic Glutamate 2 Receptor

Author

Trabanco, Andrés A., primary, Tresadern, Gary, additional, Macdonald, Gregor J., additional, Vega, Juan Antonio, additional, de Lucas, Ana Isabel, additional, Matesanz, Encarnación, additional, García, Aránzazu, additional, Linares, María Lourdes, additional, Alonso de Diego, Sergio A., additional, Alonso, José Manuel, additional, Oehlrich, Daniel, additional, Ahnaou, Abdelah, additional, Drinkenburg, Wilhelmus, additional, Mackie, Claire, additional, Andrés, José Ignacio, additional, Lavreysen, Hilde, additional, and Cid, José María, additional

Published
2012
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8. Identification of a NovelOrally Bioavailable Phosphodiesterase 10A (PDE10A) Inhibitor withEfficacy in Animal Models of Schizophrenia.

Author

Bartolomé-Nebreda, José Manuel, Alonso de Diego, Sergio A., Artola, Marta, Delgado, Francisca, Delgado, Óscar, Martín-Martín, María Luz, Martínez-Viturro, Carlos M., Pena, Miguel Ángel, Tong, Han Min, Van Gool, Michiel, Alonso, JoséManuel, Fontana, Alberto, Macdonald, Gregor J., Megens, Anton, Langlois, Xavier, Somers, Marijke, Vanhoof, Greet, and Conde-Ceide, Susana

Subjects
*ORAL medication, *ANIMAL models in research, *SCHIZOPHRENIA, *DRUG bioavailability, *PHOSPHODIESTERASE inhibitors, *DRUG efficacy, *PHARMACOKINETICS, *THERAPEUTICS
Abstract

Wereport the continuation of a focused medicinal chemistry program aimedto further optimize a series of imidazo[1,2-a]pyrazinesas a novel class of potent and selective phosphodiesterase 10A (PDE10A)inhibitors. In vitro and in vivo pharmacokinetic and pharmacodynamicevaluation allowed the selection of compound 25aforits assessment in preclinical models of psychosis. The evolution ofour medicinal chemistry program, structure–activity relationship(SAR) analysis, as well as a detailed pharmacological profile foroptimized lead 25aare described. [ABSTRACT FROM AUTHOR]

Published
2015
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9. Discovery of 6,7-Dihydropyrazolo[1,5- a ]pyrazin-4(5 H )-one Derivatives as mGluR 2 Negative Allosteric Modulators with In Vivo Activity in a Rodent's Model of Cognition.

Author

Alonso de Diego SA, Linares ML, García Molina A, de Lucas AI, Del Cerro A, Alonso JM, Ver Donck L, Cid JM, Trabanco AA, and Van Gool M

Subjects
Animals, Allosteric Regulation drug effects, Structure-Activity Relationship, Rats, Humans, Pyrazines pharmacology, Pyrazines chemistry, Pyrazines pharmacokinetics, Pyrazines chemical synthesis, Male, Maze Learning drug effects, Mice, Drug Discovery, Receptors, Metabotropic Glutamate metabolism, Cognition drug effects, Pyrazoles pharmacology, Pyrazoles chemistry, Pyrazoles chemical synthesis, Pyrazoles pharmacokinetics
Abstract

Allosteric modulators of the metabotropic group II receptors, mGluR 2 and mGluR 3 , have been widely explored due to their ability to modulate cognitive and neurological functions in mood disorders, although none have been approved yet. In our search for new and selective mGluR 2 negative allosteric modulators (NAMs), series of 6,7-dihydropyrazolo[1,5- a ]pyrazin-4(5 H )-one derivatives were identified from our published series of 1,3,5-trisubstituted pyrazoles. SAR evolution of the initial hit resulted in 100-fold improvement in the mGluR 2 NAM potency and subsequent selection of compound 11 based on its overall profile, including selectivity and ADMET properties. Further pharmacokinetic-pharmacodynamic (PK-PD) relationship built showed that compound 11 occupied the mGluR 2 receptor in a dose-dependent manner. Additionally, the compound revealed in vivo activity in V-maze as a model of cognition from a dose of 0.32 mg/kg. Compound 11 was selected to be evaluated further.

Published
2024
Full Text
View/download PDF

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