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Start Over Author "Szabó, György" Journal journal of medicinal chemistry
10 results on '"Szabó, György"'

1. Multiparameter Optimization of Naphthyridine Derivatives as Selective α5-GABAA Receptor Negative Allosteric Modulators

Author

Szabó, György, primary, Éliás, Olivér, additional, Erdélyi, Péter, additional, Potor, Attila, additional, Túrós, György I., additional, Károlyi, Benedek I., additional, Varró, Gábor, additional, Vaskó, Ágnes Gy., additional, Bata, Imre, additional, Kapus, Gábor L., additional, Dohányos, Zoltán, additional, Bobok, Amrita Á., additional, Fodor, László, additional, Thán, Márta, additional, Vastag, Mónika, additional, Komlódi, Zsolt, additional, Soukupné Kedves, Rita É., additional, Makó, Éva, additional, Süveges, Brigitta, additional, and Greiner, István, additional

Published
2022
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2. Fragment-Based Optimization of Dihydropyrazino-Benzimidazolones as Metabotropic Glutamate Receptor-2 Positive Allosteric Modulators against Migraine

Author

Szabó, György, primary, Erdélyi, Péter, additional, Kolok, Sándor, additional, Vastag, Mónika, additional, Halász, Attila S., additional, Kis-Varga, Istvánné, additional, Lévay, György I., additional, Béni, Zoltán, additional, Kóti, János, additional, Greiner, István, additional, and Keserű, György M., additional

Published
2021
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3. Multiparameter Optimization of Naphthyridine Derivatives as Selective α5-GABAA Receptor Negative Allosteric Modulators.

Author

Szabó, György, Éliás, Olivér, Erdélyi, Péter, Potor, Attila, Túrós, György I., Károlyi, Benedek I., Varró, Gábor, Vaskó, Ágnes Gy., Bata, Imre, Kapus, Gábor L., Dohányos, Zoltán, Bobok, Amrita Á., Fodor, László, Thán, Márta, Vastag, Mónika, Komlódi, Zsolt, Soukupné Kedves, Rita É., Makó, Éva, Süveges, Brigitta, and Greiner, István

Published
2022
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4. Multiparameter Optimization of Naphthyridine Derivatives as Selective α5-GABAAReceptor Negative Allosteric Modulators

Author

Szabó, György, Éliás, Olivér, Erdélyi, Péter, Potor, Attila, Túrós, György I., Károlyi, Benedek I., Varró, Gábor, Vaskó, Ágnes Gy., Bata, Imre, Kapus, Gábor L., Dohányos, Zoltán, Bobok, Amrita Á., Fodor, László, Thán, Márta, Vastag, Mónika, Komlódi, Zsolt, Soukupné Kedves, Rita É., Makó, Éva, Süveges, Brigitta, and Greiner, István

Abstract

The discovery and characterization of novel naphthyridine derivatives with selective α5-GABAAR negative allosteric modulator (NAM) activity are disclosed. Utilizing a scaffold-hopping strategy, fused [6 + 6] bicyclic scaffolds were designed and synthesized. Among these, 1,6-naphthyridinones were identified as potent and selective α5-GABAAR NAMs with metabolic stability, cardiac safety, and beneficial intellectual property (IP) issues. Relocation of the oxo acceptor function and subsequent modulation of the physicochemical properties resulted in novel 1,6-naphthyridines with improved profile, combining good potency, selectivity, ADME, and safety properties. Besides this, compound 20, having the most balanced profile, provided in vivo proof of concept (POC) for the new scaffold in two animal models of cognitive impairment associated with schizophrenia (CIAS).

Published
2022
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5. Fragment Based Optimization of Metabotropic Glutamate Receptor 2 (mGluR2) Positive Allosteric Modulators in the Absence of Structural Information

Author

Szabó, György, primary, Túrós, György I., additional, Kolok, Sándor, additional, Vastag, Mónika, additional, Sánta, Zsuzsanna, additional, Dékány, Miklós, additional, Lévay, György I., additional, Greiner, István, additional, Natsumi, Minami, additional, Tatsuya, Watanabe, additional, and Keserű, György M., additional

Published
2018
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6. Fragment Based Optimization of Metabotropic Glutamate Receptor 2 (mGluR2) Positive Allosteric Modulators in the Absence of Structural Information

Author

Szabó, György, Túrós, György I., Kolok, Sándor, Vastag, Mónika, Sánta, Zsuzsanna, Dékány, Miklós, Lévay, György I., Greiner, István, Natsumi, Minami, Tatsuya, Watanabe, and Keserű, György M.

Abstract

Metabotropic glutamate receptor 2 (mGluR2) positive allosteric modulators (PAMs) have been implicated as potential pharmacotherapy for psychiatric conditions. Screening our corporate compound deck, we identified a benzotriazole fragment (4) that was rapidly optimized to a potent and metabolically stable early lead (16). The highly lipophilic character of 16, together with its limited solubility, permeability, and high protein binding, however, did not allow reaching of the proof of concept in vivo. Since further attempts on the optimization of druglike properties were unsuccessful, the original hit 4has been revisited and was optimized following the principles of fragment based drug discovery (FBDD). Lacking structural information on the receptor–ligand complex, we implemented a group efficiency (GE) based strategy and identified a new fragment like lead (60) with more balanced profile. Significant improvement achieved on the druglike properties nominated the compound for in vivo proof of concept studies that revealed the chemotype being a promising PAM lead targeting mGluR2 receptors.

Published
2019
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7. Chemical and Biological Investigation of Cyclopropyl Containing Diaryl-pyrazole-3-carboxamides as Novel and Potent Cannabinoid Type 1 Receptor Antagonists

Author

Szabó, György, primary, Varga, Balázs, additional, Páyer-Lengyel, Dóra, additional, Szemző, Attila, additional, Erdélyi, Péter, additional, Vukics, Krisztina, additional, Szikra, Judit, additional, Hegyi, Éva, additional, Vastag, Mónika, additional, Kiss, Béla, additional, Laszy, Judit, additional, Gyertyán, István, additional, and Fischer, János, additional

Published
2009
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9. Multiparameter Optimization of Naphthyridine Derivatives as Selective α5-GABA A Receptor Negative Allosteric Modulators.

Author

Szabó G, Éliás O, Erdélyi P, Potor A, Túrós GI, Károlyi BI, Varró G, Vaskó ÁG, Bata I, Kapus GL, Dohányos Z, Bobok AÁ, Fodor L, Thán M, Vastag M, Komlódi Z, Soukupné Kedves RÉ, Makó É, Süveges B, and Greiner I

Subjects
Allosteric Regulation, Animals, Naphthyridines pharmacology, Naphthyridines therapeutic use, gamma-Aminobutyric Acid, Receptors, GABA-A metabolism, Schizophrenia drug therapy
Abstract

The discovery and characterization of novel naphthyridine derivatives with selective α5-GABA A R negative allosteric modulator (NAM) activity are disclosed. Utilizing a scaffold-hopping strategy, fused [6 + 6] bicyclic scaffolds were designed and synthesized. Among these, 1,6-naphthyridinones were identified as potent and selective α5-GABA A R NAMs with metabolic stability, cardiac safety, and beneficial intellectual property (IP) issues. Relocation of the oxo acceptor function and subsequent modulation of the physicochemical properties resulted in novel 1,6-naphthyridines with improved profile, combining good potency, selectivity, ADME, and safety properties. Besides this, compound 20 , having the most balanced profile, provided in vivo proof of concept (POC) for the new scaffold in two animal models of cognitive impairment associated with schizophrenia (CIAS).

Published
2022
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10. New celecoxib derivatives as anti-inflammatory agents.

Author

Szabó G, Fischer J, Kis-Varga A, and Gyires K

Subjects
Acetic Acid, Animals, Carrageenan, Celecoxib, Chronic Disease, Crystallization, Cyclooxygenase 1 chemistry, Cyclooxygenase 1 metabolism, Cyclooxygenase 2 chemistry, Cyclooxygenase 2 metabolism, Cyclooxygenase Inhibitors chemistry, Cyclooxygenase Inhibitors pharmacology, Edema drug therapy, Ethanol, Gastric Mucosa drug effects, Gastric Mucosa pathology, Hyperalgesia drug therapy, Male, Pyrazoles chemistry, Pyrazoles pharmacology, Rats, Rats, Wistar, Recombinant Proteins chemistry, Stereoisomerism, Stomach Ulcer chemically induced, Stomach Ulcer pathology, Stomach Ulcer prevention & control, Sulfonamides chemistry, Sulfonamides pharmacology, Cyclooxygenase Inhibitors chemical synthesis, Pyrazoles chemical synthesis, Sulfonamides chemical synthesis
Abstract

A series of 1,5-diarylpyrazoles with a substituted benzenesulfonamide moiety was synthesized and evaluated for cyclooxygenase (COX-1/COX-2) inhibitory activities. Some compounds, for example, (+/-)-2-[4-(5- p-tolyl-3-trifluoromethyl-pyrazole-1-yl)-benzenesulfonylaminooxy]-propionic acid 16 and its disodium salt 21, had a higher in vivo anti-inflammatory activity compared to celecoxib, despite having no in vitro COX-1 or COX-2 inhibitory activity. Their gastrointestinal side effect profile is essentially more favorable than that of celecoxib.

Published
2008
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