Search

Your search keyword '"Wágner, Gábor"' showing total 5 results
Start Over Author "Wágner, Gábor" Journal journal of medicinal chemistry
5 results on '"Wágner, Gábor"'

1. 4-(3-Aminoazetidin-1-yl)pyrimidin-2-amines as High-Affinity Non-imidazole Histamine H3 Receptor Agonists with in Vivo Central Nervous System Activity

Author

Wágner, Gábor, primary, Mocking, Tamara A. M., additional, Arimont, Marta, additional, Provensi, Gustavo, additional, Rani, Barbara, additional, Silva-Marques, Bruna, additional, Latacz, Gniewomir, additional, Da Costa Pereira, Daniel, additional, Karatzidou, Christina, additional, Vischer, Henry F., additional, Wijtmans, Maikel, additional, Kieć-Kononowicz, Katarzyna, additional, de Esch, Iwan J. P., additional, and Leurs, Rob, additional

Published
2019
Full Text
View/download PDF

2. Discovery and Preclinical Characterization of 3-((4-(4-Chlorophenyl)-7-fluoroquinoline-3-yl)sulfonyl)benzonitrile, a Novel Non-acetylenic Metabotropic Glutamate Receptor 5 (mGluR5) Negative Allosteric Modulator for Psychiatric Indications

Author

Galambos, János, primary, Bielik, Attila, additional, Krasavin, Mikhail, additional, Orgován, Zoltán, additional, Domány, György, additional, Nógrádi, Katalin, additional, Wágner, Gábor, additional, Balogh, György T., additional, Béni, Zoltán, additional, Kóti, János, additional, Szakács, Zoltán, additional, Bobok, Amrita, additional, Kolok, Sándor, additional, Mikó-Bakk, Mónika L., additional, Vastag, Mónika, additional, Sághy, Katalin, additional, Laszy, Judit, additional, Halász, Attila Sándor, additional, Balázs, Ottilia, additional, Gál, Krisztina, additional, Greiner, István, additional, Szombathelyi, Zsolt, additional, and Keserű, György M., additional

Published
2017
Full Text
View/download PDF

4. 4-(3-Aminoazetidin-1-yl)pyrimidin-2-amines as High-Affinity Non-imidazole Histamine H3Receptor Agonists with in Vivo Central Nervous System Activity

Author

Wágner, Gábor, Mocking, Tamara A. M., Arimont, Marta, Provensi, Gustavo, Rani, Barbara, Silva-Marques, Bruna, Latacz, Gniewomir, Da Costa Pereira, Daniel, Karatzidou, Christina, Vischer, Henry F., Wijtmans, Maikel, Kieć-Kononowicz, Katarzyna, de Esch, Iwan J. P., and Leurs, Rob

Abstract

Despite the high diversity of histamine H3receptor (H3R) antagonist/inverse agonist structures, partial or full H3R agonists have typically been imidazole derivatives. An in-house screening campaign intriguingly afforded the non-imidazole 4-(3-azetidin-1-yl)pyrimidin-2-amine 11bas a partial H3R agonist. Here, the design, synthesis, and structure–activity relationships of 11banalogues are described. This series yields several non-imidazole full agonists with potencies varying with the alkyl substitution pattern on the basic amine following the in vitro evaluation of H3R agonism using a cyclic adenosine monophosphate response element-luciferase reporter gene assay. The key compound VUF16839 (14d) combines nanomolar on-target activity (pKi= 8.5, pEC50= 9.5) with weak activity on cytochrome P450 enzymes and good metabolic stability. The proposed H3R binding mode of 14dindicates key interactions similar to those attained by histamine. In vivo evaluation of 14din a social recognition test in mice revealed an amnesic effect at 5 mg/kg intraperitoneally. The excellent in vitro and in vivo pharmacological profiles and the non-imidazole structure of 14dmake it a promising tool compound in H3R research.

Published
2019
Full Text
View/download PDF

5. 4-(3-Aminoazetidin-1-yl)pyrimidin-2-amines as High-Affinity Non-imidazole Histamine H 3 Receptor Agonists with in Vivo Central Nervous System Activity.

Author

Wágner G, Mocking TAM, Arimont M, Provensi G, Rani B, Silva-Marques B, Latacz G, Da Costa Pereira D, Karatzidou C, Vischer HF, Wijtmans M, Kieć-Kononowicz K, de Esch IJP, and Leurs R

Subjects
Amines chemistry, Animals, Behavior, Animal drug effects, HEK293 Cells, Histamine Agonists chemistry, Humans, Memory drug effects, Mice, Molecular Docking Simulation, Molecular Structure, Protein Binding, Protein Conformation, Social Behavior, Amines chemical synthesis, Amines pharmacology, Histamine Agonists chemical synthesis, Histamine Agonists pharmacology
Abstract

Despite the high diversity of histamine H 3 receptor (H 3 R) antagonist/inverse agonist structures, partial or full H 3 R agonists have typically been imidazole derivatives. An in-house screening campaign intriguingly afforded the non-imidazole 4-(3-azetidin-1-yl)pyrimidin-2-amine 11b as a partial H 3 R agonist. Here, the design, synthesis, and structure-activity relationships of 11b analogues are described. This series yields several non-imidazole full agonists with potencies varying with the alkyl substitution pattern on the basic amine following the in vitro evaluation of H 3 R agonism using a cyclic adenosine monophosphate response element-luciferase reporter gene assay. The key compound VUF16839 ( 14d ) combines nanomolar on-target activity (p K i = 8.5, pEC 50 = 9.5) with weak activity on cytochrome P450 enzymes and good metabolic stability. The proposed H 3 R binding mode of 14d indicates key interactions similar to those attained by histamine. In vivo evaluation of 14d in a social recognition test in mice revealed an amnesic effect at 5 mg/kg intraperitoneally. The excellent in vitro and in vivo pharmacological profiles and the non-imidazole structure of 14d make it a promising tool compound in H 3 R research.

Published
2019
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results