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

Autor: Attila Sándor Halász, Amrita Ágnes Bobok, Zoltán Szakács, István Greiner, Zoltán Orgován, Mónika Vastag, Sándor Kolok, Zoltán Béni, Gábor Wágner, Mónika L. Mikó-Bakk, Zsolt Szombathelyi, Attila Bielik, Krisztina Gál, Katalin Nogradi, György M. Keserű, Ottilia Balázs, Katalin Saghy, János Kóti, György T. Balogh, Judit Laszy, Mikhail Krasavin, György Domány, Janos Galambos

Publikováno v: Journal of Medicinal Chemistry. 60:2470-2484

Negative allosteric modulators (NAM) of metabotropic glutamate receptor 5 (mGluR5) have been implicated as a potential pharmacotherapy for a number of psychiatric diseases, including anxiety and depression. Most of the mGluR5 NAM clinical candidates

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4e3dc984e3e83f573a4bc24f797febd2
https://doi.org/10.1021/acs.jmedchem.6b01858

4-Aryl-3-arylsulfonyl-quinolines as negative allosteric modulators of metabotropic GluR5 receptors:From HTS hit to development candidate

Autor: Amrita Ágnes Bobok, György Domány, Zoltán Szakács, Krisztina Gál, Katalin Saghy, György M. Keserű, Katalin Nogradi, Zsolt Szombathelyi, Sándor Kolok, Janos Galambos, János Kóti, Zoltán Béni, István Greiner, Gábor Wágner, Mónika L. Mikó-Bakk, Mónika Vastag

Publikováno v: Galambos, J, Domány, G, Nógrádi, K, Wágner, G, Keseru, G M, Bobok, A, Kolok, S, Mikó-Bakk, M L, Vastag, M, Sághy, K, Kóti, J, Szakács, Z, Béni, Z, Gál, K, Szombathelyi, Z & Greiner, I 2016, ' 4-Aryl-3-arylsulfonyl-quinolines as negative allosteric modulators of metabotropic GluR5 receptors : From HTS hit to development candidate ', Bioorganic and Medicinal Chemistry Letters, vol. 26, no. 4, pp. 1249-1252 . https://doi.org/10.1016/j.bmcl.2016.01.024
Bioorganic and Medicinal Chemistry Letters, 26(4), 1249-1252. Elsevier Limited

High throughput screening of our corporate compound library followed by hit-to-lead development resulted in a 4-aryl-3-arylsulfonyl-quinoline derivative lead (2) with mGluR5 negative allosteric modulator activity. During the lead optimization process

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::34b9293cfa61b23617d4ae5ab3c9f312
https://research.vu.nl/en/publications/90c75f64-ce57-4f0f-aa17-4c3a16a1765e

Novel sulfonamides having dual dopamine D2 and D3 receptor affinity show in vivo antipsychotic efficacy with beneficial cognitive and EPS profile

Autor: Istvan Laszlovszky, Ildikó Magdó, Eva Schmidt, György M. Keserü, Györgyi Ignacz-Szendrei, Katalin Nogradi, Judit Laszy, Larisza Gémesi, Attila Bielik, István Greiner, Éva Ágai-Csongor, György Domány, Mária Zájer-Balázs, Janos Galambos, Istvan Vago, Istvan Gyertyan, Bela Kiss, Katalin Saghy

Publikováno v: Bioorganic & Medicinal Chemistry Letters. 17:5340-5344

A novel series of arylsulfonamides was prepared either by automated parallel or by traditional solution-phase synthesis. Several members of this compound library were identified as high-affinity dopamine D3 and D2 receptor ligands. The most interesti

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6050a05a57420e300744aed9be2987ff
https://doi.org/10.1016/j.bmcl.2007.08.015

Stepwise aromatic nucleophilic substitution in continuous flow. Synthesis of an unsymmetrically substituted 3,5-diamino-benzonitrile library

Autor: Katalin Nogradi, László Lengyel, Tamás Nagy, Péter Terleczky, Ferenc Darvas, László Ürge, Viktor Gyollai, Viktor Háda, Ferenc Sebők, György Dormán

Publikováno v: Molecular diversity. 15(3)

Aromatic or heteroaromatic ring precursors with 2–3 identical functionalities are often used in sequential derivatization depending on the reactivity difference or the selective execution of the reaction such as nucleophilic aromatic substitution.

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::592f2938b68c7f9dddc0245894bd0faf
https://pubmed.ncbi.nlm.nih.gov/21190134

Hit-to-lead optimization of disubstituted oxadiazoles and tetrazoles as mGluR5 NAMs

Autor: Bela Kiss, Attila Horváth, Zsolt Szombathelyi, Katalin Nogradi, Olga Nyéki, István Greiner, Csaba Wéber, Gábor Wágner, Dalma Kurkó, József Nagy, Amrita Ágnes Bobok, Sándor Kolok, Attila Bielik, Krisztina Gál, György M. Keserű, György Domány, László Molnár

Publikováno v: Bioorganicmedicinal chemistry letters. 20(12)

Here we report the discovery and early SAR of a series of mGluR5 negative allosteric modulators (NAMs). Starting from a moderately active HTS hit we synthesized 3,5-disubstituted-oxadiazoles and tetrazoles as mGluR5 NAMs. Based on the analysis of lig

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bc883ec940059d979f0a9861d34330ed
https://pubmed.ncbi.nlm.nih.gov/20483612