TY - JOUR AU - Szilágyi, Bence AU - Egyed, Attila AU - Mándity, István AU - Nagy, Tamás AU - Kátainé Fadgyas, Katalin AU - Volk, Balázs AU - Keserű, György Miklós TI - Safe and Efficient Continuous-Flow Synthesis and Batchwise Hydrolysis of Ethyl 5-Acetyl-1H-pyrazole-3-carboxylate: A Key Synthon of Darolutamide JF - SYNTHESIS-STUTTGART J2 - SYNTHESIS-STUTTGART VL - 55 PY - 2023 IS - 6 SP - 959 EP - 966 PG - 8 SN - 0039-7881 DO - 10.1055/s-0042-1751389 UR - https://m2.mtmt.hu/api/publication/33283298 ID - 33283298 LA - English DB - MTMT ER - TY - GEN AU - Poszávácz, László AU - Szilágyi, Bence AU - Nagy, Tamás AU - Egyed, Attila AU - Kátainé Fadgyas, Katalin AU - Keserű, György Miklós AU - Mándity, István AU - Volk, Balázs TI - „Semmi sem olyan egyszerű, mint amilyennek látszik”. Darolutamid intermedier generikus szemmel PY - 2022 UR - https://m2.mtmt.hu/api/publication/33106229 ID - 33106229 N1 - előadó: Nagy Tamás LA - Hungarian DB - MTMT ER - TY - JOUR AU - Kollár, Levente AU - Gobec, Martina AU - Szilágyi, Bence AU - Proj, Matic AU - Knez, Damijan AU - Ábrányi-Balogh, Péter AU - Petri, László AU - Imre, Timea AU - Bajusz, Dávid AU - Ferenczy, György AU - Gobec, Stanislav AU - Keserű, György Miklós AU - Sosič, Izidor TI - Discovery of selective fragment-sized immunoproteasome inhibitors JF - EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY J2 - EUR J MED CHEM VL - 219 PY - 2021 PG - 23 SN - 0223-5234 DO - 10.1016/j.ejmech.2021.113455 UR - https://m2.mtmt.hu/api/publication/31984014 ID - 31984014 LA - English DB - MTMT ER - TY - JOUR AU - Szepesi Kovács, Dénes AU - Hajdu, Imre AU - Mészáros, Gergely AU - Wittner, Lucia AU - Meszéna, Domokos AU - Tóth, Estilla Zsófia AU - Hegedűs, Zita AU - Randelovic, Ivan AU - Tóvári, József AU - Szabó, Tímea AU - Szilágyi, Bence AU - Milen, Mátyás AU - Keserű, György Miklós AU - Ábrányi-Balogh, Péter TI - Synthesis and characterization of new fluorescent boro-β-carboline dyes JF - RSC ADVANCES J2 - RSC ADV VL - 11 PY - 2021 IS - 21 SP - 12802 EP - 12807 PG - 6 SN - 2046-2069 DO - 10.1039/D1RA02132J UR - https://m2.mtmt.hu/api/publication/31951354 ID - 31951354 N1 - Research Centre for Natural Sciences, Medicinal Chemistry Research Group, Budapest, POB 286, Hungary Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Budapest, 1521, Hungary Research Centre for Natural Sciences, Comparative Psychophysiology Research Group, Budapest, POB 286, Hungary Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, POB 278, Hungary János Szentágothai Doctoral School of Neurosciences, Semmelweis University, Budapest, 1085, Hungary National Institute of Oncology, Department of Experimental Pharmacology, POB 21, Budapest, 1525, Hungary Egis Pharmaceuticals Plc., Directorate of Drug Substance Development, POB 100, Budapest, 1475, Hungary Export Date: 30 August 2021 CODEN: RSCAC Correspondence Address: Keserű, G.M.; Research Centre for Natural Sciences, POB 286, Hungary; email: keseru.gyorgy@ttk.hu LA - English DB - MTMT ER - TY - THES AU - Szilágyi, Bence TI - Design and synthesis of D-amino acid oxidase inhibitors PB - Budapesti Műszaki és Gazdaságtudományi Egyetem PY - 2019 UR - https://m2.mtmt.hu/api/publication/31353710 ID - 31353710 LA - English DB - MTMT ER - TY - JOUR AU - Szilágyi, Bence AU - Hargitai, Csilla Eszter AU - Kelemen, Ádám Andor AU - Rácz, Anita AU - Ferenczy, György AU - Volk, Balázs AU - Keserű, György Miklós TI - Synthesis and Biochemical Evaluation of Lid-Open D-Amino Acid Oxidase Inhibitors JF - MOLECULES J2 - MOLECULES VL - 24 PY - 2019 IS - 2 PG - 8 SN - 1420-3049 DO - 10.3390/molecules24020290 UR - https://m2.mtmt.hu/api/publication/30392129 ID - 30392129 N1 - Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok krt. 2, Budapest, H-1117, Hungary Directorate of Drug Substance Development, Egis Pharmaceuticals Plc, P.O. Box 100, Budapest, H-1475, Hungary Plasma Chemistry Research Group, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok krt. 2, Budapest, H-1117, Hungary Export Date: 29 October 2019 CODEN: MOLEF Correspondence Address: Volk, B.; Directorate of Drug Substance Development, Egis Pharmaceuticals Plc, P.O. Box 100, Hungary; email: volk.balazs@egis.hu LA - English DB - MTMT ER - TY - JOUR AU - Orgován, Zoltán AU - Ferenczy, György AU - Steinbrecher, Thomas AU - Szilágyi, Bence AU - Bajusz, Dávid AU - Keserű, György Miklós TI - Validation of tautomeric and protomeric binding modes by free energy calculations. A case study for the structure based optimization of d-amino acid oxidase inhibitors JF - JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN J2 - J COMPUT AID MOL DES VL - 32 PY - 2018 IS - 2 SP - 331 EP - 345 PG - 15 SN - 0920-654X DO - 10.1007/s10822-018-0097-y UR - https://m2.mtmt.hu/api/publication/3333356 ID - 3333356 N1 - Megjegyzés-27191071 N1 Funding details: K111862, AHF, American Hungarian Foundation N1 Funding text: Program (project KTIA NAP_13) and by the Hungarian Science Foundation OTKA (project K111862) is gratefully acknowledged. Megjegyzés-27191022 N1 Funding details: K111862, AHF, American Hungarian Foundation N1 Funding text: Program (project KTIA NAP_13) and by the Hungarian Science Foundation OTKA (project K111862) is gratefully acknowledged. Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok krt. 2, Budapest, 1117, Hungary Schrödinger GmbH, Dynamostr. 13, Mannheim, 68165, Germany Cited By :7 Export Date: 6 September 2021 CODEN: JCADE Correspondence Address: Keserű, G.M.; Medicinal Chemistry Research Group, Magyar tudósok krt. 2, Hungary; email: gy.keseru@ttk.mta.hu LA - English DB - MTMT ER - TY - JOUR AU - Szilágyi, Bence AU - Skok, Ž AU - Rácz, Anita AU - Frlan, R AU - Ferenczy, György AU - Ilaš, J AU - Keserű, György Miklós TI - Discovery of D-amino acid oxidase inhibitors based on virtual screening against the lid-open enzyme conformation JF - BIOORGANIC & MEDICINAL CHEMISTRY LETTERS J2 - BIOORG MED CHEM LETT VL - 28 PY - 2018 IS - 10 SP - 1693 EP - 1698 PG - 6 SN - 0960-894X DO - 10.1016/j.bmcl.2018.04.048 UR - https://m2.mtmt.hu/api/publication/3375019 ID - 3375019 N1 - Megjegyzés-27392941 N1 Funding details: BI-HU/17-18-009, COST, European Cooperation in Science and Technology N1 Funding details: TÉT 16-1-2016-0069, COST, European Cooperation in Science and Technology N1 Funding text: This research was supported by the bilateral Hungarian-Slovenian science and technology cooperation under Grant Number TÉT 16-1-2016-0069 and BI-HU/17-18-009. A AB - D-Amino acid oxidase (DAAO) inhibitors are typically small polar compounds with often suboptimal pharmacokinetic properties. Features of the native binding site limit the operational freedom of further medicinal chemistry efforts. We therefore initiated a structure based virtual screening campaign based on the X-ray structures of DAAO complexes where larger ligands shifted the loop (lid opening) covering the native binding site. The virtual screening of our in-house collection followed by the in vitro test of the best ranked compounds led to the identification of a new scaffold with micromolar IC50. Subsequent SAR explorations enabled us to identify submicromolar inhibitors. Docking studies supported by in vitro activity measurements suggest that compounds bind to the active site with a salt-bridge characteristic to DAAO inhibitor binding. In addition, displacement of and interaction with the loop covering the active site contributes significantly to the activity of the most potent compounds. © 2018 Elsevier Ltd LA - English DB - MTMT ER - TY - JOUR AU - Szilágyi, Bence AU - Ferenczy, György AU - Keserű, György Miklós TI - Drug discovery strategies and the preclinical development of D-amino-acid oxidase inhibitors as antipsychotic therapies JF - EXPERT OPINION ON DRUG DISCOVERY J2 - EXPERT OPIN DRUG DIS VL - 13 ET - 0 PY - 2018 IS - 10 SP - 973 EP - 982 PG - 10 SN - 1746-0441 DO - 10.1080/17460441.2018.1524459 UR - https://m2.mtmt.hu/api/publication/30353690 ID - 30353690 N1 - Export Date: 3 January 2019 Correspondence Address: Keserű, G.M.; Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Hungarian Academy of SciencesHungary; email: keseru.gyorgy@ttk.mta.hu Funding details: KTIA NAP_13-2014-0009 Funding text 1: This work was supported by the National Brain Research Program [grant number KTIA NAP_13-2014-0009]. Cited By :4 Export Date: 22 July 2020 Correspondence Address: Keserű, G.M.; Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Hungarian Academy of SciencesHungary; email: keseru.gyorgy@ttk.mta.hu AB - Introduction: D-amino-acid oxidase (DAAO) degrades D-serine, a co-agonist of the NMDA receptor whose dysfunction is involved in the positive, negative, and cognitive symptoms of schizophrenia. The inhibition of DAAO appears to be a viable strategy to increase D-serine level and to have therapeutic potential in schizophrenia. Areas covered: This review describes the efforts to develop DAAO inhibitors and to optimize their in vitro and in vivo effects in preclinical settings. The structural evolution of DAAO inhibitors is presented from simple carboxylic acid derivatives via small, planar compounds with carboxylic acid mimetics to extended compounds whose binding is possible owing to DAAO flexibility. Inhibitory potency and pharmacokinetic properties are discussed in the context of compounds’ ability to increase D-serine level and to show efficacy in animal models of schizophrenia. Expert opinion: The accumulated knowledge on the structural requirements of DAAO inhibitors and on their in vitro and in vivo effects provides appropriate basis to develop inhibitors with optimized potency, selectivity and pharmacokinetic profile including blood-brain penetration. In addition, the validation of DAAO inhibition therapy in alleviating the symptoms of schizophrenia requires further studies on the efficacy of DAAO inhibitors in behavioral assays of animals and on the species differences in D-serine metabolism. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group. LA - English DB - MTMT ER - TY - JOUR AU - Szilágyi, Bence AU - Kovacs, P AU - Ferenczy, György AU - Rácz, Anita AU - Németh, Krisztina AU - Benéné Visy, Júlia AU - Szabó, Pál Tamás AU - Ilas, J AU - Balogh, György Tibor AU - Monostory, Katalin AU - Vincze, István AU - Tábi, Tamás AU - Szökő, Éva AU - Keserű, György Miklós TI - Discovery of isatin and 1H-indazol-3-ol derivatives as d-amino acid oxidase (DAAO) inhibitors JF - BIOORGANIC & MEDICINAL CHEMISTRY J2 - BIOORGAN MED CHEM VL - 26 ET - 0 PY - 2018 IS - 8 SP - 1579 EP - 1587 PG - 9 SN - 0968-0896 DO - 10.1016/j.bmc.2018.02.004 UR - https://m2.mtmt.hu/api/publication/3344151 ID - 3344151 N1 - Megjegyzés-27393542 N1 Funding details: KTIA NAP_13 N1 Funding text: This study was supported by the National Brain Research Program grant (project KTIA NAP_13). Celesztina Domonkos is acknowledged for help in biological measurements, Katalin Tóth and Máté Déri for performing in vitro pharmacokinetic studies and Judit Müller for the performing PAMPA tests. A AB - d-Amino acid oxidase (DAAO) is a potential target in the treatment of schizophrenia as its inhibition increases brain d-serine level and thus contributes to NMDA receptor activation. Inhibitors of DAAO were sought testing [6+5] type heterocycles and identified isatin derivatives as micromolar DAAO inhibitors. A pharmacophore and structure-activity relationship analysis of isatins and reported DAAO inhibitors led us to investigate 1H-indazol-3-ol derivatives and nanomolar inhibitors were identified. The series was further characterized by pKa and isothermal titration calorimetry measurements. Representative compounds exhibited beneficial properties in in vitro metabolic stability and PAMPA assays. 6-fluoro-1H-indazol-3-ol (37) significantly increased plasma d-serine level in an in vivo study on mice. These results show that the 1H-indazol-3-ol series represents a novel class of DAAO inhibitors with the potential to develop drug candidates. LA - English DB - MTMT ER - TY - CONF AU - Somsák, László AU - M, Polyák AU - G, Varga AU - J, Begum AU - Szilágyi, Bence AU - Juhász, László AU - T, Docsa AU - P, Gergely AU - J M, Hayes TI - N-(β-D-Glucopyranosyl) Oxadiazole- and 1,2,4-Triazolecarboxamides as Glycogen Phosphorylase Inhibitors: Synthesis, Enzyme Kinetics and Computational Evaluation T2 - 27th International Carbohydrate Symposium PB - Indian Institute of Science (IISC) C1 - Bangalore PY - 2014 UR - https://m2.mtmt.hu/api/publication/2517810 ID - 2517810 N1 - (Abstracts p. 91) AB - I-P-58 (Abstracts p. 91) LA - English DB - MTMT ER - TY - CONF AU - Mária, Polyák AU - Gergő, Varga AU - Szilágyi, Bence AU - Tibor, Docsa AU - Pál, Gergely AU - Juhász, László AU - Somsák, László ED - Ernest, Giralt TI - Synthesis and enzyme kinetic evaluation of heterocyclic bioisosteric analogues of N-acyl-N’-β-D-glucopyranosyl urea type glycogen phosphorylase inhibitors T2 - 5th European Conference on Chemistry for Life Sciences, Abstract Book C1 - Barcelona PY - 2013 SP - 93 UR - https://m2.mtmt.hu/api/publication/2382460 ID - 2382460 LA - English DB - MTMT ER - TY - JOUR AU - Polyák, M AU - Varga, G AU - Szilágyi, Bence AU - Juhász, László AU - Docsa, Tibor AU - Gergely, Pál AU - Begum, J AU - Hayes, JM AU - Somsák, László TI - Synthesis, enzyme kinetics and computational evaluation of N-(beta-D-glucopyranosyl) oxadiazolecarboxamides as glycogen phosphorylase inhibitors JF - BIOORGANIC & MEDICINAL CHEMISTRY J2 - BIOORGAN MED CHEM VL - 21 PY - 2013 SP - 5738 EP - 5747 PG - 10 SN - 0968-0896 DO - 10.1016/j.bmc.2013.07.024 UR - https://m2.mtmt.hu/api/publication/2381496 ID - 2381496 LA - English DB - MTMT ER - TY - CHAP AU - Polyák, Mária AU - Varga, Gergely AU - Szilágyi, Bence AU - Docsa, Tibor AU - Gergely, Pál AU - Juhász, László AU - Somsák, László ED - Magyar, Kémikusok Egyesülete TI - N-Acil-N’-β-D-glükopiranozil-karbamid típusú glikogén foszforiláz inhibitorok heterociklusos bioizosztér analógjainak szintézise és enzimkinetikai vizsgálata T2 - Vegyészkonferencia 2013 PB - Magyar Kémikusok Egyesülete (MKE) CY - Budapest SN - 9789639970366 PY - 2013 SP - 114 UR - https://m2.mtmt.hu/api/publication/2382468 ID - 2382468 N1 - P-54 LA - Hungarian DB - MTMT ER - TY - CONF AU - Vágvölgyiné Tóth, Marietta AU - Gergely, Tibor Varga AU - Mária, Polyák AU - Szilágyi, Bence AU - Kun, Sándor AU - I, Takács AU - Juhász, László AU - Tibor, Docsa AU - Pál, Gergely AU - Somsák, László TI - SAR study of glycogen phosphorylase inhibitors: heterocycles as bioisosteric amide replacements in N-acyl-beta-D-glucopyranosylamines and N-acyl-N’-beta-D-glucopyranosyl ureas T2 - 26th International Carbohydrate Symposium PY - 2012 UR - https://m2.mtmt.hu/api/publication/2314255 ID - 2314255 LA - English DB - MTMT ER - TY - CONF AU - Vágvölgyiné Tóth, Marietta AU - Varga, G T AU - Polyák, M AU - Szilágyi, Bence AU - Kun, Sándor AU - Takács, I AU - Juhász, László AU - Docsa, T AU - Gergely, P AU - Somsák, László TI - SAR Study of Glycogen Phosphorylase Inhibitors: Heterocycles as Bioisosteric Amide Replacements in N-Acyl-beta-D-Glucopyranosylamines and N-Acyl-N’-beta-D-Glucopyranosyl Ureas T2 - 26th International Carbohydrate Symposium PY - 2012 SP - F80 EP - F80 UR - https://m2.mtmt.hu/api/publication/2034044 ID - 2034044 LA - English DB - MTMT ER -