2-Aryladenine derivatives as a potent scaffold for A1, A3 and dual A1/A3 adenosine receptor antagonists: Synthesis and structure-activity relationships |
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| Institution: | 1. Center of Chemistry, Campus de Gualtar, Universidade do Minho, 4710-057 Braga, Portugal;2. Department of Pharmacology, Universidade de Santiago de Compostela, Edificio CIMUS, Avda de Barcelona, 15782 Santiago de Compostela, Spain;3. School of Chemical Sciences & Engineering, Yachay Tech University, Yachay City of Knowledge, 100119 Urcuquí, Ecuador;1. Department of Pharmaceutical Sciences, “Department of Excellence 2018-2022”, University of Perugia, Via del Liceo 1, 06123, Perugia, Italy;2. Department of Pharmaceutical & Medicinal Chemistry, Institute of Pharmacy, Eberhard-Karls University Tuebingen, Auf der Morgenstelle 8, 72076, Tuebingen, Germany;3. CIMUS Research Center, University of Santiago de Compostela, Avda de Barcelona s/n, Planta 3, Despacho1, 15782, Santiago de Compostela, Spain;4. Department of Experimental Medicine, University of Perugia, Piazzale Gambuli, 06100, Perugia, Italy;1. Department of Synthesis and Chemical Technology of Pharmaceutical Substances, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4A Chodźki St., PL-20093, Lublin, Poland;2. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark;3. Department of Pharmacology, Universidade de Santiago de Compostela, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Avda de Barcelona, Santiago de Compostela, E-15782, Spain;4. Department of Pharmacology and Pharmacodynamics, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4A Chodźki St., PL-20093, Lublin, Poland;5. Department of General and Coordination Chemistry, Maria Curie-Skłodowska University, M. Curie-Skłodowskiej Sq. 2, PL-20031, Lublin, Poland;6. School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, P.O. Box 1627, FI-70211, Kuopio, Finland;1. Dipartimento di Scienze Chimiche e Farmaceutiche, Università Degli Studi di Trieste, Via Licio Giorgeri 1, 34127, Trieste, Italy;2. Molecular Modeling Section (MMS), Dipartimento di Scienze Del Farmaco, Università di Padova, Via Marzolo 5, 35131, Padova, Italy;3. Laboratory of Bioorganic Chemistry, NIDDK, National Institute of Health, Bethesda, MD, USA;1. Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Trieste, Piazzale Europa 1, 34127 Trieste, Italy;2. Molecular Modeling Section (MMS), Dipartimento di Scienze del Farmaco, Università di Padova, Via Marzolo 5, 35131 Padova, Italy;3. Department of Pharmacy, National University of Singapore, 3 Science Drive 2, 117543 Singapore;4. Dipartimento di Scienze Chimiche e Farmaceutiche, Università degli Studi di Ferrara, Via Fossato di Mortara 17-19, 44100 Ferrara, Italy;5. Institut für Pharmakologie und Toxicologie, Universität of Würzburg, Versbacher Strasse 9, 97078 Würzburg, Germany;1. Dipartimento NEUROFARBA, Sezione Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy;2. Department of Chemistry, Imperial College London, South Kensington, London SW7 2AZ, UK;3. Dipartimento di Farmacia, Università degli Studi di Pisa, Via Bonanno 6, 56126 Pisa, Italy;4. NEUROFARBA, Sezione Farmacologia e Tossicologia, Università degli Studi di Firenze, Viale Pieraccini 6, 50139 Firenze, Italy;1. PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany;2. CNS Research, Medicinal Chemistry & Lead Generation, UCB S.A., Chemin du Foriest, 1420 Braine l’Alleud, Belgium |
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| Abstract: | From a collection containing more than 1500 academic compounds, in silico screening identified a hit for the human A1 adenosine receptor containing a new purine scaffold. To study the structure activity relationships of this new chemical series for adenosine receptors, a library of 24 purines was synthesized and tested in radioligand binding assays at human A1, A2A, A2B and A3 adenosine receptor subtypes. Fourteen molecules showed potent antagonism at A1, A3 or dual A1/A3 adenosine receptors. This purine scaffold is an important source for novel biochemical tools and/or therapeutic drugs. |
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| Keywords: | Adenine derivatives Adenosine receptor antagonists 2-Arylpurine derivatives |
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