Literature DB >> 24900602

Discovery of 3,4-Dihydropyrimidin-2(1H)-ones As a Novel Class of Potent and Selective A2B Adenosine Receptor Antagonists.

Abel Crespo1, Abdelaziz El Maatougui1, Pierfrancesco Biagini2, Jhonny Azuaje1, Alberto Coelho1, José Brea2, María Isabel Loza2, María Isabel Cadavid2, Xerardo García-Mera2, Hugo Gutiérrez-de-Terán3, Eddy Sotelo4.   

Abstract

We describe the discovery and optimization of 3,4-dihydropyrimidin-2(1H)-ones as a novel family of (nonxanthine) A2B receptor antagonists that exhibit an unusually high selectivity profile. The Biginelli-based hit optimization process enabled a thoughtful exploration of the structure-activity and structure-selectivity relationships for this chemotype, enabling the identification of ligands that combine structural simplicity with excellent hA2B AdoR affinity and remarkable selectivity profiles.

Entities:  

Keywords:  3,4-dihydropyrimidin-2(1H)-ones; A2B receptor antagonists; Adenosine antagonists; Biginelli reaction

Year:  2013        PMID： 24900602      PMCID： PMC4027370          DOI： 10.1021/ml400185v

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  23 in total

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Authors:  Vicente Yaziji; David Rodríguez; Hugo Gutiérrez-de-Terán; Alberto Coelho; Olga Caamaño; Xerardo García-Mera; José Brea; María Isabel Loza; María Isabel Cadavid; Eddy Sotelo
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Review 2.  Recent developments in adenosine receptor ligands and their potential as novel drugs.

Authors:  Christa E Müller; Kenneth A Jacobson
Journal:  Biochim Biophys Acta       Date:  2010-12-23

Review 3.  Adenosine receptor antagonists: translating medicinal chemistry and pharmacology into clinical utility.

Authors:  Pier Giovanni Baraldi; Mojgan Aghazadeh Tabrizi; Stefania Gessi; Pier Andrea Borea
Journal:  Chem Rev       Date:  2008-01       Impact factor: 60.622

Review 4.  International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and classification of adenosine receptors--an update.

Authors:  Bertil B Fredholm; Adriaan P IJzerman; Kenneth A Jacobson; Joel Linden; Christa E Müller
Journal:  Pharmacol Rev       Date:  2011-02-08       Impact factor: 25.468

Review 5.  Adenosine A2B receptors.

Authors:  I Feoktistov; I Biaggioni
Journal:  Pharmacol Rev       Date:  1997-12       Impact factor: 25.468

6.  Molecular dynamics simulations reveal insights into key structural elements of adenosine receptors.

Authors:  David Rodríguez; Ángel Piñeiro; Hugo Gutiérrez-de-Terán
Journal:  Biochemistry       Date:  2011-04-20       Impact factor: 3.162

7.  Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine derivatives as adenosine receptor antagonists. Influence of the N5 substituent on the affinity at the human A 3 and A 2B adenosine receptor subtypes: a molecular modeling investigation.

Authors:  Giorgia Pastorin; Tatiana Da Ros; Giampiero Spalluto; Francesca Deflorian; Stefano Moro; Barbara Cacciari; Pier Giovanni Baraldi; Stefania Gessi; Katia Varani; Pier Andrea Borea
Journal:  J Med Chem       Date:  2003-09-25       Impact factor: 7.446

8.  An efficacious protocol for C-4 substituted 3,4-dihydropyrimidinones. Synthesis and calcium channel binding studies.

Authors:  Kamaljit Singh; Divya Arora; Danielle Falkowski; Qingxin Liu; Robert S Moreland
Journal:  European J Org Chem       Date:  2009-07-01

9.  5-aroyl-3,4-dihydropyrimidin-2-one library generation via automated sequential and parallel microwave-assisted synthesis techniques.

Authors:  Leonardo Pisani; Hana Prokopcová; Jennifer M Kremsner; C Oliver Kappe
Journal:  J Comb Chem       Date:  2007-03-07

10.  Progress in the discovery of selective, high affinity A(2B) adenosine receptor antagonists as clinical candidates.

Authors:  Rao V Kalla; Jeff Zablocki
Journal:  Purinergic Signal       Date:  2008-06-21       Impact factor: 3.765
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1.  A2B adenosine receptor antagonists rescue lymphocyte activity in adenosine-producing patient-derived cancer models.

Authors:  Apple Hui Min Tay; Rubén Prieto-Díaz; Shiyong Neo; Le Tong; Xinsong Chen; Valentina Carannante; Björn Önfelt; Johan Hartman; Felix Haglund; Maria Majellaro; Jhonny Azuaje; Xerardo Garcia-Mera; Jose M Brea; Maria I Loza; Willem Jespers; Hugo Gutierrez-de-Teran; Eddy Sotelo; Andreas Lundqvist
Journal:  J Immunother Cancer       Date:  2022-05       Impact factor: 12.469

2.  Structure-Based Design of Potent and Selective Ligands at the Four Adenosine Receptors.

Authors:  Willem Jespers; Ana Oliveira; Rubén Prieto-Díaz; María Majellaro; Johan Åqvist; Eddy Sotelo; Hugo Gutiérrez-de-Terán
Journal:  Molecules       Date:  2017-11-10       Impact factor: 4.411

3.  Identification of V6.51L as a selectivity hotspot in stereoselective A2B adenosine receptor antagonist recognition.

Authors:  Xuesong Wang; Willem Jespers; Rubén Prieto-Díaz; Maria Majellaro; Adriaan P IJzerman; Gerard J P van Westen; Eddy Sotelo; Laura H Heitman; Hugo Gutiérrez-de-Terán
Journal:  Sci Rep       Date:  2021-07-08       Impact factor: 4.379

Review 4.  Exploration of chalcones and related heterocycle compounds as ligands of adenosine receptors: therapeutics development.

Authors:  Chrisna Matthee; Gisella Terre'Blanche; Lesetja J Legoabe; Helena D Janse van Rensburg
Journal:  Mol Divers       Date:  2021-06-27       Impact factor: 3.364

5.  One Pot Synthesis of Micromolar BACE-1 Inhibitors Based on the Dihydropyrimidinone Scaffold and Their Thia and Imino Analogues.

Authors:  Jessica Bais; Fabio Benedetti; Federico Berti; Iole Cerminara; Sara Drioli; Maria Funicello; Giorgia Regini; Mattia Vidali; Fulvia Felluga
Journal:  Molecules       Date:  2020-09-10       Impact factor: 4.411

6.  Optimization of 2-Amino-4,6-diarylpyrimidine-5-carbonitriles as Potent and Selective A1 Antagonists.

Authors:  Cristina Val; Carlos Rodríguez-García; Rubén Prieto-Díaz; Abel Crespo; Jhonny Azuaje; Carlos Carbajales; Maria Majellaro; Alejandro Díaz-Holguín; José M Brea; Maria Isabel Loza; Claudia Gioé-Gallo; Marialessandra Contino; Angela Stefanachi; Xerardo García-Mera; Juan C Estévez; Hugo Gutiérrez-de-Terán; Eddy Sotelo
Journal:  J Med Chem       Date:  2022-01-22       Impact factor: 7.446
  6 in total

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