Literature DB >> 24900298

Discovery of LAS101057: A Potent, Selective, and Orally Efficacious A2B Adenosine Receptor Antagonist.

Paul Eastwood1, Cristina Esteve1, Jacob González1, Silvia Fonquerna1, Josep Aiguadé1, Inés Carranco1, Teresa Doménech1, Mònica Aparici1, Montserrat Miralpeix1, Joan Albertí1, Mónica Córdoba1, Raquel Fernández1, Mercè Pont1, Núria Godessart1, Neus Prats1, María Isabel Loza2, María Isabel Cadavid2, Arsenio Nueda1, Bernat Vidal1.   

Abstract

The structure-activity relationships for a series of pyrazine-based A2B adenosine receptor antagonists are described. From this work, LAS101057 (17), a potent, selective, and orally efficacious A2B receptor antagonist, was identified as a clinical development candidate. LAS101057 inhibits agonist-induced IL-6 production in human fibroblasts and is active in an ovalbumin (OVA)-sensitized mouse model after oral administration, reducing airway hyperresponsiveness to methacholine, Th2 cytokine production, and OVA-specific IgE levels.

Entities:  

Keywords:  A2B adenosine receptor antagonist; clinical candidate; ovalbumin mouse model

Year:  2010        PMID： 24900298      PMCID： PMC4018059          DOI： 10.1021/ml100249e

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


  23 in total

Review 1.  A(2B) adenosine receptors in immunity and inflammation.

Authors:  György Haskó; Balázs Csóka; Zoltán H Németh; E Sylvester Vizi; Pál Pacher
Journal:  Trends Immunol       Date:  2009-05-07       Impact factor: 16.687

Review 2.  Overexpression of G protein-coupled receptors in cancer cells: involvement in tumor progression.

Authors:  Shuyu Li; Shuguang Huang; Sheng-Bin Peng
Journal:  Int J Oncol       Date:  2005-11       Impact factor: 5.650

3.  The A2B adenosine receptor protects against inflammation and excessive vascular adhesion.

Authors:  Dan Yang; Ying Zhang; Hao G Nguyen; Milka Koupenova; Anil K Chauhan; Maria Makitalo; Matthew R Jones; Cynthia St Hilaire; David C Seldin; Paul Toselli; Edward Lamperti; Barbara M Schreiber; Haralambos Gavras; Denisa D Wagner; Katya Ravid
Journal:  J Clin Invest       Date:  2006-07       Impact factor: 14.808

4.  Hypoxia-inducible adenosine A2B receptor modulates proliferation of colon carcinoma cells.

Authors:  De-Fu Ma; Tetsuo Kondo; Tadao Nakazawa; Dong-Feng Niu; Kunio Mochizuki; Tomonori Kawasaki; Tetsu Yamane; Ryohei Katoh
Journal:  Hum Pathol       Date:  2010-11       Impact factor: 3.466

Review 5.  Purinergic receptors in airway epithelia.

Authors:  Eduardo R Lazarowski; Richard C Boucher
Journal:  Curr Opin Pharmacol       Date:  2009-03-13       Impact factor: 5.547

Review 6.  Adenosine receptors as targets for therapeutic intervention in asthma and chronic obstructive pulmonary disease.

Authors:  Riccardo Polosa; Michael R Blackburn
Journal:  Trends Pharmacol Sci       Date:  2009-09-15       Impact factor: 14.819

7.  Effect of A2B adenosine receptor gene ablation on proinflammatory adenosine signaling in mast cells.

Authors:  Sergey Ryzhov; Rinat Zaynagetdinov; Anna E Goldstein; Sergey V Novitskiy; Mikhail M Dikov; Michael R Blackburn; Italo Biaggioni; Igor Feoktistov
Journal:  J Immunol       Date:  2008-06-01       Impact factor: 5.422

Review 8.  Adenosine-receptor subtypes: their relevance to adenosine-mediated responses in asthma and chronic obstructive pulmonary disease.

Authors:  R Polosa
Journal:  Eur Respir J       Date:  2002-08       Impact factor: 16.671

9.  Attenuation of chronic pulmonary inflammation in A2B adenosine receptor knockout mice.

Authors:  Rinat Zaynagetdinov; Sergey Ryzhov; Anna E Goldstein; Huiyong Yin; Sergey V Novitskiy; Kasia Goleniewska; Vasiliy V Polosukhin; Dawn C Newcomb; Daphne Mitchell; Eva Morschl; Yang Zhou; Michael R Blackburn; R Stokes Peebles; Italo Biaggioni; Igor Feoktistov
Journal:  Am J Respir Cell Mol Biol       Date:  2009-06-25       Impact factor: 6.914

10.  Enhanced mast cell activation in mice deficient in the A2b adenosine receptor.

Authors:  Xiaoyang Hua; Martina Kovarova; Kelly D Chason; MyTrang Nguyen; Beverly H Koller; Stephen L Tilley
Journal:  J Exp Med       Date:  2007-01-02       Impact factor: 14.307
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  5 in total

Review 1.  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

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

Authors:  Abel Crespo; Abdelaziz El Maatougui; Pierfrancesco Biagini; Jhonny Azuaje; Alberto Coelho; José Brea; María Isabel Loza; María Isabel Cadavid; Xerardo García-Mera; Hugo Gutiérrez-de-Terán; Eddy Sotelo
Journal:  ACS Med Chem Lett       Date:  2013-10-03       Impact factor: 4.345

3.  The Influence of the 1-(3-Trifluoromethyl-Benzyl)-1H-Pyrazole-4-yl Moiety on the Adenosine Receptors Affinity Profile of Pyrazolo[4,3-e][1,2,4]Triazolo[1,5-c]Pyrimidine Derivatives.

Authors:  Stephanie Federico; Sara Redenti; Mattia Sturlese; Antonella Ciancetta; Sonja Kachler; Karl-Norbert Klotz; Barbara Cacciari; Stefano Moro; Giampiero Spalluto
Journal:  PLoS One       Date:  2015-12-01       Impact factor: 3.240

4.  Development of a Radiofluorinated Adenosine A2B Receptor Antagonist as Potential Ligand for PET Imaging.

Authors:  Marcel Lindemann; Rareş-Petru Moldovan; Sonja Hinz; Winnie Deuther-Conrad; Daniel Gündel; Sladjana Dukic-Stefanovic; Magali Toussaint; Rodrigo Teodoro; Cathleen Juhl; Jörg Steinbach; Peter Brust; Christa E Müller; Barbara Wenzel
Journal:  Int J Mol Sci       Date:  2020-04-30       Impact factor: 5.923

Review 5.  A2B Adenosine Receptor and Cancer.

Authors:  Zhan-Guo Gao; Kenneth A Jacobson
Journal:  Int J Mol Sci       Date:  2019-10-17       Impact factor: 5.923
  5 in total

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