Literature DB >> 12166930

Synthesis, biological properties, and molecular modeling investigation of the first potent, selective, and water-soluble human A(3) adenosine receptor antagonist.

Anna Maconi, Giorgia Pastorin, Tatiana Da Ros, Giampiero Spalluto, Zhan-Guo Gao, Kenneth A Jacobson, Pier Giovanni Baraldi, Barbara Cacciari, Katia Varani, Stefano Moro, Pier Andrea Borea.   

Abstract

A new, highly potent, selective, and water-soluble antagonist of the hA(3) adenosine receptor was synthesized and tested in binding and functional assays. Compound 4 (5-[[(4-pyridyl)amino]carbonyl]amino-8-methyl-2-(2-furyl)-pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine hydrochloride) displayed high water solubility (15 mM) and the highest affinity (K(i) = 0.01 nM) and selectivity for the hA(3) versus A(1), A(2A), and A(2B) receptors (>10000-fold) ever reported. A Schild analysis of the antagonism by 4 of agonist-induced inhibition of cAMP production in CHO cells expressing the hA(3) receptor indicated a K(B) value of 0.20 nM.

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Year:  2002        PMID： 12166930     DOI： 10.1021/jm020974x

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  16 in total

1.  Chapter 13. A3 Adenosine Receptors.

Authors:  Kenneth A Jacobson; Susanna Tchilibon; Bhalchandra V Joshi; Zhan-Guo Gao
Journal:  Annu Rep Med Chem       Date:  2003       Impact factor: 1.059

2.  Conversion of A3 adenosine receptor agonists into selective antagonists by modification of the 5'-ribofuran-uronamide moiety.

Authors:  Zhan-Guo Gao; Bhalchandra V Joshi; Athena M Klutz; Soo-Kyung Kim; Hyuk Woo Lee; Hea Ok Kim; Lak Shin Jeong; Kenneth A Jacobson
Journal:  Bioorg Med Chem Lett       Date:  2005-11-10       Impact factor: 2.823

3.  Invited Lectures : Overviews Purinergic signalling: past, present and future.

Authors: 
Journal:  Purinergic Signal       Date:  2006-05-15       Impact factor: 3.765

4.  A3 adenosine receptor antagonists delay irreversible synaptic failure caused by oxygen and glucose deprivation in the rat CA1 hippocampus in vitro.

Authors:  Anna Maria Pugliese; Elisabetta Coppi; Giampiero Spalluto; Renato Corradetti; Felicita Pedata
Journal:  Br J Pharmacol       Date:  2006-03       Impact factor: 8.739

Review 5.  Medicinal chemistry of the A3 adenosine receptor: agonists, antagonists, and receptor engineering.

Authors:  Kenneth A Jacobson; Athena M Klutz; Dilip K Tosh; Andrei A Ivanov; Delia Preti; Pier Giovanni Baraldi
Journal:  Handb Exp Pharmacol       Date:  2009

6.  Synthesis and biological evaluation of a new series of 1,2,4-triazolo[1,5-a]-1,3,5-triazines as human A(2A) adenosine receptor antagonists with improved water solubility.

Authors:  Stephanie Federico; Silvia Paoletta; Siew Lee Cheong; Giorgia Pastorin; Barbara Cacciari; Stefano Stragliotto; Karl Norbert Klotz; Jeffrey Siegel; Zhan-Guo Gao; Kenneth A Jacobson; Stefano Moro; Giampiero Spalluto
Journal:  J Med Chem       Date:  2011-01-07       Impact factor: 7.446

Review 7.  A3 Adenosine Receptors as Modulators of Inflammation: From Medicinal Chemistry to Therapy.

Authors:  Kenneth A Jacobson; Stefania Merighi; Katia Varani; Pier Andrea Borea; Stefania Baraldi; Mojgan Aghazadeh Tabrizi; Romeo Romagnoli; Pier Giovanni Baraldi; Antonella Ciancetta; Dilip K Tosh; Zhan-Guo Gao; Stefania Gessi
Journal:  Med Res Rev       Date:  2017-07-06       Impact factor: 12.944

8.  Synthesis and pharmacological characterization of a new series of 5,7-disubstituted-[1,2,4]triazolo[1,5-a][1,3,5]triazine derivatives as adenosine receptor antagonists: A preliminary inspection of ligand-receptor recognition process.

Authors:  Giorgia Pastorin; Stephanie Federico; Silvia Paoletta; Marta Corradino; Francesca Cateni; Barbara Cacciari; Karl-Norbert Klotz; Zhan-Guo Gao; Kenneth A Jacobson; Giampiero Spalluto; Stefano Moro
Journal:  Bioorg Med Chem       Date:  2010-02-25       Impact factor: 3.641

9.  Conjugable A3 adenosine receptor antagonists for the development of functionalized ligands and their use in fluorescent probes.

Authors:  Stephanie Federico; Enrico Margiotta; Stefano Moro; Eszter Kozma; Zhan-Guo Gao; Kenneth A Jacobson; Giampiero Spalluto
Journal:  Eur J Med Chem       Date:  2019-11-22       Impact factor: 6.514

10.  N6-Substituted adenosine derivatives: selectivity, efficacy, and species differences at A3 adenosine receptors.

Authors:  Zhan-Guo Gao; Joshua B Blaustein; Ariel S Gross; Neli Melman; Kenneth A Jacobson
Journal:  Biochem Pharmacol       Date:  2003-05-15       Impact factor: 5.858
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