43157-48-8Relevant academic research and scientific papers
Nucleoside-5′-monophosphates as prodrugs of adenosine A2A receptor agonists activated by ecto-5′-nucleotidase
El-Tayeb, Ali,Iqbal, Jamshed,Behrenswerth, Andrea,Romio, Michael,Schneider, Marion,Zimmermann, Herbert,Schrader, Jürgen,Müller, Christa E.
supporting information; experimental part, p. 7669 - 7677 (2010/09/03)
Prodrugs of adenosine A2A receptor agonists were developed that are activated by ecto-5′-nucleotidase (ecto-5′-NT,CD73). Because ecto-5′-NT is upregulated in inflamed tissue, the A2A agonists are expected to be released from their prodrug form at the sites of inflammation. 2-(Ar)alkyl-substituted AMP derivatives were synthesized and investigated. Certain 2-substituted AMP derivatives, including 2-hexylthio-AMP, 2-cyclopentylthio-AMP, 2-cyclohexylmethylthio-AMP, and 2-cyclohexylethylthio-AMP were accepted as substrates by ecto-5′-NT and readily converted to the corresponding 2-substituted adenosine derivatives. The 2-cyclohexylethylthio substitution was a good compromise between the requirements of the ecto-5′-NT and the adenosine A2A receptor. The corresponding AMP derivative (12g) was a similarly good substrate as AMP itself, while the resulting adenosine derivative (11g) was a relatively potent A2A agonist (radioligand binding to rat brain striatal membranes: Ki=372 nM; inhibition of anti-CD3/anti-CD28-induced IFN-γ release in mouse CD4+ cells: EC50=50 nM). Compound 11g was released from 12g by incubation with CD4+ cells isolated from wild-type mice but only to a much smaller extent by cells from ecto-5′-NT knockout mice. Compound 12g will be a new lead structure for the development of more potent and selective ecto-5′-NT- activated prodrugs of selective anti-inflammatory A2A receptor agonists.
2-Thioether A2A receptor agonists
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, (2008/06/13)
2-adenosine propargyl phenyl ether compositions having the following formula: and methods for using the compositions as A2A receptor agonists to stimulate mammalian coronary vasodilatation for therapeutic purposes and for purposes of imaging the heart.
2-thioether 5'-O-(1-thiotriphosphate)adenosine derivatives as new insulin secretagogues acting through P2Y-receptors
Fischer, Bilha,Chulkin, Ana,Boyer, Jose L.,Harden, Kendall T.,Gendron, Fernand-Pierre,Beaudoin, Adrien R.,Chapal, Jeannie,Hillaire-Buys, Dominique,Petit, Pierre
, p. 3636 - 3646 (2007/10/03)
P2-Receptors (P2-Rs) represent significant targets for novel drug development. P2-Rs were identified also on pancreatic B cells and are involved in insulin secretion. Therefore, novel P2Y-R ligands, 2-thioether 5'-O-phosphorothioate adenosine derivatives
