National Institutes of Health, a Component of the US Dept. of Health & Human Services

Saint Louis University

Dilip K Tosh

Kenneth Alan Jacobson

Daniela Salvemini

Oksana Gavrilova

Marc L Reitman

Kenneth A Jacobson

Disclosed are compounds of the formulas (I), (II), and (II): which are Aadenosine receptor agonists, pharmaceutical compositions comprising such compounds, and a method of use of these compounds, wherein Y, R-R, R-R, and R-Rare as defined in the specification. These compounds are selective to the Aadenosine receptor, and are contemplated for use in the treatment or prevention of a number of diseases or conditions, for example, for inducing and/or maintaining a hypothermic and/or hypometabolic state for treatment of a mammal.

A1 adenosine receptor agonists and methods of use thereof

Disclosed are compounds of the formula (I) and (II): which are Aadenosine receptor agonists, pharmaceutical compositions comprising such compounds, and a method of use of these compounds, wherein X, Y, Z, R-R, and R-Rare as defined in the specification. These compounds are selective to the Areceptor, and are contemplated for use in the treatment or prevention of a number of diseases or conditions, for example, neuropathic pain.

A3 adenosine receptor agonists

Disclosed are compounds of the formula (I) and (II) which are Aadenosine receptor agonists, pharmaceutical compositions comprising such compounds, and a method of use of these compounds, wherein X, Y, Z, R-R, and R-Rare as defined in the specification. These compounds are selective to the Areceptor, and are contemplated for use in the treatment or prevention of a number of diseases or conditions, for example, neuropathic pain. 

Disclosed are Aadenosine receptor antagonists and/or partial agonists and Aadenosine receptor agonists and/or partial agonists of formula (I): wherein Rto Rare as described herein, as well as pharmaceutical compositions thereof and methods of use thereof. The AAR antagonists or partial agonists find use in treating a number of diseases such as cancer, glaucoma, and inflammatory diseases, as well as in preventing cardiac ischemia. Also disclosed are radiolabeled compounds of formula (I) and the use thereof in diagnostic imaging of tissues and organs. The AAR agonists and partial agonists find use in treating diseases such as seizures, convulsion, stroke, diabetes, pain, arrhythmias, depression, and anxiety and in cardioprotection or neuroprotection.

Adenosine receptor agonists, partial agonists, and antagonists

Disclosed are (N)-methanocarba adenine nucleosides of formulas (I)-(V), for example, of formula (V): as highly potent Aadenosine receptor agonists, pharmaceutical compositions comprising such nucleosides, and a method of use of these nucleosides, wherein R-Rare as defined in the specification. These nucleosides exhibit similar selectivities as agonists of the Aversus the Areceptor for both human and mouse adenosine receptors, and are contemplated for use in the treatment a number of diseases, for example, inflammation, cardiac ischemia, stroke, asthma, diabetes, and cardiac arrhythmias.

[object Object]

Disclosed are (N)-methanocarba adenine nucleosides, e.g., of the formula (I): as Aadenosine receptor agonists, pharmaceutical compositions comprising such nucleosides, and a method of use of these nucleosides, wherein A, a, R, and Rare as defined in the specification. These nucleosides are contemplated for use in the treatment a number of diseases, for example, inflammation, cardiac ischemia, stroke, asthma, diabetes, and cardiac arrhythmias. Also disclosed are conjugates comprising a dendrimer and one or more ligands, which are functionalized congeners of an agonist or antagonist of a receptor of the G-protein coupled receptor (GPCR) superfamily. Such conjugates are have the potential of being used as dual agonists, dual antagonists, or agonist/antagonist combinations. 

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Rockville, MD, United States of America

Dilip K Tosh