Design, synthesis and evaluation of N6-substituted 2-aminoadenosine-5'-N-methylcarboxamides as A3 adenosine receptor agonists

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Abstract

A series of N6-substituted 2-aminoadenosine-5 -N- methylcarboxamides were synthesized from the versatile intermediate, O 6-(benzotriazol-1-yl)-2-amino-2 ,3 -O- isopropylideneinosine-5 -N-methylcarboxamide (1). These compounds were evaluated as A3 adenosine receptor agonists in terms of their potency and receptor sub-type selectivity in a cAMP accumulation assay and a number of potent and selective compounds were identified. One such compound, 2-amino-N6-(3-chlorobenzyl)adenosine-5 -N-methylcarboxamide (3i), was over 500-fold selective for the A3AR over the other three adenosine receptor subtypes. This represents a significantly greater selectivity profile compared with the prototypical IB-MECA.
Original languageEnglish
Pages (from-to)192 - 196
Number of pages5
JournalMedChemComm
Volume5
Issue number2
DOIs
Publication statusPublished - 2014

Cite this

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title = "Design, synthesis and evaluation of N6-substituted 2-aminoadenosine-5'-N-methylcarboxamides as A3 adenosine receptor agonists",
abstract = "A series of N6-substituted 2-aminoadenosine-5 -N- methylcarboxamides were synthesized from the versatile intermediate, O 6-(benzotriazol-1-yl)-2-amino-2 ,3 -O- isopropylideneinosine-5 -N-methylcarboxamide (1). These compounds were evaluated as A3 adenosine receptor agonists in terms of their potency and receptor sub-type selectivity in a cAMP accumulation assay and a number of potent and selective compounds were identified. One such compound, 2-amino-N6-(3-chlorobenzyl)adenosine-5 -N-methylcarboxamide (3i), was over 500-fold selective for the A3AR over the other three adenosine receptor subtypes. This represents a significantly greater selectivity profile compared with the prototypical IB-MECA.",
author = "Shane Devine and May, {Lauren Therese} and Scammells, {Peter John}",
year = "2014",
doi = "10.1039/c3md00364g",
language = "English",
volume = "5",
pages = "192 -- 196",
journal = "MedChemComm",
issn = "2040-2503",
publisher = "The Royal Society of Chemistry",
number = "2",

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T1 - Design, synthesis and evaluation of N6-substituted 2-aminoadenosine-5'-N-methylcarboxamides as A3 adenosine receptor agonists

AU - Devine, Shane

AU - May, Lauren Therese

AU - Scammells, Peter John

PY - 2014

Y1 - 2014

N2 - A series of N6-substituted 2-aminoadenosine-5 -N- methylcarboxamides were synthesized from the versatile intermediate, O 6-(benzotriazol-1-yl)-2-amino-2 ,3 -O- isopropylideneinosine-5 -N-methylcarboxamide (1). These compounds were evaluated as A3 adenosine receptor agonists in terms of their potency and receptor sub-type selectivity in a cAMP accumulation assay and a number of potent and selective compounds were identified. One such compound, 2-amino-N6-(3-chlorobenzyl)adenosine-5 -N-methylcarboxamide (3i), was over 500-fold selective for the A3AR over the other three adenosine receptor subtypes. This represents a significantly greater selectivity profile compared with the prototypical IB-MECA.

AB - A series of N6-substituted 2-aminoadenosine-5 -N- methylcarboxamides were synthesized from the versatile intermediate, O 6-(benzotriazol-1-yl)-2-amino-2 ,3 -O- isopropylideneinosine-5 -N-methylcarboxamide (1). These compounds were evaluated as A3 adenosine receptor agonists in terms of their potency and receptor sub-type selectivity in a cAMP accumulation assay and a number of potent and selective compounds were identified. One such compound, 2-amino-N6-(3-chlorobenzyl)adenosine-5 -N-methylcarboxamide (3i), was over 500-fold selective for the A3AR over the other three adenosine receptor subtypes. This represents a significantly greater selectivity profile compared with the prototypical IB-MECA.

UR - http://pubs.rsc.org/en/Content/ArticleLanding/2014/MD/c3md00364g#!divAbstract

U2 - 10.1039/c3md00364g

DO - 10.1039/c3md00364g

M3 - Article

VL - 5

SP - 192

EP - 196

JO - MedChemComm

JF - MedChemComm

SN - 2040-2503

IS - 2

ER -