ArticleJournal of medicinal chemistry2010
Structure-activity relationship of (N)-Methanocarba phosphonate analogues of 5'-AMP as cardioprotective agents acting through a cardiac P2X receptor.
Article in Journal of medicinal chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Enantioselective synthesis of axially chiral P-containing allenes for allenyl chirality.Chem catalysis · 2024Article
- Four-layer folding framework: design, GAP synthesis, and aggregation-induced emission.Frontiers in chemistry · 2023Article
- Deamination of 1-Aminoalkylphosphonic Acids: Reaction Intermediates and Selectivity.Molecules (Basel, Switzerland) · 2022Article
- Highly stereoselective and enantiodivergent synthesis of cyclopropylphosphonates with engineered carbene transferases.Chemical science · 2022Article
- IRSC advances · 2022Article
- SERS/TERS Characterization of New Potential Therapeutics: The Influence of Positional Isomerism, Interface Type, Oxidation State of Copper, and Incubation Time on Adsorption on the Surface of Copper(I) and (II) Oxide Nanoparticles.Journal of medicinal chemistry · 2022Article
- Copper(ii)-catalyzed tandem cyclization for the synthesis of benzo[RSC advances · 2020Article
- Prevention and rescue of cardiac dysfunction by methanocarba adenosine monophosphonate derivatives.Purinergic signalling · 2020Article
- Potential Therapeutic Role of Purinergic Receptors in Cardiovascular Disease Mediated by SARS-CoV-2.Journal of immunology research · 2020Review
- Identification of metabolically stable 5'-phosphate analogs that support single-stranded siRNA activity.Nucleic acids research · 2015Article
- Cardiac purinergic signalling in health and disease.Purinergic signalling · 2015Review
- 5'-Phosphate and 5'-phosphonate ester derivatives of (N)-methanocarba adenosine with in vivo cardioprotective activity.Journal of medicinal chemistry · 2013Article
- Synthesis and P2Y₂ receptor agonist activities of uridine 5'-phosphonate analogues.Bioorganic & medicinal chemistry · 2012Article
- AMP is an adenosine A1 receptor agonist.The Journal of biological chemistry · 2012Article
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Authors and funding
7 authors.
Funding
Abstract
P2X receptor activation protects in heart failure models. MRS2339 3, a 2-chloro-AMP derivative containing a (N)-methanocarba (bicyclo[3.1.0]hexane) system, activates this cardioprotective channel. Michaelis-Arbuzov and Wittig reactions provided phosphonate analogues of 3, expected to be stable in vivo due to the C-P bond. After chronic administration via a mini-osmotic pump (Alzet), some analogues significantly increased intact heart contractile function in calsequestrin-overexpressing mice (genetic model of heart failure) compared to vehicle-infused mice (all inactive at the vasodilatory P2Y(1) receptor). Two phosphonates, (1'S,2'R,3'S,4'R,5'S)-4'-(6-amino-2-chloropurin-9-yl)-2',3'-(dihydroxy)-1'-(phosphonomethylene)-bicyclo[3.1.0]hexane, 4 (MRS2775), and its homologue 9 (MRS2935), both 5'-saturated, containing a 2-Cl substitution, improved echocardiography-derived fractional shortening (20.25% and 19.26%, respectively, versus 13.78% in controls), while unsaturated 5'-extended phosphonates, all 2-H analogues, and a CH(3)-phosphonate were inactive. Thus, chronic administration of nucleotidase-resistant phosphonates conferred a beneficial effect, likely via cardiac P2X receptor activation. Thus, we have greatly expanded the range of carbocyclic nucleotide analogues that represent potential candidates for the treatment of heart failure.
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