ArticleJournal of medicinal chemistry2013
5'-Phosphate and 5'-phosphonate ester derivatives of (N)-methanocarba adenosine with in vivo cardioprotective activity.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 150 citations in OpenAlex.
- MRS2339, a cardiac P2X4 receptor nucleotide activator, improves systolic function in heart failure.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- Electrochemical Phosphorochalcogenations for the Synthesis of Phosphorochalcogenothioates.The Journal of organic chemistry · 2026Article
- Low-Valent-Tungsten-Catalyzed Aerobic Oxidative Cross-Dehydrogenative Coupling Reaction.Molecules (Basel, Switzerland) · 2023Article
- Photoinduced Synthesis of Sulfonyl-Containing Phosphorothioates via a Three-Component Reaction.Molecules (Basel, Switzerland) · 2023Article
- Gold-catalyzed alkenylation and arylation of phosphorothioates.Chemical science · 2023Article
- Visible-light-driven reactions for the synthesis of sulfur dioxide-inserted compounds: generation of S-F, S-O, and S-N bonds.RSC advances · 2023Review
- Bromide ion promoted practical synthesis of phosphinothioates of sulfinic acid derivatives and H-phosphine oxides.RSC advances · 2022Article
- Resolving the Ionotropic P2X4 Receptor Mystery Points Towards a New Therapeutic Target for Cardiovascular Diseases.International journal of molecular sciences · 2020Review
- Prevention and rescue of cardiac dysfunction by methanocarba adenosine monophosphonate derivatives.Purinergic signalling · 2020Article
- Polypharmacology of conformationally locked methanocarba nucleosides.Drug discovery today · 2017Review
- Molecular Structures of the Products of a Diphosphonate Ester Building Block with Lewis Bases.Molecules (Basel, Switzerland) · 2015Article
- Prodrugs of phosphonates and phosphates: crossing the membrane barrier.Topics in current chemistry · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Activation of a cardiac myocyte P2X4 receptor protects against heart failure. 5'-Phosphonate and 5'-phosphate analogues of AMP containing a (N)-methanocarba (bicyclo[3.1.0]hexane) system could protect from heart failure by potentially activating this cardioprotective channel. Phosphoesters and phosphonodiesters were synthesized and administered in vivo via a miniosmotic pump in a mouse ischemic heart failure model and most significantly increased intact heart contractile function (echocardiography) compared to vehicle infusion. Several new thio and deuterated phosphate derivatives were protective in a calsequestrin (CSQ) overexpressing heart failure model. Diethyl (7, MRS4084) and diisopropyl (8, MRS4074) phosphotriesters were highly protective in the ischemic model. Substitution of 2-Cl with iodo reduced protection in the CSQ model. Diisopropyl ester 16 (MRS2978) of (1'S,2'R,3'S,4'R,5'S)-4'-(6-amino-2-chloropurin-9-yl)-2',3'-(dihydroxy)-1'-(phosphonoethylene)bicyclo[3.1.0]hexane was highly efficacious (CSQ), while lower homologue 1'-phosphonomethylene derivative 14 was inactive. Thus, we identified uncharged carbocyclic nucleotide analogues that represent potential candidates for the treatment of heart failure, suggesting this as a viable and structurally broad approach.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.