ArticleJournal of medicinal chemistry2012
Structure-based discovery of highly selective phosphodiesterase-9A inhibitors and implications for inhibitor design.
Article in Journal of medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed.
- Review
- Virtual Screening-Accelerated Discovery of a Phosphodiesterase 9 Inhibitor with Neuroprotective Effects in the Kainate Toxicity In Vitro Model.ACS chemical neuroscience · 2023Article
- Computational Study on Selective PDE9 Inhibitors on PDE9-Mg/Mg, PDE9-Zn/Mg, and PDE9-Zn/Zn Systems.Biomolecules · 2021Article
- A Perspective on Natural and Nature-Inspired Small Molecules Targeting Phosphodiesterase 9 (PDE9): Chances and Challenges against Neurodegeneration.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Role of Phosphodiesterase in the Biology and Pathology of Diabetes.International journal of molecular sciences · 2020Review
- Discovery of novel PDE9A inhibitors with antioxidant activities for treatment of Alzheimer's disease.Journal of enzyme inhibition and medicinal chemistry · 2018Article
- A novel PDE9 inhibitor WYQ-C36D ameliorates corticosterone-induced neurotoxicity and depression-like behaviors by cGMP-CREB-related signaling.CNS neuroscience & therapeutics · 2018Article
- Structure-based design, synthesis, and biological evaluation of novel pyrimidinone derivatives as PDE9 inhibitors.Acta pharmaceutica Sinica. B · 2018Article
- Discovery of novel PDE9 inhibitors capable of inhibiting Aβ aggregation as potential candidates for the treatment of Alzheimer's disease.Scientific reports · 2016Article
- Structural Asymmetry of Phosphodiesterase-9A and a Unique Pocket for Selective Binding of a Potent Enantiomeric Inhibitor.Molecular pharmacology · 2015Article
- A convenient four-component one-pot strategy toward the synthesis of pyrazolo[3,4-d]pyrimidines.Beilstein journal of organic chemistry · 2015Article
- Cyclic nucleotide phosphodiesterases: important signaling modulators and therapeutic targets.Oral diseases · 2015Review
- Discovery of a phosphodiesterase 9A inhibitor as a potential hypoglycemic agent.Journal of medicinal chemistry · 2014Article
- Advances in targeting cyclic nucleotide phosphodiesterases.Nature reviews. Drug discovery · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
A new series of phosphodiesterase-9 (PDE9) inhibitors that contain a scaffold of 6-amino-pyrazolopyrimidinone have been discovered by a combination of structure-based design and computational docking. This procedure significantly saved the load of chemical synthesis and is an effective method for the discovery of inhibitors. The best compound 28 has an IC(50) of 21 nM and 3.3 μM, respectively, for PDE9 and PDE5 and about 3 orders of magnitude of selectivity against other PDE families. The crystal structure of the PDE9 catalytic domain in complex with 28 has been determined and shows a hydrogen bond between 28 and Tyr424. This hydrogen bond may account for the 860-fold selectivity of 28 against PDE1B, in comparison with about 30-fold selectivity of BAY73-6691. Thus, our studies suggest that Tyr424, a unique residue of PDE8 and PDE9, is a potential target for improvement of selectivity of PDE9 inhibitors.
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.