ArticleJournal of medicinal chemistry2011
Potent, metabolically stable benzopyrimido-pyrrolo-oxazine-dione (BPO) CFTR inhibitors for polycystic kidney disease.
Article in Journal of medicinal chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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
37 citing papers in PubMed, 81 citations in OpenAlex.
- Epithelial plasma membrane transporters as drug targets.Physiological reviews · 2026Review
- Structure of CFTR bound to (R)-BPO-27 unveils a pore-blockage mechanism.Nature communications · 2025Article
- Review
- Gut epithelial electrical cues drive differential localization of enterobacteria.Nature microbiology · 2024Article
- Structural basis for CFTR inhibition by CFTRProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Repurposing calcium-sensing receptor activator drug cinacalcet for ADPKD treatment.Translational research : the journal of laboratory and clinical medicine · 2024Article
- Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling.Frontiers in molecular biosciences · 2022Review
- Chloride transport modulators as drug candidates.American journal of physiology. Cell physiology · 2021Review
- Recent advances in understanding ion transport mechanisms in polycystic kidney disease.Clinical science (London, England : 1979) · 2021Review
- Drug development in targeting ion channels for brain edema.Acta pharmacologica Sinica · 2020Article
- Cystic fibrosis transmembrane conductance regulator dysfunction in platelets drives lung hyperinflammation.The Journal of clinical investigation · 2020Article
- Inhibition of CFTR-mediated intestinal chloride secretion as potential therapy for bile acid diarrhea.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Intestinal epithelial potassium channels and CFTR chloride channels activated in ErbB tyrosine kinase inhibitor diarrhea.JCI insight · 2019Article
- High-Potency Phenylquinoxalinone Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Activators.Journal of medicinal chemistry · 2017Article
- Nanomolar-Potency Aminophenyl-1,3,5-triazine Activators of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Chloride Channel for Prosecretory Therapy of Dry Eye Diseases.Journal of medicinal chemistry · 2017Article
- Benzopyrimido-pyrrolo-oxazine-dione CFTR inhibitor (R)-BPO-27 for antisecretory therapy of diarrheas caused by bacterial enterotoxins.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- CFTR pharmacology.Cellular and molecular life sciences : CMLS · 2017Review
- Pathogen-induced secretory diarrhea and its prevention.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2016Review
- New Insights into the Molecular Mechanisms Targeting Tubular Channels/Transporters in PKD Development.Kidney diseases (Basel, Switzerland) · 2016Review
- Benzopyrimido-pyrrolo-oxazine-dione (R)-BPO-27 Inhibits CFTR Chloride Channel Gating by Competition with ATP.Molecular pharmacology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
We previously reported the discovery of pyrimido-pyrrolo-quinoxalinedione (PPQ) inhibitors of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel and showed their efficacy in an organ culture model of polycystic kidney disease (PKD) (J. Med. Chem. 2009, 52, 6447-6455). Here, we report related benzopyrimido-pyrrolo-oxazinedione (BPO) CFTR inhibitors. To establish structure-activity relationships and select lead compound(s) with improved potency, metabolic stability, and aqueous solubility compared to the most potent prior compound 8 (PPQ-102, IC(50) ∼ 90 nM), we synthesized 16 PPQ analogues and 11 BPO analogues. The analogues were efficiently synthesized in 5-6 steps and 11-61% overall yield. Modification of 8 by bromine substitution at the 5-position of the furan ring, replacement of the secondary amine with an ether bridge, and carboxylation, gave 6-(5-bromofuran-2-yl)-7,9-dimethyl-8,10-dioxo-11-phenyl-7,8,9,10-tetrahydro-6H-benzo[b]pyrimido [4',5':3,4]pyrrolo [1,2-d][1,4]oxazine-2-carboxylic acid 42 (BPO-27), which fully inhibited CFTR with IC(50) ∼ 8 nM and, compared to 8, had >10-fold greater metabolic stability and much greater polarity/aqueous solubility. In an embryonic kidney culture model of PKD, 42 prevented cyst growth with IC(50) ∼ 100 nM. Benzopyrimido-pyrrolo-oxazinediones such as 42 are potential development candidates for antisecretory therapy of PKD.
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.