ArticleNature chemistry2023
2-Oxabicyclo[2.1.1]hexanes as saturated bioisosteres of the ortho-substituted phenyl ring.
Article in Nature chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed.
- Highlights from the 59th Bürgenstock Conference on Stereochemistry 2026.Chemical science · 2026Article
- Lewis Acid-Catalyzed Strain-Enabled (3+3) Annulation of Bicyclo[1.1.0]Butanes With Indolylalcohols: Synthesis of Indole-Fused Aza-Bicyclo[3.1.1]Heptanes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Convergent synthesis of azabicyclo[4.1.1]octanes through the formal cycloaddition of bicyclobutanes with 2-azadienes.Chemical science · 2026Article
- Polar and e-Radical Strain-Release Strategies for Accessing Functionalized 2-Oxabicyclo[2.1.1]hexan-3-ones from Bicyclo[1.1.0]butanes.Organic letters · 2026Article
- Practical synthesis of 3-Oxa/Aza-bicyclo[3.1.1]heptanes from 3-Oxa/Aza[3.1.1]propellanes.Nature communications · 2026Article
- Article
- Programmable regiodivergent light-driven cyclization of acyclic 1,5-dienes unlocks rigid bicyclic architectures.Nature chemistry · 2026Article
- Modulating endergonic triplet photosensitization for cycloadditions between bicyclo[1.1.0]butanes and alkenes.Nature chemistry · 2026Article
- Strain-Release Pentafluorosulfanylation of Carbonyl-Containing Disubstituted Bicyclobutanes: A Fortuitous Path to SFAngewandte Chemie (International ed. in English) · 2026Article
- Concise synthesis and strain-release diversification of bridgehead-substituted [2]-ladderanes.Nature chemistry · 2026Article
- Catalytic endo-stereoselective [2+2] cycloaddition of norbornadienes with internal alkynes.Nature chemistry · 2026Article
- Pulsed electrolysis enables unexpected lactonization of bicyclobutane carboxylic acids.Chemical science · 2026Article
- Beyond para- and meta-Substitution: Synthesis and Biological Validation of Chalcogen-Rich Thiabicyclo[3.1.1]heptanes as Bioisosteres of Aryl Thioether Derivatives.Angewandte Chemie (International ed. in English) · 2026Article
- Electrochemical synthesis of 2-oxa-bicyclo[2.1.1]hexanes by anodic oxidation-cyclization relay strategy.Chemical science · 2026Article
- Collective synthesis of 1,2,4-trisubstituted, meta- and ortho-substituted arene bioisosteres from bicyclobutanes.Nature chemistry · 2026Article
- Enantioselective Synthesis of 2-Oxabicyclo[2.1.1]hexanes and Bicyclo[2.1.1]hexanes via Catalytic Asymmetric Intramolecular Photocycloadditions.Nature communications · 2026Article
- Thermal [2+2] cycloaddition as a route to gem-difluoro heterobicyclo[n.1.1]alkanes.Nature chemistry · 2026Article
- Lewis Acid-Catalyzed Divergent (4+3)/(4+2) Annulations ofOrganic letters · 2026Article
- Asymmetric C-H Functionalization of Bicyclo[2.1.1]hexanes and Their 2-Oxa- and 2-Aza Derivatives via Rhodium Carbene Intermediates.Journal of the American Chemical Society · 2026Article
- Divergent Synthesis of 1-Azabicyclo[n.1.1]alkane Bioisosteres via Photoinduced Palladium Catalysis.Journal of the American Chemical Society · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
The ortho-substituted phenyl ring is a basic structural element in chemistry. It is found in more than three hundred drugs and agrochemicals. During the past decade, scientists have tried to replace the phenyl ring in bioactive compounds with saturated bioisosteres to obtain novel patentable structures. However, most of the research in this area has been devoted to the replacement of the para-substituted phenyl ring. Here we have developed saturated bioisosteres of the ortho-substituted phenyl ring with improved physicochemical properties: 2-oxabicyclo[2.1.1]hexanes. Crystallographic analysis revealed that these structures and the ortho-substituted phenyl ring indeed have similar geometric properties. Replacement of the phenyl ring in marketed agrochemicals fluxapyroxad (BASF) and boscalid (BASF) with 2-oxabicyclo[2.1.1]hexanes dramatically improved their water solubility, reduced lipophilicity and most importantly retained bioactivity. This work suggests an opportunity for chemists to replace the ortho-substituted phenyl ring in bioactive compounds with saturated bioisosteres in medicinal chemistry and agrochemistry.
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.