ArticleChemical science2021
C-H functionalisation tolerant to polar groups could transform fragment-based drug discovery (FBDD).
Article in Chemical science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 35 citations in OpenAlex.
- SAFR: Enabling Fragment-Based Drug Discovery with a Synthetic Binding Pose Data Set.Journal of chemical information and modeling · 2026Article
- Developments and challenges in hit progression within fragment-based drug discovery.Nature communications · 2026Review
- Regio- and Stereocontrolled-Synthesis of a Heterocycle Fragment Collection Using Palladium Catalyzed C-H Arylation.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Modular Synthetic Platform for the Elaboration of Fragments in Three Dimensions for Fragment-Based Drug Discovery.Journal of the American Chemical Society · 2025Article
- A review of the known MTA-cooperative PRMT5 inhibitors.RSC advances · 2024Review
- Discovery of potent SARS-CoV-2 nsp3 macrodomain inhibitors uncovers lack of translation to cellular antiviral response.bioRxiv : the preprint server for biology · 2024Article
- Enabling synthesis in fragment-based drug discovery (FBDD): microscale high-throughput optimisation of the medicinal chemist's toolbox reactions.RSC medicinal chemistry · 2023Article
- Synthesis and vectorial functionalisation of pyrazolo[3,4-RSC advances · 2023Article
- Synthesis of spOrganic & biomolecular chemistry · 2023Article
- Accelerated Chemical Reaction Optimization Using Multi-Task Learning.ACS central science · 2023Article
- Green Drug Discovery: Novel Fragment Space from the Biomass-Derived Molecule Dihydrolevoglucosenone (CyreneMolecules (Basel, Switzerland) · 2023Article
- Fragment Libraries Designed to Be Functionally Diverse Recover Protein Binding Information More Efficiently Than Standard Structurally Diverse Libraries.Journal of medicinal chemistry · 2022Article
- Puckering the Planar Landscape of Fragments: Design and Synthesis of a 3D Cyclobutane Fragment Library.ChemMedChem · 2022Article
- Article
- Fragment-to-Lead Medicinal Chemistry Publications in 2020.Journal of medicinal chemistry · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have analysed 131 fragment-to-lead (F2L) examples targeting a wide variety of protein families published by academic and industrial laboratories between 2015-2019. Our assessment of X-ray structural data identifies the most common polar functional groups involved in fragment-protein binding are: N-H (hydrogen bond donors on aromatic and aliphatic N-H, amides and anilines; totalling 35%), aromatic nitrogen atoms (hydrogen bond acceptors; totalling 23%), and carbonyl oxygen group atoms (hydrogen bond acceptors on amides, ureas and ketones; totalling 22%). Furthermore, the elaboration of each fragment into its corresponding lead is analysed to identify the nominal synthetic growth vectors. In ∼80% of cases, growth originates from an aromatic or aliphatic carbon on the fragment and more than 50% of the total bonds formed are carbon-carbon bonds. This analysis reveals that growth from carbocentric vectors is key and therefore robust C-H functionalisation methods that tolerate the innate polar functionality on fragments could transform fragment-based drug discovery (FBDD). As a further resource to the community, we have provided the full data of our analysis as well as an online overlay page of the X-ray structures of the fragment hit and leads: https://astx.com/interactive/F2L-2021/.
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.