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Record W4213215459 · doi:10.1002/cmdc.202100641

Expanding the Repertoire of Low‐Molecular‐Weight Pentafluorosulfanyl‐Substituted Scaffolds

2022· article· en· W4213215459 on OpenAlexfundno aff
Arathy Jose, Daniel Guest, Rémi Legay, Graham J. Tizzard, Simon J. Coles, Mariliza Derveni, Edward K. Wright, Lester Marrison, Alpha A. Lee, Aaron Morris, Matt Robinson, F. von Delft, D. Fearon, L. Koekemoer, Tetiana Matviuk, Anthony Aimon, Christopher J. Schofield, Tika R. Malla, Nir London, Barnaby W. Greenland, Mark C. Bagley, John Spencer

Bibliographic record

VenueChemMedChem · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBiochemical and Molecular Research
Canadian institutionsnot available
FundersInterregEuropean Regional Development FundBiotechnology and Biological Sciences Research CouncilMoonshot Research and Development ProgramEngineering and Physical Sciences Research CouncilShenzhen Gas CorporationInnovative Medicines InitiativeFundação de Apoio à Pesquisa do Distrito FederalConselho Nacional de Desenvolvimento Científico e TecnológicoNovartis PharmaCoordenação de Aperfeiçoamento de Pessoal de Nível SuperiorCancer Research UKOntario Ministry of Economic Development and InnovationMinistero dello Sviluppo EconomicoInternational Seafood Sustainability FoundationUniversity of SussexWellcome TrustEuropean Federation of Pharmaceutical Industries and AssociationsMerck KGaAGenome CanadaFundação de Amparo à Pesquisa do Estado de São PauloDiamond Light SourcePfizer
KeywordsLeflunomideBioisostereChemistryDihydroorotate dehydrogenaseIsoxazoleCombinatorial chemistryAmideTeriflunomidePharmacologyOxindoleStereochemistryMedicineBiochemistryChemical synthesisPyrimidineInternal medicineIn vitroRheumatoid arthritis

Abstract

fetched live from OpenAlex

Abstract The pentafluorosulfanyl (‐SF5) functional group is of increasing interest as a bioisostere in medicinal chemistry. A library of SF5‐containing compounds, including amide, isoxazole, and oxindole derivatives, was synthesised using a range of solution‐based and solventless methods, including microwave and ball‐mill techniques. The library was tested against targets including human dihydroorotate dehydrogenase (HDHODH). A subsequent focused approach led to synthesis of analogues of the clinically used disease modifying anti‐rheumatic drugs (DMARDs), Teriflunomide and Leflunomide, considered for potential COVID‐19 use, where SF5 bioisostere deployment led to improved inhibition of HDHODH compared with the parent drugs. The results demonstrate the utility of the SF5 group in medicinal chemistry.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0040.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.010
GPT teacher head0.256
Teacher spread0.246 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations10
Published2022
Admission routes1
Has abstractyes

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