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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 OpenAlex
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

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

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 (‐SF 5 ) functional group is of increasing interest as a bioisostere in medicinal chemistry. A library of SF 5 ‐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 SF 5 bioisostere deployment led to improved inhibition of HDHODH compared with the parent drugs. The results demonstrate the utility of the SF 5 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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.012
Threshold uncertainty score0.660

Codex and Gemma teacher scores by category

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 science0.0010.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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