Synthesis of pseudoxazolones and their inhibition of the 3C cysteine proteinases from hepatitis A virus and human rhinovirus-14
Bibliographic record
Abstract
The hepatitis A virus (HAV) and human rhinovirus (HRV) are important pathogens that belong to the picornavirus family. All picornaviruses have a 3C proteinase that processes an initially biosynthesised precursor protein and is crucial for viral maturation and replication. Monophenyl and diphenyl pseudoxazolones were prepared by cyclisation–elimination of N-α-chloroacyl amino acids or by condensation of p-substituted benzamides with glyoxylic acid followed by dehydrative cyclisation. Such pseudoxazolones are good time-dependent inhibitors of the HAV and HRV 3C proteinases with IC50 values in the micromolar range. Mechanistic insights into the mode of inhibition of the pseudoxazolones were obtained from mass spectrometry and gHMQC NMR spectroscopy of the HAV 3C enzyme–inhibitor complex using a pseudoxazolone labelled at the α-carbon with 13C, 13b(α-13C). The results indicate that HAV 3C proteinase was inactivated via the formation of a thioether bond by nucleophilic attack of the enzyme thiolate at the imine position of the pseudoxazolone 13b(α-13C).
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".