Bicyclic N,S-Acetals Containing Fused Cysteine-Amide System as New Heterocyclic Class Targeting Human Farnesyltransferase (FTase-h)
Bibliographic record
Abstract
We report in this contribution the synthesis and in vitro biological evaluation of a novel class of chiral thiazoloisoindolinone scaffolds as potent inhibitors against human farnesyltransferase (FTase-h). The targeted products, sulfides (4), sulfoxides (5,6), and sulfones (7), containing up to three points of diversification, were obtained in a short-step sequence starting from the available and cost-effective L-cysteine hydrochloride (1), which is the source of N and S atoms and the chiral pool, and α-carbonyl benzoic acids (2), which are isoindolinone precursors. Concisely, the key ester intermediates (1) provide (a) sulfide-amides (4) by solvent-free amidation, (b) sulfoxides (5,6) by selective S-oxidation using NaIO4, and (c) sulfones (7) by oxidation using MMPP. Finally, the obtained N,S-acetal systems have shown promising inhibitory activities on FTase-h in the nanomolar range with excellent half maximal inhibitory concentration (IC50) values up to 4.0 nanomolar (for example, 25.1 nM for sulfide 4bI, 67.3 nM for sulfone 7bG, and more interesting of 4.03 nM for sulfoxide 5bG).
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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 | 0.001 | 0.001 |
| 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".