Development and Application of Synthetic Methods for the Production of Small Molecule Libraries
Bibliographic record
Abstract
The synthesis of chemical libraries is a fundamental tool used to identify molecules with desirable biological activity. Recent developments in combinatorial synthesis techniques have allowed for the rapid generation of very large and diverse chemical libraries that can be used in conjunction with high-throughput screening (HTS) technology to identify lead molecules that can be potentially developed into pharmaceuticals. Libraries based around an oxindole scaffold (previously identified as inhibitors of cRAf1 kinase) were recently shown to display inhibitory effects against aminoglycoside phosphotransferases (APH) enzymes found in bacteria responsible for antibiotic resistance to aminoglycosides. Additionally, substituted quinazolines (similar in structure to the known drug Lapatinib) were identified as a potent inhibitor of both APH(2”)Id and ANT(2”). The present thesis involves the development of synthetic protocols suitable for the generation and subsequent biotesting of chemical libraries based around these hits in order to determine the pharmacophore in each case.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".