Synthesis of three 18F-labelled cyclooxygenase-2 (COX-2) inhibitors based on a pyrimidine scaffold
Bibliographic record
Abstract
Cyclooxygenase (COX) is the key enzyme within the complex conversion of arachidonic acid into prostaglandins (PGs). Inhibitors of this enzyme represent a particularly promising class of compounds for chemoprevention and cancer therapy. The experimental data on the involvement of COX isoform COX-2 in tumour development and progression, as well as the observed overexpression of COX-2 in a variety of human cancers provide the rationale for targeting COX-2 for molecular imaging and therapy of cancer. A series of trifluoromethyl-substituted pyrimidines was prepared as a novel class of selective COX-2 inhibitors, based on the lead structure 1a. All compounds were tested in cyclooxygenase (COX) assays in vitro to determine COX-1 and COX-2 inhibitory potency and selectivity. Molecular docking studies using the catalytic site of COX-1 and COX-2, respectively, provided complementary theoretical support for the obtained experimental biological structure–activity relationship data of three highly potent and selective fluorobenzyl-containing COX-2 inhibitors. Selected fluorobenzyl-substituted pyrimidine derivatives were further developed as (18)F-labelled radiotracers ([(18)F]1a, [(18)F]2a, [(18)F]3a). Radiotracers [(18)F]1a and [(18)F]2a were radiolabelled using 4-[(18)F]fluorobenzylamine ([(18)F]FBA) as a building block. Radiotracer [(18)F]3a was radiofluorinated directly using a nucleophilic aromatic substitution reaction with no-carrier-added (n.c.a.) [(18)F]fluoride on an iodylaryl compound as a labelling precursor.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.003 | 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".