Pyrrolotriazine-5-carboxylate ester inhibitors of EGFR and HER2 protein tyrosine kinases and a novel one-pot synthesis of C-4 subsitituted pyrrole-2,3-dicarboxylate diesters
Bibliographic record
Abstract
Pyrrolotriazines with an ester group at C-5 were prepared and evaluated as inhibitors of the EGFR and HER2 receptor tyrosine kinases, validated targets for cancer therapy. The C-5 ester (15) was at least as potent as its C-6 ester analogue (17), an example of a known series of pyrrolotriazine EGRF/HER2 kinase inhibitors that show good biochemical and cellular activity. The C-5 esters were synthesized from pyrrole 2,3-diesters that were made by a new, one-pot procedure. This involved reaction of readily available N-tosyl derivatives of α-amino acid esters or ketones with triphenylphosphine and diethyl acetylenedicarboxylate to form 3-pyrrolines via an intramolecular Wittig olefination. The 3-pyrroline intermediates were not isolated but treated directly with base to eliminate toluenesulfinic acid and generate the pyrrole 2,3-diesters in good yield.Key words: pyrrolotriazine, EGFR, HER2, pyrrole, intramolecular Wittig reaction.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".