N‐Pyrazolyl‐ and N‐Triazolylamines and ‐Ureas as Antileishmanial and Antitrypanosomal Drugs
Bibliographic record
Abstract
Abstract Three types of modifications of antileishmanial pyrazole lead compounds 7 and 8 were conducted to expand understanding of the relationships between structural features and antileishmanial/antitrypanosomal activity: (1) the pyrazole core was retained or replaced by a 1,2,4‐triazole ring; (2) various aryl moieties including 2‐fluorophenyl, pyridin‐3‐yl and pyrazin‐2‐yl rings were attached at 3‐position of the core azole; (3) either arylmethylamino or ureido substituents were introduced at 5‐position of the azole core. The synthesis followed established routes starting with esters 9 or 15 and anhydride 21 . The synthesized 3‐arylpyrazoles and 3‐aryl‐1,2,4‐triazoles had only very low antileishmanial activity. The 2‐fluorophenyl‐substituted pyrazole 18c revealed the highest antileishmanial activity of this series of compounds, but its IC 50 value (20 μM) still indicates low activity. However, low micromolar antitrypanosomal activity was detected for the pyridin‐3‐yl‐substituted pyrazoles 12b ( IC 50 =4.7 μM) and 14a ( IC 50 =2.1 μM). Their IC 50 values are comparable with the IC 50 values of the reference compounds benznidazole and nifurtimox. Whereas only low unspecific cytotoxicity at the primary peritoneal mouse macrophages (PMM) was detected, considerable cytotoxicity at MRC‐5 human fibroblast cells was found for both pyrazoles 12b an 14a . The activity of pyrazole 12b against T. cruzi is 4‐fold higher than its unspecific MRC‐5 cytotoxicity.
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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".